Method for purifying phytosterol

Abstract

A method for purifying phytosterols, said method comprising at least the following steps: a. providing a liquid mixture comprising phytosterols and a lower alcohol, wherein based on the amount of phytosterols, the lower alcohol is present in an amount of 25 to 800% by weight; b. cooling the mixture to form phytosterol crystals, wherein the phytosterol crystals are formed at a temperature of 10°C to 75°C, preferably 15°C to 50°C, more preferably 20°C to 45°C, even more preferably 25°C to 35°C; c. separating the phytosterol crystals from the remainder of the mixture by filtration; d. washing the phytosterol crystals with a solvent system comprising at least one polar aprotic solvent to obtain purified phytosterol crystals; e. optionally repeating step (d); f. drying the washed phytosterol crystals; g. optionally melting and drying in the molten state to remove trace amounts of remaining solvent; and h. optionally performing a granulation process to obtain solid sterol particles.

Description

Technical Field

[0001] The presently claimed invention relates to phytosterols for use in food additives, and more particularly, to a new and simplified method for purifying phytosterols suitable for use as food additives. Background Art

[0002] Phytosterols and their esters have cholesterol-lowering properties, i.e., these substances are capable of reducing the cholesterol level in the blood. Therefore, they are used as food additives, for example, for the production of margarine, frying oils, sausages, ice cream, etc. The production of sterols and other unsaponifiable components (e.g., tocopherols) from distillates obtained, for example, from the deacidification of vegetable oils has been variously described in the patent literature, see EP-A2 0 610 742 (Hoffmann-LaRoche), GB-A1 2,145,079 (Nisshin Oil Mills Japan) and EP-A1 0 333 472 (Research and Development Board of Palm Oil).

[0003] EP 0 656 894B1 (Henkel) describes a method for producing sterols, in which a distillation residue from methyl esters (consisting essentially of glycerides, sterols, sterol esters and tocopherols) is transesterified with methanol in the presence of a basic catalyst. After neutralizing the catalyst, removing the excess methanol by distillation and optionally removing the catalyst by washing, the sterols are crystallized by reducing the reaction temperature from about 65 °C to 20 °C. The crystals thus obtained are washed with methanol and water. Unfortunately, the yield of sterols is not satisfactory.

[0004] EP 2 635 592B1 (Verbio) discloses a method for obtaining phytosterols and tocopherols by using a multiphase separation system to separate sterols and / or tocopherols.

[0005] EP1179535 B1 and EP1179536 B1 (both: BASF) disclose a method for producing sterols by using two-step transesterification to obtain sterols from vegetable oil distillates. The crystallization of the resulting sterols and washing with methanol and fatty acid methyl esters (FME) are disclosed as subsequent method steps in the dependent claims. Although "methyl ester" is disclosed as the solvent used in the examples in EP1179536 B1, the "methyl ester" actually used in the examples and disclosed in the specification is FME from the transesterification of vegetable oils. EP1179535 B1 discloses the use of "FME" in its examples; it is also disclosed in

[0036] and

[0042] of EP1179535 B1 that the crystals obtained in examples a) and b) are "washed with a suitable solvent". However, which solvents these actually are is not disclosed.

[0006] EP1169335 B1 (BASF) discloses a method for crystallizing sterols from a specific mixture of methanol and fatty acid methyl esters in a specific ratio and washing the resulting crystals. The aim of this disclosure is to provide sterols with a high yield and "good color quality". According to this disclosure, the key lies in the optimal amount and ratio of methanol during the crystallization process and the crystallization temperature, which is said to lead to the required improvement. The obtained crystals are then washed with fatty acid methyl esters, and this step is said to further improve the color quality of the obtained sterol crystals. It is noteworthy that the "methyl ester" disclosed in EP1169335 B1 is clearly "ethyl fatty acid ester" because these two descriptions / terms can be used interchangeably, as can be seen, for example, from

[0008] , where the washing of the crystals is mentioned twice, but the first time "methyl ester" is used, while the second time "fatty acid methyl ester" is used. Therefore, claim 1 in the binding German version correctly uses the term "fatty acid methyl ester" (while claim 1 in the English translation wrongly uses the term "fatty acid ester").

[0007] Several methods have been reported to increase the yield of sterols. However, improving the color of sterols while maintaining other favorable characteristics of the purification process, such as increasing the yield and reducing impurities in the sterol product, remains a challenge. SUMMARY OF THE INVENTION

[0008] Surprisingly, it has been found that the color and purity of plant sterols are significantly affected by the solvents used for purification. Therefore, the choice of solvents for the purification process plays an important role in improving the color of plant sterols and reducing the amount of impurities without affecting the yield of the final product.

[0009] Accordingly, in one aspect, the presently claimed invention relates to a purification process in which the color of the final plant sterol product is significantly improved and the amount of plant sterol esters as impurities is significantly reduced by washing the final plant sterol product with at least one polar aprotic solvent.

[0010] It has also surprisingly been found that the presently claimed invention results in a significant reduction in the solvent content in the final plant sterol product. DETAILED DESCRIPTION

[0011] Although the presently claimed invention will be described with respect to specific embodiments, this description should not be construed as limiting.

[0012] Before describing exemplary embodiments of the presently claimed invention in detail, definitions that are important for understanding the presently claimed invention are given. As used in this specification and the appended claims, unless the context clearly dictates otherwise, the singular forms of "a" and "an" also include their respective plural forms. In the context of the presently claimed invention, the terms "about" and "approximately" denote an interval of accuracy that a person skilled in the art will understand to still ensure the technical effect of the feature being discussed. The terms generally denote a deviation of ±20%, preferably ±15%, more preferably ±10%, and even more preferably ±5% from the indicated value. It should be understood that the term "comprising" is not restrictive. For the purposes of the presently claimed invention, the term "consisting of" is considered a preferred embodiment of the term "including". If a group is defined hereinafter as including at least a certain number of embodiments, this means that a group consisting preferably only of these embodiments is also covered.

