ES2773497T3 - Astaxanthin purification procedure - Google Patents

Abstract

A process for the manufacture of food grade synthetic astaxanthin with a dichloromethane content <= 250 ppm, comprising the following steps: a) providing synthetic astaxanthin crystals containing dichloromethane; and b) adding methanol to synthetic astaxanthin in an amount to obtain a suspension of synthetic astaxanthin in methanol, whereby the amount of synthetic astaxanthin in said suspension is in the range of 5 to 50% by weight, based on the total weight of the suspension; and c) bringing the suspension obtained in step b) to a temperature in the range of 80 to 140 ° C, whereby the pressure is above atmospheric pressure; and d) maintaining the suspension at a temperature in the range of 80 to 140 ° C and at a pressure higher than atmospheric pressure, while separating the dichloromethane and methanol by distillation until the amount of synthetic astaxanthin in said suspension is in the range from 25 to 75% by weight, based on the total weight of the suspension; provided that the amount of synthetic astaxanthin in said suspension is greater than in the starting suspension obtained in step b); and e) cooling the synthetic astaxanthin suspension to a temperature in the range of 10 to 35 ° C; and f) optionally filtering the synthetic astaxanthin crystals; and g) drying the cooled synthetic astaxanthin suspension obtained in step e) or the filtered synthetic astaxanthin crystals obtained in step f); whereby during the process the synthetic astaxanthin is not completely dissolved in the methanol, and with which a synthetic astaxanthin of food grade with a content of dichloromethane <= 250 ppm is obtained.

Description

DESCRIPTION

Procedure for the purification of astaxanthin

The object of the invention is to provide a synthetic food grade astaxanthin (AXN) which is hitherto unknown. "Food grade" within the present invention means "suitable for human consumption". A synthetic food grade AXN thus meets all regulatory requirements for purity and can be used in the commercial production of food and dietary supplements.

AXN can be manufactured by chemical synthesis (see EP-A 908449, WO 2005/087720, EP-A 733 619), can be produced by fermentation (see EP-A 543 023) and isolated from natural sources such as waste of shells (see JP-A 11-049 972) or Haematococcus pluvialis algae (see GB-A 2,301,587), in which the isolated esters would have to be cleaved to AXN itself.

AXN isolated from natural sources is already used in products for human consumption: see, p. eg, US 2009/0297492, where AXN is described to improve cognitive performance; US 2009/0018210, which describes that AXN promotes fat degradation; EP-A 1867 327, where AXN is described to prevent neurodegenerative disease, to name just a few. Until now, however, synthetic AXN has not been used in products for human consumption.

Synthetic AXN is of standardized quality compared to AXN from natural sources, as it is much easier to use a standardized procedure for its chemical synthesis and purification than to depend on the variable quality of natural AXN that results from using natural sources than they also vary in their composition. Therefore, in the context of the present invention, the term "AXN" means "synthetic AXN".

Chemical processes for the manufacture of AXN are often carried out in halogenated hydrocarbons such as dichloromethane (see, for example, WO 2011/095571), since AXN and its precursors have a high solubility in these solvents, although there were intentions in the past to avoid the use of solvents of this type (see, for example, EP-A 908 449 and WO 2005/087720). There are also purification methods using chloroform (see JP-A 07118226). The AXN obtained in this way often crystallizes from lower alkanols, since it is hardly soluble in these types of solvents.

Therefore, it was an object of the present invention to provide a synthetic AXN which is of reliable quality, easy to obtain also on an industrial scale and suitable for human consumption.

Therefore, it was an object of the present invention to provide a food grade synthetic AXN.

There are already procedures for the purification of astaxanthin:

In example 11 of WO 2007/072529 the synthesis of astaxanthin is carried out in isopropanol. The product obtained is recrystallized in three successive rounds: one with methylene chloride, another with methanol and another with heptane. In this way, all of the astaxanthin dissolves.

According to WO 2007/128574 (see page 9, line 25) the astaxanthin filter cake is washed with methanol.

According to EP-A 633258 (see Example 2) the astaxanthin crystals have been washed with heptane.

