Detoxifying agent, detoxifying agent kit, and novel inclusion complex

Patent metadata

Field	Value
Publication number	US-2024423999-A1
Application number	US-202218702178-A
Country	US
Kind code	A1
Filing date	Oct 14, 2022
Priority date	Oct 18, 2021
Publication date	Dec 26, 2024
Grant date	—

Abstract

Provided are a detoxifying agent and detoxifying agent kit for simultaneous detoxification of CO and HCN in the body. The detoxifying agent for removal of carbon monoxide and hydrogen cyanide in the body includes as active ingredients a first inclusion complex wherein a first cyclodextrin dimer represented by general formula (1) below clathrates a first water-soluble metal porphyrin in which the central metal is divalent, and a second inclusion complex wherein a second cyclodextrin dimer represented by general formula (2) below clathrates the first water-soluble metal porphyrin in which the central metal is divalent, and further includes a reducing agent if necessary.

First claim

1 . A detoxifying agent for removal of carbon monoxide and hydrogen cyanide in the body,
wherein the detoxifying agent includes as active ingredients a first inclusion complex, wherein a first cyclodextrin dimer represented by formula (1) clathrates a first water-soluble metal porphyrin in which the central metal is divalent,

wherein each R represents a protecting group protecting a hydroxyl group of cyclodextrin, m represents an integer of 1 to 2, and n represents an integer of 1 to 3,
and a second inclusion complex, wherein a second cyclodextrin dimer represented by formula (2) clathrates the first water-soluble metal porphyrin in which the central metal is divalent,

wherein each R represents a protecting group protecting a hydroxyl group of cyclodextrin, p represents an integer of 1 to 2, and q represents an integer of 1 to 3.

2 . The detoxifying agent according to claim 1 , wherein the first water-soluble metal porphyrin is represented by formula (3) or (4),

wherein in formulas (3) and (4), R 1 and R 2 each represent a carboxyl, sulfonyl or hydroxyl group, and M 1 represents Fe 2+ , Mn 2+ , Co 2+ or Zn 2+ .

3 . The detoxifying agent according to claim 2 , wherein the first water-soluble metal porphyrin is a 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin-iron complex.

4 . A detoxifying agent kit for preparing the detoxifying agent according to claim 1 for use, wherein the detoxifying kit includes an inclusion complex mixture aqueous solution containing;
a third inclusion complex, wherein a first cyclodextrin dimer represented by formula (1) clathrates a water-soluble metal porphyrin in which the central metal is divalent or greater, and
a fourth inclusion complex, wherein a second cyclodextrin dimer represented by formula (2) clathrates a water-soluble metal porphyrin in which the central metal is divalent or greater, or a starting material for the same, and a reducing agent.

5 . An inclusion complex for detoxifying cyanide wherein a cyclodextrin dimer represented by formula (5) clathrates a first water-soluble metal porphyrin in which the central metal is divalent,

wherein each R represents a protecting group protecting a hydroxyl group of cyclodextrin, p represents an integer of 1 to 2, and q represents an integer of 1 to 3.

6 . The inclusion complex for detoxifying cyanide according to claim 5 , wherein the first water-soluble metal porphyrin is represented by formula (6) or (7),

wherein in formulas (6) and (7), R 1 and R 2 each represent a carboxyl, sulfonyl or hydroxyl group, and M 1 represents Fe 2+ , Mn 2+ , Co 2+ or Zn 2+ .

7 . The inclusion complex for detoxifying cyanide according to claim 6 , wherein the first water-soluble metal porphyrin is a 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin-iron complex.

8 . A detoxifying agent for removal of carbon monoxide and hydrogen cyanide in the body,
wherein the detoxifying agent includes as active ingredients a fifth inclusion complex, wherein a first cyclodextrin dimer represented by formula (8) clathrates a second water-soluble metal porphyrin in which the central metal is trivalent,

wherein each R represents a protecting group protecting a hydroxyl group of cyclodextrin, m represents an integer of 1 to 2, and n represents an integer of 1 to 3,
and a sixth inclusion complex, wherein a second cyclodextrin dimer represented by formula (9) clathrates the second water-soluble metal porphyrin in which the central metal is trivalent,

wherein each R represents a protecting group protecting a hydroxyl group of cyclodextrin, p represents an integer of 1 to 2, and q represents an integer of 1 to 3.

9 . The detoxifying agent according to claim 8 , wherein the second water-soluble metal porphyrin is represented by formula (10) or (11)

wherein in formulas (10) and (11), R 1 and R 2 each represent a carboxyl, sulfonyl or hydroxyl group, and M 2 represents Fe 3+ or Co 3+ .

10 . The detoxifying agent according to claim 9 , wherein the second water-soluble metal porphyrin is a 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin-iron complex.

11 . A detoxifying agent kit for preparing the detoxifying agent according to claim 8 for use, wherein the detoxifying kit
includes an inclusion complex mixture aqueous solution containing;
a fifth inclusion complex wherein the first cyclodextrin dimer represented by formula (8) clathrates the second water-soluble metal porphyrin, and
a sixth inclusion complex wherein the second cyclodextrin dimer represented by formula (9) clathrates the second water-soluble metal porphyrin,
or a starting material for the same, and a reducing agent.

12 . A novel-inclusion complex for detoxifying carbon monoxide wherein a cyclodextrin dimer represented by formula (12) clathrates a second water-soluble metal porphyrin in which the central metal is trivalent,

wherein each R represents a protecting group protecting a hydroxyl group of cyclodextrin, m represents an integer of 1 to 2, and n represents an integer of 1 to 3.

13 . The inclusion complex for detoxifying carbon monoxide according to claim 12 , wherein the second water-soluble metal porphyrin is represented by general formula (13) or (14) below.

wherein in formulas (13) and (14), R 1 and R 2 each represent a carboxyl, sulfonyl or hydroxyl group, and M 2 represents Fe 3+ or Co 3+ .

14 . The inclusion complex for detoxifying carbon monoxide according to claim 13 , wherein the second water-soluble metal porphyrin is a 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin-iron complex.

Assignees

• The Doshisha

Inventors

• Kitagishi Hiroaki
• MO Saietsu

Classifications

• A61K31/724

  Cyclodextrins · CPC title

• A61P39/02 Primary

  Antidotes · CPC title

• A61K47/6951

  using cyclodextrin (cyclodextrins used as simple excipients A61K47/40) · CPC title

• A61K31/555 Primary

  containing heavy metals, e.g. hemin, hematin, melarsoprol · CPC title

• A61K31/409

  having four such rings, e.g. porphine derivatives, bilirubin, biliverdine (hemin, hematin A61K31/555) · CPC title