[0013] Unless otherwise stated in the application as described above or below, if the terms "first", "second", "third" or "(a)", "(b)", "(c)", "(d)", "i", "ii", etc. relate to steps of a method or use or determination, there is no time or time interval consistency between these steps, i.e., these steps can be carried out simultaneously, or there can be a time interval of seconds, minutes, hours, days, weeks, months or even years between these steps. However, preferably, these steps are carried out in the numerical or hierarchical order implied, i.e., first a, then b, then c, etc., first i), then ii), then iii), etc. It should be understood that the present invention is not intended to be limited to the specific methods, protocols, reagents, etc. described herein, as these can vary, provided that the intent and purpose of the present invention are or can be achieved by these. It should also be understood that the terms used herein are for the purpose of describing particular embodiments only and are not intended to limit the scope of the presently claimed invention, which is limited only by the appended claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in the art.

[0014] Unless otherwise stated, the following definitions are presented to illustrate and define the meanings and scopes of the various terms used to describe the present invention and the appended claims. These definitions should not be construed literally as they are not general definitions and are only relevant to this application.

[0015] The term "final sterol product" means the phytosterol obtained after the purification step.

[0016] The term "(oil) distillate" encompasses edible vegetable oil distillates (VOD), which are even preferred.

[0017] The term "(oil) distillation residue" encompasses distillation residues of transesterified oils, which are even preferred. The distillation residue of the transesterified oil is preferably a fatty acid alkyl ester distillation residue, more preferably a fatty acid methyl ester distillation residue, especially residues from biodiesel production.

[0018] The term "partial glycerides" encompasses all combinations of monoglycerides, diglycerides, and / or triglycerides. In the case of oil distillates as starting materials, only triglycerides are present or almost only triglycerides are present, and there are no monoglycerides and diglycerides, while in the case of typical oil distillation residues, triglycerides and diglycerides are mainly present and only a small amount of monoglycerides.

[0019] The meanings of terms not defined herein are generally known to those skilled in the art or in the literature.

[0020] Of course, it is also intended to combine various embodiments and preferred options of the various process steps disclosed herein in an actual complete process, so that for a specific performance of the overall process of one process step, a general process is selected; for another process step in the whole process, a preferred embodiment is selected; and for yet another process step, the most preferred option, etc.

[0021] In one embodiment, the presently claimed invention relates to a method for purifying phytosterols, the method comprising at least the following steps:

[0022] a. Providing a liquid mixture comprising phytosterols and a lower alcohol, wherein the lower alcohol is present in an amount of 25 to 800% by weight based on the amount of phytosterols;

[0023] b. Cooling the liquid mixture in step a. to form phytosterol crystals, wherein the phytosterol crystals are formed at a temperature of 10°C to 75°C, preferably 15°C to 50°C, more preferably 20°C to 45°C, even more preferably 25°C to 35°C;

[0024] c. Separating the phytosterol crystals in step b. from the remainder of the liquid mixture by mechanical means (such as filtration and / or centrifugation);

[0025] d. Washing the phytosterol crystals in step c. with a solvent system to obtain purified phytosterol crystals, the solvent system comprising at least one polar aprotic solvent;

[0026] e. Optionally repeating step (d);

[0027] f. Dry the purified plant sterol crystals.

[0028] In one embodiment, the presently claimed invention relates to a purification process in which the color of the final sterol product is significantly improved and / or the amount of sterol esters as impurities is significantly reduced.

[0029] In one embodiment, the presently claimed invention relates to a significantly reduced solvent content in the final sterol product.

[0030] In one embodiment, the presently claimed invention relates to recovering plant sterols from the residue of deacidification of vegetable oil and subsequently purifying them to obtain pure plant sterols.

[0031] In one embodiment, the presently claimed invention relates to recovering plant sterols from the prior art methods disclosed in any one of EP1169335 B1, EP1169336 B1 or EP 2 635 592B1, wherein i) the method of the present invention is applied to the sterol crystals obtained by said process; or ii) the sterol-containing solution / dispersion in said method is adjusted so that they meet the requirements of defined process step a):

[0032] a) Provide a liquid mixture comprising plant sterols and a lower alcohol, wherein the lower alcohol is present in an amount of 25 to 800% by weight based on the amount of plant sterols;

[0033] Then, after further method steps, the method comprises at least the following steps:

[0034] b) Cool the liquid mixture in step a to form plant sterol crystals, wherein the plant sterol crystals are formed at a temperature of 10°C to 75°C, preferably 15°C to 50°C, more preferably 20°C to 45°C, even more preferably 25°C to 35°C;

[0035] c) Separate the plant sterol crystals in step b from the remainder of the liquid mixture by mechanical means (such as filtration and / or centrifugation);

[0036] d) Wash the plant sterol crystals in step c with a solvent system comprising at least one polar aprotic solvent to obtain purified plant sterol crystals;

[0037] e) Optionally repeat step (d);

[0038] f) Dry the purified plant sterol crystals;

[0039] g) Optionally melt and dry in the molten state to remove trace amounts of remaining solvent;

[0040] h) Optionally, a granulation process is carried out to obtain solid sterol granules.

[0041] Transesterification

[0042] In an embodiment of the presently claimed invention, the process and work-up of the transesterification of the vegetable oil methyl ester distillation residue can be carried out as described in EP 0 656 894 B1. Suitable starting materials are distillation residues obtained from vegetable oil-based processes, such as in the production of FME (also known as "biodiesel"), for example in the production of rapeseed oil-based FME, but it is also possible to use sterol-containing products obtained from processes based on tall oil as starting material, such as the recovery of sterols from tall oil pitch (such as pitch obtained from birch bark); particularly preferred starting materials are distillation residues obtained from the treatment and distillation of vegetable oils, such as distillation residues obtained in the production of FME (also known as "biodiesel"). Furthermore, when the process relates to the production of a sterol fraction, reference is made to EP 0 656 894 B1. This process is particularly suitable for the production of vegetable oil-based sterols, especially from the residues of vegetable oil methyl ester distillation.

[0043] In an embodiment of the presently claimed invention, the distillation residue from transesterification, more particularly preferably an unrefined oil having a residual acid value of less than 2, is used as a raw material for the production of sterols.

