Abstract: The invention discloses prodrugs comprising anti-proliferative drugs covalently linked, via bridging group, to a phospholipid moiety such that the active species is preferentially released, preferably by enzymatic cleavage, at the required site of action. The invention further discloses pharmaceutical compositions said prodrugs and the uses thereof for the treatment of diseases and disorders related to inflammatory, to degenerative or atrophic conditions, and to uncontrolled cell growth. FIG. 1 depicts a graph of animal survival during the course of an experiment wherein mice were i.p. transplanted with 11210 mouse leukemia cells and then treated with vehicle only (squares), MTX (triangles) or molar equivalent dose of DP-MTX071 (circles) according to the regiment described example in Example 11.

Abstract: Disclosed are compounds having non-steroidal anti-inflammatory drugs (NSAIDS) covalently linked to a phospholipid moiety via a bridging group. Also disclosed are a process for the synthesis of the compounds, pharmaceutical compositions comprising the compounds and the use thereof for the treatment of diseases and disorders related to inflammatory conditions, such as the treatment of ischemia.

Abstract: Disclosed are compounds having non-steroidal anti-inflammatory drugs (NSAIDS) covalently linked to a phospholipid moiety via a bridging group. Also disclosed are a process for the synthesis of the compounds, pharmaceutical compositions comprising the compounds and the use thereof for the treatment of diseases and disorders related to inflammatory conditions, such as the treatment of ischemia.

Abstract: The present invention relates to compounds and pharmaceutical compositions useful for treating pain. The invention also relates to methods of treating or alleviating pain in mammals, comprising administering to a mammal suffering from pain, a pain-alleviating amount of a compound of the general formula (I) or (II).

Abstract: The invention discloses stable diesters of chelating agents of divalent metal ions, processes for their preparation and pharmaceutical compositions thereof. Most preferred compounds according to the present invention are stable lipophilic diesters comprising a covalent conjugate of a BAPTA and a pharmaceutically acceptable alcohol. The diesters are useful in a method for treating a condition or disease related to an excess of divalent metal ions, and in particular for the treatment of a condition or disease related to elevated levels of intracellular calcium ions, such as in brain or cardiac ischemia, stroke, epilepsy, Alzheimer's disease or cardiac arrhythmia and in open heart surgery.

Abstract: The invention relates to a pharmaceutically acceptable prodrug which is a covalent conjugate of a pharmacologically active compound and an intracellular transporting adjuvant, characterized by the presence of a covalent bond which is scission-sensitive to intracellular enzyme activity. The prodrug may be used in a technique for treating a condition or disease in a mammal related to supranormal intracellular enzyme activity, whereby on administering it to a human having such condition or disease, the bond is broken in response to such activity, and the pharmacologically active compound is activated selectively within cells having such supranormal intracellular enzyme activity.

Abstract: The present invention relates to compounds and pharmaceutical compositions useful for treating pain. The invention also relates to methods of treating or alleviating pain in mammals, comprising administering to a mammal suffering from pain, a pain-alleviating amount of a compound of the general formula (I) or (II).

Abstract: The invention relates to a pharmaceutically acceptable prodrug which is a covalent conjugate of a pharmacologically active compound and an intracellular transporting adjuvant, characterized by the presence of a covalent bond which is scission-sensitive to intracellular enzyme activity. The prodrug may be used in a technique for treating a condition or disease in a mammal related to supranormal intracellular enzyme activity, whereby on administering it to a human having such condition or disease, the bond is broken in response to such activity, and the pharmacologically active compound is activated selectively within cells having such supranormal intracellular enzyme activity.

Abstract: The present invention provides a family of branched fatty acids and their derivatives, which improve and enable the penetration and absorption of active ingredients through biomembranes, such as blood brain barrier. The invention further provides pharmaceutical compositions comprising these branched fatty acids and methods of using these compositions to permeabilize biological membranes thereby improving the administration of bioactive or therapeutic substances to cells or organs. According to a more preferred embodiment of this invention the methods are particularly useful to treat certain kinds of CNS lesions and diseases including tumors, infections, abscesses and degenerative and behavioral disorders.

Abstract: The present invention relates to compounds, which are phospholipid derivatives of valproic acid, to compositions comprising said compounds and their use for treating epilepsy, migraine, bipolar disorders and pain.

