EP1551853A1 - Method for the separation of triglycoalkaloids - Google Patents
Method for the separation of triglycoalkaloidsInfo
- Publication number
- EP1551853A1 EP1551853A1 EP03727026A EP03727026A EP1551853A1 EP 1551853 A1 EP1551853 A1 EP 1551853A1 EP 03727026 A EP03727026 A EP 03727026A EP 03727026 A EP03727026 A EP 03727026A EP 1551853 A1 EP1551853 A1 EP 1551853A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- rhamnose
- triglycoalkaloid
- glucose
- galactose
- solid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
- C07H1/08—Separation; Purification from natural products
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/02—Heterocyclic radicals containing only nitrogen as ring hetero atoms
Definitions
- the present invention relates to a method for the separation of triglycoalkaloids. More specifically, the present invention relates to a method for the separation of triglycoalkaloids in which the triglycoside portion comprises ⁇ -L-rhamnopyranosyl- (1 ⁇ 2gal)-O- ⁇ -D-glucopyranosyl-(1 ⁇ 3gal)- ⁇ -D-galactopyranose (or 6-deoxy- ⁇ -L- mannopyranosyl-(1 ⁇ 2)-O-[ ⁇ -D-glucopyraonosyl-(1 ⁇ 3)]- ⁇ -D-galactopyranoside) and triglycoalkaloids in which the triglycoside portion is ⁇ -L-rhamnopyranosyl- (1 ⁇ 2glu)-O- ⁇ -L-rhamnopyranosyl-(1 ⁇ 4glu)- ⁇ -D-glucopyranose from a mixture containing both compounds.
- solasonine and solamargine which occur together in the same plant extracts, are triglycoalkaloids in which the alkaloid portion is common, being solasadine, but the triglycoside portion differs.
- the triglycoside portion of solasonine is ⁇ -L-rhamnopyranosyl-(1 ⁇ 2gal)-O- ⁇ -D-glucopyranosyl- (1 ⁇ 3gal)- ⁇ -D-galactopyranose (or 6-deoxy- ⁇ -L-mannopyranosyl-(1 ⁇ 2)-O-[ ⁇ -D- glucopyraonosyl-(1 ⁇ 3)]- ⁇ -D-galactopyranoside), whilst the triglycoside portion of solamargine is ⁇ -L-rhamnopyranosyl-(1 - ⁇ 2glu)-O- ⁇ -L-rhamnopyranosyl-(1 ⁇ 4glu)- ⁇
- the triglycoalkaloids ⁇ -solanine and ⁇ -chaconine occur together in plant extracts. These compounds share a common alkaloid portion, being solanidine, but, again, the triglycoside portion differs.
- the triglycoside portion of ⁇ -solanine is ⁇ -L-rhamnopyranosyl-(1 ⁇ 2gal)-O- ⁇ -D-glucopyranosyl-(1 ⁇ 3gal)- ⁇ -D- galactopyranose (or 6-deoxy- ⁇ -L-mannopyranosyi-(1 ⁇ 2)-O-[ ⁇ -D- glucopyraonosyl-(1 ⁇ 3)]- ⁇ -D-galactopyranoside), whilst the triglycoside portion of ⁇ -chaconine is ⁇ -L-rhamnopyranosyl-(1 ⁇ 2glu)-O- ⁇ -L-rhamnopyranosyl-(1 ⁇ 4glu)
- plant extracts containing mixtures of triglycoalkaloids differing only by the triglycoside portion described above have been shown to exhibit anticancer activity.
- plant extracts containing solasonine and solamargine have been shown to exhibit anticancer activity.
- solasonine and solamargine have been shown to exhibit anticancer activity.
- existing methods for separation of triglycoalkaloids having an identical alkaloid portion, such as solasonine and solamargine are time consuming and difficult to effect on any reasonable scale, meaning 'pure' compounds are extremely expensive.
- solamargine includes both the free base and solamargine salts
- solasonine includes both the free base and solasonine salts
- a method for the separation of a rhamnose-glucose-galactose triglycoalkaloid and a rhamnose- rhamnose-glucose triglycoalkaloid from a mixture containing both a rhamnose- glucose-galactose triglycoalkaloid and a rhamnose-rhamnose-glucose triglycoalkaloid comprising the steps of:
- the method comprises the further step of stripping the alcoholic solvent from the solution substantially of the rhamnose-rhamnose-glucose triglycoalkaloid to obtain a solid substantially comprising the rhamnose-rhamnose- glucose triglycoalkaloid.
- the alcoholic solvent comprises a low molecular weight alcohol.