The object of the present invention to provide a food grade synthetic AXN is accomplished by the process of the present invention which provides an AXN with extremely low levels of solvent, preferably with extremely low levels of dichloromethane, thus making this AXN suitable for consumption. human.

Therefore, the present invention is especially directed to provide a synthetic AXN with a content of dichloromethane <250 ppm, preferably with a content of dichloromethane <200 ppm, more preferably with a content of dichloromethane <100 ppm, even more preferably with a dichloromethane content <50 ppm, <35 ppm, <30 ppm, <25 ppm, <20 ppm, most preferably with a dichloromethane content <10 ppm.

In an especially preferred embodiment of the present invention, synthetic AXN has a dichloromethane content in the range of 0 to 100 ppm, preferably in the range of 10 to 100 ppm.

Preferably, the synthetic AXN obtained by the processes according to the present invention has a methanol content <500 ppm, preferably it has a methanol content <350 ppm, more preferably it has a methanol content <250 ppm, even more preferably it has a methanol content <150 ppm, <100 ppm, most preferably it has a methanol content <50 ppm, <20 ppm, <10 ppm, <5 ppm.

In an especially preferred embodiment of the present invention, the synthetic AXN has a methanol content in the range of 0 to 50 ppm, preferably in the range of 0 to 20 ppm, more preferably in the range of 0 to 10 ppm, most preferably in the range of 0 to 5 ppm.

In a further preferred embodiment, the synthetic AXN has a dichloromethane content <50 ppm and a methanol content <100 ppm.

Synthetic AXN can be used especially in dietary supplements. For these purposes, it is often provided in the form of an oily suspension or a powder formulation such as a microsphere, thus protecting the synthetic AXN from degradation.

Therefore, by the present invention it is possible to provide a human dietary supplement comprising astaxanthin, manufactured by chemical synthesis (ie synthetic astaxanthin), free of astaxanthin monoesters and diesters, and comprising <250 ppm dichloromethane. Preferably, these human dietary supplements comprising this synthetic AXN, free from monoesters and diesters of AXN, comprise <200 ppm dichloromethane, <100 ppm dichloromethane, <50 ppm dichloromethane. More preferably, these human dietary supplements comprising synthetic food grade AXN, free of monoesters and diesters of AXN, comprise dichloromethane in the range between 0 and 100 ppm, preferably in the range between 10 and 100 ppm.

Furthermore, the present invention can provide human dietary supplements comprising food grade synthetic AXN, free of AXN monoesters and diesters and with the reduced levels of dichloromethane and methanol as given above, including all preferred ranges and combinations given.

Since it is possible with the processes of the present invention to significantly reduce the content of halogenated organic solvents such as dichloromethane, there is no longer a need to use a chemical synthesis, where the use of this type of solvents is avoided.

Procedures

A synthetic AXN of food grade can be obtained by the following procedure which is an object of the present invention.

Procedure 1: A process for the manufacture of food grade synthetic astaxanthin comprises the following steps:

a) providing synthetic astaxanthin crystals containing dichloromethane; and

b) adding methanol to synthetic astaxanthin in an amount to obtain a suspension of synthetic astaxanthin in methanol, whereby the amount of synthetic astaxanthin in said suspension is in the range of 5 to 50% by weight, based on the total weight of the suspension; and c) bringing the suspension obtained in step b) to a temperature in the range of 80 to 140 ° C, whereby the pressure is above atmospheric pressure; and

d) maintaining the suspension at a temperature in the range of 80 to 140 ° C and at a pressure higher than atmospheric pressure, while the dichloromethane and methanol are separated by distillation until the amount of synthetic astaxanthin in said suspension is in the range from 25 to 75% by weight, based on the total weight of the suspension; with the proviso that the amount of synthetic astaxanthin in said suspension is greater than in the starting suspension obtained in step b); and e) cooling the synthetic astaxanthin suspension to a temperature in the range of 10 to 35 ° C; and f) optionally filtering the synthetic astaxanthin crystals; and

g) drying the cooled synthetic astaxanthin suspension obtained in step e) or the filtered synthetic astaxanthin crystals obtained in step f);

whereby during the process the synthetic astaxanthin is not completely dissolved in the methanol, and with which a synthetic astaxanthin of food grade with a content of dichloromethane <250 ppm is obtained.

