Carrier for use in delivering drug, conjugate, composition comprising same, and method for administrating same

Patent metadata

Field	Value
Publication number	US-2016287714-A1
Application number	US-201415038374-A
Country	US
Kind code	A1
Filing date	Nov 21, 2014
Priority date	Nov 22, 2013
Publication date	Oct 6, 2016
Grant date	—

Abstract

The present invention provides a vesicle, a conjugate, a composition comprising the vesicle or the conjugate, for use in delivering a drug to the brain, and a method for administering the same. The composition of the present invention is a composition for administration to a subject according to a dosing regimen, comprising a carrier for drug delivery, wherein the dosing regimen comprises administering the composition to a subject who has been fasted or caused to have hypoglycemia and inducing an increase in blood glucose level in the subject, and the carrier is modified at the outer surface thereof with a GLUT1 ligand.

First claim

1 . A composition for administration to a subject according to a dosing regimen, the composition comprising a carrier for drug delivery, wherein:
the dosing regimen comprises administering the composition to a subject who has been fasted or caused to have hypoglycemia and inducing an increase in blood glucose level in the subject; and the carrier is modified at an outer surface thereof with a GLUT1 ligand.

2 . A composition for administration to a subject according to a dosing regimen comprising a conjugate of a drug and a GLUT1 ligand,
wherein the dosing regimen comprises administering the composition to a subject who has been fasted or caused to have hypoglycemia and inducing an increase in blood glucose level in the subject.

3 . The composition according to claim 1 , wherein the composition is adapted to deliver a drug to the brain.

4 . The composition according to claim 1 , wherein the composition is adapted to function by permeating a drug across the blood-brain barrier.

5 . The composition according to claim 1 , wherein the composition is adapted to function by permeating a drug across the blood-nerve barrier, the blood-retina barrier, or the blood-cerebrospinal fluid barrier.

6 . The composition according to claim 1 , wherein the composition is adapted to function by delivering a drug to a cerebrovascular endothelial cell.

7 . The composition according to claim 1 , wherein the increase in blood glucose level is induced by glucose administration.

8 . The composition according to claim 7 , wherein the composition is administered concurrently with or before the administration of the glucose.

9 . The composition according to claim 1 , wherein the composition is administered in the form of an intravenous infusion, and the infusion administration is continued for 10 minutes or longer.

10 . The composition according to claim 1 , wherein the carrier is a vesicle, and 10 to 40% by mol of a polymer constituting the vesicle is modified with the GLUT1 ligand.

11 . The composition according to claim 1 , wherein the carrier is a vesicle, and 40 to 100% by mol of a polymer constituting the vesicle is modified with the GLUT1 ligand.

12 . The composition according to claim 1 , wherein the carrier incorporates a drug to be delivered.

13 . The composition according to claim 1 , wherein the carrier is a vesicle having a diameter of 400 nm or smaller.

14 . The composition according to claim 2 , wherein the conjugate comprises the drug and the GLUT1 ligand linked via a linker.

15 . The composition according to claim 1 , wherein the GLUT1 ligand is glucose.

16 . The composition according to claim 2 , wherein the drug is at least one selected from a biologically active substance, an antibody, a nucleic acid, a biocompatible fluorescent dye, and a contrast medium.

17 . A conjugate of one molecule of a GLUT1 ligand and one molecule of a polymer, wherein the conjugate is capable of forming a vesicle such that the GLUT1 ligand is exposed on the surface of the vesicle.

18 . The conjugate according to claim 17 , wherein the GLUT1 ligand is glucose.

19 . The conjugate according to claim 18 , wherein the glucose is conjugated via carbon at position 6 thereof with the polymer.

20 . The conjugate according to claim 19 , or a pharmaceutically acceptable salt thereof, wherein the conjugate is represented by the following formula (I), (II), (III), or (XVI):

wherein n 1 and m 1 each represent 5 to 20,000,

wherein n 2 and m 2 each represent 5 to 20,000,

wherein n 3 and m 3 each represent 5 to 20,000, and

wherein n 16 represents an integer of 5 to 20,000, and m 16 represents an integer of 2 to 5,000.

21 . A vesicle for drug delivery, the vesicle comprising a conjugate according to claim 17 , wherein the conjugate accounts for 10 to 40% by mol of all polymers constituting the vesicle.

22 . A vesicle for drug delivery, the vesicle comprising a conjugate according to claim 17 , wherein the conjugate accounts for 40 to 100% by mol of all polymers constituting the vesicle.

23 . A method for producing the composition according to claim 1 , the method comprising modifying the carrier at the outer surface thereof with the GLUT1 ligand.

Assignees

• Univ Tokyo
• Nat Univ Corp Tokyo Medical & Dental Univ

Inventors

• Kataoka Kazunori
• Anraku Yasutaka
• Nishiyama Nobuhiro
• Miyata Kanjiro
• Ishii Takehiko
• Matsumoto Yu
• Fukusato Yu
• Mizoguchi Akihiro
• Yokota Takanori
• Kuwahara Hiroya
• Nishina Kazutaka
• Mizusawa Hidehiro

Classifications

• A61P3/08

  for glucose homeostasis (pancreatic hormones A61P5/48) · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/24

  Antidepressants · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• A61P25/22

  Anxiolytics · CPC title