- the alcoholic solvent comprises methanol or ethanol.
- ethanol has the advantage of being non-toxic if left in residual amounts.
- the step of combining the mixture with a portion of alcohol solvent more specifically comprises:
- the combination of the alcoholic solvent and the mixture may be vigorously agitated.
- the method of the present invention preferably comprises the further step of:
- Adding a portion of a further solvent to cause precipitation of at least a portion of any dissolved the rhamnose-glucose-galactose triglycoalkaloid Adding a portion of a further solvent to cause precipitation of at least a portion of any dissolved the rhamnose-glucose-galactose triglycoalkaloid.
- the further solvent is ethyl acetate (ethyl ethanoate).
- the alcoholic solvent is methanol or ethanol
- the further solvent is ethyl ethanoate
- the portion of further solvent corresponds to approximately 3 to 5 times the volume of alcoholic solvent.
- the portion of further solvent corresponds to approximately 4 times the volume of alcoholic solvent.
- the further solvent may be selected from alcohol miscible solvents including: acetone; acetonithle, methyl ethyl ketone and methyl isobutyl ketone.
- the step of combining the mixture with a portion of alcohol solvent more specifically comprises the step of:
- the step of separating the solid substantially comprising the rhamnose-glucose- galactose triglycoalkaloid from the solution substantially of the rhamnose- rhamnose-glucose triglycoalkaloid may more specifically comprise physically separating the solid substantially comprising the rhamnose-glucose-galactose triglycoalkaloid from the solution substantially of the rhamnose-rhamnose-glucose triglycoalkaloid, such as by filtration and/or centrifugation.
- the method of the present invention may further comprise the step of: Purifying the solid substantially comprising the rhamnose-glucose-galactose triglycoalkaloid by recrystallisation.
- the method of the present invention may further comprise the step of:
- the steps of purifying the solid substantially comprising the rhamnose-rhamnose- glucose triglycoalkaloid and/or the solid substantially comprising the rhamnose- glucose-galactose triglycoalkaloid by recrystallisation may more specifically comprise the step of purifying the solid substantially comprising the rhamnose- rhamnose-glucose triglycoalkaloid and/or the solid substantially comprising the rhamnose-glucose-galactose triglycoalkaloid by recrystallisation in aqueous alcohol solutions. More specifically still, the step involves recrystallisation in aqueous solutions of low molecular weight alcohols. In a highly specific form of the invention, the step involves recrystallisation in aqueous solutions of methanol, ethanol or isopropanol, or mixtures of such.
- the aqueous alcohol solution comprises at least 10-15% alcohol.
- the aqueous alcohol solution is provided in the form of an aqueous methanol solution with a methanol concentration between about 40 and 80%. More specifically, the methanol concentration is between about 50 and 70%.
- the aqueous alcohol solution is provided in the form of an aqueous isopropyl alcohol solution with an isopropyl alcohol concentration of between about 20 and 50% isopropyl alcohol. More specifically, the isopropyl alcohol concentration is between about 25 and 40%.
- the steps of purifying the solid substantially comprising the rhamnose-rhamnose- glucose triglycoalkaloid and/or the solid substantially comprising the rhamnose- glucose-galactose triglycoalkaloid by recrystallisation may involve multiple dissolution and crystallisation steps.
- the mixture of the rhamnose-glucose-galactose triglycoalkaloid and the rhamnose-rhamnose- glucose triglycoalkaloid is provided in the form of a plant extract.
- Said plant extract may be produced by a method comprising the following steps:
- the mixture of the rhamnose-glucose-galactose triglycoalkaloid and the rhamnose-rhamnose-glucose triglycoalkaloid may be produced by a method comprising the following steps: Homogenising a portion of plant material containing the rhamnose-glucose- galactose triglycoalkaloid and the rhamnose-rhamnose-glucose triglycoalkaloid;
- the mixture of the rhamnose-glucose-galactose triglycoalkaloid and the rhamnose-rhamnose-glucose triglycoalkaloid may be produced by a method comprising the following steps:
- the method comprises the steps of
- a method for the production of a mixture of the rhamnose-glucose-galactose triglycoalkaloid and the rhamnose-rhamnose-glucose triglycoalkaloid as described above may comprise the additional step of:
- the acid solution is provided in the form of an acetic acid solution.
- the method may comprise the additional step of:
- the method may comprise the additional steps of:
- the second solid mixture of the rhamnose-glucose-galactose triglycoalkaloid and the rhamnose-rhamnose-glucose triglycoalkaloid may be washed with water.
