MACROPHAGE IDENTIFICATION AGENT, AND IDENTIFICATION METHOD, SORTING METHOD, EVALUATION METHOD, SCREENING METHOD AND KIT USING THE MACROPHAGE IDENTIFIER AGENT

• US 20160018389A1
• Filed: 05/29/2014
• Published: 01/21/2016
• Est. Priority Date: 05/30/2013
• Status: Active Grant

• Current Assignee: Canon Kabushiki Kaisha (Canon Inc.)
• Original Assignee: Canon Kabushiki Kaisha (Canon Inc.)
• Inventors: KOIDE, Fumiyo, NOMOTO, Tsuyoshi, YAMAUCHI, Sachiko, WATANABE, Kohei, SHINTOU, Taichi, MIYAZAKI, Takeshi, TABATA, Yasuhiko, SANDA, Eri
• Granted Patent: US 10,041,937 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: C07D 209/14 Radicals substituted by nitrogen atoms, not forming part of a nitro radical
• CPC Class Codes: C07D 209/80 [b, c]- or [b, d]-condensed
• CPC Class Codes: C07D 277/64 with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 403/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 403/08 linked by a carbon chain containing alicyclic rings
• CPC Class Codes: C07D 413/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 413/08 linked by a carbon chain containing alicyclic rings
• CPC Class Codes: C07D 417/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 417/08 linked by a carbon chain containing alicyclic rings
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: C07D 498/04 Ortho-condensed systems
• CPC Class Codes: C07F 5/022 without C-boron linkages
• CPC Class Codes: C07F 5/027 Organoboranes and organoborohydrides
• CPC Class Codes: C12N 5/0645 Macrophages, e.g. Kuepfer cells in the liver; Monocytes
• CPC Class Codes: G01N 33/5005 involving human or animal cells immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025
• CPC Class Codes: G01N 33/5094 for blood cell populations red blood cells G01N33/80
• CPC Class Codes: G01N 33/52 Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements immunological elements G01N33/54386; involving labelled immunochemicals G01N33/58; for haemoglobin or occult blood G01N33/72

Abstract

An object of the present invention is to provide an identification method for a macrophage subtype using an organic compound. Another object of the present invention is to provide a macrophage identification agent containing an organic compound in which a spectral characteristic obtained when the organic compound is added is different depending on a macrophage subtype. Still another object of the present invention is to provide an evaluation method for a macrophage subtype using a macrophage identification agent, an analysis method for correlation between a macrophage subtype and a test substance, a screening method for correlation between a macrophage subtype and a test substance, and a kit. An identification method for a macrophage subtype utilizing that a spectral characteristic obtained with an organic compound added is different depending on a macrophage subtype is provided.

Claims

1. A method for identifying macrophage subtype M1 and macrophage subtype M2, wherein the subtype M1 and the subtype M2 are identified based on a spectral characteristic obtained with an organic compound added.

2. The method according to claim 1, wherein the organic compound is a dye compound having a molecular weight of 2000 or less.

3. The method according to claim 2, wherein the organic compound comprises one or more compounds represented by general formula (1):

4. The method according to claim 3, wherein the ring formed when R₂ and R₄ of the general formula (1) are bound to each other is a cyclopentane ring.

5. The method according to claim 3, wherein R₉ is a compound represented by the general formula (2).

6. The method according to claim 3, wherein R₉ is a compound represented by the general formula (3).

7. The method according to claim 3, wherein R₉ is a compound represented by the general formula (4).

8. The method according to claim 2, wherein the organic compound contains at least compound represented by general formula (6):

9. The method according to claim 8, wherein the compound represented by the general formula (6) is represented by general formula (9):

10. The method according to claim 8, wherein A of the general formula (6) is a 3-oxocyclobutenolate ring.

11. The method according to claim 2, wherein the organic compound contains one or more compounds represented by general formula (10):

12. The method according to claim 2, wherein the organic compound contains one or more compounds represented by general formula (11):

13. The method according to claim 1, wherein the subtype M1 contained in a biological sample is identified by utilizing that the subtype M1 has different staining properties from the subtype M2.

