# US 10,869,937 B2 · Polymer derivatives, and novel polymer derivative imaging probe using same

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- Number: US 10,869,937 B2
- Document ID: US10869937B2
- Status: Granted
- Kind: B2
- Application number: 16/319,636
- Filed: 2017-07-21
- Published: 2019-10-10
- Granted: 2020-12-22
- Earliest claimed: 2016-07-30
- Assignees: Nippon Kayaku Kabushiki Kaisha
- Applicants: Nippon Kayaku Kabushiki Kaisha
- Inventors: Keiichirou Yamamoto; Yuki Kawano
- Web page: https://patentgrep.com/patent/US10869937B2

## CPC

- A61K 49/0054: {Macromolecular compounds, i.e. oligomers, polymers, dendrimers}
- A61K 9/51: Nanocapsules; {Nanoparticles; (nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00)}
- 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)
- A61K 49/00: Preparations for testing in vivo
- C08G 65/33396: {having oxygen in addition to nitrogen}
- C08G 69/40: Polyamides containing oxygen in the form of ether groups (C08G69/12, C08G69/32 take precedence)
- C08G 69/10: Alpha-amino-carboxylic acids {(polysuccinimides C08G73/1092)}
- 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)
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS

## Abstract

Provided are a block copolymer having an enhanced effect of imaging the interior of a tumor compared to known block copolymers and imaging probes using the known block copolymers; and an imaging probe using the block copolymer. Specifically, for the purpose of enhancing penetrability into a diseased target tissue and efficiently enhancing an imaging effect compared to known block copolymers and imaging probes using the known block copolymers, disclosed is a block copolymer in which a hydrophilic polymer segment containing a polyethylene glycol chain is linked to a hydrophobic polymer segment containing a polyamino acid chain having a signal group and optionally a hydrophobic substituent in a side chain, wherein the main chain polymer combining the polyethylene glycol chain and the polyamino acid chain has an average molecular weight of not less than 2 kDa and not more than 10 kDa, and the mass content percentage of the signal group and the optional hydrophobic substituent is not less than 5% by mass and not more than 50% by mass; and also disclosed is a composition including the block copolymer.

## Claims

### Claim 1

An imaging probe comprising a block copolymer comprising a hydrophilic polymer segment linked to a hydrophobic polymer segment, the hydrophilic polymer segment containing a polyethylene glycol chain, and the hydrophobic polymer segment containing a polyamino acid chain having a signal group and optionally a hydrophobic substituent in a side chain, and
wherein the block copolymer is represented by General Formula (1):
wherein R1 represents a hydrogen atom or a linear, branched or cyclic (C1-C6) alkyl group which may have a substituent; t represents an integer from 20 to 140; A represents a (C1-C6) alkylene group which may have a substituent; R2 represents a substituent selected from the group consisting of a hydrogen atom, a (C1-C6) acyl group, and a (C1-C6) alkoxycarbonyl group; R3 represents a signal group; R4 represents a hydrophobic substituent; n represents 1 or 2; x1, x2, y1, y2, and z each independently represents an integer from 0 to 20; (x1+x2) represents an integer from 1 to 10; (x1+x2+y1+y2+z) represents an integer from 3 to 20; and the various constituent units to which R3 and R4 are bonded, and a constituent unit formed by intramolecular cyclization of a side-chain carbonyl group constitute a structure with those constituent units being each independently randomly arranged;
wherein said signal group of R3 contains a fluorescent group, a radioisotope-containing group, or a magnetic group, said fluorescent group including a group derived from a member selected from the group consisting of a fluorescein-based dye, an indocyanine-based dye, a rhodamine-based dye, a BODIPY-based dye, a xanthene-based dye, a Nile Red-based dye and a quantum dot, said radioisotope-containing group including a group derived from a member selected from the group consisting of a sugar, an amino acid and a nucleic acid, all being labeled with radioisotopes, said magnetic group including a group selected from the group consisting of ferrichrome, ferrite nanoparticles and magnetic nanoparticles;
wherein the main chain polymer of the block copolymer combining the polyethylene glycol chain and the polyamino acid chain has an average molecular weight of not less than 2 kDa and not more than 10 kDa, said average molecular weight of the main chain polymer being a calculated value obtained by summing the (1) average molecular weight of the polyethylene glycol chain and the (2) average molecular weight of the polymer main chain portion of the polyamino acid chain excluding the signal group and the optional hydrophobic substituent, said average molecular weight of the polyethylene glycol chain being determined from the peak top molecular weight measured by a GPC method based on polyethylene glycol standards, and average molecular weight of the polymer main chain portion of the polyamino acid chain being a calculated value obtained by multiplying the average molecular weight of the polymerized monomer unit of the polyamino acid chain by the average number of units of the polyamino acid obtained by neutralization titration method, and a mass content percentage of the signal group and the optional hydrophobic substituent is not less than 5% by mass and not more than 50% by mass, and
wherein the block copolymer has a particle size of less than 20 nm.

### Claim 2 (depends on 1)

The imaging probe according to claim 1, wherein the signal group is a fluorescent group.

### Claim 3 (depends on 1)

The imaging probe according to claim 1, wherein the polyethylene glycol chain has an average molecular weight of not less than 1 kDa and not more than 6 kDa.