GEL COMPOSITION FOR CELLULAR ADHESION INHIBITION
First Claim
1. A composition for inhibiting cellular adhesion comprising:
- 0.1 to 8 weight percent of a cellular adhesion inhibitory agent based upon the total weight of the composition, the inhibitory agent being selected from the group consisting of alginate, chondroitan sulfate, dermatan sulfate, dextran sulfate, hyaluronic acid, heparin, heparin sulfate, keratan sulfate, and pentosan polysulfate; and
92 to 99.9 weight percent of a crosslinked hydrogel matrix based upon the total weight of the composition, the crosslinked hydrogel matrix comprising;
a first hydrogel component comprising a polyethylene glycol polymer having at least one electrophilic group; and
at least one additional hydrogel component having at least one nucleophilic group, the at least one additional hydrogel component being selected from the group consisting of polyethylene glycol polymers, polypeptides, and polysaccharides.
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Abstract
The invention includes compositions for inhibiting cellular adhesion, methods of preparation of such compositions, and methods for preventing cell adhesion at a surgical site comprising application of such compositions. The compositions generally comprise a cellular adhesion inhibitory agent, such as dextran sulfate, and a crosslinked hydrogel matrix, preferentially physically entrapping the adhesion inhibitory agent. The hydrogel matrix can include a first gel component, such as an electrophilically functionalized polyethylene glycol polymer, and at least one additional gel component, preferably nucleophilically functionalized, and preferentially selected from the group consisting of polyethylene glycol polymers, polypeptides, and polysaccharides. The compositions are useful for delivering the cellular adhesion inhibitory agent to a site in need of adhesion inhibition and providing either immediate or metered delivery of the inhibitory agent.
77 Citations
41 Claims
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1. A composition for inhibiting cellular adhesion comprising:
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0.1 to 8 weight percent of a cellular adhesion inhibitory agent based upon the total weight of the composition, the inhibitory agent being selected from the group consisting of alginate, chondroitan sulfate, dermatan sulfate, dextran sulfate, hyaluronic acid, heparin, heparin sulfate, keratan sulfate, and pentosan polysulfate; and
92 to 99.9 weight percent of a crosslinked hydrogel matrix based upon the total weight of the composition, the crosslinked hydrogel matrix comprising;
a first hydrogel component comprising a polyethylene glycol polymer having at least one electrophilic group; and
at least one additional hydrogel component having at least one nucleophilic group, the at least one additional hydrogel component being selected from the group consisting of polyethylene glycol polymers, polypeptides, and polysaccharides. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17, 18, 19, 20, 21, 22, 23)
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16. The composition according to claim 16, wherein the at least one additional hydrogel component includes collagen.
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24. A method for preparing a cell anti-adhesive crosslinked hydrogel matrix comprising:
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providing a first gel component comprising a polyethylene glycol polymer having one or more electrophilic groups;
combining the first gel component with at least one cellular adhesion inhibitory agent selected from the group consisting of alginate, chondroitan sulfate, dermatan sulfate, dextran sulfate, hyaluronic acid, heparin, heparin sulfate, keratan sulfate, and pentosan polysulfate; and
reacting the first gel component with a second gel component having one or more nucleophilic groups, the second gel component being selected from the group consisting of polyethylene glycol polymers, polypeptides, and polysaccharides, thereby forming a crosslinked hydrogel matrix and physically entrapping the at least one cellular adhesion inhibitory agent within the matrix. - View Dependent Claims (25, 26, 27, 28, 29, 30)
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31. A method for preparing a cell anti-adhesive crosslinked hydrogel matrix comprising:
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providing a first gel component comprising a polyethylene glycol polymer having one or more electrophilic groups;
mixing the first gel component with chitosan;
providing a second gel component comprising a polyethylene glycol polymer having one or more nucleophilic groups;
combining the second gel component with at least one cellular adhesion inhibitory agent selected from the group consisting of alginate, chondroitan sulfate, dermatan sulfate, dextran sulfate, hyaluronic acid, heparin, heparin sulfate, keratan sulfate, and pentosan sulfate; and
reacting the second gel component with the first gel component to form a crosslinked hydrogel matrix, physically entrapping the cellular adhesion inhibitory agent within the matrix. - View Dependent Claims (32, 33, 34, 35, 36)
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37. A method for preparing a cell anti-adhesive crosslinked hydrogel matrix comprising:
- combining (a) at least one cellular adhesion inhibitory agent selected from the group consisting of alginate, chondroitan sulfate, dermatan sulfate, dextran sulfate, hyaluronic acid, heparin, heparin sulfate, keratan sulfate, and pentosan sulfate,
(b) a first polyethylene glycol polymer having at least one electrophilic group, (c) a second polyethylene glycol polymer having at least one nucleophilic group, and (d) optionally, a polysaccharide, to form a cell anti-adhesive combination;
wherein each of the at least one cellular adhesion inhibitory agent, first polyethylene glycol polymer, second polyethylene glycol polymer and optional polysaccharide are in a non-hydrated form; and
hydrating the cell anti-adhesive combination to form a cell anti-adhesive crosslinked hydrogel matrix.
- combining (a) at least one cellular adhesion inhibitory agent selected from the group consisting of alginate, chondroitan sulfate, dermatan sulfate, dextran sulfate, hyaluronic acid, heparin, heparin sulfate, keratan sulfate, and pentosan sulfate,
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38. A method for preventing cell adhesion at a surgical site comprising:
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(a) providing a cell anti-adhesive crosslinked hydrogel matrix, wherein the hydrogel matrix comprises;
(i) 0.1 to 8 weight percent of a cellular adhesion inhibitory agent selected from the group consisting of alginate, chondroitan sulfate, dermatan sulfate, dextran sulfate, hyaluronic acid, heparin, heparin sulfate, keratan sulfate, and pentosan polysulfate; and
(ii) 92 to 99.9 weight percent of a crosslinked hydrogel matrix based upon the total weight of the composition, the crosslinked hydrogel matrix comprising;
a first hydrogel component comprising a polyethylene glycol polymer having at least one electrophilic group; and
at least one additional hydrogel component having at least one nucleophilic group, the at least one additional hydrogel component being selected from the group consisting of polyethylene glycol polymers, polypeptides, and polysaccharides; and
(b) applying the cell anti-adhesive crosslinked hydrogel matrix to a surgical site where cell adhesion prevention is desired. - View Dependent Claims (39, 40, 41)
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Specification