Saccharide-measuring fluorescent monomer, saccharide-measuring fluorescent sensor substance, and implantable, saccharide-measuring sensor

• US 20080021236A1
• Filed: 08/07/2007
• Published: 01/24/2008
• Est. Priority Date: 07/23/2004
• Status: Active Grant

• Current Assignee: Terumo Kabushiki Kaisha
• Original Assignee: Terumo Kabushiki Kaisha
• Inventors: Ochiai, Shouji, Matsumoto, Atsushi, Kawanishi, Tetsuro
• Granted Patent: US 7,524,985 B2
• Time in Patent Office: Days
• US Class Current: 562/7
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds
• CPC Class Codes: C09K 11/06 containing organic luminescent materials
• CPC Class Codes: C09K 2211/1007 Non-condensed systems
• CPC Class Codes: C09K 2211/1011 Condensed systems
• CPC Class Codes: C09K 2211/1014 bridged by heteroatoms, e.g. N, P, Si or B

Abstract

A fluorescent monomer compound represented by the following formula (1) is provided:
wherein Q, Q′ and D³ may be the same or different, may be combined together into a fused ring, and are each a substituent selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxyl group, and substituted or unsubstituted alkyl, acyl, oxyalkyl, carboxyl, carboxylate ester, carboxamido, cyano, nitro, amino and aminoalkyl groups; and D¹, D² and D⁴ each represent a substituent, wherein at least one of D¹, D² and D⁴ is a substituent group comprising a vinyl group at an end thereof, and wherein the substituent group comprising a vinyl group at an end thereof enables the fluorescent monomer compound to be soluble in water.

Claims

1. A saccharide-measuring fluorescence sensor substance comprising a copolymer of at least the following two compounds (I) and (II):

(I) a fluorescent monomer compound represented by the following formula (1);

wherein;

Q, Q′ and

D³ may be the same or different, may be combined together into a fused ring, and are each a substituent selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxyl group, and substituted or unsubstituted alkyl, acyl, oxyalkyl, carboxyl, carboxylate ester, carboxamido, cyano, nitro, amino and aminoalkyl groups; and

D¹, D² and D⁴ each represent a substituent, wherein at least one of D¹, D² and D⁴ is a substituent group comprising a vinyl group at an end thereof, and wherein the substituent group comprising a vinyl group at an end thereof enables the fluorescent monomer compound to be soluble in water, and

(II) at least one hydrophilic, polymerizable monomer having a vinyl group.

2. The fluorescence sensor substance according to claim 1, wherein said polymerizable monomer (II) is a polymerizable monomer comprising a (meth)acrylamide residual group.

13. An implantable, saccharide-measuring sensor comprising the fluorescence sensor substance as defined in claim 1.

3. A saccharide-measuring fluorescence sensor substance comprising a copolymer of at least the following two compounds (I) and (II):

(I) a fluorescent monomer compound represented by the following formula (1);

wherein;

Q and Q′

may be the same or different, may be combined together into a fused ring, and are each a substituent selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxyl group, and substituted or unsubstituted alkyl, acyl, oxyalkyl, carboxyl, carboxylate ester, carboxamido, cyano, nitro, amino and aminoalkyl groups;

and in D¹, D², D³ and D⁴,

(i) D¹ and D² may be the same or different and are each a substituted or unsubstituted alkyl group, D³ is a hydrogen atom, and D⁴ is a substituent group represented by the following formula (2), or

(ii) D¹ and D² may be the same or different and are each a substituent group represented by the following formula (3), and D³ and D⁴ may be the same or different, may be combined together into a fused ring, and are each a substituent selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxyl group, and substituted or unsubstituted alkyl, acyl, oxyalkyl, carboxyl, carboxylate ester, carboxamido, cyano, nitro, amino and aminoalkyl groups;

wherein;

X, in a case of the definition (i), is a substituent group selected from the group consisting of —

COO—

, —

OCO—

, —

CH₂NR—

, —

CH₂S—

, —

CH₂O—

, —

NR—

, —

NRCO—

, —

CONR—

, —

SO₂NR—

, —

NRSO₂—

, —

O—

, —

S—

, —

SS—

, —

NRCOO—

, —

OCONR— and

—

CO—

, and in a case of the definition (ii), represents a C₁ to C₃₀ alkylene group comprising at least one substituent group selected from the group consisting of —

COO—

, —

OCO—

, —

CH₂NR—

, —

NR—

, —

NRCO—

, —

CONR—

, —

SO₂NR—

, —

NRSO₂—

, —

O—

, —

S—

, —

SS—

, —

NRCOO—

, —

OCONR— and

—

CO—

, in which R represents a hydrogen atom or a substituted or unsubstituted alkyl group,

Y is a substituted or unsubstituted, divalent, organic residual group, and

Z represents —

O—

or —

NR″

—

, and R″

represents a hydrogen atom or a substituted or unsubstituted alkyl group, and

(II) at least one hydrophilic, polymerizable monomer having a vinyl group.

4. The fluorescence sensor substance according to claim 3, wherein said polymerizable monomer (II) is a polymerizable monomer comprising a (meth)acrylamide residual group.

5. The fluorescence sensor substance according to claim 3, wherein D₁, D₂, D₃ and D₄ have the same meanings as defined under said definition (i), and a molar ratio of said fluorescent monomer compound (I) to said polymerizable monomer (II) in said copolymer is from 1:

10 to 1;

4,000.

6. The fluorescence sensor substance according to claim 3, wherein D₁, D₂, D₃ and D₄ have the same meanings as defined under said definition (ii), and a molar ratio of said fluorescent monomer compound (I) to said polymerizable monomer (II) in said copolymer is from 1:

50 to 1;

6,000.

7. The fluorescence sensor substance according to claim 3, wherein said polymerizable monomer (II) is a compound represented by the following formula (6):

8. The fluorescence sensor substance according to claim 3, wherein at least a portion of said copolymer comprises intermolecular crosslinks formed therein, and has a three-dimensional crosslinked structure.

14. An implantable, saccharide-measuring sensor comprising the fluorescence sensor substance as defined in claim 3.

9. A fluorescence sensor substance represented by the following formula (7):

10. The fluorescent monomer compound according to claim 9, wherein Y comprises a structure represented by the following formula (4) or formula (5):

11. The fluorescent monomer compound according to claim 9, wherein D¹⁰, D²⁰, D³⁰ and D⁴⁰ have the meanings as defined under said definition (x), and Y is a substituted or unsubstituted, linear, divalent, organic residual group having a number of atoms of from 3 to 500.

12. The fluorescence sensor substance according to claim 9, wherein at least a portion of said copolymer comprises intermolecular crosslinks formed therein, and has a three-dimensional crosslinked structure.

15. An implantable, saccharide-measuring sensor comprising the fluorescence sensor substance as defined in claim 9.