[0044] Such residues can be obtained using known prior art methods as outlined above. Particularly suitable residues are from the work-up of vegetable oils containing sterols and usually also tocopherols. These residues are obtained by several esterification and transesterification steps, acid treatment, etc., all of which are known in the art. One such known method is the method for producing biodiesel, i.e., fatty acid methyl ester (FME).

[0045] Preferably, the oil distillation residue comprises residues derived from oils selected from the group consisting of soybean oil, sunflower oil, rapeseed oil, high erucic acid rapeseed oil (HEAR), low erucic acid rapeseed oil (CANOLA; low erucic acid CANadian oil), coconut oil, palm oil, palm kernel oil, and mixtures thereof; more preferably, the oil distillation residue comprises residues derived from soybean oil, sunflower oil, rapeseed oil (such as HEAR or CANOLA); even more preferably, the oil distillation residue comprises residues derived from sunflower oil, rapeseed oil, preferably HEAR.

[0046] These residues are preferably residues from: coconut oil, palm kernel oil, palm oil, soybean oil, sunflower oil, rapeseed oil (such as HEAR and / or CANOLA); more preferably from soybean oil, sunflower oil, rapeseed oil (such as HEAR); even more preferably from sunflower oil and / or rapeseed oil, and especially HEAR, having an acid value of 0 to 10, preferably 0 to 6, and containing a mixture of diglycerides and triglycerides, FME, sterol esters, wax esters and free sterols, preferably 1 to 7 wt% triglycerides, 3 to 15 wt% diglycerides, 15 to 40 wt% FME, 40 to 50 wt% (especially 42 to 47 wt%) sterol esters, 3 to 4 wt% wax esters and 3 to 15 wt% free sterols and a small amount of monoglycerides.

[0047] In another embodiment of the presently claimed invention, an oil distillate is used as a raw material for the production of sterols. These distillates are preferably distillates from: coconut oil, palm kernel oil, palm oil, soybean oil, sunflower oil, rapeseed oil (such as from HEAR and / or CANOLA); more preferably from soybean oil, sunflower oil, rapeseed oil (such as from HEAR); even more preferably sunflower oil and / or rapeseed oil from HEAR, containing 45 to 65 wt% triglycerides and 35 to 55 wt% sterol esters (sum to 100%).

[0048] Thus, in a preferred embodiment of the presently claimed invention, a transesterified and distilled phytosterol-rich fraction from rapeseed oil (“rapeseed sterols”) or soybean oil (“soybean sterols”), sunflower oil is used as a starting material.

[0049] Using the present invention, the methods disclosed in EP1179535B1, EP1179536B1 and EP 2 635 592B1 can also be used and modified.

[0050] Thus, in three further embodiments, the processes as carried out in EP1179535B1, EP1179536B1 or EP2635 592B1 can be implemented for a transesterification reaction to yield sterols, followed by the crystallization process, in particular the purification process, of the present disclosure.

[0051] After crystallization and purification as outlined in detail below, typical further work-up procedures can be used: the washed sterol crystals can be dried using various types of conventional dryers to remove the remaining solvent. Applying reduced pressure helps to increase the removal of solvent traces. After such drying, the crystals can preferably be remelted under reduced pressure to also remove trace amounts of solvent encapsulated in the crystals. The molten sterol can then be formed into particles by typical known procedures, such as granulation (i.e., forming droplets that are close to spherical) or simply in a dropping tower, where the molten material is dropped into cooler air or gas, all such methods ultimately yielding particulate solid sterol, which preferably is in a form that does not exhibit dust but has good flowability and preferably a high density, to obtain sterol microparticles with easy-to-handle characteristics.

[0052] Crystallization

[0053] In another embodiment, the purification of the sterol fraction is carried out according to known methods, the sterol fraction mainly containing methyl esters in addition to lower alcohols (especially when those residues originate from the transesterification and distillation of vegetable oils, such as in the so-called biodiesel process), i.e., the hot mixture (about 50 °C - 65 °C when working at atmospheric pressure, thus at a higher temperature when working at high pressure and usually not preferred - at a lower temperature when working under reduced pressure; all the following temperatures and temperature ranges are given for atmospheric pressure, and thus, as is readily understandable to the person skilled in the art, an increase or decrease in pressure provides an increased or decreased temperature) is slowly cooled to form phytosterol crystals, the sterol crystals being formed in a crystallizer at a temperature of 15 °C to 50 °C, preferably 20 °C to 45 °C, more preferably 25 °C to 35 °C, even more preferably 20 °C to 30 °C. If necessary, the basic catalyst from the transesterification present in the mixture can be neutralized in advance, for example by adding citric acid or other organic or inorganic acids that are also suitable or acceptable for the intended use of the sterol subsequently; preferably, such neutralization is omitted if the feed for crystallization permits.

[0054] In an embodiment of the presently claimed invention, the lower alcohol is selected from the group consisting of: methanol, ethanol, and isopropanol. The lower alcohol is preferably methanol.

[0055] In an embodiment of the presently claimed invention, only those mixtures which already have a weight ratio of sterol to methanol of from 100:25 to 100:75 in their production should be used for initiating the crystallization procedure and further process steps of the presently claimed invention. Otherwise, methanol must be added or distilled off to adjust to the desired ratio, and such adjustment is readily accomplished by standard methods and equipment. Under these conditions, and the temperatures given subsequently at atmospheric pressure, for higher or lower pressures, higher or lower temperatures are applied as described above, crystallization starts at a temperature of 60 °C – 65 °C, but can also be carried out at higher temperatures if the crystallization is carried out at elevated pressure and / or if the solvent mixture used has a higher boiling point than the preferred solvents disclosed herein.

[0056] In an embodiment of the presently claimed invention, the sterol:methanol ratio is in the range of 1:0.1 to 1:5, preferably 1:0.5 to 1:3, more preferably 1:0.5 to 1:2.5.

[0057] In an embodiment of the presently claimed invention, the sterol-containing phase mainly comprising sterol crystals can subsequently be washed with methanol, wherein in each case, based on the amount of the sterol crystal phase, the amount of methanol is in the range of 20% to 800%, preferably in the range of 125% to 600%, more preferably in the range of 200% to 400%.

