USE OF IN SITU SOLIDIFYING INJECTABLE COMPOSITIONS FOR FILLING A VOID IN A SUBJECT
Described herein are injectable compositions that have properties suited for filling a void in a subject. The injectable compositions are composed of (i) one or more polycationic polyelectrolytes and anionic counterions and (ii) one or more one polyanionic polyelectrolytes and cationic counterions. The injectable compositions have an ion concentration that is sufficient to prevent association of the polycationic polyelectrolytes and the polyanionic polyelectrolytes in water. For example, the counterions are of sufficient concentration to prevent the polycations and polyanions from associating electrostatically, which results in the formation of a stable injectable composition. Upon introduction of the composition into a subject, a solid is produced in situ. The viscosity of the injectable compositions can be varied depending upon the application of the injectable composition. By varying the molecular weight, charge densities, and/or concentrations of the polycationic and polyanionic salts, it is possible to produce injectable compositions having a useful range of viscosities.
1 . A method for filling a void in a subject comprising introducing into the void a composition comprising water, one or more polycationic polyelectrolytes and anionic counterions, and one or more one polyanionic polyelectrolytes and cationic counterions, wherein the composition has an ion concentration that is (i) sufficient to prevent association of the polycationic polyelectrolytes and the polyanionic polyelectrolytes in water and (ii) greater than the concentration of ions in the subject, whereupon introduction of the composition into the subject a solid is produced in situ in the void of the subject.
2 . The method of claim 1 , wherein the void is within a bone, muscle, skin, cartilage, tissue, or organ or the void is a pouch or sac attached to a bone, muscle, skin, cartilage, tissue, or organ in the subject.
3 . The method of claim 1 , wherein the void is a left atrial appendage.
4 . The method of claim 1 , wherein the void is in a lymph node.
5 . The method of claim 1 , wherein the composition is introduced into the void by a catheter or needle.
6 . The method of claim 1 , wherein the total positive/negative charge ratio of the polycationic polyelectrolytes to the polyanionic polyelectrolytes is from 4 to 0.25 and the ion concentration in the composition is from 0.5 M to 2.0 M.
7 . The method of claim 1 , wherein the concentration of the polycationic polyelectrolytes and the polyanionic polyelectrolytes is sufficient to yield a charge ratio of polycationic polyelectrolytes to polyanionic polyelectrolytes from 0.5:1 to 2:1.
8 . The method of claim 1 , wherein the polycationic polyelectrolyte is derived from a polycationic hydrochloride salt in water.
9 . The method of claim 1 , wherein the polycationic polyelectrolyte is derived by dissolving a polycationic salt in water.
10 . The method of claim 9 , wherein the polycationic salt comprises a pharmaceutically-acceptable salt of a polyamine.
11 . The method of claim 9 , wherein the polycationic salt comprises a pharmaceutically-acceptable salt of a protamine, salmine, or clupein.
12 . The method of claim 9 , wherein the polycationic salt is a pharmaceutically-acceptable salt of natural polymer or a synthetic polymer containing two or more guanidinyl sidechains.
13 . The method of claim 9 , wherein the polycationic salt comprises a pharmaceutically-acceptable salt of a polyacrylate comprising two or more pendant guanidinyl groups.
14 . The method of claim 9 , wherein the polycationic salt comprises a pharmaceutically-acceptable salt of a synthetic polyguanidinyl copolymer comprising an acrylate, methacrylate, acrylamide, or methacrylamide backbone and two or more guanidinyl groups pendant to the backbone.
15 . The method of claim 9 , wherein the polycationic salt comprises a pharmaceutically-acceptable salt of a synthetic polyguanidinyl copolymer comprising the polymerization product between a monomer selected from the group consisting of an acrylate, a methacrylate, an acrylamide, a methacrylamide, or any combination thereof and a pharmaceutically-acceptable salt of compound of formula I
wherein R 1 is hydrogen or an alkyl group, X is oxygen or NR 5 , where R 5 is hydrogen or an alkyl group, and m is from 1 to 10.
16 . The method of claim 1 , wherein the polyanionic polyelectrolyte is derived by dissolving a polyanionic salt in water.
17 . The method of claim 16 , wherein the polyanionic salt comprises a pharmaceutically-acceptable salt of an inorganic polyphosphate, an organic polyphosphate, or a phosphorylated sugar.
18 . The method of claim 16 , wherein the polyanionic salt comprises a hexametaphosphate salt.
19 . The method of claim 16 , wherein the polyanionic salt comprises sodium hexametaphosphate.
20 . The method of claim 1 , wherein the composition further comprises a contrast agent, a reinforcing component, a bioactive agent, or any combination thereof.