Methods and compositions for treating bleeding disorders
View Patent ↗Aspects of the invention include methods for enhancing blood coagulation in a subject. In practicing methods according to certain embodiments, an amount of a non-anticoagulant sulfated polysaccharide (NASP) is administered to a subject to enhance blood coagulation in the subject. Also provided are methods for preparing a NASP composition having blood coagulation enhancing activity. Compositions and kits for practicing methods of the invention are also described.
1. A method of enhancing blood coagulation in a subject, the method comprising (i) administering to the subject diagnosed as having a blood coagulation disorder a procoagulant amount of a composition comprising a purified non-anticoagulant sulfated polysaccharide (NASP) comprising 70% or more fucose saccharide residues;
the NASP having fucoidan selected from the group consisting of Fucoidan 5307002, Fucus vesiculosus , max. MW peak 126.7 kD; Fucoidan VG49, Fucus vesiculosus , hydrolyzed sample of 5307002 of lower MW, max. MW peak 22.5 kD; Fucoidan VG57, Undaria pinnatifida , high charge high sulphation, deacetylated; Fucoidan 5508005, Undaria pinnatifida , depyrogenated; Fucoidan L/FVF-01091, Fucus vesiculosus , depyrogenated, max. MW peak 125 kD; Fucoidan L/FVF-01092, Fucus vesiculosus , depyrogenated, max. MW peak 260 kD; Fucoidan L/FVF-01093, Fucus vesiculosus , hydrolyzed depyrogenated, max. MW peak 36 kD; fucoidan from Ecklonia radiata ; fucoidan from Ecklonia maxima ; fucoidan from Macrocystis pyrifera ; and combinations thereof;
wherein the procoagulant amount is an effective amount of the composition to enhance blood coagulation in the subject.
2. The method according to claim 1 , wherein the NASP is extracted from a biological source.
3. The method according to claim 1 , wherein at least two of the saccharide residues of the NASP are selected from the group consisting of fucose, galactose, glucose, xylose and mannose.
4. The method according to claim 1 , wherein the NASP comprises 70% or more fucose saccharide residues and 20% or more galactose saccharide residues.
5. The method according to claim 1 , wherein the NASP is a branched polysaccharide.
6. The method according to claim 1 , wherein the NASP is a linear polysaccharide.
7. The method according to claim 1 , wherein 75% or more saccharide residues of the NASP are monosulfated.
8. The method according to claim 1 , wherein the NASP comprises 40% or more sulfated esters of fucose saccharide residues.
9. The method according to claim 1 , further comprising administering a blood coagulation factor to the subject.
10. The method according to claim 9 , wherein the blood coagulation factor is selected from the group consisting of factor Xa, factor IXa, factor Xia, factor XIIa, VIIIa, prekallekrein, and high-molecular weight kininogen, tissue factor, factor VIIa, factor Va, factor Xa, factor II, factor V, factor VII, factor VIII, factor IX, factor X, factor XI, factor XII, factor XIII, von Willebrands factor and combinations thereof.
11. The method according to claim 1 , wherein the NASP is administered at a dosage ranging from 0.01 mg/kg to 100 mg/kg.
12. The method according to claim 1 , wherein the NASP has a molecular weight that ranges from 10 to 30,000 daltons.
13. The method according to claim 1 , wherein the subject has been diagnosed as having a bleeding disorder selected from the group consisting of a chronic or acute bleeding disorder, a congenital coagulation disorder caused by a blood factor deficiency, and an acquired coagulation disorder.