[0058] In an embodiment of the presently claimed invention, the sterol-containing phase mainly comprising sterol crystals can subsequently be washed with methanol, wherein in each case, based on the mass of the sterol crystal phase, the amount of methanol is in the range of 20% to 100%, preferably in the range of 25% to 90%, more preferably in the range of 25% to 75%, more preferably in the range of 25% to 60%, even more preferably in the range of 30% to 50%. This embodiment is superior to embodiments using a larger amount of solvent in this step because it is more economical in terms of solvent use.

[0059] In an embodiment of the presently claimed invention, phytosterol crystals are formed at a temperature of 10 °C to 75 °C, preferably 15 °C to 50 °C, more preferably 20 °C to 45 °C, even more preferably 25 °C to 35 °C, even more preferably 20 °C to 30 °C, such as 20 °C, 21 °C, 22 °C, 23 °C, 24 °C, 25 °C, 26 °C, 27 °C, 28 °C, 29 °C, 30 °C, 31 °C, 32 °C, 33 °C, 34 °C or 35 °C.

[0060] Purification of Phytosterols

[0061] In yet another embodiment of the presently claimed invention, the sterol crystals are separated by mechanical means (such as filtration and / or centrifugation, preferably filtration).

[0062] In a further embodiment of the presently claimed invention, a further purification step is carried out on the isolated sterol crystals.

[0063] In yet another embodiment of the presently claimed invention, the sterol crystals are further purified using a solvent system.

[0064] In yet another embodiment of the presently claimed invention, the purification of the sterol crystals occurs in the presence of a solvent system comprising at least one polar aprotic solvent.

[0065] In a further embodiment of the presently claimed invention, the purification of the sterol fraction occurs in the presence of at least one polar aprotic solvent selected from the group consisting of ethyl acetate, methyl ethyl ketone, methyl acetate, dichloromethane, N-methylpyrrolidone, tetrahydrofuran, acetone, dimethylformamide, acetonitrile, dimethyl sulfoxide, heptane, and hexane, wherein ethyl acetate, acetone, methyl ethyl ketone, methyl acetate, heptane, and hexane are preferred, and wherein ethyl acetate, methyl ethyl ketone, and methyl acetate are even more preferred.

[0066] In yet another embodiment of the presently claimed invention, the purification of the sterol fraction occurs in the presence of at least one polar aprotic solvent selected from the group consisting of ethyl acetate, acetone, methyl ethyl ketone, and methyl acetate, and even more preferably selected from ethyl acetate, methyl ethyl ketone, and / or methyl acetate.

[0067] In a particularly preferred embodiment, methyl acetate is used as the sole polar aprotic solvent.

[0068] In a further embodiment of the presently claimed invention, the purification of the sterol fraction occurs in the presence of at least one polar aprotic solvent and at least one polar protic solvent, the polar aprotic solvent and the polar protic solvent being mixed together and / or forming an azeotrope in the solvent system.

[0069] In an embodiment of the presently claimed invention, the at least one polar protic solvent is selected from the group consisting of water, ethanol, methanol, isopropanol, butanol, and acetic acid.

[0070] In yet another embodiment of the presently claimed invention, the at least one polar protic solvent is selected from water, ethanol, methanol, and / or isopropanol.

[0071] In a particularly preferred embodiment, methanol is used as the sole polar protic solvent, although it may contain a small amount of water, which is not preferred.

[0072] In an embodiment of the presently claimed invention, the polar aprotic solvent is present in an amount ranging from 25 to 75 wt % based on the amount of phytosterols, preferably ranging from 30 to 50 wt % based on the amount of phytosterols, and each value is between 30% and 50% based on the amount of phytosterols.

[0073] In an embodiment of the presently claimed invention, the polar protic solvent is present in an amount ranging from 5 to 50 wt % based on the amount of phytosterols, preferably ranging from 10 to 30 wt % based on the amount of phytosterols, and each value is between 10% and 30% based on the amount of phytosterols.

[0074] In an embodiment of the presently claimed invention, the method for purifying phytosterols comprises at least the following steps:

[0075] a. providing a liquid mixture comprising phytosterols and a lower alcohol, wherein the lower alcohol is present in an amount of 25 to 75% by weight based on the amount of phytosterols;

[0076] b. cooling the liquid mixture in step a. to form phytosterol crystals, wherein the phytosterol crystals are formed at a temperature of 10°C to 75°C, preferably 15°C to 50°C, more preferably 20°C to 45°C, even more preferably 25°C to 35°C;

[0077] c. separating the phytosterol crystals in step b. from the remainder of the liquid mixture by mechanical means (such as filtration and / or centrifugation);

[0078] d. washing the phytosterol crystals in step c. with a solvent system to obtain purified phytosterol crystals, wherein the solvent system comprises at least one polar aprotic solvent and at least one polar protic solvent;

[0079] e. optionally repeating step d. at least once, more preferably at least 2 times, even more preferably at least 3 times;

[0080] f. Optionally, repeating steps a. to e. before proceeding to step g below, in the following manner: re-dissolving the phytosterols in the liquid mixture according to step a., and then repeating steps b. to f.;

[0081] g. The purified phytosterol crystals obtained from the preceding step are dried;

[0082] h. optionally melting and drying in the molten state to remove traces of residual solvent;

[0083] i. optionally performing a particle formation process to obtain solid sterol particles;

[0084] Wherein said at least one polar aprotic solvent is selected from the group consisting of ethyl acetate, methyl ethyl ketone, methyl acetate, dichloromethane, N-methylpyrrolidone, tetrahydrofuran, acetone, dimethylformamide, acetonitrile, dimethyl sulfoxide, heptane and hexane, wherein ethyl acetate, acetone, methyl ethyl ketone, methyl acetate, heptane and hexane are preferred, and wherein ethyl acetate, methyl ethyl ketone and methyl acetate are even more preferred, and

[0085] Wherein said at least one polar aprotic solvent is selected from the group consisting of water, ethanol, methanol, isopropanol, butanol and acetic acid, wherein water, ethanol, methanol and / or isopropanol are more preferred, and methanol is most preferred, and even more preferably methanol as the sole polar aprotic solvent.