Abstract: The invention relates to a pharmaceutically acceptable prodrug which is a covalent conjugate of a pharmacologically active compound and an intracellular transporting adjuvant, characterized by the presence of a covalent bond which is scission-sensitive to intracellular enzyme activity. The prodrug may be used in a technique for treating a condition or disease in a mammal related to supranormal intracellular enzyme activity, whereby on administering it to a human having such condition or disease, the bond is broken in response to such activity, and the pharmacologically active compound is activated selectively within cells having such supranormal intracellular enzyme activity.

Abstract: A compound having formula (I): wherein R1 is a saturated or unsaturated chain of 1-5 carbons in length; and R2 is a saturated or unsaturated chain of 3-10 carbons in length; and A is selected from the group consisting of COOL and CONR′—R″, wherein L is a lipid moiety selected from the group consisting of glycerol, C3-20 fatty acid monoglycerides, C3-20 fatty acid diglycerides, hydroxy-C2-6-alkyl esters of C3-20 fatty acids, hydroxy-C2-6-alkyl esters of lysophosphatidic acids, lyso plasmalogens, lysophospholipids, lysophosphatidic acid amides, glycerophosphoric acids, sphingolipids, lysophosphatidylethanolamines, and N-mono and N,N-di-(C1-4)alkyl derivatives of the amines thereof; and R′ and R″ are each independently selected from the group consisting of hydrogen and a lower alkyl group comprising 1-5 carbon atoms; and pharmaceutically acceptable salts thereof. In addition, there is provided methods for using these compositions.

Abstract: The invention relates to a pharmaceutically acceptable prodrug which is a covalent conjugate of a pharmacologically active compound and an intracellular transporting adjuvant, characterized by the presence of a covalent bond which is scission-sensitive to intracellular enzyme activity. The prodrug may be used in a technique for treating a condition or disease in a mammal related to supranormal intracellular enzyme activity, whereby on administering it to a human having such condition or disease, the bond is broken in response to such activity, and the pharmacologically active compound is activated selectively within cells having such supranormal intracellular enzyme activity.

Abstract: The invention relates to a pharmaceutically acceptable prodrug which is a covalent conjugate of a pharmacologically active compound and an intracellular transporting adjuvant, characterized by the presence of a covalent bond which is scission-sensitive to intracellular enzyme activity. The prodrug may be used in a technique for treating a condition or disease in a human related to supranormal intracellular enzyme (.e.g. phospholipase and/or esterase) activity, whereby on administering it to a human having such condition or disease, the bond is broken in response to such activity, and the pharmacologically active compound accumulates selectively within cells having such supranormal intracellular enzyme activity. Exemplary conjugates are esters of the carboxylic function in the formula, with e.g. heptanoyl-sn-3-glycerophosphoryl-choline or octanoyl-sn-3-glycerophosphoryl-choline.

Abstract: The invention relates to a pharmaceutically acceptable prodrug which is a covalent conjugate of a pharmacologically active compound and an intracellular transporting adjuvant, characterized by the presence of a covalent bond which is scission-sensitive to intracellular enzyme activity. The prodrug may be used in a technique for treating a condition or disease in a mammal related to supranormal intracellular enzyme activity, whereby on administering it to a human having such condition or disease, the bond is broken in response to such activity, and the pharmacologically active compound is activated selectively within cells having such supranormal intracellular enzyme activity.

Abstract: The invention relates to a pharmaceutically acceptable prodrug which is a covalent conjugate of a pharmacologically active compound and an intracellular transporting adjuvant, characterized by the presence of a covalent bond which is scission-sensitive to intracellular enzyme activity. The prodrug may be used in a technique for treating a condition or disease in a human related to supranormal intracellular enzyme (.e.g. phospholipase and/or esterase) activity, whereby on administering it to a human having such condition or disease, the bond is broken in response to such activity, and the pharmacologically active compound accumulates selectively within cells having such supranormal intracellular enzyme activity. Exemplary conjugates are esters of the carboxylic function in the formula, with e.g. heptanoyl-sn-3-glycerophosphoryl-choline or octanoyl-sn-3-glycerophosphoryl-choline.

Abstract: Fluid treatment apparatus including a vessel having a fluid inlet port, a fluid outlet port and a deflector plate and containing a medium and an inlet having an inlet end in flow communication with the fluid inlet port and a discharge end providing an incoming flow of untreated fluid against the deflector plate for reversal thereby to an outgoing flow of fluid passing through the medium for treatment, the clearance between the discharge end and the deflector plate being selectively adjustable for controlling the flow of fluid through the vessel.