Multilayer beads for pharmaceutical use having a drug-in-polymer layer are disclosed. The disclosed multilayer beads for pharmaceutical use have (a) a core particle; (b) an optional barrier layer coated on the surface of the core particle; (c) a drug-in-polymer layer coated on the surface of the core or the barrier layer, (d) an optional sealant layer coated on the surface of the drug-in-polymer layer; and (e) optionally one or more outer layers external to the drug-in-polymer layer or the sealant layer. The drug-in-polymer layer consists essentially of (i) a drug selected from the group consisting of a 15-keto prostaglandin drug, a 13,14-dihydro prostaglandin drug, and a 13,14-dihydro-15-keto prostaglandin drug; and (ii) a polymer selected from the group consisting of polyvinylpyrrolidone, vinylpyrrolidone-vinylacetate copolymer or a mixture thereof. The drug-in-polymer layer may be solid dispersion of the drug in the polymer. Pharmaceutical compositions comprising a plurality of multilayer beads and a pharmaceutically acceptable excipient and methods of treating a gastrointestinal disorder are also disclosed.

Multilayer beads for pharmaceutical use having a drug-in-polymer layer are disclosed. The disclosed multilayer beads for pharmaceutical use have (a) a core particle; (b) an optional barrier layer coated on the surface of the core particle; (c) a drug-in-polymer layer coated on the surface of the core or the barrier layer, (d) an optional sealant layer coated on the surface of the drug-in-polymer layer; and (e) optionally one or more outer layers external to the drug-in-polymer layer or the sealant layer. The drug-in-polymer layer consists essentially of (i) a drug selected from the group consisting of a 15-keto prostaglandin drug, a 13,14-dihydro prostaglandin drug, and a 13,14-dihydro-15-keto prostaglandin drug; and (ii) a polymer selected from the group consisting of polyvinylpyrrolidone, vinylpyrrolidone-vinylacetate copolymer or a mixture thereof. The drug-in-polymer layer may be solid dispersion of the drug in the polymer. Pharmaceutical compositions comprising a plurality of multilayer beads and a pharmaceutically acceptable excipient and methods of treating a gastrointestinal disorder are also disclosed.

A drug-polymer conjugate, which is a copolymer of at least one monomer of formula (I) where: X may be the same or different at each occurrence and represents a terminal functional group comprising an alkyne or an azide; Q is independently selected at each occurrence and may be present or absent and when present, represents a linking group; R is selected from the group consisting of linear or branched hydrocarbon, optionally substituted aryl and optionally substituted heteroaryl; D is a releasable bicyclic prostaglandin; L is a linker group; and at least one co-monomer of Formula III J-(Y.sup.1-A).sub.n, J represents a linking functional group, n is 2 to 8 preferably 3 to 8; Y.sup.1 comprises a polyether of formula (OR.sup.a).sub.m wherein R.sup.a is independently ethylene, propylene and butylene and m is from 1 to 300 (preferably 2 to 300) and the polyether is in chain with one or more groups which are preferably selected from one or more of optionally substituted straight or branched C.sub.1 to C.sub.10 alkylene, amino, ether, ester, amide, carbonate and carbamate; A may be the same or different at each occurrence and represents a group comprising a terminal functional group comprising an alkyne or an azide functionality, wherein said terminal functional group is complementary to the terminal functional group X of formula (I) providing triazole moieties from reaction of X and A.

A drug-polymer conjugate, which is a copolymer of at least one monomer of formula (I) where: X may be the same or different at each occurrence and represents a terminal functional group comprising an alkyne or an azide; Q is independently selected at each occurrence and may be present or absent and when present, represents a linking group; R is selected from the group consisting of linear or branched hydrocarbon, optionally substituted aryl and optionally substituted heteroaryl; D is a releasable bicyclic prostaglandin; L is a linker group; and at least one co-monomer of Formula III J-(Y.sup.1-A).sub.n, J represents a linking functional group, n is 2 to 8 preferably 3 to 8; Y.sup.1 comprises a polyether of formula (OR.sup.a).sub.m wherein R.sup.a is independently ethylene, propylene and butylene and m is from 1 to 300 (preferably 2 to 300) and the polyether is in chain with one or more groups which are preferably selected from one or more of optionally substituted straight or branched C.sub.1 to C.sub.10 alkylene, amino, ether, ester, amide, carbonate and carbamate; A may be the same or different at each occurrence and represents a group comprising a terminal functional group comprising an alkyne or an azide functionality, wherein said terminal functional group is complementary to the terminal functional group X of formula (I) providing triazole moieties from reaction of X and A.

Since a compound represented by the general formula (I) (wherein definition of each group is as described in the specification), a salt thereof, a solvate thereof, or a prodrug thereof has strong and sustaining intraocular pressure lowering activity and, further, has no side effect on eyes such as ocular stimulating property (hyperemia, corneal clouding etc.), aqueous humor protein rise etc., it has high safety, and can be an excellent agent for preventing and/or treating glaucoma etc. ##STR00001##

Since a compound represented by the general formula (I) (wherein definition of each group is as described in the specification), a salt thereof, a solvate thereof, or a prodrug thereof has strong and sustaining intraocular pressure lowering activity and, further, has no side effect on eyes such as ocular stimulating property (hyperemia, corneal clouding etc.), aqueous humor protein rise etc., it has high safety, and can be an excellent agent for preventing and/or treating glaucoma etc. ##STR00001##

Since a compound represented by the general formula (I) (wherein definition of each group is as described in the specification), a salt thereof, a solvate thereof, or a prodrug thereof has strong and sustaining intraocular pressure lowering activity and, further, has no side effect on eyes such as ocular stimulating property (hyperemia, corneal clouding etc.), aqueous humor protein rise etc., it has high safety, and can be an excellent agent for preventing and/or treating glaucoma etc.

##STR00001##

Since a compound represented by the general formula (I) (wherein definition of each group is as described in the specification), a salt thereof, a solvate thereof, or a prodrug thereof has strong and sustaining intraocular pressure lowering activity and, further, has no side effect on eyes such as ocular stimulating property (hyperemia, corneal clouding etc.), aqueous humor protein rise etc., it has high safety, and can be an excellent agent for preventing and/or treating glaucoma etc.

##STR00001##

Provided herein are methods and compositions for treating a Nurr1-mediated and/or PPARγ-mediated condition. Also provided herein are methods and compositions for increasing Nurr1 or PPARγ activity and/or levels in a cell.

Provided herein are methods and compositions for treating a Nurr1-mediated and/or PPARγ-mediated condition. Also provided herein are methods and compositions for increasing Nurr1 or PPARγ activity and/or levels in a cell.