Storage stable formulations of sulfated glycosaminoglycans and fragments derived therefrom for the treatment of pain and other medical conditions
One aspect of the present application relates to a storage stable pharmaceutical composition comprising a sulfated glycosaminoglycan having an average molecular weight ranging from 3,000 to 15,000 Daltons, and a pharmaceutical carrier, where the pharmaceutical carrier is mixed with the sulfated glycosaminoglycan, as well as this composition's use in a method of treating a subject for a medically observable improvement. Another aspect of the present application relates to a process for producing a storage stable purified sulfated glycosaminoglycan.
1. A process for producing a storage stable purified polysulfated glycosaminoglycan, said process comprising:
providing a polysulfated glycosaminoglycan starting material containing components above 1,000 Daltons and components below 1,000 Daltons;
subjecting said polysulfated glycosaminoglycan starting material to tangential flow filtration under conditions effective to reduce the amount of components below 1,000 Daltons in the starting material to produce a purified polysulfated glycosaminoglycan having an average molecular weight ranging from 3,000 to 15,000 Daltons, wherein the purified polysulfated glycosaminoglycan includes no more than 10 wt % of carbohydrates or other contaminants with a molecular weight below 1,000 Daltons; and
recovering the purified polysulfated glycosaminoglycan.
2. The process of claim 1 , wherein said purified polysulfated glycosaminoglycan contains less than 5,000 ppm of acetic acid.
3. The process of claim 1 , wherein said purified polysulfated glycosaminoglycan contains less than 1,000 ppm of acetic acid.
4. The process of claim 1 , wherein said purified polysulfated glycosaminoglycan contains less than 5,000 ppm of acetic acid after storage at room temperature for at least 12 months following initiation of storage.
5. The process of claim 1 , wherein said purified polysulfated glycosaminoglycan maintains a white or off-white color after storage at room temperature for at least 6 months following initiation of storage.
6. The process of claim 1 , wherein said purified polysulfated glycosaminoglycan maintains a white or off-white color after storage at room temperature for at least 12 months following initiation of storage.
7. The process of claim 1 , wherein said tangential flow filtration is carried out by ultrafiltration.
8. The process of claim 1 , wherein said tangential flow filtration is carried out by diafiltration.
9. The process of claim 1 , wherein said tangential flow filtration is carried out by size exclusion or another porous membrane.
10. The process of claim 1 further comprising:
storing said purified polysulfated glycosaminoglycan for at least 12 months storage at room temperature.
11. The process of claim 10 , wherein said purified polysulfated glycosaminoglycan contains less than 5,000 ppm of acetic acid for at least 12 months of storage at room temperature.
12. The process of claim 10 , wherein said purified polysulfated glycosaminoglycan is stored in a container composed of plastic, paper, cardboard, or metal.
13. The process of claim 12 , wherein said container is treated to remove residual oxygen or air before, during, or after said storing.
14. The process of claim 1 , wherein said purified polysulfated glycosaminoglycan has an average molecular weight ranging from 7,000 to 9,500 Daltons.
15. The process of claim 1 , wherein said purified polysulfated glycosaminoglycan is selected from the group consisting of mucopolysaccharide polysulfate, polysulfated glycosaminoglycan, and combinations thereof.
16. The process of claim 1 , wherein said purified polysulfated glycosaminoglycan includes no more than 5 wt % of carbohydrates or other contaminants with a molecular weight below 1,000 Daltons.
17. The process of claim 1 , wherein said purified polysulfated glycosaminoglycan includes no more than 1 wt % of carbohydrates or other contaminants with a molecular weight below 1,000 Daltons.
18. The process of claim 1 , wherein said purified polysulfated glycosaminoglycan contains less than 500 ppm of acetic acid.
19. The process of claim 1 , wherein said purified polysulfated glycosaminoglycan contains less than 1,000 ppm of acetic acid after storage at room temperature for at least 12 months following initiation of storage.
20. The process of claim 1 , wherein said purified polysulfated glycosaminoglycan contains less than 500 ppm of acetic acid after storage at room temperature for at least 12 months following initiation of storage.