Ginkgo Biloba Extract Production via Segmented Solvent Extraction
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Solution Overview
Problem
Current methods for producing Ginkgo biloba leaf extracts often fail to meet European pharmacopoeia standards due to variations in ingredient content, particularly increased levels of terpene lactones and flavonoids, and cannot use pure compounds or concentrates, which are not allowed for drug use.
Innovation Solution
An improved multistep method involving extraction with acetone-water or methanol, followed by distillation, precipitation, ammonium sulfate addition, and multiple solvent extractions with methyl ethyl ketone and aliphatic solvents to achieve the required flavonoid, bilobalide, and ginkgolides content, while avoiding excessive terpene lactones and flavonoids, resulting in a dry extract with specific weight percentages and low water content.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If Ginkgo leaves with increased terpene lactone content are used for extraction, then the terpene lactone content in the extract increases, but the extract fails to meet European pharmacopoeia standards
Solution Approach 1:
The patent applies liquid-liquid extraction using methyl ethyl ketone to selectively remove excessive terpene lactones from the aqueous Ginkgo extract. The terpene lactones partition into the methyl ethyl ketone phase, allowing their removal while retaining the desired flavonoid and ginkgolide components in the aqueous phase, thus achieving compliance with pharmacopoeia standards.
Solution Approach 2:
The patent changes the chemical composition parameters of the extract by controlling the ratio of methyl ethyl ketone to aqueous solution and adjusting the extraction conditions. This allows selective modification of the terpene lactone content while preserving the required flavonoid (22-27%) and ginkgolide (2.6-3.4%) concentrations within pharmacopoeia specifications.
2Quantity of substance
If Ginkgo leaves with increased flavonoid content are used for extraction, then the flavonoid content in the extract increases, but the extract fails to meet European pharmacopoeia standards
Solution Approach 1:
The patent uses sequential liquid-liquid extraction: first with methyl ethyl ketone to remove excessive terpene lactones, then with n-heptane to selectively remove excess flavonoids. The flavonoids partition into the n-heptane phase, allowing precise control of their final concentration to fall within the 22-27% range required by pharmacopoeia standards.
Solution Approach 2:
The patent segments the extraction process into multiple distinct steps using different solvents for different components: methyl ethyl ketone for terpene lactones, n-heptane for flavonoids, and butanol/pentanol for ginkgolides. This segmented approach allows independent control of each component's concentration to meet specific pharmacopoeia requirements.
3Manufacturing precision
If multiple extraction steps with different solvents are performed, then the compliance with pharmacopoeia standards improves, but the process complexity increases
Solution Approach 1:
The patent divides the extraction process into segmented steps using different solvents for different components: methyl ethyl ketone for terpene lactones, n-heptane for flavonoids, and butanol/pentanol for ginkgolides. This segmentation allows precise control of each component's concentration to meet pharmacopoeia standards while maintaining process organization and efficiency.
Solution Approach 2:
The patent uses ammonium sulfate as an intermediary substance added to the aqueous extract before solvent extraction. This creates optimal extraction conditions by adjusting the aqueous phase composition, enhancing the selectivity and efficiency of subsequent solvent extractions, and facilitating better separation of different Ginkgo components.
4Ease of manufacture
If conventional extraction methods are used, then the production process is simple, but the extract cannot meet pharmacopoeia standards when leaves with unfavorable ingredient spectra are used
Solution Approach 1:
The patent applies segmented liquid-liquid extraction using methyl ethyl ketone, n-heptane, and butanol/pentanol to selectively adjust different components. This maintains relative process simplicity while achieving precise control over flavonoid (22-27%), ginkgolide (2.6-3.4%), and terpene lactone content to meet pharmacopoeia standards even with variable raw material quality.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The method consistently produces Ginkgo biloba leaf extracts that meet European pharmacopoeia standards, ensuring the required flavonoid and ginkgolides content, even with leaves having unfavorable ingredient spectra, without the use of pure compounds or concentrates.
Implementation Method 1
the major amount of the organic solvent is separated from the extract to a content of not more than 10% by weight, wherein in the last distillation steps water is added, if necessary
Implementation Method 2
the remaining concentrated aqueous solution is diluted with water to a solid content of 5 to 25% by weight, cooled to a temperature below 25° C. while stirring, left till the formation of a precipitate
Implementation Method 3
ammonium sulfate is added to the remaining aqueous solution and the formed solution is extracted with methyl ethyl ketone or a mixture of methyl ethyl ketone and acetone
Implementation Method 4
the butanol and pentanol phases, respectively, are concentrated to a solid content of 50 to 70%
Implementation Method 5
the aqueous alcoholic solution is extracted with an aliphatic or cycloaliphatic solvent having a boiling point of 60 to 100° C. for the further separation of alkyl phenol compounds
Implementation Method 6
the water phase is concentrated under reduced pressure and is dried at a temperature of not more than 60 to 80° C. to a dry extract having a water content of less than 5%
Implementation Method 7
the water phase is concentrated under reduced pressure
Data Source
AI summary
The present invention relates to an improved multistep method for the production of an extract of Ginkgo biloba leaves for use as a drug.