Uses of pegylated albumin
View Patent ↗The present invention is directed to uses of PEGylated albumins which include methods of treating reduced functional capillary density, reduced blood volume, septic shock and cardiac arrhythmia in a subject, which comprise administering to the subject a therapeutically effective amount of a PEGylated albumin.
1. A method of treating cardiac arrhythmia in a subject having cardiac arrhythmia which comprises administering to the subject an amount of a PEGylated albumin effective to treat cardiac arrhythmia in the subject.
2. The method of claim 1 , wherein the cardiac arrhythmia is a ventricular arrhythmia.
3. The method of claim 1 , wherein the cardiac arrhythmia is an atrial arrhythmia.
4. The method of claim 1 , wherein the albumin is human serum albumin or bovine serum albumin.
5. The method of claim 1 , wherein the concentration of PEGylated albumin is 1.5 g/dL-5.0 g/dL.
6. The method of claim 5 , wherein the PEGylated albumin is administered at a dose of 16 to 30 ml/kg body weight/hr.
7. The method of claim 1 , wherein the PEGylated albumin has a molecular weight of about 130 kDa.
8. The method of claim 1 , wherein 6-18 PEG chains are conjugated to albumin.
9. The method of claim 1 , wherein each PEG chain of the PEGylated albumin has a molecular weight of 200 daltons to 20,000 daltons.
10. The method of claim 9 , wherein each PEG chain has a molecular weight of 3,000 to 5,000 daltons.
11. The method of claim 1 , wherein the PEGylated albumin has a molecular radius of 8-9 nm.
12. The method of claim 1 , wherein the PEGylated albumin has a colloid osmotic pressure of 37-40 mm Hg.
13. The method of claim 1 , wherein the PEGylated albumin has a viscosity of 2.0 to 4.0 cP.
14. The method of claim 1 , wherein a polyethylene glycol (PEG) used to make the PEGylated albumin is a maleimide PEG, an alkylamide PEG, an iodoacetamide PEG, a p-nitro thio-phenyl PEG, a vinyl sulfone PEG, or a mixed disulfide PEG.
15. The method of claim 14 , wherein the maleimide PEG is a maleimide phenyl PEG or a maleimide PEG comprising an alkyl linker.
16. The method of claim 1 , wherein the PEG is attached to the albumin via a linker and/or an extension arm.
17. The method of claim 16 , wherein the linker comprises an alkyl, aryl and/or heteroaryl group.
18. The method of claim 16 , wherein the linker or extension arm comprises a δ-mercapto butyrimidyl chain or a γ-mercapto propylamide chain.
19. The method of claim 1 , wherein the PEGylated albumin comprises a polyethylene glycol (PEG) attached to a thiolated amino group of albumin, and wherein the amino group is thiolated using dithiobis(sulfosuccinimidyl propionate) (DTSSP) or dithiobis(succinimidyl propionate) (DTSP) or dithiobispropionimidate.
20. The method of claim 1 , wherein PEGylation of albumin does not alter the surface charge of albumin.
21. The method of claim 1 , wherein the subject is undergoing anaesthesia and surgery.
22. The method of claim 1 , wherein the concentration of PEGylated albumin is 2.5 g/dL.
23. The method of claim 22 , wherein the PEGylated albumin is administered at a dose of 24 ml/kg body weight/hr.
24. The method of claim 1 , wherein 12 PEG chains are conjugated to albumin.
25. The method of claim 1 , wherein each PEG chain of the PEGylated albumin has a molecular weight of 5,000 daltons.
26. The method of claim 1 , wherein administration of PEGylated albumin decreases sinoatrial automaticity, partially normalizes ventricular contraction, and increases the duration of the cardiac monophasic action potential.
27. The method of claim 1 , wherein the cardiac arrhythmia is induced by a drug or by nerve stimulation during surgery or is associated with cardiac disease, hypoxia, acidosis, hypercarbia or an electrolyte disturbance.