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 method of treating wounds of a mammal by delivering 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 at a target site of the wound 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 method of claim 1 , wherein the mammal is a human or an animal.
3. The method of claim 1 , wherein the liquid component comprises water, saline, a buffer, a therapeutic agent, or a combination thereof.
4. The method of claim 1 , wherein the solid first compound is a MULTIARM (5k-50k) polyol derivative comprising polyglycol subunits and more than two nucleophilic groups, and wherein the solid second compound is a MULTIARM (5k-50k) polyol derivative comprising polyglycol subunits and more than two electrophilic groups.
5. The method of claim 4 , 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 solid second compound is a MULTIARM-(5-50k)-SG, a MULTIARM-(5-50k)-SGA, a MULTIARM-(5-50k)-SS, or a combination thereof.
6. The method of claim 5 , 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 solid second compound is 4ARM-10k-SG, 8ARM-15k-SG, 4ARM-20k-SGA, 4ARM-10k-SS, or a combination thereof.
7. The method of claim 6 , wherein the solid first compound is 8ARM-20k-NH2 and/or 8ARM-20k-AA, and the solid second compound is 4ARM-20k-SGA.
8. A method of treating arthritis in a joint space in a mammal by delivering 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 at a target site in the joint space 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.
9. The method of claim 8 , wherein the mammal is a human or an animal.
10. The method of claim 8 , wherein the liquid component comprises water, saline, a buffer, a therapeutic agent or a combination thereof.
11. The method of claim 8 , wherein the solid first compound is a MULTIARM (5k-50k) polyol derivative comprising polyglycol subunits and more than two nucleophilic groups, and wherein the solid second compound is a MULTIARM (5k-50k) polyol derivative comprising polyglycol subunits and more than two electrophilic groups.
12. The method of claim 11 , 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 solid second compound is a MULTIARM-(5-50k)-SG, a MULTIARM-(5-50k)-SGA, a MULTIARM-(5-50k)-SS, or a combination thereof.
13. The method of claim 12 , 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 solid second compound is 4ARM-10k-SG, 8ARM-15k-SG, 4ARM-20k-SGA, 4ARM-10k-SS, or a combination thereof.
14. The method of claim 13 , wherein the solid first compound is 8ARM-20k-NH2 and/or 8ARM-20k-AA, and the solid second compound is 4ARM-20k-SGA.
15. A method of treating navicular disease in a hoof of a horse by delivering 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 at a target site in the hoof of the horse 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.
16. The method of claim 15 , wherein the liquid component comprises water, saline, a buffer, a therapeutic agent or a combination thereof.
17. The method of claim 15 , wherein the solid first compound is a MULTIARM (5k-50k) polyol derivative comprising polyglycol subunits and more than two nucleophilic groups, and wherein the solid second compound is a MULTIARM (5k-50k) polyol derivative comprising polyglycol subunits and more than two electrophilic groups.
18. The method of claim 17 , 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 solid second compound is a MULTIARM-(5-50k)-SG, a MULTIARM-(5-50k)-SGA, a MULTIARM-(5-50k)-SS, or a combination thereof.
19. The method of claim 18 , 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 solid second compound is 4ARM-10k-SG, 8ARM-15k-SG, 4ARM-20k-SGA, 4ARM-10k-SS, or a combination thereof.
20. The method of claim 19 , wherein the solid first compound is 8ARM-20k-NH2 and/or 8ARM-20k-AA, and the solid second compound is 4ARM-20k-SGA.