Solid polyglycol-based biocompatible pre-formulation
View Patent ↗Provided herein are pre-formulations forming a biocompatible hydrogel polymer comprising at least one nucleophilic compound or monomer unit, at least one electrophilic compound or monomer unit, and optionally a therapeutic agent and/or viscosity enhancer. In some embodiments, the biocompatible hydrogel polymer covers a wound in a mammal and adheres to the surrounding skin tissue. In other embodiments, the hydrogel polymer is delivered into a joint space to treat joint disease or navicular disease.
1. A solid polyglycol-based, fully synthetic, pre-formulation, comprising:
(a) at least one solid first compound comprising more than two nucleophilic groups;
(b) at least one solid second compound comprising more than two electrophilic groups;
(c) optionally, a solid buffer component;
(d) optionally, a solid therapeutic agent; and
(e) optionally, a solid viscosity enhancer
wherein the solid polyglycol-based, fully synthetic, pre-formulation polymerizes and/or gels to form a polyglycol-based, fully synthetic, biocompatible hydrogel polymer after addition of a liquid component, wherein the liquid component does not contain any first compound or second compound, and provided that the solid polyglycol-based, fully synthetic, pre-formulation does not contain any aqueous component.
2. The solid polyglycol-based, fully synthetic, pre-formulation of claim 1 , wherein the liquid component comprises water, saline, a buffer, a therapeutic agent or a combination thereof.
3. The solid polyglycol-based, fully synthetic, pre-formulation of claim 1 , wherein the nucleophilic group comprises a thiol or amino group.
4. The solid polyglycol-based, fully synthetic, pre-formulation of claim 1 , wherein the solid first compound is a MULTIARM (5k-50k) polyol derivative comprising polyglycol subunits and more than two nucleophilic groups.
5. The solid polyglycol-based, fully synthetic, pre-formulation of claim 1 , wherein the electrophilic group comprises an epoxide, N-succinimidyl succinate, N-succinimidyl glutarate, N-succinimidyl succinamide or N-succinimidyl glutaramide.
6. The solid polyglyol-based, fully synthetic, pre-formulation of claim 1 , wherein the solid second compound is a MULTIARM (5k-50k) polyol derivative comprising polyglycol subunits and more than two electrophilic groups.
7. The solid polyglycol-based, fully synthetic pre-formulation of claim 1 , wherein the solid first compound is a MULTIARM-(5-50k)-SH, a MULTIARM-(5-50k)-NH2, a MULTIARM-(5-50k)-AA, or a combination thereof, and the second compound is a MULTIARM-(5-50k)-SG, a MULTIARM-(5-50k)-SGA, a MULTIARM-(5-50k)-SS, or a combination thereof.
8. The solid polyglycol-based, fully synthetic pre-formulation of claim 7 , wherein the solid first compound is 4ARM-5k-SH, 4ARM-2k-NH2, 4ARM-5k-NH2, 8ARM-20k-NH2, 4ARM-20k-AA, 8ARM-20k-AA, or a combination thereof, and the second compound is 4ARM-10k-SG, 8ARM-15k-SG, 4ARM-20k-SGA, 4ARM-10k-SS, or a combination thereof.
9. The solid polyglycol-based pre-formulation of claim 8 , wherein the solid first compound is 8ARM-20k-NH2 and/or 8ARM-20k-AA, and the second compound is 4ARM-20k-SGA.
10. The solid polyglycol-based, fully synthetic, pre-formulation of claim 2 , wherein the therapeutic agent is selected from an antibacterial agent, an antifungal agent, an immunosuppressant agent, an anti-inflammatory agent, a bisphosphonate, gallium nitrate, stem cells, an antiseptic agent, and a lubricity agent.
11. The solid polyglycol-based, fully synthetic, pre-formulation of claim 10 wherein the therapeutic agent is a lubricity agent.
12. The solid polyglycol-based, fully synthetic, pre-formulation of claim 11 , wherein the lubricity agent is hyaluronic acid.
13. The polyglycol-based, fully synthetic, biocompatible hydrogel polymer of claim 1 .
14. The solid polyglycol-based, fully synthetic, pre-formulation of claim 1 , wherein the solid therapeutic agent is selected from an antibacterial agent, an antifungal agent, an immunosuppressant agent, an anti-inflammatory agent, a bisphosphonate, gallium nitrate, stem cells, an antiseptic agent, and a lubricity agent.
15. The solid polyglycol-based, fully synthetic, pre-formulation of claim 14 , wherein the solid therapeutic agent is a lubricity agent.
16. The solid polyglycol-based, fully synthetic, pre-formulation of claim 15 , wherein the lubricity agent is hyaluronic acid.