- the mixture of the rhamnose-glucose-galactose triglycoalkaloid and the rhamnose-rhamnose-glucose triglycoalkaloid is dissolved in boiling ethanol to produce a third solution of the rhamnose-glucose-galactose triglycoalkaloid and the rhamnose-rhamnose-glucose triglycoalkaloid, the third solution being filtered when hot, before a volume of water is added, thereby inducing precipitation of a third solid mixture of the rhamnose-glucose-galactose triglycoalkaloid and the rhamnose-rhamnose-glucose triglycoalkaloid.
- the volume of water added corresponds to approximately 6 times the volume of the ethanolic solution of the rhamnose-glucose-galactose triglycoalkaloid and the rhamnose-rhamnose-glucose triglycoalkaloid.
- This technique has the advantage of minimising the presence of water-soluble glycoalkaloids in the solid mixture of solasonine and solamargine.
- the third solid mixture of the rhamnose-glucose-galactose triglycoalkaloid and the rhamnose-rhamnose-glucose triglycoalkaloid may then be collected by centrifugation.
- the antioxidant is provided in the form of sodium metabisulphite.
- the metabisulphite is preferably added to a concentration of approximately 0.5% by weight of the fresh plant material.
- the inert atmosphere is provided by way of a nitrogen atmosphere.
- the method may involve the step of heating the solution of the rhamnose-glucose-galactose triglycoalkaloid and the rhamnose-rhamnose- glucose triglycoalkaloid.
- the step comprises heating the solution to about 40-60°C.
- the step involves heating the solution to approximately 50°C.
- the step(s) of inducing the precipitation of the first solid mixture of the rhamnose- glucose-galactose triglycoalkaloid and the rhamnose-rhamnose-glucose triglycoalkaloid may comprise the step of adding sufficient ammonium hydroxide to raise the pH of the solution to the point where the rhamnose-glucose-galactose triglycoalkaloid and the rhamnose-rhamnose-glucose triglycoalkaloid precipitate as a mixture of the free bases.
- step of inducing the precipitation of the first solid mixture of the rhamnose-glucose-galactose triglycoalkaloid and the rhamnose-rhamnose- glucose triglycoalkaloid may comprise the addition of an ammonium salt of an acid, whereupon the rhamnose-glucose-galactose triglycoalkaloid and the rhamnose-rhamnose-glucose triglycoalkaloid precipitate as a mixture of the salts of the acid.
- the acid is phenylacetic acid.
- a pharmaceutical composition comprising an aqueous solution of a phenylacetate salt of the rhamnose-glucose-galactose triglycoalkaloid and/or the rhamnose-rhamnose- glucose triglycoalkaloid.
- the mixture of solasonine and solamargine is provided in the form of an extract from a plant of the genus Solanum.
- the mixture of solasonine and solamargine is provided in the form of an extract from a plant of the species Solanum linnaeanum.
- the extract is preferably from the fruit of the plant.
- the extract is from the green fruit of the plant.
- the rhamnose-glucose-galactose triglycoalkaloid is provided in the form of solasonine and the rhamnose-rhamnose-glucose triglycoalkaloid in the form of solamargine.
- the solid substantially comprising the rhamnose-glucose-galactose triglycoalkaloid in the form of solasonine preferably comprises at least 80% by weight solasonine.
- the solid substantially comprising solasonine comprises at least 90% by weight solasonine.
- the solid substantially comprising solasonine comprises approximately 94% by weight solasonine.
- the solid substantially comprising the rhamnose-rhamnose-glucose triglycoalkaloid in the form of solamargine preferably comprises at least 80% by weight solamargine.
- the solid substantially comprising solamargine comprises at least 90% by weight solamargine.
- the solid substantially comprising solamargine comprises approximately 97% by weight solamargine.
- the step of causing or allowing a substantial portion of the rhamnose-rhamnose-glucose triglycoalkaloid in the from of solamargine to dissolve, thereby generating an alcoholic solution substantially of solamargine, and a solid substantially comprising the rhamnose-glucose- galactose triglycoalkaloid in the form of solasonine more specifically comprises: Causing or allowing a substantial portion of the solamargine to dissolve over a period of approximately 1 to 3 hours at room temperature, thereby generating an alcoholic solution substantially of solamargine, and a solid substantially comprising solasonine.
- a pharmaceutical composition comprising an aqueous solution of a phenylacetate salt of the solasonine and/or solamargine.
- a portion of green fruit from a plant or plants of the species Solanum linnaeanum is minced and passed through a 5mm sieve.