Step f) is optional, which means that it may or may not be carried out.

If step f) is not carried out, the procedure is as follows: Procedure 2:

A process for the manufacture of food grade synthetic astaxanthin comprises the following steps:

i) providing synthetic astaxanthin crystals containing dichloromethane; and

ii) adding methanol to synthetic astaxanthin in an amount to obtain a suspension of synthetic astaxanthin in methanol, whereby the amount of synthetic astaxanthin in said suspension is in the range of 5 to 50% by weight, based on the total weight of the suspension; and iii) bringing the suspension obtained in step b) to a temperature in the range of 80 to 140 ° C, whereby the pressure is above atmospheric pressure; and

iv) maintaining the suspension at a temperature in the range of 80 to 140 ° C and at a pressure higher than atmospheric pressure while the dichloromethane and methanol are separated by distillation until the amount of synthetic astaxanthin in said suspension is in the range of 25 to 75% by weight, based on the total weight of the suspension, provided that the amount of synthetic astaxanthin in said suspension is greater than in the starting suspension obtained in step ii); and v) cooling the synthetic astaxanthin suspension to a temperature in the range of 10 to 35 ° C; and vi) drying the chilled synthetic astaxanthin suspension obtained in step v), whereby during the process the synthetic astaxanthin is not completely dissolved in methanol, and with which a food grade synthetic astaxanthin is obtained with a content dichloromethane <250 ppm.

If step f) is carried out, the procedure is as follows: Procedure 3:

A process for the manufacture of food grade synthetic astaxanthin comprises the following steps:

A) provide synthetic astaxanthin crystals containing dichloromethane: and

B) adding methanol to synthetic astaxanthin in an amount to obtain a suspension of synthetic astaxanthin in methanol, whereby the amount of synthetic astaxanthin in said suspension is in the range of 5 to 50% by weight, based on the total weight of the suspension; and

C) bringing the suspension obtained in step b) to a temperature in the range of 80 to 140 ° C, whereby the pressure is above atmospheric pressure; and

D) maintaining the suspension at a temperature in the range of 80 to 140 ° C and at a pressure higher than atmospheric pressure while separating the dichloromethane and methanol by distillation until the amount of synthetic astaxanthin in said suspension is in the range from 25 to 75% by weight, based on the total weight of the suspension, provided that the amount of synthetic astaxanthin in said suspension is greater than in the initial suspension obtained in step B); and

E) cooling the synthetic astaxanthin suspension to a temperature in the range of 10 to 35 ° C; and

F) separating the synthetic astaxanthin crystals by filtration; and

G) drying the filtered synthetic astaxanthin crystals obtained in step F); whereby during the process the synthetic astaxanthin is not completely dissolved in the methanol, and with which a synthetic astaxanthin of food grade with a content of dichloromethane <250 ppm is obtained.

Preferably, the synthetic food grade astaxanthin thus obtained has a dichloromethane content <100 ppm. Furthermore, said synthetic food grade astaxanthin preferably has a methanol content <250 ppm.

These procedures will now be described in greater detail below. They are inexpensive and can be done on an industrial scale. During the procedure, the total amount of astaxanthin does not completely dissolve in the methanol at any time. This is in contrast to a crystallization process in which the total amount of astaxanthin dissolves completely on heating and recrystallizes when the temperature drops again.

Stage a) / Stage i) / Stage A)

Synthetic AXN crystals are used as starting material. Synthetic AXN crystals are those obtained from any of the chemical syntheses after removing the dichloromethane solvent, in which the synthesis has been carried out. The dichloromethane may have been removed by distillation or by solvent exchange. Preferably, the dichloromethane has been removed by solvent exchange with methanol. In this case, the mixture of synthetic astaxanthin and dichloromethane is heated to a temperature of 38 to 40 ° C at atmospheric pressure and the dichloromethane is distilled off. At the same time, methanol is added so that the volume of the mixture remains constant. Then the solvent (dichloromethane methanol) is distilled off until the internal temperature has risen to 64 ° C (boiling point of methanol), which means that only methanol is distilled off, but dichloromethane is no longer needed .

