A supercritical fluid (SCF) extract of a cardiac glycoside-containing plant mass is provided. The extract can be included in a pharmaceutical composition containing an extract-solubilizing amount of solubilizer. Oleandrin is included within the extract when a cardiac glycoside-containing plant, such
A supercritical fluid (SCF) extract of a cardiac glycoside-containing plant mass is provided. The extract can be included in a pharmaceutical composition containing an extract-solubilizing amount of solubilizer. Oleandrin is included within the extract when a cardiac glycoside-containing plant, such as Nerium oleander, is extracted by SCF extraction. The extract can also contain one or more other SCF extractable pharmacologically active agents. The composition can be used to treat a wide range of disorders that are therapeutically responsive to a cardiac glycoside.
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1. A pharmaceutical composition comprising: a supercritical fluid extract of Nerium species comprising oleandrin and at least one other supercritical fluid extractable pharmacologically active agent obtained by way of the supercritical fluid extraction, wherein the extract comprises less than 0.5% b
1. A pharmaceutical composition comprising: a supercritical fluid extract of Nerium species comprising oleandrin and at least one other supercritical fluid extractable pharmacologically active agent obtained by way of the supercritical fluid extraction, wherein the extract comprises less than 0.5% by weight polysaccharide; andan extract-solubilizing amount of at least one solubilizer. 2. The composition of claim 1, wherein the pharmaceutical composition comprises: a supercritical fluid extract of Nerium species; andan extract-solubilizing amount of solubilizer comprising at least one component selected from the group consisting of water soluble (miscible) co-solvent, water insoluble (immiscible) co-solvent, antioxidant, and surfactant. 3. The composition of claim 2, wherein the pharmaceutical composition comprises: a supercritical fluid extract of Nerium species; andan extract-solubilizing amount of solubilizer comprising at least three components selected from the group consisting of water soluble (miscible) co-solvent, water insoluble (immiscible) co-solvent, antioxidant, and surfactant. 4. The composition of claim 3, wherein the surfactant is selected from the group of solubilizing agent, emulsifying agent, and a combination thereof. 5. The composition of claim 4, wherein the pharmaceutical composition comprises: a supercritical fluid extract of Nerium species;at least one water miscible solvent;at least one antioxidant; andat least one solubilizing agent. 6. The composition of claim 1, wherein the Nerium species is Nerium oleander, and the extract comprises oleandrin. 7. The composition of claim 6, wherein the at least one water miscible solvent is selected from the group consisting of glycol, alcohol, and poly(ethylene glycol). 8. The composition of claim 6, wherein the at least one solubilizing agent is a surfactant selected from the group consisting of a pegylated surfactant, vitamin E-TPGS, chremophor, labrasol, labrafil, poloxamer. 9. The composition of claim 6, wherein the at least one antioxidant is selected from the group consisting of Vitamin E, BHT, vitamin C palmitate. 10. The composition of claim 6 further comprising at least one emulsifying agent. 11. The composition of claim 10, wherein the at least one emulsifying agent is selected from the group consisting of Vitamin E-TPGS, chremophor, labrafil, labrasol, poloxamer. 12. The composition of claim 10 further comprising at least one water immiscible solvent. 13. The composition of claim 12, wherein the at least one water immiscible solvent is selected from the group consisting of glycerol monooleate, triglycerides, oleic acid, and combinations thereof. 14. The composition of claim 6 further comprising at least one water immiscible solvent. 15. The composition of claim 13, wherein the at least one water immiscible solvent is selected from the group consisting of glycerol monooleate, triglycerides, oleic acid, and combinations thereof. 16. The composition of clam 6, wherein the composition is anhydrous or comprises only endogenous water. 17. A capsule formulation comprising a capsule shell, and a pharmaceutical composition according to claim 1. 18. The formulation of claim 17 further comprising an enteric coating exterior to and surrounding the capsule. 19. The formulation of claim 18, wherein the enteric coating comprises a polymer soluble or erodible in water at a pH of 5 or greater. 20. A pharmaceutical dosage form comprising the composition of claim 1. 21. The composition of claim 1, wherein the supercritical fluid extract has been prepared by a supercritical fluid extraction process comprising: treating a cardiac glycoside-containing Nerium species plant mass with a supercritical fluid for a period of time sufficient to extract the cardiac glycoside from the plant mass;separating the plant mass from the supercritical fluid; andremoving the supercritical fluid thereby forming a supercritical fluid extract comprising cardiac glycoside. 