# US 2021/0331997 A1 · Method for separating trans isomeric crocetin from cis isomeric crocetin > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0331997 A1 - Document ID: US20210331997A1 - Status: Published application - Kind: A1 - Application number: 17/273,314 - Filed: 2019-09-05 - Published: 2021-10-28 - Earliest claimed: 2018-09-05 - Assignees: Huanwen RAO - Inventors: Huanwen RAO - Web page: https://patentgrep.com/patent/US20210331997A1 ## CPC - C07C 51/02: from salts of carboxylic acids - C07C 51/43: by change of the physical state, e.g. crystallisation - C07C 51/412: {by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part} - C07C 51/50: Use of additives, e.g. for stabilisation - C07B 63/04: Use of additives {(anti-oxidant compositions or compositions inhibiting chemical change in general C09K15/00)} - C07B 2200/09: Geometrical isomers - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS - C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F) ## Abstract A method for separating trans isomer crocetin from cis isomer crocetin is provided. The method comprises crystallizing all-trans crocetin with calcium ions first by using different binding capabilities between cis and trans isomeric crocetin to calcium ions and acidifying the all-trans crocetin to obtain 13-cis crocetin. ## Claims ### Claim 1 A method for separating trans isomeric crocetin from cis isomeric crocetin, comprising: crystallizing all-trans crocetin with calcium ions first by using different binding capabilities between cis and trans isomeric crocetin to calcium ions and, obtaining 13-cis crocetin via acidification. ### Claim 2 (depends on 1) The method for separating trans isomeric crocetin from cis isomeric crocetin according to claim 1, wherein the calcium ions in this method are derived from a soluble calcium salt solution, such as calcium acetate, calcium chloride, and calcium citrate, and a mass concentration thereof is 1% to 20%. ### Claim 3 (depends on 1) The method for separating trans isomeric crocetin from cis isomeric crocetin according to claim 1, wherein the method includes the following steps: (1) placing crude crocetin and water in a beaker, adjusting pH to 7-14 with alkali, heating to dissolve the crude crocetin, filtering out insoluble matters while hot; (2) slowly dripping calcium ions into a filtrate for crocetin calcium salt to be precipitated, keeping precipitated crocetin calcium salt warm to allow for full crystallization; (3) filtering the filtrate; (4) washing filter residues with ethanol, acidifying the filter residues with acid, keeping the filter residues warm, filtering the filter residues, washing the filter residues with pure water, vacuum drying the filter residues to obtain all-trans crocetin; and (5) adding acid to the filtrate of (3) for acidification, keeping the filtrate warm, filtering the filtrate, washing the filter residues with pure water, vacuum drying the filter residues to obtain cis-crocetin. ### Claim 4 (depends on 3) The method for separating trans isomeric crocetin from cis isomeric crocetin according to claim 3, wherein the method further includes the following steps: (1) placing 5 g to 50 g of crude crocetin and 500 ml to 5,000 ml of water in a beaker, adjusting pH to 8-14 with alkali, heating to dissolve the crude crocetin, filtering out insoluble matters while hot; (2) slowly dripping calcium ions into a filtrate for crocetin calcium salt to be precipitated, keeping precipitated crocetin calcium salt warm to allow for full crystallization; (3) filtering the filtrate; (4) washing filter residues with ethanol of 50% or greater first, adjusting pH to 3-6 with acid, keeping the filter residues warm, filtering the filter residues, washing the filter residues with pure water, vacuum drying the filter residues to obtain a brick red solid, that is, the all-trans crocetin; and (5) adding acid to the filtrate of (3), adjusting pH to 2-5, keeping the filtrate warm to allow the filtrate to be fully precipitated (crystallized), filtering the filtrate, washing the filter residues with pure water, vacuum drying the filter residues to obtain a dark red solid, that is, the 13-cis crocetin. ### Claim 5 (depends on 4) The method for separating trans isomeric crocetin from cis isomeric crocetin according to claim 4, wherein the method specifically includes the following steps: (1) placing 10 g of crude crocetin and 700 mL of pure water in a beaker, adjusting pH to 11 with