IP Library Granted Patent US 11,746,141
Granted Patent B2
US 11,746,141 · App. 16/537,339 · Granted Sep 5, 2023

Modified collagen

Inventors: Alexandra Dietrich (Saal/Donau, DE); Michael Myers (Ashburn, VA)
Assignee: INNOCOLL PHARMACEUTICALS LIMITED
C07K14/78A61K31/445A61K31/7036A61K47/42A61L27/24A61L27/54C08L89/00C08L89/06A61K38/39A61L2300/204A61L2300/23A61L2300/402A61L2300/406
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Quick Facts
Patent No.
US 11,746,141
App. No.
16/537,339
Granted
Sep 5, 2023
Kind
B2
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.

Claims (28)

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 CaCl 2 )) 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.

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 22, 2026
From: INNOCOLL PHARMACEUTICALS LIMITED
To: GURNET FINANCE (JERSEY) LIMITED
Reel/Frame 074437/0384 →
SECURITY INTEREST Recorded Nov 7, 2023
From: OAKTREE FUND ADMINISTRATION, LLC
To: GURNET FINANCE SA
Reel/Frame 065484/0092 →
SECURITY INTEREST Recorded Feb 24, 2022
From: INNOCOLL PHARMACEUTICALS LIMITED
To: OAKTREE FUND ADMINISTRATION, LLC
Reel/Frame 059096/0842 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 24, 2021
From: DIETRICH, ALEXANDRA; MYERS, MICHAEL
To: INNOCOLL TECHNOLOGIES LIMITED
Reel/Frame 055391/0808 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 24, 2021
From: INNOCOLL TECHNOLOGIES LIMITED
To: INNOCOLL PHARMACEUTICALS LIMITED
Reel/Frame 055392/0012 →
Priority Claims (2)
EP 12150527 · Jan 9, 2012 · regional
GB 1220868 · Nov 20, 2012 · national
Continuity (2)
Division 14371161
Related Publication 20190359689A1 · Nov 28, 2019