22. The composition of claim 1, wherein the at least one other supercritical fluid extractable pharmacologically active agent is selected from the group consisting of oleandrigenin, ursolic acid, betulinic acid, odoroside, neritaloside, oleanolic acid and one or more triterpenes. 23. The composition of claim 1, wherein the SCF extract comprises less than 0.01% by weight polysaccharide. 24. The composition of claim 22, wherein the SCF extract further comprises one or more compounds selected from the group consisting of neritaloside; oleanolic acid; ursolic acid; betulinic acid; betulin (urs-12-ene-3β,28-diol); 28-norurs-12-en-3β-ol; urs-12-en-3β-ol; 3β,3β-hydroxy-12-oleanen-28-oic acid; 3β,20α-dihydroxyurs-21-en-38-oic acid; 3β,27-dihydroxy-12-ursen-38-oic acid; 3β,13β-dihydroxyurs-11-en-28-oic acid; 3β,12α-dihydroxyoleanan-28,13β-olide; and 3β,27-dihydroxy-12-oleanan-28-oic acid. 25. The composition of claim 1, wherein the SCF extract comprises one or more cardiac glycosides and one or more cardiac glycoside precursors. 26. The composition of claim 25, wherein the one or more cardiac glycoside precursors is selected from the group consisting of an aglycone constituent of a cardiac glycoside and a glycone constituent of a cardiac glycoside. 27. The composition claim 26, wherein: the aglycone is selected from the group consisting of oleandrigenin, digitoxin, acetyl digitoxins, digitoxigenin, digoxin, acetyl digoxins, digoxigenin, medigoxin, strophanthins, cymarine, ouabain, strophanthidin; andthe glycone is selected from the group consisting of glucoside, fructoside, and glucuronide. 28. The composition of claim 27 further comprising one or more of neritaloside; oleanolic acid; ursolic acid; betulinic acid; betulin (urs-12-ene-3β,28-diol); 28-norurs-12-en-3β-ol; urs-12-en-3β-ol; 3β,3β-hydroxy-12-oleanen-28-oic acid; 3β,20α-dihydroxyurs-21-en-38-oic acid; 3β,27-dihydroxy-12-ursen-38-oic acid; 3β,13β-dihydroxyurs-11-en-28-oic acid; 3β,12α-dihydroxyoleanan-28,13β-olide; and 3β,27-dihydroxy-12-oleanan-28-oic acid. 29. The composition of claim 25, wherein the SCF extract comprises one or more cardiac glycosides selected from the group consisting of Apocannoside, cymarin, Calotropin, 16α-acetoxycalotropin, 15β-hydroxycalotropin, calactin, 15β-hydroxycalactin, asclepin, 16α-hydroxyasclepin, uscharidin, uscharin, uzarigenin, Digitoxigenin, oleandrigenin, digitoxigenin, α-L-cymaroside, digitoxigenin β-gentiobiosyl-α-L-cymaroside, Δ16-digitoxigenin β-D-glucosyl-α-L-cymaroside, Calotropin, calactin, uscharin, voruscharin, 2″-oxovoruscharin, 2′-O-Acetyl cerleaside A, 17α-neriifolin, 17β-neriifolin, cerberin, Hyrcanoside, Securigenin-3β-O-β-6-deoxyguloside, 19-hydroxy-sarmentogenin-3β-O-β-6-deoxyguloside, sarmentogenin-3β-O-[α-allosyl-(1→4)-β-6-deoxyalloside], securigenin-3β-O-[α-allosyl-(1→4)-β-6-deoxyalloside], Digoxin, digitoxin, gitoxin, Elaeodendrosides, Acovenosigenin A 3-O-α-L-ramnopyranoside, euonymoside A, euonymusoside A, Euonymoside A, Maquiroside A, Oleander, oleandrin, cardenolide N-1, cardenolide N-4, 3β-O-(β-D-sarmentosyl)-16β-acetoxy-14-hydroxy-5β,14β-card-20-(22)-enolide, 16β-acetoxy-3β,14-dihydroxy-5β,14β-card-20-(22)-enolide, 17-epi-11α-hydroxy-6,7-dehydrostrophanthidin-3-O-β-boivinopyranoside, 6,7-dehydrostrophanthidin-3-O-β-boivinopyranoside, 6,7-dehydrostrophanthidin-3-O-β-oleandropyranoside, Convallatoxin, 3′-O-β-D-glucopyranosylcalactin, 12-dehydroxyghalakinoside, 6′-dehydroxyghala-kinoside, ghalakinoside, calactin, Periplocin isomers, Rhodexin A, 3-O-β-D-fucopyranosylstrophanthidin, 3-O-β-D-quinovopyranosylperiplogenin, 3-O-β-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosylcannogenin, 3-O-β-D-xylopyranosylperiplogenin, 3-O-β-D-quinovopyranosylstrophanthidin, 3-O-β-D-xylopyranosylstrophanthidin, 3-O-β-D-fucopyranosylperiplogenin, 3-O-α-L-rhamnopyranosylcannogenol, convallatoxin, 3-O-α-L-rhamnpyranosylacovenosigenin A, Stebloside, mansonin, Periplogenin digitoxoside, Periplocymarin, digitoxigenin 3-O—[O-β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranosyl-(1→4)-β-D-digitoxopyranoside, echujin, corchorusoside C, 3-O-(β-glucopyranosyl)acovenosigenin A, Ouabain, Neriifolin, 3′-O-methylevomonoside, 2′ acetylneriifolin, Thevetin A and B, thevetoside, Proscillaridin A, and scillaren A. 30. A method of treating a disease or disorder therapeutically responsive to cardiac glycoside therapy in a subject in need thereof, the method comprising administering to the subject a formulation according to claim 20.
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이 특허에 인용된 특허 (15)
Rowley ; Jr. Frank F. (Valley Center KS), Closed loop gradient force comminuting and dehydrating system.
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