Compositions and methods for treating HIV/AIDS
Compositions and methods for inhibiting HIV protease are disclosed. The compositions include an extract from Cassia acutifolia stems, or a fraction thereof, alone or in a pharmaceutically acceptable carrier. The extracts can be obtained by subjecting Cassia acutifolia pulverized stems to methanol/dichloromethane (1:1) extraction. In a first extraction stage, Cassia acutifolia pulverized stems are macerated in a mixture of methanol/dichloromethane. In a second stage methanol is added to the remaining marc vortex and extracted for a suitable time period at room temperature. The extract from the first and second stages are combined. The extracts can be further processed for formulation into a suitable pharmaceutical form.
1 . A composition comprising an extract from a non-leaf portion of Cassia acutifolia and an organic solvent or mixture of organic solvents,
wherein the organic solvent or mixture of organic solvents comprises a non-naturally occurring organic solvent and wherein the non-naturally occurring solvent is a solvent comprising one or more of dichloromethane, dimethyl sulfoxide, propylene glycol, poly(ethylene glycol), ethyl acetate, benzyl alcohol, glycerol, ethanol, dimethyl formamide, and/or acetone; and
wherein the extract from said non-leaf portion of Cassia acutifolia increases inhibition of viral proteases in a subject as compared to administration of an extract from a leaf portion of Cassia acutifolia.
2 . The composition of claim 1 , wherein the non-leaf portion of Cassia acutifolia comprises a stem portion.
3 . The composition of claim 1 , wherein the extract comprises one or more primary phytochemicals of Cassia acutifolia selected from the group consisting of L-alanine, L-valine, ethanolamine, glycerol, L-isoleucine, L-proline, butanedioic acid, glyceric acid, pipecolic acid, L-threonine, 4-ketoglucose, malic acid, ribitol, 4-aminobutanoic acid, 2,3-dihydroxy-2-methylpropanoic acid, D-(−)-erythrose, erythronic acid, xylose, L-proline, D-arabinose, D-(−)-lyxose, ribitol, D-(−)-rhamnose, D-(+)-ribono-1,4-lactonc, D-allofuranose, D-(−)-tagatofuranose, D-(−)-fructopyranose, D-pinitol, D-(−)-fructose, D-(−)-fructose, D-galactose, D-glucose, D-mannose, D-chiro-inositol, β-D-(+)-mannopyranose, palmitic acid, linoleic acid, α-linolenic acid, sucrose, aucubin, methyl galactoside, lactose, D-(+)-cellobiose, D-(+)-turanose, and oleic acid.
4 . The composition of claim 1 , wherein the extract comprises one or more secondary metabolites occurring in Cassia acutifolia selected from the group consisting of N-propyloctadecanamide, 2(5H)-furanone, phloroglucinol, 3-vinylaniline, pantothenic acid, 4-indolecarbaldehyde, resorcinol, rhamnosyllactone A, saponaroxin C, sinapinic acid, isorhamnetin, aloesin, diosmetin, styrene, delta-15-cis-mononervonin, and stigmasterol.
5 . The composition of claim 1 , wherein the mixture of organic solvents comprises an alcohol/non-naturally occurring organic solvent mixture.
6 . The composition of claim 1 , wherein the mixture of organic solvents comprises a methanol/non-naturally occurring organic solvent mixture.
7 . The composition of claim 1 , wherein the mixture of organic solvents comprises an ethanol/non-naturally occurring organic solvent mixture.
8 . The composition of claim 1 , wherein the non-naturally occurring organic solvent comprises dichloromethane or dimethyl sulfoxide.
9 . A composition of claim 1 , comprising said extract from a non-leaf portion of Cassia acutifolia and (i) dichloromethane or dimethyl sulfoxide, or (ii) a mixture of methanol/dichloromethane or methanol/dimethyl sulfoxide.
