Extract from leaves of ginkgo biloba for intravenous injection or infusion
AssigneeDr. Willmar Schwabe GmbH & Co.
InventorKlaus-Peter Schwabe
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Abstract
The present application relates to an extract from the leaves of Ginkgo biloba containing most of the flavone glycosides, ginkgolides and bilobalide originally present in the leaves, characterized in that it is essentially free of components of the leaves with serum-precipitating and/or haemagglutinating properties, method of its preparation and pharmaceutical compositions containing the extract.
Claims20
An extract from the leaves of Ginkgo biloba containing most of the flavone glycosides, ginkgolides and bilobalide originally present in the leaves, comprising 20 to 30 weight percent flavone glycosides, 2.5 to 4.5 weight percent ginkgolides selected from the group consisting of ginkgolide A, B, C and J and mixtures thereof, 2.0 to 4.0 weight percent bilobalide and less than 10 ppm alkylphenol compounds, said extract being essentially free of components of the leaves with serum-precipitating or hemagglutinating properties.
A method for preparing an extract from Ginkgo biloba leaves, comprising 20 to 30 weight percent flavone glycosides, 2.5 to 4.5 weight percent of ginkgolides selected from the group consisting of ginkgolide A, B, C and J and mixtures thereof, 2.0 to 4.0 weight percent bilobalide and less than 10 ppm of alkylphenol compounds, which is essentially free of components of the leaves with serum-precipitating or hemagglutinating properties, wherein
- (a) fresh or dried green leaves from Ginkgo biloba are extracted at a temperature of approximately 40 to 100.degree. C. with an organic solvent selected from the group consisting of aqueous acetone, an aqueous alkanol with 1 to 3 C-atoms and anhydrous methanol to form an extract,
- (b) most of the organic solvent in said extract of step (a) is separated by a distillation step to a maximum organic solvent content of 10 weight percent, whereby water is optionally added near the end of the distillation step, to form a concentrated solution,
- (c) the concentrated solution of step (b) is diluted with water to a solids content of 5-25 weight percent, allowed to cool while being stirred to a temperature below 25.degree. C. until a precipitate forms, and this precipitate, consisting of lipophilic components which do not dissolve well in water, is removed to form a filtered solution,
- (d) ammonium sulfate is added to the filtered solution to achieve an ammonium sulfate content of 30 weight percent to form an ammonium sulfate solution which is extracted with methylethylketone or a mixture containing methylethylketone and acetone in a ratio of 9:1 to 4:6 to form a methylethylketone containing extract,
- (e) the methylethylketone containing extract is concentrated to a solids content of 50-70% and is diluted with water to a solids content of 5-20%, forming a diluted solution,
- (f) the diluted solution is subjected to an extraction with butanol or pentanol to form a butanol or pentanol phase,
- (g) the butanol or pentanol phase is concentrated to a solids content of 50-70% to form a first concentrate,
- (h) the first concentrate of step (g) is diluted with sufficient water and ethanol to obtain an aqueous alcohol solution of 5 to 20 weight percent dry extract in 20 to 60 weight percent aqueous ethanol,
- (i) the aqueous alcohol solution is extracted with an aliphatic or cycloaliphatic solvent with a boiling point of approximately 60.degree. to 100.degree. C. to further remove the alkylphenol compounds, forming a water phase,
- (j) the water phase is concentrated under reduced pressure to form a second concentrate,
- (k) the second concentrate of step (j) is taken up in a mixture of water and acetone in a ratio of 10:90 to 60:40 weight percent, fed onto a column filled with a cross-linked polyvinyl pyrrolidone substrate and eluted with said mixture of water and acetone in a ratio of 10:90 to 60:40 weight percent to produce an eluate, and
- (l) the eluate is dried at a maximum temperature of 60.degree. to 80.degree. C. to recover a dry extract with a water content of less than 5%.
In a method of preparing an extract of Ginkgo biloba leaves for intravenous administration, wherein said extract contains most of the flavone glycosides, ginkgolides and bilobalides present in the leaves from which said extract is derived, wherein said leaves contain also a predetermined amount of substances causing serum-precipitating or hemagglutinating properties, the improvement comprising including in said method a chromatographic treatment with cross-linked polyvinyl pyrrolidone or a polyamide substrate, thereby reducing the level of said serum-precipitating or hemagglutinating substances below said predetermined amount.
Dependencies are inferred from the claim text.