Pharmaceutical formulations employing short-chain sphingolipids and their use
First Claim
1. A pharmaceutical formulation comprising:
- (i) a drug; and
(ii) a short-chain sphingolipid selected from compounds of the following formula;
wherein;
R1 is independently;
an O-linked saccharide group;
or an O-linked polyhydric alcohol group;
or;
R1 is independently;
an O-linked (optionally N—
(C1-4alkyl)-substituted amino)-C1-6alkyl-phosphate group;
or an O-linked (polyhydric alcohol-substituted)-C1-6alkyl-phosphate group;
R2 is independently C3-9alkyl, and is independently unsubstituted or substituted;
R3 is independently C7-19alkyl, and is independently unsubstituted or substituted;
R4 is independently —
H, —
OH, or —
O—
C1-4alkyl;
RN is independently —
H or C1-4alkyl;
the bond marked with an alpha (α
) is independently a single bond or a double bond;
if the bond marked with an alpha (α
) is a double bond, then R5 is —
H;
if the bond marked with an alpha (α
) is a single bond, then R5 is —
H or —
OH;
the carbon atom marked (*) is independently in an R-configuration or an S-configuration;
the carbon atom marked (**) is independently in an R-configuration or an S-configuration;
and pharmaceutically acceptable salts, solvates, esters, ethers, chemically protected forms thereof.
1 Assignment
0 Petitions
Accused Products
Abstract
This invention pertains to pharmaceutical formulations which comprise (i) a drug (e.g., an amphiphilic drug) (e.g., an anthracycline) (e.g., doxorubicin) and (ii) a short-chain sphingolipid (e.g., a short-chain glycosphingolipid or a short-chain sphingomyelin) (e.g., N-octanoyl-glucosylceramide, referred to as C8-GlcCer) (e.g., N-hexanoyl-sphingomyelin, referred to herein as C6-SM), and which provide improved drug delivery and efficacy. The short-chain sphingolipidis selected from compounds of the following formula:
wherein: R1 is independently: an O-linked saccharide group; or an O-linked polyhydric alcohol group; or: R1 is independently: an O-linked (optionally N-(C1-4alkyl)-substituted amino)-C1-6alkyl-phosphate group; or an O-linked (polyhydric alcohol-substituted)-C1-6alkyl-phosphate group; R2 is independently C3-9alkyl, and is independently unsubstituted or substituted; R3 is independently C7-19alkyl, and is independently unsubstituted or substituted; R4 is independently —H, —OH, or —O—C1-4alkyl; RN is independently —H or C1-4alkyl; the bond marked with an alpha (α) is independently a single bond or a double bond; if the bond marked with an alpha (α) is a double bond, then R5 is —H; if the bond marked with an alpha (α) is a single bond, then R5 is —H or —OH; the carbon atom marked (*) is independently in an R-configuration or an S-configuration; the carbon atom marked (**) is independently in an R-configuration or an S-configuration; and pharmaceutically acceptable salts, solvates, esters, ethers, chemically protected forms thereof. In one embodiment, the pharmaceutical formulation is a liposomal pharmaceutical formulation prepared using a mixture of lipids comprising, at least, vesicle-forming lipids (e.g., phospholipids) (e.g., phosphatidylcholines) (e.g., fully hydrogenated soy phosphatidylcholine (HSPC)) (e.g., dipalmitoyl-phosphatidylcholine (DPPC)) and said short-chain sphingolipid, and optionally cholesterol and optionally a vesicle-forming lipid which is derivatized with a polymer chain (e.g., a phosphatidylethanolamine (PE) which is derivatized with polyethyleneglycol (PEG)) (e.g., N-(carbonyl-methoxypolyethylene glycol 2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine sodium salt (MPEG2000-DSPE). The present invention also pertains to methods for the preparation and use of such formulations.
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Citations
2 Claims
-
1. A pharmaceutical formulation comprising:
-
(i) a drug; and
(ii) a short-chain sphingolipid selected from compounds of the following formula;
wherein;
R1 is independently;
an O-linked saccharide group;
oran O-linked polyhydric alcohol group;
or;
R1 is independently;
an O-linked (optionally N—
(C1-4alkyl)-substituted amino)-C1-6alkyl-phosphate group;
oran O-linked (polyhydric alcohol-substituted)-C1-6alkyl-phosphate group;
R2 is independently C3-9alkyl, and is independently unsubstituted or substituted;
R3 is independently C7-19alkyl, and is independently unsubstituted or substituted;
R4 is independently —
H, —
OH, or —
O—
C1-4alkyl;
RN is independently —
H or C1-4alkyl;
the bond marked with an alpha (α
) is independently a single bond or a double bond;
if the bond marked with an alpha (α
) is a double bond, then R5 is —
H;
if the bond marked with an alpha (α
) is a single bond, then R5 is —
H or —
OH;
the carbon atom marked (*) is independently in an R-configuration or an S-configuration;
the carbon atom marked (**) is independently in an R-configuration or an S-configuration;
and pharmaceutically acceptable salts, solvates, esters, ethers, chemically protected forms thereof.
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2-91. -91. (canceled)
Specification