[0086] In a further embodiment of the presently claimed invention, after washing with at least one polar aprotic solvent and at least one polar protic solvent, the sterol crystals can be washed with a methyl ester, such as methyl acetate.

[0087] In a further embodiment of the presently claimed invention, after step c and before step d, the sterol crystals can be washed with a methyl ester (e.g., methyl ethyl ester and / or methyl fatty acid ester) to "pre-wash" the crystals, further increasing the purity and / or color of the sterol crystals to be obtained.

[0088] The washed sterol crystals can be dried using various types of conventional dryers to remove the remaining solvent. Applying reduced pressure helps to increase the removal of solvent traces. This step is for drying or "pre-drying", depending on the method employed and the desired content of residual solvent in the final sterol product to be obtained. The latter, of course, mainly depends on the intended use of the sterol.

[0089] After "conventional" drying in the previous step (g), the (pre)-dried crystals can be preferably melted under reduced pressure to remove trace amounts of solvent encapsulated within the crystals. In this way, the residual content of the solvent can be further reduced, thereby obtaining certain higher product quality, i.e., also suitable for critical applications, such as direct application to humans in nutritional products or pharmaceutical products.

[0090] The molten sterol needs to be solidified. This can be done by simple cooling with any form of agitation, such as in an extruder, paddle dryer, etc. Other known methods for solidifying melts are granulation, in equipment such as granulators (including spray granulators), which can form near-spherical droplets, or simply in a dropping tower, where the molten material is dropped into cooler air or gas. All such methods ultimately obtain particulate solid sterols, which are preferably in a form that does not show dust, but has good flowability and preferably high density, to obtain sterol microparticles with easy-to-handle characteristics.

[0091] Thus, in a further embodiment, the obtained and preferably (pre)-dried sterols are subjected to a granulation process, preferably granulation, more preferably spray granulation, which is preferably carried out under liquid nitrogen, to obtain nearly spherical, low to dust-free solid sterol particles with a very low content of organic solvents, suitable for direct use (including human oral administration). In addition, rolling, pressing, melting and spraying (drying) are suitable granulation processes.

[0092] In an embodiment of the presently claimed invention, the phytosterols are provided in the form of a 10 wt% pyridine solution for measuring the Gardner color number.

[0093] In an embodiment of the presently claimed invention, when measured as 10 wt% sterols in pyridine, the Gardner color number of the final sterol product is less than 4.0.

[0094] In an embodiment of the presently claimed invention, when measured as 10 wt% sterols in pyridine, the Gardner color number of the final sterol product is less than 3.0, preferably less than 2.0, more preferably less than 1.5, even more preferably less than 1, such as less than 0.9, 0.8, 0.7, 0.6, 0.5, and any value between and below 4 and 0.5.

[0095] In an embodiment of the presently claimed invention, based on the total weight of the purified phytosterols, the solvent content in the purified phytosterols is less than 100 ppm, preferably less than 50 ppm, more preferably less than 20 ppm, and even more preferably less than 10 ppm, such as 5 or 1 ppm or even lower, and each value is between 100 and 1 ppm.

[0096] In an embodiment of the presently claimed invention, based on the total weight of the purified phytosterols, the sterol ester content in the purified phytosterols is less than 10 wt%, preferably less than 5 wt%, more preferably less than 2 wt%, even more preferably less than 1 wt%, and most preferably less than 0.5 wt%, such as 0.1 wt%, 0.05 wt%, and each value is between 5 wt% and 0.05 wt% and below.

[0097] Advantages:

[0098] The presently claimed invention is associated with at least one, preferably two, even more preferably all three of the following advantages:

[0099] 1. When measured as 10 wt% of sterols in pyridine, the Gardner color number of the obtained sterol product is less than 4.0, preferably less than 3.0, preferably less than 2.0, more preferably less than 1.5, even more preferably less than 1, for example less than 0.9, 0.8, 0.7, 0.6, 0.5, and any value between and below 4 and 0.5.

[0100] 2. By using the above purification method, phytosterols are obtained in high yield with a very low sterol ester content (i.e., <10%), based on the total weight of the purified phytosterols, preferably below 5 wt%, more preferably below 2 wt%, even more preferably below 1 wt%, and most preferably below 0.5 wt%, for example 0.1 wt%, 0.05 wt%, and each value between and below 5 wt% and 0.05 wt%.

[0101] 3. Based on the total weight of the purified phytosterols, the solvent content of the final product is very low, i.e., below 100 ppm, preferably below 50 ppm, more preferably below 10 ppm, for example 5 or 1 ppm or even lower, and each value between 100 and 1 ppm.

[0102] A list of embodiments is provided below to further illustrate the present disclosure and is not intended to limit the present disclosure to the specific embodiments listed below.

[0103] Preferred embodiments

[0104] 1. A method for purifying phytosterols, the method comprising at least the following steps:

[0105] a. Providing a liquid mixture comprising phytosterols and a lower alcohol, wherein the lower alcohol is present in an amount of 25 to 800 wt% based on the amount of phytosterols;

[0106] b. Cooling the liquid mixture of step a. to form phytosterol crystals, wherein the phytosterol crystals are formed at a temperature of 10°C to 75°C, preferably 15°C to 50°C, more preferably 20°C to 45°C, even more preferably 25°C to 35°C;

[0107] c. Separating the phytosterol crystals of step b. from the remainder of the liquid mixture by mechanical means such as filtration and / or centrifugation;

[0108] d. Washing the phytosterol crystals of step c. with a solvent system comprising at least one polar aprotic solvent to obtain purified phytosterol crystals;

[0109] e. Optionally repeating step (d) one, two, or three times, preferably once;

[0110] f. Optionally, wash the phytosterol crystals obtained in step d or, if step e is optionally employed, in step e, with at least one lower alcohol, preferably with methanol only, and optionally repeat this step f one or two or three times, preferably only one or two times, more preferably only once;

[0111] g. Dry the purified phytosterol crystals;

[0112] h. Optionally, melt and dry in the molten state to remove trace amounts of residual solvent;

[0113] i. Optionally, carry out a granulation process to obtain solid sterol particles.