- the sieved mixture is then placed in an inert atmosphere, whereupon a portion of antioxidant in the form of sodium metabisulphite, corresponding to approximately 0.5% of the mass of the fresh fruit, is added to such, as is an amount of pectinase, corresponding to approximately 1mg per kg of fruit.
- the mixture is then physically separated by pressure filtration and/or centrifugation to separate the solids from the solution containing both solasonine and solamargine.
- the solids are then washed with a volume of 3% acetic acid corresponding to the volume of solution obtained from the pulp mixture, and the washings combined with the supernatant from the centrifugation.
- the solid mixture of free bases of solasonine and solamargine are collected by centrifugation, with the supernatant being discarded.
- the solid mixture so produced is then dissolved in a 3% solution of acetic acid, with the resulting solution being separated from any residual solids by filtration.
- a further portion of ammonium hydroxide is added, inducing the precipitation of a solid mixture of the free bases, which are then washed in water, before being dissolved in boiling ethanol and filtered.
- An amount of water equivalent to six times the volume of the ethanolic solution is then added, thereby inducing the precipitation of a solid mixture of solasonine and solamargine at a ratio of between about 40:60 and 60:40.
- the solid is then collected by centrifugation.
- the mixture is typically 80-100% pure, with mono- and diglycoalkaloids and other water soluble impurities being largely removed.
- a desired quantity of the mixture of solasonine and solamargine is weighed and introduced into a suitable vessel.
- a volume of methanol, corresponding to 10 ml_ per gram of the mixture is slowly added, portion wise, over a period of 10-15 minutes with vigorous stirring/agitation.
- the colour of the solution should darken to light brown-tan with simultaneous appearance of a fine white precipitate.
- stirring commences the undissolved lumps of solid mixture should gradually break up, and the process may be accelerated using a sonic bath and breaking up lumps with a spatula/stirring rod.
- a milky white suspension/slurry is obtained. Whilst this solid may be collected, a better yield, albeit at lower purity, is obtained by adding (in one addition) 4 equivalents of ethyl acetate i.e. 4 x volume of methanol employed, resulting in the immediate precipitation of a white suspension.
- the white suspension may then be filtered by Buchner vacuum filtration (using Whatman #1 filter paper), with any material remaining in the flask being washed out with small amounts of ethyl acetate.
- the resulting white solid should then be left to dry on the filter (under vacuum) until touch dry, producing a solid substantially comprising solasonine. After drying in a vacuum oven at 60°C for a period of 2-3 hours, analysis should show that the solid comprises approximately 85% solasonine, with the recovery of material being approximately 90-100%).
- the filtrate solution (supernatant) remaining in the Buchner flask may then be transferred to a round bottom flask (washing with methanol) and the solvent removed to leave a white solid.
- the white solid obtained may be further dried using a vacuum oven (see above). On analysis the solid should contain approximately 97% solamargine, with the recovery of material being approximately 90-100%.
- the solid solasonine and solamargine are then further purified by recrystallisation in an aqueous solution of isopropanol, ethanol or methanol, with the precise conditions representing a trade-off between speed of recrystallisation and %recovery vs purity of recovered solid.
- a portion of green fruit from a plant or plants of the species Solanum linnaeanum was minced and passed through a 5mm sieve. The sieved mixture was then placed in an inert atmosphere, whereupon a portion of 3% acetic acid (corresponding to 1 litre per 500 g of plant material) and a portion of antioxidant in the form of sodium metabisulphite, corresponding to approximately 0.5% of the mass of the fresh fruit, is added to such, as is an amount of pectinase, corresponding to 1 mg per kg of fruit.
- the mixture was then filtered and centrifuged to separate the solids from a solution containing both solasonine and solamargine. After the solution was heated to approximately 50°C, precipitation of a mixture of the free bases of solamargine and solasonine was induced by the addition of a portion of ammonium hydroxide.
- the solid mixture of the free bases of solasonine and solamargine were collected by centrifugation, with the supernatant being discarded.
- the solid mixture so produced was then dissolved in a 3% solution of acetic acid, with the resulting solution being separated from any residual solids by filtration.
- a further portion of ammonium hydroxide was added, inducing the precipitation of a solid mixture of the free bases of solasonine and solamargine, which was then washed in water, before being dissolved in boiling ethanol and filtered.
- the equivalent of six volumes of water were added to the filtrate to induce precipitation of a solid mixture of solasonine and solamargine at a ratio of about 50:50, and with a purity of 98-99%, which was collected by centrifugation.
- solasonine and solamargine in an approximately 1 :1 ratio
- 1.0 g was dissolved in 10 mL of 3% acetic acid.
