Metselex, Inc.

Meselex, Inc.

Clifford Steer

Walter C Low

Cyrus B Munshi

Michael D Finch

Ingrid Gunda Georg

Peter Dosa

Cecilia M P Rodrigues

Susana Dias Lucas De Oliveira

Susana Dias Lucas De Oliveria

Mai Lan Leong

Martin Wessendorf

Cecilia Rodrigues

This disclosure relates to deuterated bile acid compositions. A deuterated compound is selected from the bile acids such as ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA), and their derivatives, analogs and salts. At least one of the hydrogen atoms in the compound is replaced with deuterium. Also disclosed are pharmaceutical compositions and methods of using the deuterated bile acids.

Deuterated bile acids

This disclosure relates to deuterated bile acid compositions. A deuterated compound is selected from the disclosed groups of bile acids and their derivatives, analogs and salts. At least one of the hydrogen atoms in the compound is replaced with deuterium.

Methods of reducing or abolishing neuropathic pain in humans and animals are discussed. In some examples administration of the apoptosis inhibitor tauroursodeoxycholic acid (TUDCA), greatly reduced both neuronal loss and the increase in glia, and partially reversed spinal nerve ligation (SNL)-induced mechanical hypersensitivity. Among RVM neurons, serotonergic (5-HT) neurons decreased by 35% ipsilateral to SNL. In some examples, the density of 5-HT immunoreactive varicosities in the superficial dorsal horn of the spinal cord was lower ipsilateral to SNL. The RVM 5-HT neurons that remained after SNL appeared to facilitate nociception. When rats that had undergone SNL were treated with the 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), mechanical withdrawal thresholds increased significantly. In some examples nerve injury induces death of antinociceptive RVM neurons which can be reduced or abolished by TUDCA. In some examples, that the loss of RVM neurons shifts the balance of descending control from pain inhibition to pain facilitation.

Prevention or attenuation of neuropathic pain by bile acids

Ursodeoxycholic acid (UDCA) is a bile acid with demonstrated anti-apoptotic activity in both in vitro and in vivo models. Water-soluble prodrugs of UDCA for use in indications where intravenous administration of UDCA may be preferable, such as reducing damage from stroke or acute kidney injury, are disclosed. The disclosed prodrugs showed significant anti-apoptotic activity in a series of in vitro assays.

Water-soluble ursodeoxycholic acid prodrugs

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Eagan, MN, United States of America

Clifford Steer