Methods of manufacturing a high molecular weight heparin compound
AssigneeNexEos Diagnostics, Inc.
InventorsLi Fu, Zhenyu Wang, Jessica Pax
Life of this patent
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Abstract
A method of manufacturing a high molecular weight heparin (HMWH) compound is disclosed. The method comprises dissolving heparin to form a heparin solution and fractionating the heparin solution via tangential flow filtration (TFF) using a membrane with a molecular weight cut off (MWCO) between about 8 kDa and about 12 kDa. The TFF yields a retentate comprising fractionated heparin with a weight average molecular weight of about 20 kDa or greater, i.e., a high molecular weight heparin compound. A substantial proportion of heparin chains in the fractionated heparin may have a high molecular weight, e.g., 50% of the heparin chains or greater may have a molecular weight of 20 kDa or greater.
Claims32
A method of manufacturing fractionated heparin, the method comprising:
- dissolving heparin in a solvent to form a heparin solution;
- filtering the heparin solution through a submicron membrane to sterilize the heparin solution;
- and
- fractionating the filtered heparin solution by tangential flow filtration using a fractionation membrane with a molecular weight cut off between about 8 kDa and about 12 kDa, thereby yielding fractionated heparin with a weight average molecular weight of about 20 kDa or greater,
- wherein at least 50% of heparin chains in the fractionated heparin have a molecular weight of 20 kDa or greater.
A method of manufacturing a high molecular weight (HMW) heparin, the method comprising:
- dissolving a heparin salt in a salt solution to form a heparin solution;
- sterilizing the heparin solution by filtering through a sterilization membrane having a pore size of about 0.2 μm, thereby yielding a sterilized heparin solution;
- fractionating the sterilized heparin solution by tangential flow filtration using a fractionation membrane with a pore size of about 5 nm, thereby yielding fractionated heparin with a weight average molecular weight of about 20 kDa or greater, wherein at least 50% of heparin chains in the fractionated heparin have a molecular weight of 20 kDa or greater;
- desalting the fractionated heparin by tangential flow filtration using a desalting membrane with a pore size of about 3 nm, thereby yielding desalted heparin;
- and
- drying the desalted heparin by lyophilization to yield the HMW heparin.
Dependencies are inferred from the claim text.