Compositions for fecal floral transplantation and methods for making and using them and device for delivering them
This application provides compositions, e.g., formulations, used for gastric, gastrointestinal and/or colonic treatments, and methods for making, storing and using them, including storage, including long term storage, at room temperature. Compositions provided herein are useful for treating various diseases or conditions such as autism spectrum disorder, Crohn's Disease, ulcerative colitis, irritable bowel syndrome, and recurrent or primary C. difficile infection.
1. A pharmaceutical composition comprising a microbial preparation in a lyophilized formulation comprising one or more cryoprotectants selected from the group consisting of trehalose, mannitol, sucrose, and any combination thereof,
wherein said microbial preparation comprises viable purified microorganisms from two or more genera selected from the group consisting of Akkermansia, Anaerotruncus, Blautia, Clostridium , and Dorea,
wherein after at least 4 weeks of storage at room temperature, said microbial preparation is capable of maintaining at least 50% cell viability relative to the initial cell viability immediately prior to storage.
2. The pharmaceutical composition of claim 1 , wherein said microbial preparation comprises viable purified microorganisms from three or more genera selected from the group consisting of Akkermansia, Anaerotruncus, Blautia, Clostridium , and Dorea.
3. The pharmaceutical composition of claim 1 , wherein said microbial preparation comprises viable purified microorganisms from Anaerotruncus, Blautia, Clostridium , and Dorea.
4. The pharmaceutical composition of claim 3 , wherein said microbial preparation further comprises viable purified microorganisms from two or more genera selected from the group consisting of Eubacterium, Ruminococcus , and Subdoligranulum.
5. The pharmaceutical composition of claim 1 , wherein said microbial preparation comprises viable purified Clostridium selected from the group consisting of Clostridium innocuum and Clostridium symbiosum.
6. The pharmaceutical composition of claim 1 , wherein said microbial preparation comprises viable purified Dorea longicatena.
7. The pharmaceutical composition of claim 1 , wherein said microbial preparation comprises viable purified Blautia producta.
8. The pharmaceutical composition of claim 1 , wherein said microbial preparation comprises viable purified microorganisms from Blautia producta, Clostridium innocuum, Clostridium symbiosum , and Dorea longicatena.
9. The pharmaceutical composition of claim 8 , wherein said microbial preparation further comprises viable purified microorganisms from two or more genera selected from the group consisting of Eubacterium, Ruminococcus , and Subdoligranulum.
10. The pharmaceutical composition of claim 1 , wherein said microbial preparation further comprises viable purified microorganisms from one or more genera selected from the group consisting of Eubacterium, Ruminococcus , and Subdoligranulum.
11. The pharmaceutical composition of claim 10 , wherein said microbial preparation comprises viable purified Eubacterium.
12. The pharmaceutical composition of claim 10 , wherein said microbial preparation comprises viable purified Ruminococcus torques.
13. The pharmaceutical composition of claim 1 , wherein said microbial preparation further comprises viable purified microorganisms from two or more genera selected from the group consisting of Eubacterium, Ruminococcus , and Subdoligranulum.
14. The pharmaceutical composition of claim 1 , wherein said one or more cryoprotectants are also lyoprotectants.
15. The pharmaceutical composition of claim 1 , wherein said lyophilized formulation comprises trehalose.
16. The pharmaceutical composition of claim 15 , wherein said lyophilized formulation comprises 6% to 10% trehalose.
17. The pharmaceutical composition of claim 15 , wherein said lyophilized formulation comprises at least 5% trehalose.
18. The pharmaceutical composition of claim 1 , wherein said lyophilized formulation comprises trehalose and sucrose.
19. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition is for oral administration.
20. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition is formulated as a geltab, pill, microcapsule, capsule, or tablet.
21. The pharmaceutical composition of claim 1 , wherein every 200 mg of said pharmaceutical composition comprises a pharmacologically active dose of microbes or spores of 10 5 to 10 12 colony forming units (CFU) or total cell count.
22. The pharmaceutical composition of claim 1 , wherein every 200 mg of said pharmaceutical composition comprises a pharmacologically active dose of microbes or spores of 10 6 to 10 11 colony forming units (CFU) or total cell count.
23. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition is effective for treating recurrent or primary C. difficile infection.
24. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition further comprises an amino acid.
25. The pharmaceutical composition of claim 24 , wherein said amino acid is histidine.
26. The pharmaceutical composition of claim 1 , wherein said one or more cryoprotectants comprise sucrose.
27. The pharmaceutical composition of claim 1 , wherein said one or more cryoprotectants are at least 10% trehalose.
28. The pharmaceutical composition of claim 1 , wherein said one or more cryoprotectants are at least 2.5% sucrose.
29. The pharmaceutical composition of claim 1 , wherein said one or more cryoprotectants are trehalose and mannitol.
30. The pharmaceutical composition of claim 1 , wherein said one or more cryoprotectants are at least 5% mannitol.
31. The pharmaceutical composition of claim 1 , wherein said one or more cryoprotectants are at least 10% mannitol.
32. The pharmaceutical composition of claim 1 , wherein said viable purified microorganisms comprise spore-forming bacteria.
33. The pharmaceutical composition of claim 32 , wherein said spore-forming bacteria are one or more Clostridium species.
34. The pharmaceutical composition of claim 1 , wherein the viable purified microorganisms are cultured.
35. A capsule comprising a pharmaceutical composition comprising a microbial preparation in a lyophilized formulation comprising one or more cryoprotectants selected from the group consisting of trehalose, mannitol, sucrose, and any combination thereof,
wherein said microbial preparation comprises viable purified microorganisms from two or more genera selected from the group consisting of Akkermansia, Anaerotruncus, Blautia, Clostridium , and Dorea,
wherein after at least 4 weeks of storage at room temperature, said microbial preparation is capable of maintaining at least 50% cell viability relative to the initial cell viability immediately prior to storage.
36. The pharmaceutical composition of claim 35 , wherein said viable purified microorganisms comprise spore-forming bacteria.
37. The pharmaceutical composition of claim 35 , wherein said viable purified microorganisms comprise spore-forming bacteria of at least two or more of said genera.
38. The pharmaceutical composition of claim 35 , wherein said one or more cryoprotectants are trehalose and mannitol.
39. The pharmaceutical composition of claim 35 , wherein said one or more cryoprotectants are trehalose and sucrose.
40. The pharmaceutical composition of claim 35 , wherein said one or more cryoprotectants are at least 5% trehalose.
41. The pharmaceutical composition of claim 35 , wherein the viable purified microorganisms are cultured.