IP Library Granted Patent US 6,956,123
Granted Patent B2
US 6,956,123 · App. 10/664,539 · Granted Oct 18, 2005

Purification of taxanes and taxane mixtures using polyethyleneimine-bonded resins

Assignee: Natural Pharmaccuticals, Inc.
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Quick Facts
Patent No.
US 6,956,123
App. No.
10/664,539
Granted
Oct 18, 2005
Kind
B2
Abstract

This invention is directed to a method for isolating and/or purifying one or more taxanes from materials comprising taxanes. In one embodiment, the method comprises the steps of: (a) treating a taxane containing material with an amino containing material attached to a solid matrix, such as a polyethyleneimine-bonded silica chromatographic resin; (b) eluting the desired taxane compound from the resin; and (c) recovering the eluted taxane compound.

Claims (73)

1. A method of isolating one or more taxanes from a taxane containing mixture, the method comprising the steps of:

(a) loading or injecting the mixture on a column comprising a PBS resin; wherein the one or more taxanes are derived from one or more Taxus plants, wherein the one or more taxanes are not derived solely from Taxus brevifolia;

(b) eluting the one or more taxanes from the PBS resin with an eluant; and

(c) recovering the eluted one or more taxanes.

2. A method of isolating one or more taxanes from a taxane containing mixture, the method comprising the steps of:

(a) loading or injecting the mixture on a column comprising a PBS resin; wherein the mixture comprises less than 25% or greater than 40% by weight of primary taxanes;

(b) eluting the one or more taxanes from the PBS resin; and

(c) recovering the eluted one or more taxanes.

3. A method of isolating one or more taxanes, the method comprising the steps of:

(a) loading or injecting a taxane containing mixture on a column comprising a PBS resin; wherein the mixture comprises from about 25% to 40% by weight of primary taxanes; wherein the one or more taxanes are not derived solely from Taxus brevifolia;

(b) eluting the one or more taxanes from the PBS resin; and

(c) recovering the eluted one or more taxanes.

4. A method of isolating one or more taxanes from material comprising taxane compounds obtained from a semi-synthesis or total synthesis process, the method comprising the steps of:

(a) loading or injecting the material on a column comprising a PBS resin; wherein molecules used as reactants in the semi-synthetic or total synthetic process are not derived solely from Taxus brevifolia;

(b) eluting the one or more taxanes from the PBS resin; and

(c) recovering the eluted one or more taxanes.

5. A method of isolating one or more taxanes from material comprising taxane compounds obtained from a semi-synthesis or total synthesis process:

(a) loading or injecting the material on a column comprising a PBS resin; wherein the material comprises less than about 8% by weight of C-2′ benzoates of taxol A, B, C, D, E, F or G, combined;

(b) eluting the one or more taxanes; and

(c) recovering the eluted one or more taxanes.

6. A method of isolating one or more taxanes from material comprising taxane compounds obtained from a semi-synthesis or total synthesis process:

(a) loading or injecting the material on a column comprising a PBS resin; wherein the material comprises less than 1.0% by weight of C-2′ benzoates of taxol B, C, D, E, F, or G, combined;

(b) eluting the one or more taxanes; and

(c) recovering the eluted one or more taxanes.

7. A method of isolating taxol A from a naturally derived taxane containing mixture, said method comprising the steps of:

(a) loading or injecting the taxane mixture on a column comprising a PBS resin;

(b) eluting the taxol A from the PBS resin; and

(c) recovering the eluted taxol A.

8. A method of purifying one or more taxanes from a biomass extract, said method comprising the step of:

(a) preparing the biomass extract by means other than chromatography;

(b) loading or injecting the biomass extract on a column comprising a PBS resin;

(c) eluting the one or more taxanes from the PBS resin; and

(d) recovering the eluted one or more taxanes.

9. The method of any of claims 1 - 3 , wherein the taxane containing material comprises a biomass extract derived from Taxus media cultivars.

10. The method of any of claims 1 - 3 , wherein the taxane containing material comprises a biomass extract derived from Taxus media ‘Hicksii’.

11. The method of any of claims 1 - 3 , wherein the taxane containing material comprises a biomass extract derived from Taxus media ‘Dark Green Spreader’.

12. The method of any of claims 1 - 3 , wherein the taxane containing material comprises a biomass extract derived from Taxus baccata.

13. The method of any of claims 1 - 3 , wherein the taxane containing material comprises a biomass extract derived from Taxus cuspidata.

14. The method of any of claims 1 - 3 , wherein the taxane containing material comprises a biomass extract derived from Taxus floridana.

15. The method of any of claims 1 - 3 , wherein the taxane containing material comprises a biomass extract derived from Taxus canadensis.

16. The method of any of claims 1 - 3 , wherein the taxane containing material comprises a biomass extract derived from Taxus wallichiana.

17. The method of any of claims 1 - 3 , wherein the taxane containing material comprises a biomass extract derived from Taxus yunnanensis.

