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JP-7855655-B2 - Collagenase preparation and method for manufacturing the same

JP7855655B2JP 7855655 B2JP7855655 B2JP 7855655B2JP-7855655-B2

Inventors

  • スクル、カルナカル

Assignees

  • エンド グローバル エステティックス リミテッド

Dates

Publication Date
20260508
Application Date
20240930
Priority Date
20190106

Claims (20)

  1. A method for producing a freeze-dried collagenase preparation, wherein the method is To form a frozen collagenase preparation, the process involves freezing a composition containing collagenase, disaccharides, mannitol, and Tris-HCl, and To form the freeze-dried collagenase preparation, the process involves drying the freeze-dried collagenase preparation at a pressure of 380 μbar to 4000 μbar, Methods that include...
  2. The method according to claim 1, wherein the method is To form the frozen collagenase preparation, the composition is frozen in a temperature range of -25 °C to -55°C, and/or A step of drying the frozen collagenase preparation in a temperature range of 25 °C to 50 °C. Methods that include...
  3. The method according to claim 2, wherein the method is To form the aforementioned frozen collagenase preparation, the process involves freezing the composition at a single temperature between -25 °C and -55°C, and The process involves drying the aforementioned frozen collagenase preparation at a single temperature between 25 °C and 50 °C, Methods that include...
  4. A method according to any one of claims 1 to 3, wherein the freezing step is carried out at -25 °C , -30°C , -35 °C , -40°C , -45°C , -50°C, or -55 °C.
  5. A method according to any one of claims 1 to 4, wherein the drying step is carried out at 25 °C , 30 °C , 35 °C , 40 °C , 45°C, or 50 °C.
  6. A method according to any one of claims 1 to 5, wherein the drying step is carried out at a pressure of 500 μbar to 4000 μbar.
  7. A method according to any one of claims 1 to 5 , wherein the drying step is performed at 380 μbar, 500 μbar, 750 μbar, 1000 μbar, 1500 μbar, 2000 μbar, 2500 μbar, 3000 μbar, 3500 μbar, or 4000 μbar.
  8. A method according to any one of claims 1 to 7, wherein the disaccharide is sucrose or trehalose.
  9. A method according to any one of claims 1 to 8, wherein the collagenase comprises collagenase I.
  10. The method according to claim 9, wherein the collagenase I comprises the amino acid sequence with sequence ID number: 1.
  11. A method according to any one of claims 1 to 8, wherein the collagenase comprises collagenase II.
  12. The method according to claim 11, wherein the collagenase II comprises the amino acid sequence with sequence ID number: 2.
  13. A method according to any one of claims 1 to 8, wherein the collagenase comprises a mixture of collagenase I and collagenase II.
  14. The method according to claim 13, wherein collagenase I comprises the amino acid sequence with sequence ID number: 1, and collagenase II comprises the amino acid sequence with sequence ID number: 2.
  15. A method according to claim 13 or 14, wherein the collagenase is collagenase Clostridium histolyticum (CCH).
  16. A method according to any one of claims 1 to 15, wherein the collagenase is produced by recombinant technology.
  17. In the method according to any one of claims 1 to 16, the composition is : The aforementioned disaccharides in concentrations of 30 mM to 240 mM , The mannitol in a concentration of 50 mM to 800 mM, and The Tris-HCl in a concentration of 6 mM to 10 mM, Methods that include...
  18. The method according to claim 17, wherein the pH of the composition is 7.8 to 8.8 .
  19. In the method according to claim 17 or 18, the composition is 60 mM sucrose and , 2. 25 mM mannitol, and It contains 10 mM Tris-HCl, The composition has a pH of 8.5 . method.
  20. A method according to any one of claims 17 to 19, wherein the composition comprises a surfactant selected from polysorbate 20, polysorbate 80, and poloxamer 188.