alkali, heating to dissolve the crude crocetin, filtering out insoluble matters while hot; (2) slowly dripping 5 ml of a 5% calcium chloride solution into a filtrate for crocetin calcium salt to be precipitated, keeping precipitated crocetin calcium salt warm to allow for full crystallization; (3) filtering the filtrate; (4) washing filter residues twice with ethanol of 50%, dispersing the filter residues with 50 mL of pure water, adjusting pH to 4-5 with citric acid, keeping the filter residues at 60° C. for 2 hours, filtering the filter residues, washing the filter residues with pure water, vacuum drying the filter residues to obtain high-purity all-trans crocetin; and (5) acidifying the filtrate of (3) with citric acid until pH becomes 4-5, keeping the filtrate warm to age floc, filtering the filtrate, washing the filter residues with pure water, vacuum drying the filter residues to obtain cis-crocetin. ### Claim 6 (depends on 4) The method for separating trans isomeric crocetin from cis isomeric crocetin according to claim 4, wherein the method further includes the following steps: (1) placing 20 g of crude crocetin and 1,500 mL of pure water in a beaker, adjusting pH to 11 with alkali, heating to dissolve the crude crocetin, filtering out insoluble matters while hot, collecting a filtrate; (2) slowly dripping 10 ml of 5% calcium chloride into the filtrate, keeping the filtrate at 60° C. for 4 hours; (3) filtering the filtrate; (4) washing filter residues twice with ethanol of 50% first, dispersing the filter residues with 200 mL of pure water, adjusting pH to 4-5 with acid, keeping the filter residues at 60° C. for 2 hours, filtering the filter residues, washing the filter residues with pure water, vacuum drying the filter residues to obtain high-purity all-trans crocetin; and (5) adding acid to the filtrate of (3) until pH becomes 4-5, keeping the filtrate warm for 2 hours, filtering the filtrate, washing the filter residues with pure water, vacuum drying the filter residues to obtain 13-cis crocetin. ### Claim 7 (depends on 3) The method for separating trans isomeric crocetin from cis isomeric crocetin according to claim 3, wherein the alkali used is a soluble alkali solution, such as sodium hydroxide and potassium hydroxide, and the acid used is an acid that does not form a precipitate with calcium ions, such as hydrochloric acid and citric acid. ### Claim 8 (depends on 4) The method for separating trans isomeric crocetin from cis isomeric crocetin according to claim 4, wherein the alkali used is a soluble alkali solution, such as sodium hydroxide and potassium hydroxide, and the acid used is an acid that does not form a precipitate with calcium ions, such as hydrochloric acid and citric acid. ### Claim 9 (depends on 2) The method for separating trans isomeric crocetin from cis isomeric crocetin according to claim 2, wherein the method includes the following steps: (1) placing crude crocetin and water in a beaker, adjusting pH to 7-14 with alkali, heating to dissolve the crude crocetin, filtering out insoluble matters while hot; (2) slowly dripping calcium ions into a filtrate for crocetin calcium salt to be precipitated, keeping precipitated crocetin calcium salt warm to allow for full crystallization; (3) filtering the filtrate; (4) washing filter residues with ethanol, acidifying the filter residues with acid, keeping the filter residues warm, filtering the filter residues, washing the filter residues with pure water, vacuum drying the filter residues to obtain all-trans crocetin; and (5) adding acid to the filtrate of (3) for acidification, keeping the filtrate warm, filtering the filtrate, washing the filter residues with pure water, vacuum drying the filter residues to obtain cis-crocetin. ### Claim 10 (depends on 5) The method for separating trans isomeric crocetin from cis isomeric crocetin according to claim 5, wherein the alkali used is a soluble alkali solution, such as sodium hydroxide and potassium hydroxide, and the acid used is an acid that does not form a precipitate with calcium ions, such as hydrochloric acid and citric acid. ### Claim 11 (depends on 6) The method for separating trans isomeric crocetin from cis isomeric crocetin according to claim 6, wherein the alkali used is a soluble alkali solution, such as sodium hydroxide and potassium hydroxide, and the acid used is an acid that does not form a precipitate with calcium ions, such as hydrochloric acid and citric acid.