- Phenylacetic acid (0.255 g) was dissolved in 0.5M ammonium hydroxide (3.75 mL) and added dropwise to the solution.
- the mixture was left at 4°C overnight to give a settled fine white powder.
- the suspension was centrifuged to give a solid and supernatant.
- the solid composition contained solasonine:solamargine salts in the ratio 63:37.
- the supernatant composition of solasonine:solamargine was 34:66.
- a desired quantity of a mixture of solasonine and solamargine was weighed and added portion-wise to a stirred methanol solution, corresponding in volume to 10 mL per gram of the mixture, over a period of 10-15 minutes. As dissolution occurred the colour of the solution darkened to light brown-tan with simultaneous appearance of a fine white precipitate. As stirring commenced the undissolved lumps of solid mixture gradually broke up.
- the filtrate solution (supernatant) remaining in the Buchner flask was transferred to a round bottom flask (washing with methanol) and the solvent stripped by rotary vacuum evaporation (bath temp. 60°C), leaving a white solid.
- the white solid obtained can be further dried using a vacuum oven (see above). On HPLC analysis the solid contained approx. 97% solamargine (% recovery of material -90-100%).
- Recrystallisation of 90-95% solamargine to 98-99% purity is achievable in 2-3 steps (usually 3) e.g. 1 step from 89.5% solamargine generates 93.1% solamargine material with 52% recovery. If solamargine % purity is 96-97% (or above) purification to 98-99% solamargine can be achieved in 1-2 recrystallisation steps -see Table 4 and 5.
- the experiments also demonstrated that if the alcohol content of the solvent mixture exceeds 80% recrystallisation is usually very slow (1-2 weeks) with poor recovery (20-30%). However, % purity is generally high even after 1 step (98- 99%). Further, it was discovered that if alcohol content drops below 10-15%, recrystallisation is not possible due to aqueous insolubility of the solid (even when hot).
- the present invention demonstrates an effective and straightforward method for the separation of solasonine and solamargine from a mixture containing both compounds.
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
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- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AUPS326302 | 2002-06-28 | ||
AUPS3263A AUPS326302A0 (en) | 2002-06-28 | 2002-06-28 | Method for the separation of solamargine and solasonine |
PCT/AU2003/000738 WO2004002998A1 (en) | 2002-06-28 | 2003-06-13 | Method for the separation of triglycoalkaloids |
Publications (2)
Publication Number | Publication Date |
---|---|
EP1551853A1 true EP1551853A1 (en) | 2005-07-13 |
EP1551853A4 EP1551853A4 (en) | 2007-09-05 |
Family
ID=3836820
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP03727026A Withdrawn EP1551853A4 (en) | 2002-06-28 | 2003-06-13 | Method for the separation of triglycoalkaloids |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP1551853A4 (en) |
AU (1) | AUPS326302A0 (en) |
CA (1) | CA2489682A1 (en) |
NZ (1) | NZ537268A (en) |
WO (1) | WO2004002998A1 (en) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0020029A1 (en) * | 1979-05-02 | 1980-12-10 | Aruba (Qld.) Pty. Ltd. | Pharmaceutical compositions comprising steroid alkaloids |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3385844A (en) * | 1966-02-01 | 1968-05-28 | Searle & Co | Process for isolation of solanum alkaloids from solanum plants |
AUPP968699A0 (en) * | 1999-04-09 | 1999-05-06 | Cura Nominees Pty Ltd | Therapeutic compositions and method for their preparation |
-
2002
- 2002-06-28 AU AUPS3263A patent/AUPS326302A0/en not_active Abandoned
-
2003
- 2003-06-13 EP EP03727026A patent/EP1551853A4/en not_active Withdrawn
- 2003-06-13 NZ NZ537268A patent/NZ537268A/en unknown
- 2003-06-13 WO PCT/AU2003/000738 patent/WO2004002998A1/en not_active Application Discontinuation
- 2003-06-13 CA CA002489682A patent/CA2489682A1/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0020029A1 (en) * | 1979-05-02 | 1980-12-10 | Aruba (Qld.) Pty. Ltd. | Pharmaceutical compositions comprising steroid alkaloids |
Non-Patent Citations (1)
Title |
---|
See also references of WO2004002998A1 * |
Also Published As
Publication number | Publication date |
---|---|
EP1551853A4 (en) | 2007-09-05 |
CA2489682A1 (en) | 2004-01-08 |
NZ537268A (en) | 2005-08-26 |
AUPS326302A0 (en) | 2002-07-18 |
WO2004002998A1 (en) | 2004-01-08 |
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