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US 2017/0246340 A1Published application
Bioadhesive for occluding vessels
AssigneeCovidien LP
InventorGaurav Girdhar
Life of this patent
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Abstract
Bioadhesives and crosslinked gels therefrom are disclosed. The bioadhesives can be applied to a vessel for occluding the vessel. The present disclosure also describes kits that comprise the various components for preparing and applying the bioadhesives. Bioadhesives of the present disclosure include: (i) a biopolymer having one or more first chemically reactive amine groups; (ii) a biocompatible crosslinker having at least two second chemically reactive groups that can chemically react with the one or more first chemically reactive amine groups of the biopolymer; and (iii) a biocompatible rheological modifier.
Claims26
1:
- A method of treating a vascular malformation of a mammal, the method comprising:
- injecting a bioadhesive into a vascular malformation of a mammal to displace blood in the malformation and prevent blood flow back into the malformation and to crosslink the bioadhesive in the malformation to form an occlusion in the malformation,
- wherein the bioadhesive comprises:
- (i) a biopolymer having one or more first chemically reactive amine groups;
- (ii) a biocompatible crosslinker having at least two second chemically reactive groups that can chemically react with the one or more first chemically reactive amine groups of the biopolymer;
- and (iii) a biocompatible rheological modifier, and
- wherein the biopolymer and crosslinker form a crosslinked network and the biocompatible rheological modifier does not substantially react with the biopolymer or the biocompatible crosslinker.
4 more elements
2:
- The method of claim 1 wherein the biocompatible rheological modifier has a viscosity sufficient to displace fluid within the malformation while the biopolymer and biocompatible crosslinker crosslink.
3:
- The method of claim 1 comprising injecting the bioadhesive into the malformation by a syringe.
4:
- The method of claim 1 further comprising preparing the bioadhesive by combining the biopolymer, the biocompatible crosslinker and the biocompatible rheological modifier prior to injecting the bioadhesive into the malformation.
The method of claim 1 wherein the bioadhesive has a gelation time of between 0.5 minute and 40 minutes.
6:
- The method of claim 1, wherein the rheological modifier displaces blood and prevents blood flow back into the blood malformation while the biopolymer crosslinks with the biocompatible crosslinker.
7:
- The method of claim 1, wherein the rheological modifier is absorbed into tissue surrounding the blood malformation after the bioadhesive has crosslinked.
8:
- The method of claim 1 wherein the biocompatible rheological modifier is a shear thinning fluid with a non-sheared viscosity between 0.5 Pa·s and 200 Pa·s.
9:
- The method of claim 1 wherein the biopolymer is an albumin having one or more primary amines as the first chemically reactive amine groups, the biocompatible crosslinker is a multi-arm PEG having at least two or more N-hydroxysuccinimide ester groups as the second chemically reactive groups and the biocompatible rheological modifier is sodium hyaluronate.
10:
- The method of claim 1 wherein the biopolymer is a protein or a polysaccharide having one or more primary amines as the first chemically reactive groups.
11:
- The method of claim 1 wherein the biopolymer is albumin.
12:
- The method of claim 1 wherein the biocompatible cross linker is a multi-arm polyethylene glycol (PEG) having at least two or more N-hydroxysuccinimide (NHS) ester groups as the second chemically reactive groups.
13:
- The method of claim 1 wherein the biocompatible rheological modifier is hyaluronic acid or a salt thereof.
14:
- The method of claim 13 wherein the hyaluronic acid or salt thereof has a non-sheared viscosity between 0.5 Pa·s and 200 Pa·s.
15:
- The method of claim 1 wherein the concentration of the biopolymer in the bioadhesive is less than 15 wt %.
16:
- The method of claim 1 wherein the bioadhesive has a pH of less than 7.4.
17:
- The method of claim 1 wherein the biopolymer crosslinks with the biocompatible crosslinker to form a bioadhesive gel.
18:
- The method of claim 1, wherein the bioadhesive has a gelation time of between 5 minutes and 40 minutes.
19:
- The method of claim 1 wherein the bioadhesive has a pH of between about 6.5 and about 5.0.
20:
- The method of claim 1 wherein the occluded malformation is absorbed into surrounding tissue over time after injection of the bioadhesive into the malformation.
21:
- The method of claim 1 wherein the vascular malformation comprises an aneurysm.
22:
- The method of claim 1 wherein the vascular malformation comprises an AVM.
23:
- The method of claim 1 wherein the vascular malformation comprises a fistula.
24:
- The method of claim 1 wherein the biopolymer comprises chitosan.
25:
- The method of claim 1 wherein the biocompatible crosslinker comprises genipin.
26:
- The method of claim 1 wherein the rheological modifier comprises hydroxypropylmethyl cellulose (HPMC).
Dependencies are inferred from the claim text.