[0114] 2. A method for purifying phytosterols, comprising at least the following steps:

[0115] a. Provide a liquid mixture comprising phytosterols and a lower alcohol, wherein the lower alcohol is present in an amount of 25 to 800% by weight based on the amount of phytosterols;

[0116] b. Cool the liquid mixture of step a to form phytosterol crystals, wherein the phytosterol crystals are formed at a temperature of 15°C to 45°C, preferably 20°C to 30°C;

[0117] c. Separate the phytosterol crystals of step b from the remainder of the liquid mixture by mechanical means such as filtration and / or centrifugation;

[0118] d. Wash the phytosterol crystals of step c with a solvent system to obtain purified phytosterol crystals, the solvent system comprising at least one polar aprotic solvent and at least one polar protic solvent;

[0119] e. Optionally repeat step d at least once, more preferably at least 2 times, even more preferably at least 3 times;

[0120] f. Optionally, wash the phytosterol crystals obtained in step d or, if step e is optionally employed, in step e, with at least one lower alcohol, preferably with methanol only, and optionally repeat this step f one or two or three times, preferably only one or two times, more preferably only once;

[0121] g. Optionally repeat steps a to e as follows: redissolve the phytosterols in a liquid mixture according to step a, and then repeat steps b to f;

[0122] h. Dry the purified phytosterol crystals obtained from the foregoing steps;

[0123] i. Optionally, melt and dry in the molten state to remove trace amounts of residual solvent;

[0124] j. Optionally, a granulation process is carried out to obtain solid sterol granules.

[0125] 3. The method according to embodiment 1 or 2, wherein the at least one polar aprotic solvent is selected from the group consisting of ethyl acetate, methyl ethyl ketone, methyl acetate, dichloromethane, N-methylpyrrolidone, tetrahydrofuran, acetone, dimethylformamide, acetonitrile, dimethyl sulfoxide, heptane, and hexane, wherein ethyl acetate, acetone, methyl ethyl ketone, methyl acetate, heptane, and hexane are preferred, and wherein ethyl acetate, methyl ethyl ketone, and methyl acetate are even more preferred, and

[0126] wherein the at least one polar protic solvent is selected from the group consisting of water, ethanol, methanol, isopropanol, butanol, and acetic acid, wherein water, ethanol, methanol, and / or isopropanol are more preferred, and methanol is most preferred, and even more preferably methanol as the sole polar protic solvent.

[0127] 4. The method according to any one of the preceding embodiments, wherein the lower alcohol is present in an amount of 30 to 50% by weight based on the amount of phytosterol.

[0128] 5. The method according to any one of the preceding embodiments, wherein the lower alcohol is selected from the group consisting of ethanol, methanol, and isopropanol.

[0129] 6. The method according to any one of the preceding embodiments, wherein the at least one polar aprotic solvent is selected from the group consisting of ethyl acetate, methyl ethyl ketone, acetone, and methyl acetate.

[0130] 7. The method according to any one of the preceding embodiments, wherein the solvent system further comprises at least one polar protic solvent.

[0131] 8. The method according to embodiment 7, wherein the polar protic solvent is selected from the group consisting of water, ethanol, methanol, and isopropanol.

[0132] 9. The method according to any one of the preceding embodiments, wherein the solvent system comprises the polar protic solvent and the at least one polar aprotic solvent as a mixture or an azeotrope.

[0133] 10. The method according to any one of the preceding embodiments, wherein the liquid mixture comprises a phytosterol-containing fraction produced by a process including transesterification and distillation of a plant-based oil.

[0134] 11. The method according to embodiment 10, wherein the oil is selected from the group consisting of rapeseed oil, sunflower oil, and soybean oil.

[0135] 12. The method according to any one of the foregoing embodiments further comprises the following step: washing the separated plant sterol crystals obtained in step d. with a fatty acid ester.

[0136] 13. A method for purifying plant sterols, the method comprising at least the following steps:

[0137] a. Providing a liquid mixture comprising plant sterols and a lower alcohol, wherein the lower alcohol is present in an amount of 25 to 800% by weight based on the amount of plant sterols;

[0138] b. Cooling the liquid mixture of step a. to form plant sterol crystals, wherein the plant sterol crystals are formed at a temperature of 10°C to 75°C, preferably 15°C to 50°C, more preferably 20°C to 45°C, even more preferably 25°C to 35°C;

[0139] c. Separating the plant sterol crystals of step b. from the remainder of the liquid mixture by mechanical means such as filtration and / or centrifugation;

[0140] d. Washing the plant sterol crystals of step c. with a solvent system to obtain purified plant sterol crystals, the solvent system comprising at least one polar aprotic solvent and at least one polar protic solvent;

[0141] e. Optionally repeating steps a. to d.;

[0142] f. Optionally washing the plant sterol crystals obtained in step d. or optionally in step e. with at least one lower alcohol, preferably only with methanol, and optionally repeating this step f. one or two or three times, preferably only once or twice, more preferably only once;

[0143] g. Optionally repeating step e. in the following manner: redissolving the plant sterols according to step a. to obtain a liquid mixture, and then repeating steps b. to f.;

[0144] h. Drying the purified plant sterol crystals;

[0145] i. Optionally melting and drying in the molten state to remove trace amounts of residual solvent;

[0146] j. Optionally performing a granulation process to obtain solid sterol granules.

[0147] 14. A method for purifying plant sterols, the method comprising

[0148] a. Provide a phytosterol-containing fraction produced by the transesterification of an oil selected from the group consisting of rapeseed oil, sunflower oil, and soybean oil, wherein the phytosterol-containing fraction contains phytosterols and methanol, and wherein the methanol is present in an amount of 30 to 50% by weight based on the amount of phytosterols;

[0149] b. Cool the phytosterol-containing fraction of step a. to form phytosterol crystals, wherein the phytosterol crystals are formed at a temperature of 22 °C to 35 °C;

[0150] c. Separate the phytosterol crystals of step b. from the remainder of the phytosterol-containing fraction by mechanical means such as filtration and / or centrifugation;

[0151] d. Wash the phytosterol crystals of step c. with a solvent system comprising at least one polar aprotic solvent and at least one polar protic solvent to obtain purified phytosterol crystals;

[0152] e. Optionally repeat step d. one, two, or three times;

[0153] f. Optionally wash the phytosterol crystals obtained in step d or optionally employed step e with at least one lower alcohol, preferably with methanol only, and optionally repeat this step f one, two, or three times, preferably only one or two times, more preferably only once;

[0154] g. Dry the purified phytosterol crystals;

[0155] h. Optionally melt and dry in the molten state to remove trace amounts of remaining solvent;

[0156] i. Optionally carry out a granulation process to obtain solid sterol granules.