10 . A pharmaceutical composition comprising:
(i) an extract from a non-leaf portion of Cassia acutifolia according to claim 1 or obtained therefrom, wherein the extract from said non-leaf portion of Cassia acutifolia is present in an amount sufficient to increase inhibition of viral proteases in a subject as compared to administration of an extract from a leaf portion of Cassia acutifolia ; and
(ii) an effective amount of an added pharmaceutically-acceptable excipient that preserves the extract.
11 . The pharmaceutical composition of claim 10 , wherein the non-leaf portion of Cassia acutifolia comprises a stem portion.
12 . The pharmaceutical composition of claim 10 , wherein the extract comprises an alcoholic/non-naturally occurring organic solvent extract of Cassia acutifolia , and wherein the non-naturally occurring solvent is a solvent comprising one or more of dichloromethane, dimethyl sulfoxide, propylene glycol, poly(ethylene glycol), ethyl acetate, benzyl alcohol, glycerol, ethanol, dimethyl formamide, and/or acetone.
13 . The pharmaceutical composition of claim 10 , wherein the extract comprises an alcoholic/dichloromethane extract of Cassia acutifolia.
14 . The pharmaceutical composition of claim 10 , wherein the extract comprises one or more primary phytochemicals of Cassia acutifolia selected from the group consisting of L-alanine, L-valine, ethanolamine, glycerol, L-isoleucine, L-proline, butanedioic acid, glyceric acid, pipecolic acid, L-threonine, 4-ketoglucose, malic acid, ribitol, 4-aminobutanoic acid, 2,3-dihydroxy-2-methylpropanoic acid, D-(−)-erythrose, erythronic acid, xylose, L-proline, D-arabinose, D-(−)-lyxose, D-(−)-rhamnose, D-(+)-ribono-1,4-lactonc, D-allofuranose, D-(−)-tagatofuranose, D-(−)-fructopyranose, D-pinitol, D-(−)-fructose, D-galactose, D-glucose, D-mannose, D-chiro-inositol, β-D-(+)-mannopyranose, palmitic acid, linoleic acid, α-linolenic acid, sucrose, aucubin, methyl galactoside, lactose, D-(+)-cellobiose, D-(+)-turanose, and oleic acid.
15 . The pharmaceutical composition of claim 10 , wherein the extract comprises one or more secondary metabolites occurring in Cassia acutifolia selected from the group consisting of N-propyloctadecanamide, 2(5H)-furanone, phloroglucinol, 3-vinylaniline, pantothenic acid (vitamin B5), 4-indolecarbaldehyde, resorcinol, rhamnosyllactone a, saponaroxin c, sinapinic acid, isorhamnetin, aloesin, diosmetin, styrene, delta-15-cis-mononervonin, and stigmasterol.
16 . The pharmaceutical composition of claim 10 , where the composition is in the form of tablets, capsules, powders, lozenges, chews, gels, solid solutions, microparticles, nanoparticles, films, sprays, or a combination thereof.
17 . The pharmaceutical composition of claim 10 , where the composition is in the form of an extended-release formulation.
18 . A method of treating a subject in need thereof, the method comprising:
administering to the subject an effective amount of the composition of claim 1 , wherein the subject has, or is diagnosed as having, a viral infection.
19 . A method of treating a subject in need thereof, the method comprising:
administering to the subject an effective amount of the pharmaceutical composition of claim 10 , wherein the subject has, or is diagnosed as having, a viral infection.
20 . A composition comprising:
(i) an extract of Cassia acutifolia obtained from a non-leaf portion of the Cassia acutifolia by solid-liquid extraction, wherein the extract from said non-leaf portion of Cassia acutifolia is present in an effective amount to increases inhibition of viral proteases in a subject as compared to administration of an extract from a leaf portion of Cassia acutifolia ; and
(ii) an organic solvent or mixture of organic solvents,
wherein the organic solvent or mixture of organic solvents is used to perform the extraction,
wherein the organic solvent is dichloromethane or dimethyl sulfoxide, and
wherein the mixture of organic solvents is methanol/dichloromethane or methanol/dimethyl sulfoxide.