Enhancer of physiological activity of hepatocyte growth factor
AssigneesKyowa Hakko Bio Co., Ltd., Kyushu University, National University Corporation
InventorsEtsuo OHSHIMA, Ryuichi TATSUMI, Mako NAKAMURA
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Abstract
Disclosed is an enhancer of the physiological activity of a hepatocyte growth factor, the enhancer comprising a trisulfide compound. The trisulfide compound comprises at least one component selected from the group consisting of glutathione trisulfide, a pharmaceutically acceptable salt of glutathione trisulfide, a compound represented by formula (1), a pharmaceutically acceptable salt of the compound, a cyclodextrin inclusion complex of the compound or the pharmaceutically acceptable salt, a compound represented by formula (6), a pharmaceutically acceptable salt of the compound, and a cyclodextrin inclusion complex of the compound or the pharmaceutically acceptable salt.
Claims15
-8. (canceled)
A method for enhancing the physiological activity of hepatocyte growth factor, comprising administering a trisulfide compound to a subject in need thereof, wherein the trisulfide compound is at least one selected from the group consisting of:
- (a) glutathione trisulfide and a pharmaceutically acceptable salt thereof;
- (b) a compound represented by Formula (1):
- wherein R1 is
- a group represented by Formula (2):
- wherein R2 and R3 are each independently a C1-4 alkylene group, and * is a bond;
- a group represented by Formula (3):
- wherein R4 and R5 are each independently a hydrogen atom or a C1-4 alkyl group optionally having a substituent, R4 and R5 may form a ring together with the atom bonded thereto, and * is a bond;
- a group represented by Formula (4):
- wherein * is a bond;
- or
- a group represented by Formula (5):
- wherein * is a bond,
- a pharmaceutically acceptable salt thereof, and a cyclodextrin clathrate thereof;
- and
- (c) a compound represented by Formula (6):
- wherein X is —OR6 or —NR7R8,
- wherein R6, R7, and R8 are each independently a hydrogen atom;
- a C1-6 alkyl group optionally having at least one substituent selected from the group consisting of a carboxy group, —OR9, —NR10R11, and —N+R12R13R14;
- or —(CH2CH2O)nR15,
- wherein R9, R10, R11, R12, R13, R14, and R15 are each independently a hydrogen atom or a C1-3 alkyl group, and n is an integer of 2 to 5,
- a pharmaceutically acceptable salt thereof, and a cyclodextrin clathrate thereof.
A method for enhancing the physiological activity of hepatocyte growth factor, comprising administering a trisulfide compound and hepatocyte growth factor to a patient in need thereof, wherein the trisulfide compound is at least one selected from the group consisting of:
- (a) glutathione trisulfide and a pharmaceutically acceptable salt thereof;
- (b) a compound represented by Formula (1):
- wherein R1 is
- a group represented by Formula (2):
- wherein R2 and R3 are each independently a C1-4 alkylene group, and * is a bond;
- a group represented by Formula (3):
- wherein R4 and R5 are each independently a hydrogen atom or a C1-4 alkyl group optionally having a substituent, R4 and R5 may form a ring together with the atom bonded thereto, and * is a bond;
- a group represented by Formula (4):
- wherein * is a bond;
- or
- a group represented by Formula (5):
- wherein * is a bond, a pharmaceutically acceptable salt thereof,
- a cyclodextrin clathrate thereof, and
- (c) a compound represented by Formula (6):
- wherein X is —OR6 or —NR7R8,
- wherein R6, R7, and R8 are each independently a hydrogen atom;
- a C1-6 alkyl group optionally having at least one substituent selected from the group consisting of a carboxy group, —OR9, —NR10R11, and —N+R12R13R14;
- or —(CH2CH2O)nR15,
- wherein R9, R10, R11, R12, R13, R14, and R15 are each independently a hydrogen atom or a C1-3 alkyl group, and n is an integer of 2 to 5,
- a pharmaceutically acceptable salt thereof, and a cyclodextrin clathrate thereof.
A kit for enhancing the physiological activity of hepatocyte growth factor, comprising a preparation comprising a trisulfide compound and a preparation comprising hepatocyte growth factor, wherein the trisulfide compound is at least one selected from the group consisting of:
- (a) glutathione trisulfide and a pharmaceutically acceptable salt thereof;
- (b) a compound represented by Formula (1):
- wherein R1 is a group represented by Formula (2):
- wherein R2 and R3 are each independently a C1-4 alkylene group, and * is a bond;
- a group represented by Formula (3):
- wherein R4 and R5 are each independently a hydrogen atom or a C1-4 alkyl group optionally having a substituent, R4 and R5 may form a ring together with the atom bonded thereto, and * is a bond;
- a group represented by Formula (4):
- wherein * is a bond;
- or
- a group represented by Formula (5):
- wherein * is a bond,
- a pharmaceutically acceptable salt thereof, and a cyclodextrin clathrate thereof;
- and
- (c) a compound represented by Formula (6):
- wherein X is —OR6 or —NR7R8,
- wherein R6, R7, and R8 are each independently a hydrogen atom;
- a C1-6 alkyl group optionally having at least one substituent selected from the group consisting of a carboxy group, —OR9, —NR10R11, and —N+R12R13R14;
- or —(CH2CH2O)nR15,
- wherein R9, R10, R11, R12, R13, R14, and R15 are each independently a hydrogen atom or a C1-3 alkyl group, and n is an integer of 2 to 5,
- a pharmaceutically acceptable salt thereof, and a cyclodextrin clathrate thereof.
Dependencies are inferred from the claim text.