Method to enhance permeability of the blood/brain blood/nerve bariers to therapeutic agents

• US 5,670,477 A
• Filed: 04/20/1995
• Issued: 09/23/1997
• Est. Priority Date: 04/20/1995
• Status: Expired due to Term

• Current Assignee: Geoffrey L. Curran, Joseph F. Poduslo
• Original Assignee: Geoffrey L. Curran, Joseph F. Poduslo
• Inventors: Poduslo, Joseph F., Curran, Geoffrey L.
• Primary Examiner(s): MacMillan, Keith
• Application Number:
  US08/425,576
• Time in Patent Office: 887 Days
• Field of Search: 514/2
• US Class Current: 514/8.3
• CPC Class Codes: A61K 38/185 Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 38/446 Superoxide dismutase (1.15)
• CPC Class Codes: A61K 47/543 Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002

Abstract

A method is provided to enhance the ability of a neurologically active compound to penetrate the blood nerve barrier (BNB) or blood brain barrier (BBB), by administration of a conjugate comprising the neurologically active compound linked to a carrier molecule that has been shown to have a substantial permeability coefficient across the BNB and BBB.

Claims

1. A method to enhance the ability of a neurologically active compound to penetrate the blood-nerve-barrier or blood-brain-barrier comprising parenterally administering to a mammal in need of treatment with said neurologically active compound, a conjugate consisting of an effective amount of said neurologically active compound linked to a polyamine having a substantial permeability coefficient across the blood-nerve-barrier or blood-brain-barrier.

2. The method of claim 1 wherein the neurologically active compound is selected from the group consisting of a compound acting at a synaptic andr neuroeffector junctional site, a compound acting on the central or peripheral nervous system, an antioxidant, or a neurotrophic protein.

3. The method of claim 1 wherein the neurologically active compound is an antioxidant or a neurotrophic protein.

4. The method of claim 3 wherein the neurologically active compound is superoxide dismutase or neuronal growth factor.

5. The method of claim 1 wherein the polyamine is selected from the group consisting of putrescine, spermidine and spermine.

6. The method of claim 1 wherein the mammal is a human.

7. The method of claim 1 wherein said conjugate is administered in combination with a pharmaceutically acceptable carrier.

8. The method of claim 7 wherein the pharmaceutically acceptable carrier is a solid.

9. The method of claim 7 wherein the pharmaceutically acceptable carrier is a liquid.

10. A pharmaceutical composition comprising a neurologically active compound linked to a polyamine in combination with a pharmaceutically acceptable carrier.

11. The pharmaceutical composition of claim 10 which is adapted for parenteral administration.

12. The pharmaceutical composition of claim 11 wherein the pharmaceutically acceptable carrier is a liquid vehicle.

13. The pharmaceutical composition of claim 10 wherein the neurologically active compound is selected from the group consisting of a compound acting at a synaptic and/or neuroeffector junctional site, a compound acting on the central or peripheral nervous system, an antioxidant, or a neurotrophic protein.

14. The pharmaceutical composition of claim 10 wherein the neurologically active compound is an antioxidant or a neurotrophic protein.

15. The pharmaceutical composition of claim 14 wherein the neurologically active compound is superoxide dismutase or neuronal growth factor.

16. The pharmaceutical composition of claim 10 wherein the polyamine is selected from the group consisting of putrescine, spermidine or spermine.

17. An isolated and purified composition consisting of a neurologically active compound linked to a polyamine, wherein the polyamine is present in an amount effective to increase the ability of the composition to cross the brain-nerve barrier or blood-brain barrier of a mammal to which said composition is administered.

18. The composition of claim 17 wherein the neurologically active compound is selected from the group consisting of a compound acting at a synaptic and/or neuroeffector junctional site, a compound acting on the central or peripheral nervous system, an antioxidant, or a neurotrophic protein.

19. The composition of claim 18 wherein the neurologically active compound is an antioxidant or a neurotrophic protein.

20. The composition of claim 19 wherein the neurologically active compound is neuronal growth factor or superoxide dismutase.

21. The composition of claim 17 wherein the polyamine is selected from the group consisting of putrescine, spermine, or spermidine.