These synthetic AXN crystals still contain dichloromethane which cannot be removed simply by prolonging the drying time of these synthetic AXN crystals, even if the temperature and / or the vacuum. Typical amounts of dichloromethane remaining in synthetic AXN crystals are 0.2 to 0.3% by weight, based on the total weight of synthetic AXN crystals.

Since the process of the present invention is very efficient in removing dichloromethane, it is also possible to directly use a solution of synthetic AXN in dichloromethane as a starting material instead of crystals of synthetic AXN. Then, the stage stage a) / stage i) / stage A) is as follows:

a) / i) / A) provide a solution of synthetic astaxanthin in dichloromethane.

In this case, it is advantageous to first reduce the amount of dichloromethane in the solution by distillation. Preferably this is done by simultaneously adding methanol.

Therefore, if a solution of synthetic AXN in dichloromethane is used as starting material, advantageously steps a2) and a3) are carried out after step a) / step i) / step A) and before step b) / stage ii) / stage B).

a2) optionally, add methanol to the synthetic astaxanthin solution from step a1);

a3) removing dichloromethane by distillation;

in case step a2) has been carried out by distilling off dichloromethane and methanol.

Stage b) / Stage ii) / Stage B)

Preferably step b) is carried out in a closed reactor.

Preferably, the methanol is added to the synthetic astaxanthin crystals under nitrogen.

Stage c) / Stage iii) / Stage B)

Preferably, the suspension obtained in stage b) / stage ii) / stage B) is brought to a temperature in the range of 80 to 140 ° C, more preferably to a temperature in the range of 100 to 120 ° C, most preferably at a temperature in the range of 105 to 115 ° C. This increases the pressure.

Stage d) / Stage iv) / Stage D)

When the desired temperature is reached, the temperature is kept constant and dichloromethane and methanol are distilled off until the amount of synthetic AXN in said suspension is in the range of 25 to 75% by weight, preferably in the range of 35 to 65 % by weight, even more preferably in the range of 45 to 55% by weight, based on the total weight of the suspension. Therefore, in any case, the concentration of the suspension increases, which means that the amount of solvent in said suspension decreases in comparison with the suspension of stage b) / stage ii) / stage B).

Stage e) / Stage v) / Stage E)

Preferably, the methanolic synthetic astaxanthin suspension, whereby its dichloromethane content is <250 ppm, is cooled to a temperature in the range of 15-30 ° C, more preferably to a temperature in the range of 20 to 25 ° C, leading to synthetic astaxanthin crystals.

Stage f) / Stage F)

Optionally, the synthetic astaxanthin crystals can be separated by filtration. This step is preferably carried out. Therefore, procedure 3 is preferably performed.

Stage g) / Stage vi) / Stage G

The drying of the synthetic AXN crystals obtained is generally carried out at a temperature below 140 ° C, preferably at a temperature in the range of 40 to 140 ° C, and under vacuum. The vacuum is preferably in the range of between 0 and 20 mbara.

In one embodiment of the present invention, drying of the synthetic AXN crystals is carried out at a temperature of 80 ° C and a pressure of 20 mbar. In a further embodiment of the present invention, drying of synthetic AXN crystals is carried out at a temperature in the range of 55 to 70 ° C and at a pressure below 20 mbar.

Especially preferred embodiments of the present invention are those processes in which one or more of the preferred conditions given above are carried out. The most preferred processes of the present invention are those in which all of the preferred conditions given above are carried out.

