Gamma-hydroxybutyrate compositions containing carbohydrate, lipid or amino acid carriers
AssigneeOrphan Medical, Inc.
InventorsMortimer Mamelak, William C. Houghton, Dayton T. Reardan, Brian L. Miller
Life of this patent
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Abstract
The present invention provides compositions comprising at least one GHB moiety bonded to at least one physiologically compatible carrier molecule. The compositions can enhance the uptake of the drug, deliver effective therapeutic doses in a time-delayed fashion, or can target specific organs.
Claims15
A compound of the formula (III):
- wherein R1 is H or a hydroxyl-protecting group, R is H, (C1-C4)alkyl or benzyl, X is a residue of a naturally occurring hydroxy group-containing α-amino acid or a naturally occurring bis(carboxy) group containing amino acid, Z is the residue of a naturally occurring hydroxy group-containing α-amino acid or a naturally occurring bis(carboxy) group-containing amino acid, Y is a moiety covalently linking X and Z, n is 0-1, m is 0 to the number of available hydroxy groups in amino acid X and Z, p is 1 to the number of available CO2H groups on the amino acid X and Z, or a pharmaceutically acceptable salt thereof.
A compound of formula (IV):
- wherein L and L′ are individually H, (C1-C6)alkyl or a hydroxyl protecting group, wherein at least one of L′ or L is -(A)(Y)(Z)n, wherein A is (C1-C6)alkyl, Y is H, OH, N(R1)(R2)(R3) or (O(PO331)-AN(R1)(R2)(R3,), wherein R1, R2 and R3 are each (C1-C4)alkyl or R1 and R2 together with N are a (C5-C7)heterocyclic ring, optionally substituted with 1 or 2 N(R3), S, non-peroxide O or a combination thereof;
- n is 1-2 and Z is XR, wherein X is O, S, NH, N(CH3), NHC(O) or OC(O) and R is (C8-C22)alkyl, optionally substituted with 1-2 double bonds, or a pharmaceutically acceptable salt thereof, with the proviso that when one of L or L′ is 1,3-dihexadecanoyloxyprop-2-yl, the other is not H.
A method for treating a mammal afflicted with a condition or pathology amenable to treatment by gamma-hydroxy butyrate (GHB) comprising administering to said mammal an effective amount of a compound of formula (IV):
- wherein L and L′ are individually H, (C1-C6)alkyl or a hydroxyl protecting group, wherein at least one of L′ or L is -(A)(Y)(Z)n, wherein A is (C1-C6)alkyl, Y is H, OH, N(R1)(R2)(R3) or O(PO331)-AN(R1)(R2)(R3) , wherein R1, R2 and R3 are each (C1-C4)alkyl or R1 and R2 together with N are a (C5-C7)heterocyclic ring, optionally substituted with 1 or 2 N(R3), S, non-peroxide O or a combination thereof;
- n is 1-2 and Z is XR, wherein X is O, S, NH, N(CH3), NHC(O) or OC(O) and R is (C8-C22)alkyl, optionally substituted with 1-2 double bonds, or a pharmaceutically acceptable salt thereof, with the proviso that when one of L or L′ is 1,3-dihexdecanoyloxyprop-2-yl, the other is not H.
A compound of the formula (I):
- (R′O(CH2)3CO2)4(—(X)—(Y)n—(Z)n—)(CO2(CH2)3CO2R)p
- Wherein R′ is H or a hydroxyl-protecting group, R is H, (C1-C4)alkyl or benzyl, X and Z are each residues of a naturally occurring hydroxy group-containing α-amino acid or a naturally occurring bis(carboxy)amino acid, Y is a moiety covalently linking X and Z, n is 0-1, m is 0 to the number of available hydroxy groups on amino acid X and Z, p is 0 to the number of available CO2H groups on amino acids X and Z, with the proviso that both m and p are not zero, or a pharmaceutically acceptable salt thereof.
A method for treating a mammal afflicted with a condition or pathology amenable to treatment by gamma-hydroxy butyrate (GHB) comprising administering to said mammal an effective amount of a compound of the formula (I):
- (R′O(CH2)3CO2)m(—(X)—(Y)n—(Z)n—)(CO2(CH2)3CO2R)p
- wherein R′ is H or a hydroxyl-protecting group, R is H, (C1-C4)alkyl or benzyl, X and Z are each residues of a naturally occurring hydroxy group-containing α-amino acid or a naturally occurring bis(carboxy)amino acid, Y is a moiety covalently linking X and Z, n is 0-1, m is 0 to the number of available hydroxy groups on amino acid X and Z, p is 0 to the number of available CO2H groups on amino acids X and Z, with the proviso that both m and p are not zero, or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.