| 主权项 |
1. A method of processing a low molecular weight heparin (LMWH) preparation, the method comprising:
digesting the LMWH preparation with a heparinase I, a heparinase II, a heparinase III, a 2-O-sulfatase, and a Δ4,5 glycuronidase; providing a determination made using reverse phase high performance liquid chromatography (RP-HPLC), of whether all the structural moieties of the following first table:PeakComment on #Identitybuilding blocks1ΔUHNAcNatural2Linkage region isomer Natural3ΔUGalGalXyl-O—CH2—COOH Natural4ΔUgalHNSModified5ΔUHNS (α)Natural6ΔUHNS (β)Natural7ΔUHNS (1,6 anhydro)Modified8ΔUManNS (1,6 anhydro)Modified9ΔUHNAc6SNatural10ΔU2SHNAc (α)Natural11ΔU2SHNAc (β)Natural12ΔUHNS3SNatural13ΔUHNS6S (α)Natural14ΔUgalHNS6S (α)Modified15ΔUgalHNS6S (β)Modified16ΔUHNS6S (β)Natural17ΔU2SHNS (α)Natural18ΔU2SHNS ( (β)Natural19ΔU2SHNS (1,6 anhydro)Modified20ΔU2SManNS (1,6 anhydro)Modified21ΔU2SHNAc6S (α)Natural22ΔU2SHNAc6S (β)Natural23ΔU2SManNAc,6SModified24ΔUHNAc6SGHNS,3S (α)Natural25ΔUHNAc6SGHNS,3S (β)Natural26ΔU2SManNS6S (α)Modified27ΔU2SHNS6S (α)Natural28ΔUHNAc6SGHNS,3S,6S (α)Natural29ΔU2SHNS6S (β)Natural30ΔU2SHNS6SI2S (α)Modified31ΔU2SHNS6SI2S (β)Modified32ΔUHNS6SGHNS3S6S (α)Natural33ΔUHNS6SGHNS3S6S (β)Natural34ΔU2SHNS6SI2SHNS (1,6 anhydro)Modified35ΔU2SHNS3S6SNatural36ΔU2SHNS6SI2SManNS (1,6 anhydro)Modified37ΔU2SHNS6SGHNS3S6S (β)Natural38ΔU2SHNS6SGHNS3S6S (α)Naturalare present in the preparation in an amount which falls within Range A (mole %) of the following second table:PeakRange A#Identity(mole %)1ΔUHNAc1.12.42Linkage region isomer 0.00.43ΔUGalGalXyl-O—CH2—COOH 0.44.74ΔUgalHNS0.00.75ΔUHNS (α)1.62.06ΔUHNS (β)0.30.47ΔUHNS (1,6 anhydro)0.20.38ΔUManNS (1,6 anhydro)0.30.59ΔUHNAc6S3.14.210ΔU2SHNAc (α)0.40.911ΔU2SHNAc (β)1.01.512ΔUHNS3S0.00.513 + 14ΔUHNS6S (α) + ΔUgallHNS6S (α) 7.410.615 + 16ΔUgaIHNS6S (β) + ΔUHNS6S (β)0.61.117ΔU2SHNS (α)5.46.418ΔU2SHNS ( (β)0.61.219ΔU2SHNS (1,6 anhydro)1.41.720ΔU2SManNS (1,6 anhydro)0.00.321ΔU2SHNAc6S (α)0.40.722ΔU2SHNAc6S (β)0.81.123ΔU2SManNAc,6S0.00.224ΔUHNAc6SGHNS,3S (α)0.51.125ΔUHNAc6SGHNS,3S (β)0.10.326ΔU2SManNS6S (α)1.52.527ΔU2SHNS6S (α)43.447.428ΔUHNAc6SGHNS,3S,6S (α)2.14.529ΔU2SHNS6S (β)4.56.730ΔU2SHNS6SI2S (α)0.51.031ΔU2SHNS6SI2S (β)0.91.632ΔUHNS6SGHNS3S6S (α)0.20.933ΔUHNS6SGHNS3S6S (β)0.10.734ΔU2SHNS6SI2SHNS (1,6 anhydro)0.00.635ΔU2SHNS3S6S0.10.436ΔU2SHNS6SI2SManNS (1,6 anhydro)4.55.737ΔU2SHNS6SGHNS3S6S (β)0.20.638ΔU2SHNS6SGHNS3S6S (α)0.40.7 and if said structural moieties are present in an amount that falls within Range A of the second table, then processing the LMWH preparation by a process selected from the group consisting of: classifying, selecting, accepting, releasing, shipping, formulating, labeling, and packaging, the LMWH preparation. |