[0157] 15. The method according to embodiment 13 or 14, wherein the at least one polar aprotic solvent is selected from the group consisting of ethyl acetate, methyl ethyl ketone, methyl acetate, dichloromethane, N-methylpyrrolidone, tetrahydrofuran, acetone, dimethylformamide, acetonitrile, dimethyl sulfoxide, heptane, and hexane, wherein ethyl acetate, acetone, methyl ethyl ketone, methyl acetate, heptane, and hexane are preferred, and wherein ethyl acetate, methyl ethyl ketone, and methyl acetate are even more preferred, and

[0158] wherein the at least one polar protic solvent is selected from the group consisting of water, ethanol, methanol, isopropanol, butanol, and acetic acid, wherein water, ethanol, methanol, and / or isopropanol are more preferred, and methanol is most preferred, and even more preferably methanol as the sole polar aprotic solvent.

[0159] 16. The method according to any one of embodiments 13 to 15, wherein the at least one polar aprotic solvent is selected from the group consisting of ethyl acetate, acetone, methyl ethyl ketone, and methyl acetate.

[0160] 17. The method according to any one of embodiments 13 or 16, wherein the at least one polar protic solvent is selected from the group consisting of water, ethanol, methanol, and isopropanol.

[0161] 18. The method according to any one of embodiments 13 to 16, wherein the solvent system comprises the at least one polar protic solvent and the at least one polar aprotic solvent as a mixture or an azeotrope.

[0162] Examples

[0163] The presently claimed invention is illustrated in detail by the following non-limiting working examples. More specifically, the test methods specified below are part of the general disclosure of the present application and are not limited to the specific working examples.

[0164] Using the method disclosed in EP1179535B1, rapeseed oil was used as the starting material for the method to obtain the starting material, "residue", for Example 1. The residue yields obtained in the processes disclosed in EP1179536B1 and EP 2 635 592B1 produce very similar products to those produced in EP1179535B1 and are therefore equally applicable and can thus be subjected to the same methods outlined in Examples 1 and 2 of the present invention.

[0165] Example 1

[0166] Based on the content of free sterols and bound sterols, the starting material used was rapeseed methyl ester residue, additionally containing 100 wt% methanol.

[0167] The mixture was continuously cooled from about 100 °C to 10 °C, and the first crystals started to separate at 65 °C. The reaction mixture was cooled from 65 °C to about 25 °C - 30 °. After crystallization was complete, the crystals were filtered out, washed with methanol to remove FME, and dried to constant weight. Based on the sterol content of the transesterification product, the yield was 78 wt%.

[0168] Example 2 - Purification of Sterol Crystals

[0169] As in Example 1, after crystallization was complete, the crystals were filtered out, washed with pure methanol to remove FME, and further washed with the following solvents:

[0170] - ethyl acetate and its azeotrope with methanol; or

[0171] - methyl ethyl ketone and its azeotrope with methanol; or

[0172] - Methyl acetate and its azeotrope with methanol;

[0173] Subsequently, it was washed with pure methanol.

[0174] The crystals were further melted and dried to a constant weight by known methods and granulated to form particles.

[0175] The results obtained were compared with the experiment, where the crystals were washed with FME and subsequently with pure methanol.

[0176] The results obtained were summarized in Tables 1 - 3 (laboratory scale) and Tables 1a - 3a (industrial scale, e.g., plant level). In each table, Examples C1 and T1 refer to the same batch of sterols from the same rapeseed methyl ester distillation residue. This also applies to C2 and T2, C3 and T3, and C4 and T4 (if applicable). Therefore, Example C1 must be compared with Example T1, and so on.

[0177] Table 1 - The solvent used was the azeotrope of ethyl acetate and methanol (laboratory scale)

[0178] Experiment Number Solvent for Washing Color Purity Yield C1 1 FME Wash + 3 Methanol Washes 2.1 98.8 73.7 C2 1 FME Wash + 3 Methanol Washes 2.4 96.8 65.6 C3 1 FME Wash + 3 Methanol Washes 4 98.4 58.1 C4 1 FME Wash + 3 Methanol Washes 1 99.6 72 T1 2 Ethyl Acetate / Methanol Azeotrope Washes + 1 Methanol Wash 1.2 99.5 74.6 T2 2 Ethyl Acetate / Methanol Azeotrope Washes + 1 Methanol Wash 1.2 98.4 72.6 T3 2 Ethyl Acetate / Methanol Azeotrope Washes + 1 Methanol Wash 3 100 69.5 T4 2 Ethyl Acetate / Methanol Azeotrope Washes + 1 Methanol Wash 0.6 99.7 72

[0179] n.d. = Not determined

[0180] Table 1a - The solvent used was the azeotrope of ethyl acetate and methanol (industrial scale)

[0181] Experiment Number Solvent for Washing Color Purity Yield C1 1 FME Wash + 3 Methanol Washes 2.7 n.d. 62.5 T1 2 Ethyl Acetate / Methanol Azeotrope Washes + 1 Methanol Wash 0.7 n.d. 61.2

[0182] n.d. = Not determined

[0183] Table 2 - The solvent used was the azeotrope of methyl ethyl ketone and methanol (laboratory scale)

