IP Library › Granted Patent US 10,307,390
Granted Patent B2
US 10,307,390 · App. 15/392,370 · Granted Jun 4, 2019

Method of synthesising sulforaphane

Inventors: Sahadeva Reddy Damireddi (Brevard, NC); Kpakpo Ambroise Akue (Asheville, NC); Jared K Nelson (Pisgah Forest, NC); Albert Roger Frisbee (Hendersonville, NC); Peter Wyatt Newsome (Horseshoe, NC)
Assignee: Pharmagra Labs, Inc.
A61K31/26A61K31/724A61K47/6951B82Y5/00C07C315/02C07C331/20C08B37/0015C08L5/16
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Quick Facts
Patent No.
US 10,307,390
App. No.
15/392,370
Granted
Jun 4, 2019
Kind
B2
Abstract

The present invention relates to a method of synthesizing sulforaphane by reacting a compound of formula (A) with an oxidizing agent in an aqueous solvent and in the presence of a catalyst. The invention further provides a method of synthesizing a stabilized complex of sulforaphane and cyclodextrin by mixing the sulforaphane prepared by the methodology defined herein with cyclodextrin in an aqueous solvent.

Claims (25)

1. A process for the preparation of a complex of sulforaphane and cyclodextrin, the process comprising:

(i) reacting, in an aqueous solvent, a compound of formula A:

 with an oxidizing agent and in the presence of a catalyst to form sulforaphane; and

(ii) mixing the sulforaphane from step (i) with cyclodextrin in an aqueous solvent to form a precipitate of the sulforaphane-cyclodextrin complex,

wherein in step (i) 1 to 2 molar equivalents of oxidizing agent, relative to the compound of formula A, is used.

2. A process according to claim 1 , wherein the solvent in step (i) and step (ii) is water.

3. A process according to claim 1 or claim 2 , wherein the oxidizing agent is hydrogen peroxide or a water soluble or miscible organic per-acid, or a mixture thereof.

4. A process according to claim 3 , wherein the oxidizing agent is hydrogen peroxide.

5. A process according to claim 1 , wherein the catalyst is selected from cyclodextrin and organic or inorganic acids, such as ascorbic acid, formic acid, acetic acid, and/or sulphuric acid.

6. A process according to claim 5 , wherein the catalyst is a cyclodextrin.

7. A process according to claim 6 , wherein the catalyst is alpha-cyclodextrin.

8. A process according to claim 1 , wherein 0.0001 to 1.0 molar equivalents of catalyst are present, relative to the compound of formula A.

9. A process according to claim 1 , wherein in step (i) the temperature of the reaction is maintained at a temperature of 25° C. or less or 15° C. or less when the oxidising agent is added to the reaction mixture.

10. A process according to claim 1 , wherein the cyclodextrin used in step (ii) is selected from one or more of W6 alpha cyclodextrin, a six sugar ring molecule, W7 beta cyclodextrin, a seven sugar ring molecule, W8 gamma cyclodextrin, an eight sugar ring molecule, derivatives thereof, and mixtures thereof.

11. A process according to claim 10 , wherein the cyclodextrin used in step (ii) is alpha-cyclodextrin.

12. A process according to claim 11 , wherein the mixture is cooled to a temperature within the range of about −8° C. to about 10° C.

13. A process according to claim 11 , wherein the mixture is cooled to a temperature within the range of about −5° C. to about 4° C.

14. A process according to claim 11 , wherein the molar ratio of sulforaphane to cyclodextrin in the resultant complex is within the range of 0.4:1 to 1:1.

15. A process according to claim 1 , wherein the process comprises a further step of recrystallizing the resulting complex.

16. A sulforaphane-cyclodextrin complex obtainable by a process as defined in claim 1 , wherein the cyclodextrin used in step (ii) is alpha-cyclodextrin and wherein the sulforaphane and alpha-cyclodextrin are present in the complex in a molar ratio of 0.98:1 to 1:1, and wherein the complex has a purity by HPLC greater than 98%.

17. A method of treating and/or preventing microbial infections and/or cancer, the method comprising administering to an individual in need of such treatment a therapeutically effective amount of a sulforaphane-cyclodextrin complex according to claim 16 .

18. A pharmaceutical composition comprising a sulforaphane-cyclodextrin complex according to claim 16 and one or more additional pharmaceutical excipients.

19. A process according to claim 1 , wherein in step (i) 1 to 1.5 molar equivalents of oxidizing agent, relative to the compound of formula A, is used.

20. A process according to claim 1 , wherein in step (i) 1 to 1.1 molar equivalents of oxidizing agent, relative to the compound of formula A, is used.

21. A sulforaphane-cyclodextrin complex according to claim 16 , wherein the purity by HPLC is greater than 98.5%.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 31, 2017
From: DAMIREDDI, SAHADEVA REDDY; AKUE, KPAKPO AMBROISE; NELSON, JARED K; FRISBEE, ALBERT ROGER; NEWSOME, PETER WYATT
To: PHARMAGRA LABS, INC.
Reel/Frame 042537/0357 →
Continuity (3)
Continuation 14404773
Provisional Application 61654277 · Jun 1, 2012
Related Publication 20170112796A1 · Apr 27, 2017
Cited By (1)
US 12,558,384