# US 9,750,827 B2 · Near-infrared dye-conjugated hyaluronic acid derivative and contrast agent for optical imaging including them

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- Number: US 9,750,827 B2
- Document ID: US9750827B2
- Status: Granted
- Kind: B2
- Application number: 14/767,362
- Filed: 2014-02-21
- Published: 2015-12-31
- Granted: 2017-09-05
- Earliest claimed: 2013-02-22
- Assignees: Canon Kabushiki Kaisha
- Applicants: Canon Kabushiki Kaisha
- Inventors: Koji Miki; Tatsuhiro Inoue; Yasuhito Kobayashi; Katsuya Nakano; Kouichi Ohe; Fumio Yamauchi; Tetsuya Yano; Masato Minami
- Web page: https://patentgrep.com/patent/US9750827B2

## CPC

- A61K 49/221: {characterised by the targeting agent or modifying agent linked to the acoustically-active agent}
- A61K 49/0034: {Indocyanine green, i.e. ICG, cardiogreen}
- A61K 49/0054: {Macromolecular compounds, i.e. oligomers, polymers, dendrimers}
- C08B 37/0072: {Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates}
- A61K 47/50: the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K 47/51: the non-active ingredient being a modifying agent
- A61K 47/55: the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug
- A61K 47/56: the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K 47/61: the organic macromolecular compound being a polysaccharide or a derivative thereof
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C08B: POLYSACCHARIDES; DERIVATIVES THEREOF (polysaccharides containing less than six saccharide radicals attached to each other by glycosidic linkages C07H; fermentation or enzyme-using processes C12P19/00; sugar industry C13; production of cellulose D21)

## Abstract

Provided is a compound having a high ICG content that has high accumulation property in a tumor and has a large intensity of a photoacoustic signal emitted from the tumor even when a time period elapses after administration. Specifically, provided is a hyaluronic acid derivative to which polyethylene glycol and an ICG derivative are conjugated.

## Claims

### Claim 1

A polymer formed of units each represented by general formula (1):
wherein:
R1's are independent of each other from unit to unit in the general formula (1); and
the polymer contains at least one unit in which R1 is selected from the group consisting of general formula (2) and general formula (25), and at least one unit in which R1 is general formula (3):
provided that: in the general formula (2), the general formula (3), and the general formula (25), L's represent linkers independent of each other from unit to unit, and * represents a binding site with N in the general formula (1); and in the general formula (3), R2 represents any one of H, OH, OMe, NH2, and COOH, and k represents an integer of 20 or more and 200 or less,
wherein 0.13<x/N≦0.78,
where:
x is a number of units in the polymer in which R1 is the general formula (2) or the general formula (25) and N is a number of all units in the polymer.

### Claim 2

A polymer formed of units each represented by general formula (1):
wherein:
R1's are independent of each other from unit to unit in the general formula (1);
R1 is selected from the group consisting of general formulae (2) to (5), general formula (25), and general formula (29); and
the polymer contains at least one unit in which R1 is selected from the group consisting of the general formula (2) and the general formula (25), and at least one unit in which R1 is the general formula (3):
provided that: in the general formulae (2) to (5), the general formula (25), and the general formula (29), L's represent linkers independent of each other from unit to unit, and * represents a binding site with N in the general formula (1); in the general formula (3), R2 represents any one of H, OH, OMe, NH2, and COOH, and k represents an integer of 20 or more and 200 or less; and in the general formula (5), R3 represents any one of N3, H, CH3, NH2, SH, and COOH,
wherein 0.13<x/(x+y+z)≦0.78,
where:
x is a number of units in the polymer in which R1 is the general formula (2) or the general formula (25),
y is a number of units in the polymer in which R1 is the general formula (3), and
z is a number of units in the polymer in which R1 is the general formula (4) or the general formula (29).

### Claim 3 (depends on 2)

The polymer according to claim 2, wherein the polymer contains at least one unit in which R1 is selected from the group consisting of the general formula (4) and the general formula (29).

### Claim 4

A polymer formed of units each represented by any one of general formulae (6) to (9), general formula (28), and general formula (30), wherein the polymer contains at least one unit selected from the group consisting of the general formula (6) and the general formula (28), and at least one unit represented by the general formula (7):

### Claim 5 (depends on 4)

The polymer according to claim 4,
wherein 0.13<x/(x+y+z)≦0.78,
where:
x is a number of units in the polymer each represented by the general formula (6) or the general formula (28);
y is a number of units in the polymer each represented by the general formula (7); and
z is a number of units in the polymer each represented by the general formula (8), (9), or (30).

### Claim 6 (depends on 1)

A particle, comprising the polymer according to claim 1.

### Claim 7 (depends on 1)

A contrast agent for photoacoustic imaging, comprising:
the polymer according to claim 1; and
a dispersion medium.

### Claim 8 (depends on 6)

The particle according to claim 6, wherein the particle has an average particle diameter of 10 nm to 180 nm.

### Claim 9 (depends on 6)

A contrast agent for photoacoustic imaging, comprising:
the particle according to claim 6; and
a dispersion medium for the particle.