18. The method of any of claims 1 - 3 , wherein the taxane containing material comprises a biomass extract derived from Taxus chinensis.

19. The method of any of claims 1 - 3 , wherein the taxane containing material comprises a biomass extract derived from Taxus media ‘Densiformis’.

20. The method of any of claims 1 - 3 , wherein the taxane containing material comprises a biomass extract derived from Taxus media ‘Brownii’.

21. The method of any of claims 1 - 3 , wherein the taxane containing material comprises a biomass extract derived from Taxus media ‘Hicksii’.

22. The method of any of claims 1 - 3 , wherein the taxane containing material comprises a biomass extract derived from Taxus media ‘Runyan’.

23. The method of any of claims 1 - 3 , wherein the taxane containing material comprises a biomass extract derived from Taxus media ‘Wardii’.

24. The method of any of claims 1 - 3 , wherein the taxane containing material comprises a biomass extract derived from Taxus media ‘Tautonii’.

25. The method of any of claims 4 - 6 , wherein the taxane is taxol A.

26. The method of any of claims 4 - 6 , wherein the taxane is taxol B.

27. The method of any of claims 4 - 6 , wherein the taxane is taxol C.

28. The method of any of claims 4 - 6 , wherein the taxane taxol D.

29. The method of any of claims 4 - 6 , wherein the taxane taxol E.

30. The method of any of claims 4 - 6 , wherein the taxane taxol f.

31. The method of any of claims 4 - 6 , wherein the taxane is taxol G.

32. The method of any of claims 4 - 6 , wherein the taxane is docetaxel.

33. The method of any of claims 1 - 8 , wherein the PBS resin has an average pore size ranging from about 60 to about 300 Angstrom Units.

34. The method of any of claims 1 - 8 , wherein the PBS has an average pore size ranging from about 100 to about 200 Angstrom Units.

35. The method of any of claims 1 - 8 , wherein the PBS has an average pore size from about 120 Angstrom Units .

36. The method of any of claims 1 - 8 , wherein the PBS has an average particle size ranging from about 0.25 to about 500 microns.

37. The method of any of claims 1 - 8 , wherein the PBS resin has an average particle size ranging from to 100 microns.

38. The method of any of claims 1 - 8 , wherein the PBS has an average particle size ranging from about 10 to about 120 microns.

39. The method of any of claims 1 - 8 , wherein the PBS has an average particle size of about 20 to about 60 microns.

40. The method of any of claims 1 - 8 , wherein the PBS has an average particle size of about 40 microns.

41. The method of any of claims 1 - 8 , wherein the PBS resin is DEAM.

42. The method of any of claims 1 - 8 , wherein the PBS resin is PEI.

43. The method of any of claims 1 - 8 , wherein the PBS resin has an average pore size ranging from about 60 to about 800 Angstrom Units.

44. The method of any of claims 1 - 8 , wherein the PBS resin has a primary or secondary amino group on the polyethyleneimine moiety.

45. The method of any of claims 1 - 8 , wherein the amino groups of the PEI polymer are functionalized.

46. The method of any of claims 4 - 6 , wherein the eluted one or more taxanes have a purity of at least about 70%.

47. The method of any of claims 4 - 6 , wherein the eluted one or more taxanes have a purity of at least about 80%.

48. The method of any of claims 4 - 6 , wherein the eluted one or more taxanes have a purity of at least about 90%.

Assignments (6)
CHANGE OF NAME Recorded Jan 14, 2010
From: PHYTON, INC.
To: PHYTON HOLDINGS, LLC
Reel/Frame 023786/0389 →
CHANGE OF NAME Recorded Jan 14, 2010
From: PHYTON, INC.
To: PHYTON HOLDINGS, LLC
Reel/Frame 023786/0690 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 13, 2010
From: NATURAL PHARMA CANADA, ULC; NATURAL PHARMACEUTICALS, INC.
To: PHYTON, INC.
Reel/Frame 023768/0757 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 12, 2010
From: NATURAL PHARMA CANADA, ULC; NATURAL PHARMACEUTICALS, INC.
To: PHYTON, INC.
Reel/Frame 023768/0626 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 7, 2010
From: NATURAL PHARMA CANADA, ULC; NATURAL PHARMACEUTICALS, INC.
To: PHYTON, INC.
Reel/Frame 023741/0771 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 18, 2003
From: JOHNSON, JAMES H.; SAMBANDAM, T.G.; HAND BARRY J.; HOWE, CHRISTOPHER D.; FRANKE, ROLAND R.; BUCHER, BRIAN A.; JUCHUM, JOHN S.; GALLAGHER, REX T.; PLANTE, MARC A.; DE SIMONE III., EDWARD M.; YANG, DONG S.
To: NATURAL PHARMACEUTICALS, INC.
Reel/Frame 014551/0671 →
Continuity (3)
Provisional Application 6045537700 · Mar 17, 2003
Provisional Application 6045647800 · Mar 21, 2003
Related Publication 20040186305A1 · Sep 23, 2004