Description

This application claims priority to U.S. Provisional Application No. 62/788,916, filed on January 6, 2019, the disclosures thereof being incorporated herein by reference in their entirety. This application includes a sequence listing electronically submitted on January 3, 2020, as a text file titled "117326_000001_Sequence_Listing.txt" with a size of 17,447 bytes. This sequence listing is incorporated herein by reference. This specification discloses collagenase-containing formulations with improved stability and shelf life. XIAFLEX® (collagenase derived from Clostridium histolyticum (CCH)) is currently approved for the treatment of Dupuytren's contracture (DC) and Peyronie's disease (PD). The currently approved XIAFLEX® formulation is supplied as a lyophilized cake containing 0.9 mg of CCH in a 3 CC vial with a diluent. The current XIAFLEX® formulation (before lyophilization) has a lyophilization cycle time of approximately 72 hours in the vial. Efficient lyophilization is necessary for shelf life and enzyme stability. The following are prior art documents related to the invention of this application (including documents cited in the international phase after the international filing date and documents cited when the application was filed in other countries as national phase entries): (Prior art document) (Patent Document) (Patent Document 1) International Publication No. 2013/059619 (Patent Document 2) International Publication No. 2007/100675 (Patent Document 3) International Publication No. 2018/160905 (Patent Document 4) U.S. Patent Application Publication No. 2011/033464 (Patent Document 5) U.S. Patent Application Publication No. 2018/099049 (Patent Document 6) U.S. Patent Application Publication No. 2006/263347 This summary and the following detailed description will be better understood in conjunction with the accompanying drawings. For illustrative purposes, the drawings show exemplary embodiments of the disclosed formulation; however, the formulation is not limited to the specific embodiments disclosed. Figure 1 shows the effect of pH on protein interactions in exemplary formulations containing trehalose, mannitol, and various collagenases.Figures 2A and 2B illustrate an exemplary hydrogen peroxide problem analyzing the effects of pH and excipients on turbidity. NTU - Nephelometric Turbidity Units, PS - Polysorbate, T - Trehalose, S - Sucrose, M - Mannitol, H₂O₂- Hydrogen peroxide, 7.5, 8.0, and 8.5 represent the pH of the formulation.Figures 2A and 2B illustrate an exemplary hydrogen peroxide problem analyzing the effects of pH and excipients on turbidity. NTU - Nephelometric Turbidity Units, PS - Polysorbate, T - Trehalose, S - Sucrose, M - Mannitol, H₂O₂- Hydrogen peroxide, 7.5, 8.0, and 8.5 represent the pH of the formulation.Figures 3A, 3B, 3C, 3D, 3E, 3F, 3G, 3H, 3I, 3J, 3K, 3L, 3M, 3N, 3O, 3P, 3Q, and 3R show various lyophilized formulations (Va: 0.93 mg/ml CCH; 60 mM sucrose; 112.5 mM mannitol; 10 mM Tris/HCl buffer pH 8.5; Vb: 0.93 mg/ml CCH; 60 mM sucrose; 225 mM mannitol; 10 mM Tris/HCl buffer pH 8.5; and Vc: 0.93 mg/ml CCH; 60 mM sucrose; 337.5 mM mannitol; 10 mM Tris/HCl buffer pH 8.5).Figures 3A, 3B, 3C, 3D, 3E, 3F, 3G, 3H, 3I, 3J, 3K, 3L, 3M, 3N, 3O, 3P, 3Q, and 3R show various lyophilized formulations (Va: 0.93 mg/ml CCH; 60 mM sucrose; 112.5 mM mannitol; 10 mM Tris/HCl buffer pH 8.5; Vb: 0.93 mg/ml CCH; 60 mM sucrose; 225 mM mannitol; 10 mM Tris/HCl buffer pH 8.5; and Vc: 0.93 mg/ml CCH; 60 mM sucrose; 337.5 mM mannitol; 10 mM Tris/HCl buffer pH 8.5).Figures 3A, 3B, 3C, 3D, 3E, 3F, 3G, 3H, 3I, 3J, 3K, 3L, 3M, 3N, 3O, 3P, 3Q, and 3R show various lyophilized formulations (Va: 0.93 mg/ml CCH; 60 mM sucrose; 112.5 mM mannitol; 10 mM Tris/HCl buffer pH 8.5; Vb: 0.93 mg/ml CCH; 60 mM sucrose; 225 mM mannitol; 10 mM Tris/HCl buffer pH 8.5; and Vc: 0.93 mg/ml CCH; 60 mM sucrose; 337.5 mM mannitol; 10 mM Tris/HCl buffer pH 8.5).Figures 3A, 3B, 3C, 3D, 3E, 3F, 3G, 3H, 3I, 3J, 3K, 3L, 3M, 3N, 3O, 3P, 3Q, and 3R show various lyophilized formulations (Va: 0.93 mg/ml CCH; 60 mM sucrose; 112.5 mM mannitol; 10 mM Tris/HCl buffer pH 8.5; Vb: 0.93 mg/ml CCH; 60 mM sucrose; 225 mM mannitol; 10 mM Tris/HCl buffer pH 8.5; and Vc: 0.93 mg/ml CCH; 60 mM sucrose; 337.5 mM mannitol; 10 mM Tris/HCl buffer pH 8.5).Figures 3A, 3B, 3C, 3D, 3E, 3F, 3G, 3H, 3I, 3J, 3K, 3L, 3M, 3N, 3O, 3P, 3Q, and 3R show various lyophilized formulations (Va: 0.93 mg/ml CCH; 60 mM sucrose; 112.5 mM mannitol; 10 mM Tris/HCl buffer pH 8.5; Vb: 0.93 mg/ml CCH; 60 mM sucrose; 225 mM mannitol; 10 mM Tris/HCl buffer pH 8.5; and Vc: 0.93 mg/ml CCH; 60 mM sucrose; 337.5 mM mannitol; 10 mM Tris/HCl buffer pH 8.5).Figures 4A, 4B, and 4C show images of cakes from various lyophilized formulations under pressures of 128 μbar (Figure 4A), 380 μbar (Figure 4B), and 1030 μbar (Figure 4C).Figures 5A and 5B show images of cakes from various freeze-dried formulations under pressures of 128 μbar (Figure 5A) and 4000 μbar (Figure 5B).Figure 6 shows