Steroid compound for use in the treatment of hepatic encephalopathy
Inventors
Doverskog, Magnus • Möhler, Hanns • Felipo, Vicente • Bäckström, Torbjörn
Assignees
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Publication Number
US-10342804-B2
Publication Date
2019-07-09
Expiration Date
Abstract
The present invention provides the steroidal compound 3α-ethynyl-3β-hydroxyandrostan-17-one oxime, or a pharmaceutically acceptable salt thereof, for use in treatment of hepatic encephalopathy.
Core Innovation
The invention relates to administering 3α-ethynyl-3β-hydroxyandrostan-17-one oxime, or a pharmaceutically acceptable salt thereof, to a patient in need for treating hepatic encephalopathy. The hepatic encephalopathy is selected from minimal hepatic encephalopathy, overt hepatic encephalopathy, type A hepatic encephalopathy, type B hepatic encephalopathy and type C hepatic encephalopathy. The treatment comprises the co-administration of 3α-ethynyl-3β-hydroxyandrostan-17-one oxime with an ammonia-lowering compound.
The disclosure positions the steroidal compound as a GABAA receptor modulating steroid antagonist that selectively inhibits positive modulation by endogenous neuroactive steroids while not antagonizing GABA itself. The compound does not lower blood ammonia in vivo, indicating a complementary approach with ammonia-lowering compound co-administration.
The disclosure further includes use for prevention and peri–liver transplantation contexts. Preventing hepatic encephalopathy comprises administering 3α-ethynyl-3β-hydroxyandrostan-17-one oxime, or a pharmaceutically acceptable salt, to a patient in need, and providing the compound before, during or after a liver transplantation.
Claims Coverage
The independent claims cover two core methods: treating and preventing hepatic encephalopathy. Across both independent claims, the inventive coverage centers on using 3α-ethynyl-3β-hydroxyandrostan-17-one oxime, or a pharmaceutically acceptable salt, together with co-administration of an ammonia-lowering compound, with the hepatic encephalopathy subtype limited to minimal/overt and type A/B/C.
Treating hepatic encephalopathy with co-administration
Administering a pharmaceutically effective amount of 3α-ethynyl-3β-hydroxyandrostan-17-one oxime or a pharmaceutically acceptable salt thereof to a patient in need, where the hepatic encephalopathy is selected from minimal hepatic encephalopathy, overt hepatic encephalopathy, type A hepatic encephalopathy, type B hepatic encephalopathy and type C hepatic encephalopathy, and wherein the treatment comprises the co-administration of 3α-ethynyl-3β-hydroxyandrostan-17-one oxime with an ammonia-lowering compound.
Preventing hepatic encephalopathy with co-administration
Administering a pharmaceutically effective amount of 3α-ethynyl-3β-hydroxyandrostan-17-one oxime or a pharmaceutically acceptable salt thereof to a patient in need, where the hepatic encephalopathy is selected from minimal hepatic encephalopathy, overt hepatic encephalopathy, type A hepatic encephalopathy, type B hepatic encephalopathy and type C hepatic encephalopathy, and wherein the treatment comprises the co-administration of 3α-ethynyl-3β-hydroxyandrostan-17-one oxime with an ammonia-lowering compound.
Overall, the claim coverage is directed to treating and preventing hepatic encephalopathy by administering 3α-ethynyl-3β-hydroxyandrostan-17-one oxime, or a pharmaceutically acceptable salt, with co-administration of an ammonia-lowering compound, with the targeted encephalopathy limited to minimal/overt and type A/B/C subtypes.
Stated Advantages
The compound does not lower blood ammonia in vivo, indicating complementary therapy when co-administered with ammonia-lowering agents.
Documented Applications
Treating hepatic encephalopathy including minimal hepatic encephalopathy, overt hepatic encephalopathy, and type A hepatic encephalopathy, type B hepatic encephalopathy and type C hepatic encephalopathy.
Preventing hepatic encephalopathy including minimal hepatic encephalopathy, overt hepatic encephalopathy, and type A hepatic encephalopathy, type B hepatic encephalopathy and type C hepatic encephalopathy.
Peri–liver transplantation use, including providing the compound before, during or after a liver transplantation.
Related conditions include liver decompensation and portal hypertension.
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