Photodynamic diagnostic agent and photobleaching inhibitor

Patent metadata

Field	Value
Publication number	US-9517267-B2
Application number	US-201314373341-A
Country	US
Kind code	B2
Filing date	Jan 22, 2013
Priority date	Jan 26, 2012
Publication date	Dec 13, 2016
Grant date	Dec 13, 2016

Abstract

The objects of the present invention are to inhibit photobleaching of porphyrins as well as to provide a superior photodynamic diagnostic agent and a photodynamic diagnostic method employing the photobleaching inhibitor for porphyrins. The present invention provides a photodynamic diagnostic agent containing a precursor of porphyrins and a gallic acid. The present invention also provides a photobleaching inhibitor for porphyrins containing a gallic acid.

First claim

The invention claimed is:

1. A method for detecting a porphyrin accumulation site, comprising:
irradiating a subject with the excitation light for porphyrins, wherein said subject has been administered in advance of said irradiation a precursor of porphyrins and a compound of the following formula (I):

wherein R 1 is selected from the group consisting of an alkyl group having 1-10 carbons, a cycloalkyl group having 3-8 carbons, an aryl group having 6-14 carbons, and an aralkyl group having 7-15 carbons, and R 2 , R 3 , and R 4 each represent a hydroxyl group,
or a salt thereof, said precursor of porphyrins and compound of formula (I) having been administered to said subject at simultaneous or different times, and
detecting the fluorescence of porphyrins, thereby detecting the porphyrin accumulation site.

2. A photodynamic diagnostic method for measuring a range of a lesion site in a subject, comprising:
administering to said subject a precursor of porphyrins and a compound of the following formula (I):

wherein R 1 is selected from the group consisting of an alkyl group having 1-10 carbons, a cycloalkyl group having 3-8 carbons, an aryl group having 6-14 carbons, and an aralkyl group having 7-15 carbons, and R 2 , R 3 , and R 4 each represent a hydroxyl group
or a salt thereof, at simultaneous or different times,
irradiating the subject with the excitation light for porphyrins,
identifying the porphyrins accumulation site by detecting the fluorescence of porphyrins, and
measuring the range of the lesion site.

3. The method according to claim 1 , wherein R 1 is selected from the group consisting of a methyl group, a propyl group, a butyl group, and an octyl group.

4. The method according to claim 2 , wherein R 1 is selected from the group consisting of a methyl group, a propyl group, a butyl group, and an octyl group.

5. The method according to claim 1 , wherein said precursor of porphyrins is a 5-aminolevulinic acid (ALA).

6. The method according to claim 2 , wherein said precursor of porphyrins is a 5-aminolevulinic acid (ALA).

7. The method according to claim 1 , wherein said precursor of porphyrins is a compound of the following formula (II):
R 1 —NHCH 2 COCH 2 CH 2 COOR 2   (II),

wherein R 1 represents a hydrogen atom or an acyl group, and R 2 represents a hydrogen atom, a linear or branched alkyl group, a cycloalkyl group, an aryl group, or an aralkyl group,
or a salt thereof.

8. The method according to claim 2 , wherein said precursor of porphyrins is a compound of the following formula (II):
R 1 —NHCH 2 COCH 2 CH 2 COOR 2   (II),

wherein R 1 represents a hydrogen atom or an acyl group, and R 2 represents a hydrogen atom, a linear or branched alkyl group, a cycloalkyl group, an aryl group, or an aralkyl group,
or a salt thereof.

9. The method according to claim 1 , wherein said porphyrins are selected from the group consisting of protoporphyrin IX, uroporphyrin I, uroporphyrin III, coproporphyrin I, coproporphyrin III, heptacarboxylporphyrin I, heptacarboxylporphyrin III, hexacarboxylporphyrin I, hexacarboxylporphyrin III, pentacarboxylporphyrin I, pentacarboxylporphyrin III, isocoproporphyrin, harderoporphyrin, isoharderoporphyrin, mesoporphyrin IX, deuteroporphyrin IX, and pemptoporphyrin.

10. The method according to claim 2 , wherein said porphyrins are selected from the group consisting of protoporphyrin IX, uroporphyrin I, uroporphyrin III, coproporphyrin I, coproporphyrin III, heptacarboxylporphyrin I, heptacarboxylporphyrin III, hexacarboxylporphyrin I, hexacarboxylporphyrin III, pentacarboxylporphyrin I, pentacarboxylporphyrin III, isocoproporphyrin, harderoporphyrin, isoharderoporphyrin, mesoporphyrin IX, deuteroporphyrin IX, and pemptoporphyrin.

11. The method according to claim 9 , wherein said porphyrins are protoporphyrin IX (PpIX).

12. The method according to claim 10 , wherein said porphyrins are protoporphyrin IX (PpIX).

Assignees

• Sbi Pharmaceuticals Co Ltd
• Tokyo Inst Tech

Inventors

• Ishizuka Masahiro
• Tanaka Tohru
• Ogura Shun-Ichiro
• Ishii Takuya

Classifications

• C07C69/84

  of monocyclic hydroxy carboxylic acids, the hydroxy groups and the carboxyl groups of which are bound to carbon atoms of a six-membered aromatic ring · CPC title

• A61K41/0057

  Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent · CPC title

• A61K31/216

  of acids having aromatic rings, e.g. benactizyne, clofibrate · CPC title

• A61K49/0036

  Porphyrins (used in photodynamic therapy A61K41/0071 or A61K41/0076; used as targeting group or modifying agent for targeting a therapeutic compound A61K47/546) · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title