Claims for Patent: 10,017,712

Summary for Patent: 10,017,712

Title:	Method for producing vitamin E-enriched, especially tocotrienol-enriched, compositions from natural oils
Abstract:	The present disclosure relates generally to a process for manufacturing products enriched in the content of at least one vitamin E component, preferably tocotrienol, using solvent extraction and membrane filtration.
Inventor(s):	Boam; Andrew (Hertfordshire, GB), Bouwhuis; Yuri (Princeton, NJ), Koleva; Velichka Yordanova (Haltern am See, DE), Rocha; Maria Ines Fontes (Sra da Hora, PT), Schwarm; Michael (Alzenau, DE)
Assignee:	Evonik Degussa GmbH (Essen, DE)
Application Number:	15/118,021
Patent Claims:	1. A process, comprising: (a) mixing a fatty acid oil mixture, comprising vitamin E components, with an immiscible organic solvent to form a heterogeneous, two-phase mixture; (b) separating the resulting two-phase mixture to provide a first phase comprising a vitamin E depleted fatty acid oil mixture and a second phase comprising the organic solvent, vitamin E components and optionally at least one impurity; (c) passing the second phase obtained in step (b) across at least one selective membrane, wherein a retentate forms comprising greater than 50% of the desired vitamin E components present in the second phase, and a permeate forms comprising the solvent and any component that is not retained by the membrane; (d) removing the organic solvent from the retentate obtained in step (c) to provide as product 1 a composition enriched in at least one vitamin E component compared to the fatty acid oil mixture, (e) optionally removing the organic solvent from the permeate obtained in step (c) to form as product 3 an impurity composition, and (f) optionally separating the solvent from the first phase obtained in step (b) to obtain as product 2 a fatty acid oil mixture depleted in vitamin E components compared to the raw material; wherein the fatty acid oil mixture comprises triglyceride oils, phospholipid oils, or any combination thereof; and wherein the membrane used in step (c) is characterized by a rejection R.sub.Vit of the target vitamin E components which is greater than the membrane rejection of the at least one impurity species R.sub.imp. 2. The process according to claim 1, characterized in that the process comprises a solvent selection step and a solvent screening step, wherein in the solvent screening step partition coefficients PC for organic solvents or mixtures thereof are determined, optionally for different mixing ratios of organic solvent to fatty acid oil mixture, by a process comprising the following steps: Extracting a sample of a fatty acid oil mixture with an organic solvent or mixture of organic solvents to obtain a bottom fraction and an extract fraction, Measuring the concentration of at least one tocopherol and at least one tocotrienol in the bottom fraction as well as in the extract fraction, and Calculating partition coefficients PCTocotrienol=concentration of a tocotrienol in the extract/concentration of the same tocotrienol in the bottom fraction and PCTocopherol=concentration of a tocopherol in the extract/concentration of the same tocopherol in the bottom fraction, for at least one tocotrienol and at least one tocopherol comprised in the fatty acid oil mixture, and wherein in the solvent selection step an organic solvent is selected for use in step (a) which has a PCTocotrienol that is higher than the PCTocopherol for at least one mixing ratio of organic solvent to fatty acid oil mixture. 3. The process according to claim 2, characterized in that an organic solvent is selected for step (a) having a ratio of the PCTocotrienol to PCTocopherol for at least one mixing ratio of organic solvent to fatty acid oil mixture of from >1 to about 1000. 4. The process according to claim 1, further comprising at least one of the following: wherein the process in step a) comprises a solvent extraction process selected from the group consisting of a counter-current equilibrium stage extraction processes, a crosscurrent equilibrium stage extraction process a co-current equilibrium stage extraction process and a combination of at least two of these processes; wherein step (a) of the process is performed at a pressure of (i) 1-10 atm absolute when organic solvents are used other than liquefied gases or supercritical gases, (ii) 1-80 atm absolute when an organic solvent system containing or consisting of liquefied gases is used, and (iii) 1-400 atm absolute when an organic solvent system containing or consisting of supercritical gases is used; and wherein the process in step (a) is performed at a temperature in the range -20.degree. C. to 200.degree. C. 5. The process according to claim 1, further comprising at least one of the following: wherein the passing of the second phase obtained in step (b) across the at least one selective membrane in step (c) comprises diafiltration, cross-flow filtration, or a combination of diafiltration and cross-flow filtration; wherein process step (c) is performed at a temperature ranging from about -10.degree. C. to about 60.degree. C. and wherein the filtration pressure in step (c) ranges from about 5 bar to about 70 bar. 6. The process according to claim 1, further comprising passing the retentate obtained in step (c) or product 1 obtained after step (d) across at least one second selective membrane to form a second retentate comprising enriched content of vitamin E components, and a second permeate comprising at least one impurity compound, wherein the at least one second selective membrane may be the same as, or different from, the at least one selective membrane. 7. The process according to claim 2, further comprising passing the retentate obtained in step (c) or product 1 obtained after step (d) across at least one second selective membrane to form a second retentate comprising enriched content of vitamin E components, and a second permeate comprising at least one impurity compound, wherein the at least one second selective membrane may be the same as, or different from, the at least one selective membrane. 8. The process according to claim 1, further comprising at least one of the following: treating the vitamin E enriched composition obtained after step (c) or (d) with at least one adsorption process comprising at least one absorbent or adsorbent, at least one solvent extraction process, at least one distillation or evaporation process or at least one chromatography process; recovering any solvent in steps (e) and/or (f) for re-use in step (a); and repeating the individual process steps (a) to (d) for a period of time ranging from about 10 minutes to about twenty hours. 