# US 10,864,186 B2 · Method of synthesising sulforaphane

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,864,186 B2
- Document ID: US10864186B2
- Status: Granted
- Kind: B2
- Application number: 16/429,726
- Filed: 2019-06-03
- Published: 2019-09-19
- Granted: 2020-12-15
- Earliest claimed: 2012-06-01
- Assignees: PharmAgra Labs, Inc.
- Applicants: PharmAgra Labs, Inc.
- Inventors: Sahadeva Reddy Damireddi; Kpakpo Ambrioise Akue; Jared K. Nelson; Albert Roger Frisbee; Peter Wyatt Newsome
- Web page: https://patentgrep.com/patent/US10864186B2

## CPC

- A61K 31/26: Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters
- A61K 31/724: Cyclodextrins
- A61K 47/6951: {using cyclodextrin (cyclodextrins used as simple excipients A61K47/40)}
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 35/00: Antineoplastic agents
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- C07C 315/02: by formation of sulfone or sulfoxide groups by oxidation of sulfides, or by formation of sulfone groups by oxidation of sulfoxides
- C07C 331/20: of a saturated carbon skeleton
- C08B 37/0015: {Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes}
- C08L 5/16: Cyclodextrin; Derivatives thereof
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C08B: POLYSACCHARIDES; DERIVATIVES THEREOF (polysaccharides containing less than six saccharide radicals attached to each other by glycosidic linkages C07H; fermentation or enzyme-using processes C12P19/00; sugar industry C13; production of cellulose D21)
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)

## Abstract

The present invention relates to a method of synthesising 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 synthesising a stabilised complex of sulforaphane and cyclodextrin by mixing the sulforaphane prepared by the methodology defined herein with cyclodextrin in an aqueous solvent.

## Claims

### Claim 1

A complex of sulforaphane and alpha-cyclodextrin, which has a molar ratio of sulforaphane to alpha-cyclodextrin within the range 0.95:1 to 1:1, and wherein the complex has a purity as determined by HPLC of greater than 98%.

### Claim 2 (depends on 1)

The complex of claim 1, wherein the molar ratio of sulforaphane to alpha-cyclodextrin is within the range 0.98:1 to 1:1.

### Claim 3 (depends on 1)

The complex of claim 1, which has a purity as determined by HPLC of greater than 98.5%.

### Claim 4 (depends on 1)

A process for the preparation of the complex of claim 1, comprising:
(i) reacting, in water, a compound of formula A:
with hydrogen peroxide in the presence of a catalyst to form sulforaphane; and
(ii) mixing the sulforaphane from step (i) with alpha-cyclodextrin in water to form a precipitate of the complex.

### Claim 5 (depends on 4)

The process of claim 4, wherein the catalyst is alpha-cyclodextrin.

### Claim 6 (depends on 4)

The process of claim 4, wherein 0.005 to 0.05 molar equivalents of the catalyst are used relative to the compound of formula A in step (i).

### Claim 7 (depends on 4)

The process of claim 4, wherein 1 to 2 molar equivalents of hydrogen peroxide relative to the compound of formula A is used in step (i).

### Claim 8 (depends on 4)

The process of claim 4, wherein about 1 molar equivalent of alpha-cyclodextrin relative to the compound of formula A is used in step (ii).

### Claim 9 (depends on 4)

The process of claim 4, wherein the compound of formula A has a purity as determined by HPLC of at least 98%.

### Claim 10 (depends on 4)

The process of claim 4, wherein the mixture in step (ii) is cooled to a temperature from about −5° C. to about 2° C. for a time period of about 0.5 hour to about 4 hours.

### Claim 11 (depends on 10)

The process of claim 10, further comprising isolating the precipitated complex by filtration.

### Claim 12 (depends on 1)

The complex of claim 1, wherein the molar ratio of sulforaphane to alpha-cyclodextrin is within the range 0.98:1 to 1:1 and the purity as determined by HPLC is greater than 98.5%.

### Claim 13 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of the complex of claim 1, and one or more pharmaceutical excipients.

### Claim 14 (depends on 13)

The pharmaceutical composition of claim 13, which is suitable for oral administration.

### Claim 15 (depends on 14)

The pharmaceutical composition of claim 14, which is a tablet or a capsule.