Oily suspensions

Synthetic food grade AXN can be mixed with an edible oil to obtain an oily suspension of synthetic food grade AXN. Edible oil can be selected from the following group consisting of vegetable oils, such as corn oil, safflower oil, sunflower oil, medium chain triglyceride (MCT) oil, peanut oil, soybean oil, rapeseed oil, palm oil, palm kernel oil, cottonseed oil, olive oil, coconut oil, and synthetic oils, and any mixtures thereof, but not limited to. Especially preferred edible oils are selected from the group consisting of safflower oil, corn oil, sunflower oil, medium chain triglyceride (MCT) oil, and any mixture thereof.

Generally, the content of synthetic food grade AXN in such suspension is in the range of 0.5 to 20% by weight, based on the total weight of the suspension. Preferably, the AXN content in said suspension is in the range of 1.0 to 10% by weight, based on the total weight of the suspension. More preferably, oily suspensions are marketed with a food grade synthetic AXN content of 5 and 10% by weight, respectively.

The oily suspension may further comprise an antioxidant, especially a fat-soluble antioxidant. An especially preferred fat-soluble antioxidant is dl-alpha-tocopherol. The amount of such an antioxidant is preferably in the range of 0.1 to 3% by weight, based on the total weight of the suspension. The amount of oil is then so much that the amount of the three ingredients (food grade synthetic AXN; antioxidant, oil) adds up to 100% by weight.

The oily suspension can be used directly as such for the manufacture of dietary supplements in the form of capsules, especially in the form of soft gelatin capsules.

Powder forms

Powdered forms can be used to make tablets.

An especially preferred powder form is a microsphere comprising the food grade synthetic astaxanthin as described above, encapsulated in a matrix comprising a modified food starch.

The amount of synthetic food grade astaxanthin in said microsphere is preferably in the range of 0.5 to 20% by weight, based on the total weight of the microsphere.

The microspheres may further comprise a water-soluble antioxidant (such as sodium ascorbate) and / or a fat-soluble antioxidant (such as DL-alpha-tocopherol), as well as a saccharide as an adjuvant. The amount of each of the antioxidants is preferably in the range of 0.5 to 3.0% by weight, based on the total weight of the microsphere.

A particularly preferred modified food starch of this invention has the following formula (I)

where St is a starch, R is an alkylene radical and R 'is a hydrophobic group. Preferably R is a lower alkylene radical such as dimethylene or trimethylene. R 'can be an alkyl or alkenyl group, preferably with 5 to 18 carbon atoms. A preferred compound of formula (I) is an "OSA starch" (sodium octenyl succinate starch). The degree of substitution, that is, the number of esterified hydroxyl groups to the number of free non-esterified hydroxyl groups, generally varies in a range of 0.1% to 10%, preferably in a range of 0.5% to 4%, more preferably in a range of 3% to 4%.

The term "OSA starch" designates any starch (from any natural source such as corn, waxy corn, waxy cereal, wheat, tapioca and potato, or synthesized) that was treated with octenyl succinic anhydride (OSA). The degree of substitution, that is, the number of hydroxyl groups esterified with OSA to the number of unesterified free hydroxyl groups generally ranges from 0.1% to 10%, preferably from 0.5% to 4%. , more preferably in a range of 3% to 4%. OSA starches are also known under the term "modified food starch".

The term "OSA starches" also encompasses starches that are commercially available, eg. eg, from National Starch under the trade names HiCap 100, Capsul (amylodextrin octenylbutanedioate), Capsu1HS, Purity Gum 2000, Clear Gum Co03, UNI-PURE, HYLON VII; National Starch and Roquette Freres, respectively; from CereStar under the trade name C * EmCap or from Tate & Lyle.

In a preferred embodiment of the present invention a commercially available modified food starch is used, such as, e.g. eg HiCap 100 (from National Starch) and ClearGum Co03 (from Roquette Freres). It is especially advantageous that such a starch or an OSA starch in general is further improved according to a process as described in WO 2007/090614, especially according to a process as described in examples 28, 35 and / or 36 of WO 2007/090614.

