Treatment of newborn jaundice

• US 5,589,504 A
• Filed: 07/26/1994
• Issued: 12/31/1996
• Est. Priority Date: 07/26/1994
• Status: Expired due to Fees

• Current Assignee: Cornell Research Foundation Incorporated (Cornell University), Albert Einstein College of Medicine (Yeshiva University)
• Original Assignee: Albert Einstein College of Medicine of Yeshiva University, Cornell Research Foundation Incorporated (Cornell University)
• Inventors: Chowdhury, Jayanta R., Dannenberg, Andrew J.
• Primary Examiner(s): Criares, Theodore J.
• Application Number:
  US08/279,899
• Time in Patent Office: 889 Days
• Field of Search: 514/706, 514/731, 514/562, 514/764, 514/739, 514/578, 514/456
• US Class Current: 514/456
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/085 having an ether linkage to aromatic ring nuclear carbon
• CPC Class Codes: A61K 31/11 Aldehydes
• CPC Class Codes: A61K 31/122 having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
• CPC Class Codes: A61K 31/22 of acyclic acids, e.g. pravastatin
• CPC Class Codes: A61K 31/26 Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 31/385 having two or more sulfur atoms in the same ring

Abstract

Based on the discovery that the human bilirubin/phenol UDP-glucuronosyltransferase ugt1 gene complex contains an electrophile responsive element and the knowledge that the rat NADP(H):quinone reductase gene contains an electrophile responsive element, agents which at a concentration of less than 50 μM double the quinone reductase specific activity of Hepa 1clc7 cells, e.g., BHT and sulforaphane, are used for the prophylaxis or treatment of newborn jaundice.

Claims

1. A method of prophylaxis or treatment of newborn jaundice comprising administering to a subject in need of said prophylaxis or treatment a therapeutically effective amount of a compound which is not habit-forming and which does not cause drowsiness and which does not contain heavy metals or arsenic and which at a concentration of less than 50 μ

M doubles the quinone reductase specific activity of Hepa 1clc7 cells, said compound being selected from the group consisting of Michael reaction acceptors;

diphenols, quinones and compounds which are metabolized to these in Hepa 1clc7 cells;

isothiocyanates;

fumarates;

maleates;

1,2-dithiole-3-thione;

beta-naphthoflavone;

methyl propiolate; and

crotonaldehyde.

3. The method of claim 1 wherein the compound is selected from the group consisting of isothiocyanates.

4. The method of claim 1 wherein the compound is selected from the group consisting of diphenols, quinones and compounds which are metabolized to these in Hepa 1clc7 cells.

5. The method of claim 4 wherein the compound is butylated hydroxytoluene.

6. The method of claim 3 wherein the compound is CH₃ --S(O)--(CH₂)₄ --N═

C═

S.

2. A method of prophylaxis or treatment of newborn jaundice comprising administering to a subject in need of said prophylaxis or treatment, a therapeutically effective amount of a compound which at a concentration of less than 50 μ

M doubles the quinone reductase specific activity of Hepa 1clc7 cells and which does not contain heavy metals or arsenic and is not phenobarbital, said compound being selected from the group consisting of Michael reaction acceptors;

diphenols, quinones and compounds which are metabolized to these in Hepa 1clc7 cells;

isothiocyanates;

fumarates;

maleates;

1,2-dithiole-3-thione;

beta-napthoflavone;

methyl propiolate; and

crotonaldehyde.