14. The method according to claim 1, wherein the subtype M2 contained in a biological sample is identified by utilizing that the subtype M1 has different staining properties from the subtype M2.

15. The method according to claim 1, wherein the subtype M1 and the subtype M2 contained in a biological sample are identified by utilizing that the subtype M1 has different staining properties from the subtype M2.

28. The method according to claim 1, wherein the organic compound is exposed to a biological sample.

29. A method for sorting a macrophage subtype that is contained in a biological sample and is identified by the identifying method according to claim 1, the sorting method comprising sorting the identified macrophage subtype.

30. An evaluation method for a macrophage subtype, the method comprising:

detecting a type, a number, a ratio, or an optical characteristic of a macrophage subtype that is contained in a biological sample and is identified by the identifying method according to claim 1; and

evaluating the detected macrophage subtype.

33. An analysis method for analyzing a correlation between a macrophage subtype and a test substance based on the evaluation method according to claim 30, the analysis method comprising detecting an optical characteristic derived from the test substance.

41. A screening method for examining a correlation between a macrophage subtype and a test substance by using the analysis method according to claim 33, the screening method comprising screening for the correlation between the macrophage subtype and the test substance.

16. A macrophage identification agent for identifying macrophage subtypes M1 and M2, comprising at least one organic compound, wherein a spectral characteristic obtained when the organic compound is added is different between the subtype M1 and the subtype M2.

17. The macrophage identification agent according to claim 16, wherein the organic compound is an organic compound having a molecular weight of 2000 or less.

18. The macrophage identification agent according to claim 17, wherein the organic compound contains one or more compounds represented by general formula (1):

19. The macrophage identification agent according to claim 18, wherein the ring formed when R₂ and R₄ of the general formula (1) are bound to each other is a cyclopentane ring.

20. The macrophage identification agent according to claim 18, wherein R₉ is a compound represented by the general formula (2).

21. The macrophage identification agent according to claim 18, wherein R₉ is a compound represented by the general formula (3).

22. The macrophage identification agent according to claim 18, wherein R₉ is a compound represented by the general formula (4).

23. The macrophage identification agent according to claim 17, wherein the organic compound contains one or more compounds represented by general formula (6):

24. The macrophage identification agent according to claim 23, wherein the organic compound is a compound represented by general formula (9):

25. The macrophage identification agent according to claim 23, wherein A of the general formula (6) is a 3-oxocyclobutenolate ring.

26. The macrophage identification agent according to claim 17, wherein the organic compound contains one or more compounds represented by general formula (10):

27. The macrophage identification agent according to claim 17, wherein the organic compound contains one or more compounds represented by general formula (11):

31. An evaluation method for a macrophage subtype, comprising allowing the macrophage identification agent according to claim 16 and a test substance to work on a part or whole of a biological sample.

32. An analysis method for analyzing a correlation between a macrophage subtype and a test substance based on the evaluation method according to claim 31, the analysis method comprising analyzing the correlation between the macrophage subtype and the test substance.

34. A screening method for examining a correlation between a macrophage subtype and a test substance by using the analysis method according to claim 32, the screening method comprising screening for the correlation between the macrophage subtype and the test substance.

36. A sorting method for macrophages, comprising using more than one of the macrophage identification agent according to claim 16.

37. An evaluation method for macrophages, comprising using more than one of the macrophage identification agent according to claim 16.

38. An analysis method for macrophages, comprising using more than one of the macrophage identification agent according to claim 16.

39. A screening method for macrophages, comprising using more than one of the macrophage identification agent according to claim 16.

40. An identification kit for a macrophage subtype, comprising more than one of the macrophage identification agent according to claim 16.

35. An identification kit for a macrophage subtype, comprising at least a macrophage identification agent for identifying macrophage subtypes M1 and M2, the macrophage identification agent comprising at least one organic compound,

wherein a spectral characteristic obtained when the organic compound is added is different between the subtype M1 and the subtype M2.