Compositions and methods for preferential distribution of active agents to injury sites

Patent metadata

Field	Value
Publication number	US-9486478-B2
Application number	US-201414506140-A
Country	US
Kind code	B2
Filing date	Oct 3, 2014
Priority date	Mar 26, 2009
Publication date	Nov 8, 2016
Grant date	Nov 8, 2016

Abstract

Compositions are provided for preferential distribution of active agents to injury sites. Such compositions may comprise a ligand with hydrophilic properties and one or more active agents, such as compounds comprising hydrophilic metal ions. Because the delivery ligand and the active agent are specifically selected so the interactions between them are mainly of an ionic nature so that binding of the active agent to the delivery ligand and release of the active agent into the target site are not dependent on enzymatic activity. Methods of using such compositions are also disclosed.

First claim

What is claimed is:

1. A method of preferential distribution of one or more active agents to a site of injury comprising: identifying a patient having an organ affected by a biological condition known to cause vessels supplying the organ to leak; and administering to the patient a composition comprising a delivery ligand and one or more active agents at a dose of about 0.5 to about 10 ml of composition per kg of patient's weight.

2. The method of claim 1 , wherein the composition comprises about 0.1 to about 3 g of ligand and about 4 to about 80 mg of the active agent per kg of patient's body weight.

3. The method of claim 1 , wherein the delivery ligand comprises a ligand with hydrophilic properties.

4. The method of claim 1 , wherein the delivery ligand comprises polyethylene glycol (PEG).

5. The method of claim 1 , wherein the delivery ligand has a molecular weight between about 300 DA and about 9000 DA.

6. The method of claim 5 , wherein a single dose is administered within one half-life of the delivery ligand.

7. The method of claim 1 , wherein the active agent is a metal ion.

8. The method of claim 1 , wherein the concentration of the active agent is between about 0.1 and 20 percent weight per volume.

9. The method of claim 1 , wherein the active agent is a compound comprising a magnesium ion.

10. The method of claim 1 , wherein the composition comprises between about 10 and about 60% weight per volume of the delivery ligand.

11. A method of treating organs affected by one or more biological conditions known to cause vessels supplying the organ to leak by preferentially distributing an active agent known to treat the one or more biological conditions, the method comprising:
identifying a patient having such an organ; and administering to the patient a composition comprising a delivery ligand and one or more active agents at a dose of about 0.5 to about 10 ml of composition per kg of patient's weight.

12. The method of claim 11 , wherein the composition comprises about 0.1 to about 3 g of ligand and about 4 to about 80 mg of the active agent per kg of patient's body weight.

13. The method of claim 11 , wherein the delivery ligand comprises polyethylene glycol (PEG).

14. The method of claim 11 , wherein the active agent has a molecular weight between about 300 DA and about 9000 DA.

15. The method of claim 14 , wherein a single dose is administered within two half-lives of the delivery ligand.

16. The method of claim 11 , wherein the active agent is a metal ion.

17. The method of claim 11 , wherein the concentration of the active agent is between about 0.1 and 20% weight per volume.

18. The method of claim 11 , wherein the active agent is a compound comprising a magnesium ion.

19. The method of claim 11 , wherein the composition comprises between about 10 and about 60% of the delivery ligand.

20. A method of preferentially distributing magnesium to a site of neuronal injury, the method comprises: administering a composition comprising PEG and between about 0.1% and about 20% weight per volume of a compound comprising magnesium, wherein the compound comprising magnesium is distributed by PEG to the area surrounding the site of injury.

Assignees

• Warsaw Orthopedic Inc

Inventors

• Roy Josee
• Kimble Toya

Classifications

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61K33/06 Primary

  Aluminium, calcium or magnesium; Compounds thereof {, e.g. clay} · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title