IP Library Granted Patent US 8,609,844
Granted Patent B2
US 8,609,844 · App. 12/939,660 · Granted Dec 17, 2013

Method for extracting and purifying bisbenzylisoquinolines

Inventor: Ron D. Carroll (Fayetteville, NY)
Assignee: CBA Pharma, Inc.
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Quick Facts
Patent No.
US 8,609,844
App. No.
12/939,660
Granted
Dec 17, 2013
Kind
B2
Abstract

A method for purifying extracted crude d-tetrandrine by dissolving the crude d-tetrandrine powder in ethanol, treating the solution with a decolorizing agent, filtering, reducing the filtered solution under heat and vacuum, cooling the solution, filtering it and drying the filtered cake to yield substantially pure d-tetrandrine.

Claims (11)

1. A method for purifying extracted crude d-tetrandrine comprising dissolving the crude d-tetrandrine powder in ethanol, treating the solution with a decolorizing agent, filtering, reducing the filtered solution under heat and vacuum, cooling the solution, filtering it and drying the filtered cake to yield substantially pure d-tetrandrine.

2. The method of claim 1 wherein the crude d-tetrandrine powder is dissolved in the ethanol with stirring and slowly increased heat to about 60° C.; the decolorizing agent being stirred into the resulting mixture and filtered while the solution is still at about 60° C. to remove the decolorizing agent.

3. The method of claim 2 in which the filtered solution with decolorizing agent removed is heated under vacuum at about 50-60° C. to reduce the volume of the ethanol solution by from about four-fifths to about five-sixths; breaking the vacuum and slowly cooling the solution with stirring to about 0 to about 10° C. to form a solid; granulating the cold slurry for about one to two hours, and then vacuum filtering and washing the filtered cake with ice cold ethanol; and drying the resulting powder.

4. The method of claim 1 in which the crude d-tetrandrine is obtained by extracting bisbenzylisoquinolines from Stephania Tetrandra S. Moore tuber; separating crude d-tetrandrine from other bisbenzylisoquinolines including fangchinoline, by stirring the extract vigorously in benzene or toluene, allowing the mixture to settle and decanting the top benzene layer into a holding tank; polish filtering the benzene or toluene liquid and concentrating it under vacuum at about 60° C. to a thick oil, which is then dried under vacuum at about 60-80° C. to a solid; and grinding the resulting solid to a powder.

5. The method of claim 4 in which the benzene step is repeated several times on each settled solid following decanting of the benzene layer.

6. The method of claim 4 in which said extraction step is conducted on the dried powder from ground or macerated Stephania Tetrandra S. Moore tuber using methanol or ethanol in a vessel heated to about 50° C., with vigorous stirring; filtering the resulting slurry, collecting the resulting methanol or ethanol solution, concentrating it using heat and vacuum to a thick oil; drying the oil in a vacuum and grinding the resulting solid to a powder.

7. The method of claim 6 in which methanol is used for the extraction from Stephania Tetrandra S. Moore tuber.

8. The method of claim 7 in which ethanol is used for the extraction from Stephania Tetrandra S. Moore tuber.

9. The method of claim 6 in which the methanol or ethanol extracted powder is dissolved in water, and concentrated acid is added, with cooling, until the pH of the aqueous solution reaches about one or less; the resulting slurry is filtered, and the acidic aqueous solution is cooled and stirred to maintain a temperature of about 25° C.; sodium hydroxide is then added until the pH reaches 11-12 and a thick slurry is formed; the slurry is stirred for about one hour at about 25° C., vacuum filtered, and the filtered cake washed with water and dried at about 60-80° C. under a vacuum.

10. The method of claim 4 in which the crude d-tetrandrine is dissolved in acetone or a mixture of acetone and ethyl acetate in an acetone:ethyl acetate ratio range of from about 10:1 to about 5:1; polished filtering the solution and concentrating it to about one-fourth its volume; granulating the resulting solid, collecting it on a filter, washing it and drying it.

11. The method of claim 1 in which the crude d-tetrandrine is dissolved in acetone or a mixture of acetone and ethyl acetate in an acetone:ethyl acetate ratio range of from about 10:1 to about 5:1; polished filtering the solution and concentrating it to about one-fourth its volume; granulating the resulting solid, collecting it on a filter, washing it and drying it.

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 21, 2015
From: VOT FUNDING LLC, A DELAWARE LIMITED LIABILITY COMPANY ("VOT'')
To: VISIONCARE, INC.
Reel/Frame 036846/0545 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 9, 2015
From: VISIONCARE OPHTHALMIC TECHNOLOGIES, INC., ("VISIONCARE US") AND VISIONCARE OPHTHALMIC TECHNOLOGIES LTD. (VISIONCARE ISRAEL)
To: VOT FUNDING LLC, A DELAWARE LIMITED LIABILITY COMPANY ("VOT'')
Reel/Frame 036765/0392 →
PATENT SECURITY AGREEMENT Recorded Sep 18, 2013
From: VISIONCARE OPHTHALMIC TECHNOLOGIES, INC.
To: LIFE SCIENCES ALTERNATIVE FUNDING LLC
Reel/Frame 031239/0756 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 21, 2012
From: CBA INTERNATIONAL, INC. I
To: CBA PHARMA, INC.
Reel/Frame 028238/0871 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 21, 2010
From: CARROLL, RON D.
To: CBA INTERNATIONAL, INC.
Reel/Frame 025539/0067 →
Continuity (3)
Provisional Application 61258421 · Nov 5, 2009
Related Publication 20110105755A1 · May 5, 2011
Related Publication 20130231483A2 · Sep 5, 2013