Local delivery forms of acriflavine for treating tumors

• US 10,195,190 B2
• Filed: 02/11/2016
• Issued: 02/05/2019
• Est. Priority Date: 02/11/2015
• Status: Active Grant

• Current Assignee: Johns Hopkins University
• Original Assignee: Johns Hopkins University
• Inventors: Brem, Henry, Mangraviti, Antonella, Olivi, Alessandro, Tyler, Betty M., Raghavan, Tula
• Primary Examiner(s): Baek, Bong-Sook
• Application Number:
  US15/549,547
• Publication Number:
  US 20180036301A1
• Time in Patent Office: 1,090 Days
• Field of Search: None
• CPC Class Codes: A61K 31/4188 condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
• CPC Class Codes: A61K 31/473 ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

Local delivery formulations of the antineoplastic and microbicide agent acriflavine, and methods of making and using thereof are significantly more efficacious at increasing the median survival of subjects with proliferative disease than systemic administrations of acriflavine. The local delivery formulations of acriflavine show a dose-dependent increase in the median survival of subjects. The local delivery forms provide the increased efficacy without the toxicity associated with systemic administration of the agent.

Claims

1. A method of treating an individual with a solid tumor comprising administering a composition comprising acriflavine or its derivatives in a local delivery formulation for controlled local administration of an effective amount of the acriflavine or its derivatives to the tumor, onto the tumor, or at a resected tumor site, to reduce tumor size and/or, prolong survival of the individual;

wherein the local delivery formulation does not produce systemic level of the acriflavine or its derivatives producing unacceptable side effects;

wherein the solid tumor is a brain tumor; and

wherein the local delivery formulation is in the form of a polymeric implant, polymeric particles or a microchip.

2. The method of claim 1, wherein the effective amount of acriflavine or its derivatives is released over a period of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more weeks.

3. The method of claim 1 further comprising administering additional anti-cancer therapies to the subject.

4. The method of claim 1, wherein the composition is administered to the subject at an area close to the tumor.

5. The method of claim 1, wherein the composition is administered to the subject at an area of a resected tumor.