[0184] Experiment Number Solvent for Washing Color Purity Yield C1 1 FME Wash + 3 Methanol Washes 3.6 99.2 54.4 C2 1 FME Wash + 3 Methanol Washes 2.7 99.1 62.0 C3 1 FME Wash + 3 Methanol Washes 4 98.4 58.1 T1 2 Methyl Ethyl Ketone / Methanol Azeotrope Washes + 1 Methanol Wash 1.9 99.3 70.3 T2 2 Methyl Ethyl Ketone / Methanol Azeotrope Washes + 1 Methanol Wash 1.9 99.4 75.7 T3 2 Methyl Ethyl Ketone / Methanol Azeotrope Washes + 1 Methanol Wash 2.8 99.4 70.6

[0185] n.d. = Not determined

[0186] Table 2a - The solvent used was the azeotrope of methyl ethyl ketone and methanol (industrial scale)

[0187] Experiment Number Solvent for Washing Color Purity Yield C1 1 FME Wash + 3 Methanol Washes 1.9 n.d. 59.2 T1 2 Methyl Ethyl Ketone / Methanol Azeotrope Washes + 1 Methanol Wash 1.2 n.d. 64.9

[0188] n.d. = Not determined

[0189] Table 3 - The solvent used was the azeotrope of methyl acetate and methanol (laboratory scale)

[0190] Experiment Number Solvent for Washing Color Purity Yield C1 1 FME Wash + 3 Methanol Washes 4 98.4 58.4 C2 1 FME Wash + 3 Methanol Washes 2.7 99.1 62.6 C3 1 FME Wash + 3 Methanol Washes 3.6 99.1 62.6 C4 1 FME Wash + 3 Methanol Washes 3.0 100 75.1 T1 2 Methyl Acetate / Methanol Azeotrope Washes + 1 Methanol Wash 3.2 99.3 71.8 T2 2 Methyl Acetate / Methanol Azeotrope Washes + 1 Methanol Wash 1.2 99.1 74.7 T3 2 Methyl Acetate / Methanol Azeotrope Washes + 1 Methanol Wash 1.6 99.1 74.7 T4 3 Methyl Acetate / Methanol Azeotrope Washes 0.5 100 77

[0191] n.d. = Not determined

[0192] Table 3a - The solvent used is an azeotrope of methyl acetate and methanol (industrial scale)

[0193] Experiment Number Solvent for Washing Color Purity Yield C1 1 FME Wash + 3 Methanol Washes 2.2 n.d. 62.7 T1 2 Methyl Acetate / Methanol Azeotrope Washes + 1 Methanol Wash 1.0 n.d. 67.7

[0194] n.d. = not determined

[0195] Conclusion:

[0196] According to Table 1 (laboratory scale), compared with the cases of C1 to C4, in the cases of T1 to T4, the color of the final sterol product is significantly better. Compared with the former, the purity is at least slightly better, and for T1 to T4, the yield is at least the same or even better. As can be seen from Table 1a (plant scale), compared with C1, the color of T1 is significantly improved, while the yield remains more or less unchanged.

[0197] According to Table 2 (laboratory scale), the color of the final sterol product, and especially the yield, is significantly better in the cases of T1 to T3 compared with the cases of C1 to C3. Compared with the former, the purity of T1 to T3 is slightly better. As can be seen from Table 2a (plant scale), compared with C1, the color and yield of T1 are improved.

[0198] According to Table 3 (laboratory scale), compared with the cases of C1 to C4, in the cases of T1 to T4, the yield of the final sterol product, and especially the color, is significantly better. Compared with the former, for T1 to T4, the purity is at least the same or even slightly better. As can be seen from Table 3a (plant scale), compared with C1, the color and yield of T1 are improved.

[0199] Those skilled in the art will understand that changes can be made to the above-described embodiments without departing from their broad inventive concept. Accordingly, it should be understood that the present invention is not limited to the specific embodiments disclosed, but is intended to cover modifications within the spirit and scope of the presently claimed invention as defined by the appended claims.

Claims

1. A method for purifying phytosterols, the method comprising at least the following steps: a. Providing a liquid mixture comprising phytosterols and a lower alcohol, wherein the lower alcohol is selected from methanol, ethanol, and isopropanol, and based on the amount of phytosterols, the lower alcohol is present in an amount of 25 to 800% by weight; b. Cooling the liquid mixture of step a. to form phytosterol crystals, wherein the phytosterol crystals are formed at a temperature of 10°C to 75°C; c. Separating the phytosterol crystals of step b. from the remainder of the liquid mixture by mechanical means; d. Washing the phytosterol crystals of step c. with an azeotropic solvent system to obtain purified phytosterol crystals, the azeotropic solvent system comprising at least one polar aprotic solvent and at least one polar protic solvent, wherein the at least one polar aprotic solvent is selected from the group consisting of ethyl acetate, methyl ethyl ketone, and methyl acetate, and the at least one polar protic solvent is selected from the group consisting of ethanol, methanol, and isopropanol; e. Repeating step d. at least once; f. Optionally washing the phytosterol crystals obtained in step e. with at least one lower alcohol selected from methanol, ethanol, and isopropanol, and optionally repeating this step f. one or two or three times; g. Optionally repeating steps a. to f. as follows: redissolving the phytosterols in a liquid mixture according to step a., and then repeating steps b. to f.; h. Drying the purified phytosterol crystals obtained from the foregoing steps; i. Optionally melting and drying in the molten state to remove trace amounts of residual solvent; j. Optionally performing a granulation process to obtain solid sterol particles.

2. The method according to claim 1, wherein the at least one polar aprotic solvent is selected from the group consisting of ethyl acetate, methyl ethyl ketone, and methyl acetate, and wherein the at least one polar protic solvent is methanol.

3. The method according to claim 1, wherein based on the amount of phytosterols, the lower alcohol is present in an amount of 30 to 50% by weight.

4. The method according to claim 1, wherein the lower alcohol is methanol.

5. The method according to any one of claims 1 to 4, wherein the liquid mixture comprises a phytosterol-containing fraction produced by a process comprising transesterification and distillation of a plant-based oil.

6. The method according to claim 5, wherein the oil is selected from rapeseed oil, sunflower oil, and soybean oil.

7. The method according to any one of claims 1 to 4, which further comprises the following step: Washing the separated phytosterol crystals obtained in step d. with a fatty acid ester.