Hydroswellable, Segmented, Aliphatic Polyurethanes and Polyurethane Ureas

Abstract

Hydroswellable, absorbable and non-absorbable, aliphatic, segmented polyurethanes and polyurethane-urea capable of swelling in the biological environment with associated increase in volume of at least 3 percent have more than one type of segments, including those derived from polyethylene glycol and the molecular chains are structurally tailored to allow the use of corresponding formulations and medical devices as carriers for bioactive agents, rheological modifiers of cyanoacrylate-based tissue adhesives, as protective devices for repairing defective or diseased components of articulating joints and their cartilage, and scaffolds for cartilage tissue engineering.

Description

[0001]The present application claims the benefit of prior provisional application, U.S. Ser. No. 61 / 069,046, filed Mar. 12, 2008.FIELD OF THE INVENTION[0002]The present invention is directed to hydroswellable (or water-swellable) absorbable and non-absorbable aliphatic, segmented polyurethanes and polyurethane-ureas, which can undergo swelling when placed in the biological environment manifested through an at least 3 percent increase in volume by virtue of having a highly hydrophilic polyalkylene oxide as an inherent part of their segmented chain molecules. By varying the type and fraction of the different segments constituting the copolymers, their pharmaceutical and biomedical applications as non-absorbable and absorbable materials entail their use in carriers for the controlled release of bioactive agents, rheological modifiers of absorbable and non-absorbable cyanoacrylate tissue adhesives, synthetic cartilage-like materials, and scaffolds for tissue engineering cartilage tissue...

AI Technical Summary

Benefits of technology

[0009]A clinically important aspect of the invention deals with a hydroswellable, segmented, aliphatic polyurethane-urea comprising polyoxyalkylene chains covalently interlinked with polyalkylene urethane segments, which are further interlinked with aliphatic urea chain segments, the composition exhibiting at least 5 percent increase in volume when placed in the biological environment, wherein the polyurethane-urea (1) can be chemically crosslinked, wherein the crosslinking is achieved using an alkylene diisocyanate; (2) can exhibit microporosity with a practically continuous cellular structure; (3) can comprise at least one covalently bonded aromatic group to stabilize the chain against radiation and oxidation degradation; and / or (4) can be used as an artificial cartilage for restoring the function of diseased or defective articulating joints in humans and animals.

[0011]For prolonged effective device performance, the present invention is directed to a hydroswellable, segmented, aliphatic polyurethane-urea comprising a combination of linear functionalized polysiloxane and polyoxyalkylene chains interlinked with polyalkylene urethane segments, which are further interlinked with aliphatic urea chain segments, the composition exhibiting at least 5 percent increase in volume when placed in the biological environment, wherein the polyoxyalkylene chain comprises at least one type of oxyalkylene sequences selected from the group represented by oxyethylene, oxypropylene, oxytrimethylene, and oxytetramethylene repeat units and the functionalized polysiloxane is derived from bis-hydroxyalkyl-terminated polysiloxane comprising at least dimethoxysiloxane internal sequences and two hydroxyalkyl or aminoalkyl terminals and further wherein the urethane segments are derived from at least one diisocyanate selected from the group represented by hexamethylene diisocyanate, octamethylene diisocyanate, decamethylene diisocyanate, dodecamethylene diisocyanate, 1,4 cyclohexane diisocyanate, lysine-derived diisocyanate, and cyclohexane bis(methylene isocyanate) and wherein the resulting polyoxyalkylene urethane molecules having at least one isocyanate terminal group are further chain-extended with an alkylene diamine selected from the group represented by ethylene-, trimethylene, tetramethylene-, hexamethylene- and octamethylene-diamine, thus forming polyetherurethane-urea segmented chains, wherein the polyurethane-urea (1) can be chemically crosslinked wherein the crosslinking is achieved using an alkylene diisocyanate; (2) can exhibit microporosity with a practically continuous cellular structure; (3) can comprise at least one covalently bonded aromatic group to stabilize the chain against radiation and oxidation degradation; and / or (4) can be used as an artificial cartilage for restoring the function of diseased or defective articulating joints in humans and animals.

Problems solved by technology

Of the cited drawbacks are those associated with (1) the generation of aromatic diamines, which are considered to be toxic upon degradation of segmented copolymers made using aromatic diisocyanates for interlinking; (2) chain degradation due to oxidation or radiation degradation of the polyether component of segmented copolymers, and particularly those which encounter frequent mechanical stresses in the biological environment; and (3) chemical degradation in chemically and mechanically hostile biological environments of the urethane links of segmented copolymers and particularly those comprising reactive aromatic urethane linkages.

However, the prior art is virtually silent on self-standing PEU and PEUU liquid solventless compositions for use in pharmaceutical formulations and / or medical devices.

Similarly, the prior art on polyether-urethanes is practically silent on hydroswellable (or water-swellable) systems, in spite of the fact that it covered elastomeric, segmented, hydrophilic polyether-urethane-based, lubricious coating compositions based on aromatic diisocyanate and polyethylene glycol (U.S. Pat. No. 4,990,357)—it did not suggest a self-standing material for medical device applications.