Processing

Please wait...

Settings

Settings

Goto Application

1. WO2006099635 - ISOLATION OF GALANTHAMINE FROM BIOLOGICAL MATERIAL

Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

[ EN ]

What is claim is:

1. A process for isolation of galanthamine from galanthamine containing biomaterial comprising :
a) extraction of the biomaterial with aqueous solution of suitable organic or
inorganic acid obtaining thus a primary extract
b) adsorption of the organic compounds from the primary extract on an
absorbent, washing the adsorbent with water, and elution of the organic
compounds from the adsorbent using a water miscible organic solvent,
obtaining a concentrate of alkaloids.
2. The process according to the Claim 1, wherein the galanthamine containing
biomaterial are dried or fresh parts of plants of Amaryllidaceae family.
3. The process according to the Claim 2, wherein the plants of Amaryllidaceae family are plants of the genera Galanthus, Narcissus, Leucojum and/or Lycoris.
4. The process according to the Claim 2 , wherein the fresh parts of plants are bulbs and or whole aerial parts of the plants.
5. The process according to the Claim 2 , wherein the dried parts are leaves or the whole aerial parts of the plants.
6. The process according to the Claim 1, wherein the organic or inorganic acid used for the extraction of the biomass is selected from group consisting of acetic acid, tartaric acid, citric acid, phosphoric acid, sulfuric acid and hydrochloric acid.
7. The process according to the Claim 6, wherein the concentration of the organic or inorganic acid in water is from 0.05 to about 2 %.
8. The process according to the Claim 1, wherein the biomass is extracted with aqueous solution of phosphoric acid in concentration about 0.1 % (w/w).
9. The process according to the Claim 1, wherein the extraction of the biomass is
accomplished counter current way on a battery of percolators.
10. The process according to the Claim 1, wherein froml to 3 weight parts of the primary extract are obtained from one weight part of the biomass.
11. The process according to the Claim 1, wherein the adsorbent used for the adsorption of alkaloids from the primary extract is a poly(styrene-divinylbenzene) co-polymer.

12. The process according to the Claim 1, wherein the adsorption of alkaloids on the adsorbent is accomplished at the pH from about 8 to about 11.

13. The process according to the Claim 1, wherein the polar organic solvent used for the elution of alkaloids from the adsorbent is methanol, ethanol, 2-propanol, acetone, mixtures thereof or their aqueous mixtures.
14. The process according to the Claim 1, wherein the concentrate of alkaloids is further purified by adsorption of alkaloids from the concentrate on a cation exchange resin and elution of the alkaloids from the cation exchange resin is carried out with the aqueous solution of a suitable base to obtain an aqueous alkaloid concentrate.
15. The process according to the Claim 14, wherein the cation exchange resin is a strongly acidic cation exchange resin of gel type.
16. The process according to the Claim 14 , wherein the cation exchange resin is a polysulphonated (styrene - divinylbenzene) co-polymer crosslinked with not more than 4 % of divinylbenzene.
17. The process according to the Claim 14, wherein the base used for the elution of alkaloids from the cation exchange resin is aqueous ammonia.
18. The process according to the Claim 1, wherein the concentrate of alkaloids is concentrated in order to remove the organic solvent, obtaining thus an aqueous alkaloid concentrate.
19. The process according to the Claims 14 and 18, wherein the aqueous alkaloid concentrate is further purified by extraction of the alkaloids into an organic solvent not miscible with water and the obtained extract is concentrated to obtain a crude alkaloid mixture.
20. The process according to the Claim 19, wherein the organic solvent not miscible with water is methyl isobutyl ketone, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, toluene or mixtures thereof.
21. The process according to the Claim 19, wherein the crude alkaloid mixture is further purified by a chromatography on alumina using an organic solvent not miscible with water as the mobile phase, obtaining thus a purified galanthamine.
22. The process according to the Claim 21, wherein the organic solvent not miscible with water is methyl isobutyl ketone, propyl acetate, isopropyl acetate, butyl acetate, isobutyl acetate, toluene or mixtures thereof.
23. The process according to the Claims 19 and 21, wherein the same solvent is used for the extraction of alkaloids from the aqueous concentrate and for the chromatographic purification.

24. The process according to the Claims 19 and 21, wherein methyl isobutyl ketone is used both for extraction and chromatography.
25. The process according to the Claim 21, wherein the purified galanthamine is concentrated and crystallized from methyl isobutyl ketone, acetone, or tert-butyl methyl ether, obtaining crystalline galanthamine.
26. The process according to the Claim 21, wherein the purified galanthamine is concentrated, the residue is dissolved in ethanol and one equivalent of hydrochloric acid is added to facilitate galanthamine hydrochloride crystallization.
27. The process according to the Claim 25, wherein the crystalline galanthamine is further purified by re-crystallization from methyl isobutyl ketone, tert-butyl methyl ether or mixtures thereof.
28. The process according to the Claim 26, wherein the galanthamine hydrochloride is transferred to the base and the base is further purified by crystallization from methyl isobutyl ketone, tert-butyl methyl ether or mixtures thereof.
29. The process according to the claim 26, wherein the crystalline galanthamine hydrochloride containing more than 0.5 % (w/w) of narwedine is purified by dissolving in a suitable solvent and adding a reducing agent capable of reducing the carbonyl group of narwedine to the alcoholic group.
30. The process according to the Claim 29, wherein the suitable solvent is water.
31. The process according to the Claim 29, wherein the reducing agent is sodium borohydride.
32. The process according to the Claim 29, wherein not more than 0.1 mol of sodium borohydride is used for 1 mol of galanthamine containing more than 0.5 % (w/w) narwedine.
33. The process according to the Claims 27 and 28, wherein the purity of the crystalline galanthamine obtained is more than 99 %.
34. The process according to the Claims 27 and 28, wherein the crystalline galanthamine is used for preparation of galanthamine hydrobromide.
35. A process for isolation of galanthamine from galanthamine containing biomaterial comprising :
a) extraction of the biomaterial with aqueous solution of suitable organic or
inorganic acid obtaining thus a primary extract b) adsorption of the organic compounds from the primary extract on an
absorbent,
c) elution of the organic compounds from the adsorbent to obtain a concentrate
of alkaloids.
36. The process according to the Claim 35 characterized in that the obtained galanthamine is recrystallized from a suitable medium.
37. The process according to Claim 35 wherein galanthamine obtained is used in pharmaceutical dosage forms.