Increasing blood-brain barrier permeability with permeabilizer peptides

• US 5,268,164 A
• Filed: 04/23/1991
• Issued: 12/07/1993
• Est. Priority Date: 04/23/1990
• Status: Expired due to Fees

• Current Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Original Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Inventors: Malfroy-Camine, Bernard, Musso, Gary F., Kozarich, John W.
• Primary Examiner(s): Hollrah, Glennon H.
• Assistant Examiner(s): Hollinden, Gary E.
• Application Number:
  US07/690,522
• Time in Patent Office: 959 Days
• Field of Search: 530/314, 514/25, 514/929, 424/1.1, 424/9
• US Class Current: 424/1.11
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/043 Kallidins; Bradykinins; Related peptides
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: C07K 7/02 Linear peptides containing at least one abnormal peptide link
• CPC Class Codes: C07K 7/18 Kallidins; Bradykinins; Related peptides

Abstract

Polypeptides called receptor mediated permeabilizers (RMP) increase the permeability of the blood-brain barrier to molecules such as therapeutic agents or diagnostic agents. These receptor mediated permeabilizers are more efficacious than bradykinin in causing the blood-brain barrier to become more permeable. The permeabilizer A-7 or conformational analogues can be intravenously co-administered to a host together with molecules whose desired destination is the cerebrospinal fluid compartment of the brain. The permeabilizer A-7 or conformational analogues allow these molecules to penetrate the blood-brain barrier and arrive at this destination.

Claims

1. A method for increasing the permeability of the blood-brain barrier of a host to a molecule present in the bloodstream of the host comprising the intravascular administration of an effective amount of a blood-brain barrier permeabilizer comprising a peptide with the amino acid sequence of NH₂ -arginine-proline-hydroxyproxyproline-glycine-thienylalanine-serine-proline-4-Me-tyrosineΨ

(CH₂ NH) arginine-COOH (Seq. ID NO.

     1) or a conformational analogue thereof.

2. The method of claim 1 wherein the host is a human being.

3. The method of claim 1 wherein said permeabilizer A-7 or conformational analogues and said molecule are intravascularly co-administered to said host.

4. The method of claim 1 wherein said molecule comprises a diagnostic imaging agent.

5. The method of claim 4 wherein said diagnostic imaging agent is radiolabelled.

6. The method of claim 1 wherein said molecule comprises a neuropharmaceutical agent.

7. The method of claim 6 wherein said neuropharmaceutical agent and said permeabilizer A-7 or conformational analogues are intravascularly co-administered to said host.