9. The process according to claim 2, further comprising at least one of the following: treating the vitamin E enriched composition obtained after step (c) or (d) with at least one adsorption process comprising at least one absorbent or adsorbent, at least one solvent extraction process, at least one distillation or evaporation process or at least one chromatography process; recovering any solvent in steps (e) and/or (f) for re-use in step (a); and repeating the individual process steps (a) to (d) for a period of time ranging from about 10 minutes to about twenty hours. 10. The process according to claim 1, comprising at least one of the following: wherein the initial fatty acid oil mixture has an acid value in the range 0.2 to 25 mg KOH/g; wherein the initial fatty acid oil mixture comprises greater than 20%, triglycerides and/or phospholipid oils; and wherein the initial fatty acid oil mixture comprises greater than 100 ppm total tocopherols and tocotrienols. 11. The process according to claim 1, comprising at least one of the following: wherein the initial fatty acid oil mixture comprises at least from about 10% to about 30% by weight of omega-3 fatty acids; and wherein the initial fatty acid oil mixture comprises vegetable oil, oil derived from marine sources, oil derived from algae, oil derived from microbes, animal fat, or animal oil. 12. The process according to claim 1, comprising at least one of the following: wherein the at least one impurity is selected from the group consisting of free cholesterol, esterified cholesterol, sterols, esterified sterols, phenolic compounds, free fatty acids, monoglycerides, oxidation products, components that create unwanted smell or taste in the fatty acid oil mixture, vitamin A, vitamin D, astaxanthin, canthaxanthin, and other carotenoids; and wherein the at least one impurity is an environmental pollutant from the group consisting of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), agrochemicals, chlorinated pesticides, polycyclic aromatic hydrocarbons (PAHs), hexachlorocyclohexanes (HCH), dichlorodiphenyltrichloroethane (DDT), dioxins, furans, and nonortho-PCBs. 13. The process according to claim 1, wherein the organic solvent comprises aliphatic hydrocarbons, aromatic hydrocarbons, ketones, esters, alcohols, liquefied gases, supercritical gases or mixtures thereof. 14. The process according to claim 1, wherein the at least one selective membrane comprises a material selected from the group consisting of polyethylene, polypropylene, polytetrafluoroethylene (PTFE), polyvinylidene difluoride (PVDF), polysulfone, polyethersulfone, polyacrylonitrile, polyamide, polyimide, polyamideimide, polyetherimide, cellulose acetate, polyaniline, polypyrrole, polyetheretherketone (PEEK), polybenzimidazole, and mixtures thereof. 15. The process according to claim 12, comprising at least one of the following: wherein the at least one selective membrane has a molecular weight cut-off ranging from about 150 g/mol to about 1,500 g/mol wherein the at least one selective membrane has a contact angle for water of more than 70.degree. at 25.degree. C.; and wherein the selective membrane is a polyimide membranes. 16. The process according to claim 1, wherein the permeate in step (c) comprises at least one of free cholesterol, esterified cholesterol, sterols, esterified sterols, phenolic compounds, oxidation products, components that create unwanted smell or taste in the oil mixture, vitamin A, vitamin D, astaxanthin, canthaxanthin, or other carotenoids with an increased concentration compared to the fatty acid oil mixture. 17. The process according to claim 1, further comprising purifying the vitamin E enriched composition obtained after step (c) or (d) using a method selected from the group consisting of HPLC, supercritical fluid chromatography, distillation, molecular distillation, short path evaporation, thin film evaporation, extraction, absorption, crystallisation and any combination thereof. 18. The process according to claim 1, wherein said vitamin E component is tocotrienol. 19. The process according to claim 3, wherein the ratio of the PCTocotrienol to PCTocopherol is from 2 to 50. 20. The process according to claim 4, wherein the process in step (a) is performed at a temperature in the range 20.degree. C. to 100.degree. C. 21. The process according to claim 5, comprising cross-flow filtration in step (c) with a linear velocity ranging from about 0.1 m/s to about 5 m/s. 22. The process according to claim 10, wherein the initial fatty acid oil mixture comprises greater than 60% triglycerides. 23. The process according to claim 10, wherein the initial fatty acid oil mixture comprises greater than 750 ppm total tocopherols and tocotrienols. 24. The process according to claim 10, wherein the initial fatty acid oil mixture comprises vegetable oil selected from the group consisting of palm oil, soybean oil, rapeseed oil, sunflower oil, peanut oil, cottonseed oil, palm kernel oil, coconut oil, olive oil, corn oil, grape seed oil, hazelnut oil, linseed oil, rice bran oil, safflower oil, sesame oil, almond oil, pecan oil, pistachio oil, walnut oil, castor oil, jojoba oil, shea oil and annatto oil. 25. The process according to claim 13, wherein the organic solvent is selected from the group consisting of primary alcohols and solvent mixtures containing said alcohols. 26. The process according to claim 15, comprising at least one of the following: wherein the at least one selective membrane has a molecular weight cut-off ranging from about 300 g/mol to about 600 g/mol; wherein the at least one selective membrane has a contact angle for water of more than 95.degree. at 25.degree. C.; and wherein the selective membrane is made of P84, whose CAS registry number is 9046-51-9, or P84HT whose CAS registry number is 134119-41-8, or mixtures thereof, which is optionally crosslinked, organic coated, or crosslinked and organic coated. 27. The process according to claim 26, wherein the selective membrane is coated with silicone acrylates as coating agents.

Details for Patent 10,017,712

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Aimmune Therapeutics, Inc.	PALFORZIA	peanut (arachis hypogaea) allergen powder	Powder	125696	01/31/2020		2034-02-11