Claims for Patent: 11,746,141

Summary for Patent: 11,746,141

Title:	Modified collagen
Abstract:	The present invention relates to a modified collagen obtainable by providing isolated collagen; freezing the isolated collagen; dehydrating the frozen collagen; and maturing the dehydrated collagen. Also disclosed are methods of preparing the modified collagen and uses thereof.
Inventor(s):	Alexandra Dietrich, Michael Myers
Assignee:	INNOCOLL PHARMACEUTICALS Ltd
Application Number:	US16/537,339
Patent Claims:	1. A matured collagen composition obtainable by a process comprising the steps of: (a) obtaining isolated collagen; (b) freeze-drying the isolated collagen to obtain freeze-dried collagen; (c) maturing the freeze-dried collagen by storing the freeze-dried collagen at a temperature of at least 40° C. for a period of at least six weeks to obtain matured collagen; (d) dispersing the matured collagen in an aqueous dispersion; and (e) freeze-drying the dispersed matured collagen to obtain the matured collagen composition, wherein a time required for degradation of 50% of a matured collagen composition sample relative to maximum possible degradation with collagenase is at least 25% shorter than a time required for degradation of 50% of a collagen composition sample comprising non-matured collagen relative to maximum possible degradation with collagenase, wherein the non-matured collagen is obtainable by a process comprising steps (a), (b), (d′) dispersing the matured collagen in an aqueous dispersion; and (e′) freeze-drying the dispersed matured collagen to obtain the matured collagen composition, but excluding step (c), and wherein the degrading of a collagen composition sample comprises: placing the collagen composition sample into a 15 mL solution of 0.2 N phosphate buffer (pH 7.4 with CaCl2)) maintained at a temperature of 37° C.; adding 100 μl of 10 mg/mL Collagenase Type IA-S to the solution and agitating the solution by shaking at 120 rpm; and measuring UV absorption spectra of the solution between 210 nm and 230 nm after 5, 10, 15, 25, 40, 60, and 90 minutes and calculating a degradation fraction at a corresponding time point relative to a maximum absorption at 90 minutes, wherein higher absorbance correlates with higher degradation. 2. The matured collagen composition according to claim 1, further comprising bupivacaine or a pharmaceutically acceptable salt thereof. 3. The matured collagen composition according to claim 1, wherein the storing is at a temperature of at least 40° C. for a period of at least six weeks and at a relative humidity of less than 80%. 4. The matured collagen composition according to claim 1, wherein the storing is at a temperature of at least 40° C. for a period of at least six weeks and at a relative humidity of 75%. 5. The matured collagen composition according to claim 1, wherein the storing is at a temperature of 40° C. for a period of six weeks to two months or six weeks to six months. 6. The matured collagen composition according to claim 1, wherein the isolated collagen comprises a dispersion comprising collagen particles having a concentration of 3-30% (w/w). 7. The matured collagen composition according to claim 1, wherein step (b) comprises freezing the isolated collagen to a temperature of −33° C. to −42° C. 8. The matured collagen composition according to claim 1, wherein step (b) comprises removing the aqueous phase by reducing the pressure to 0.05 to 0.5 mbar. 9. The matured collagen composition according to claim 1, wherein step (b) comprises increasing the temperature of the collagen to +30° C. 10. The matured collagen composition according to claim 1, wherein step (b) comprises an equilibrating step, wherein the equilibrating step comprises maintaining the temperature constant for at least 10 mins. 11. The matured collagen composition according to claim 7, wherein step (b) comprises six equilibrating steps, each equilibrating step being conducted when the temperature is increased by 10° C. 12. The matured collagen composition according to claim 1, the process further comprising milling the freeze-dried collagen prior to maturing. 13. The matured collagen composition according to claim 1, further comprising bupivacaine HCl. 14. The matured collagen composition according to claim 13, wherein the concentration of bupivacaine HCl is from 25% w/w to 57% w/w.