Thus, in a further improved embodiment of the present invention, such a commercially available starch has been centrifuged as an aqueous solution or suspension prior to use. Centrifugation can be carried out at 1000 to 20000 g depending on the dry mass content of the modified polysaccharide in the aqueous solution or suspension. If the dry mass content of the modified polysaccharide in the aqueous solution or suspension is high, the applied centrifugal force is also high. For example, for an aqueous solution or suspension with a dry mass content of the modified polysaccharide of 30% by weight, a centrifugal force of 12000 g may be adequate to achieve the desired separation.

Centrifugation can be carried out at dry matter contents in the range of 0.1-60% by weight, preferably in the range of 10-50% by weight, more preferably in the range of 15-40% by weight at temperatures in the range of 2-99 ° C, preferably in the range of 10-75 ° C, most preferably in the range of 40-60 ° C.

The term "saccharide" in the context of the present invention encompasses mono-, di-, oligo- and polysaccharides, as well as any of their mixtures.

Examples of monosaccharides are fructose, glucose (= dextrose), mannose, galactose, sorbose, as well as any mixtures thereof.

Preferred monosaccharides are glucose and fructose, as well as any mixture thereof.

The term "glucose" in the context of the present invention does not only mean the pure substance, but also a glucose syrup with an ED> 90. This also applies for the other monosaccharides.

The term "dextrose equivalent" (DE) designates the degree of hydrolysis and is a measure of the amount of reducing sugar calculated as D-glucose based on dry weight; the scale is based on native starch which has a DE close to 0 and glucose which has a DE of 100.

Examples of disaccharides are sucrose, isomalt, lactose, maltose, and nigerose, as well as any mixture thereof.

An example of an oligosaccharide is maltodextrin.

An example of a polysaccharide is dextrin.

An example of a mixture of mono- and dis-saccharides is invert sugar (glucose fructose sucrose).

Mixtures of mono- and polysaccharides are commercially available, e.g. eg, under the trade names Glucidex IT 47 (ex Roquette Freres), Dextrose Monohydrate ST (ex Roquette Freres), Sirodex 331 (ex Tate & Lyle) and Glucamyl F 452 (ex Tate & Lyle).

In a preferred embodiment, the amount of the modified food starch is in the range of 20 to 80% by weight, more preferably in the range of 40 to 60% by weight, and the amount of the saccharide (adjuvant) is in the range of 5 to 30% by weight, based on the total amount of the composition.

More preferably, the microspheres are manufactured according to the procedure described below, whereby especially corn starch is used as a dust trapping agent. Most preferably, the microspheres thus resulting contain from 10 to 25% by weight of cornstarch, based on the total weight of the microsphere.

Microspheres are preferred, the preparation of which comprises the following steps:

a) providing a modified food starch, a saccharide, a water-soluble / fat-soluble antioxidant and a synthetic food grade AXN according to the present invention;

b) preparing an aqueous nano-emulsion of said ingredients;

c) converting the nano-emulsion into a microsphere through a dust capture process.

Human dietary supplements

For human dietary supplements any synthetic food grade AXN can be used as described above (with all preferences given).

"Human dietary supplements" means dietary supplements to be administered and consumed by humans.

The invention is now further illustrated in the following non-limiting examples.

Examples

Examples 1-2: Procedures to Obtain Food Grade Synthetic Astaxanthin

Example 1

120 g of astaxanthin (97%) containing 2000 mg / kg of dichloromethane are introduced into a 1000 ml steel autoclave under inert conditions with 680 ml of methanol. The autoclave is closed, the mixture is stirred at 350 rpm (rotations per minute) and heated to 105 ° C.

Once the desired internal temperature (105 ° C) is reached, the solvent is distilled off at a flow rate of 1.35 ml / min for 7 hours (meaning that 567 ml of methanol is distilled off). After that, the mixture is cooled to 25 ° C and diluted with 150 ml of methanol. The crystals are filtered off, washed with 150 ml of methanol and dried in a drying oven for 16 hours at 80 ° C under 20 mbara. 117.4 g of dry astaxanthin are obtained containing 55 mg / kg of dichloromethane and 57 mg / kg of methanol.

Example 2

120 g of astaxanthin (97%) containing 2000 mg / kg of dichloromethane are introduced into a 1000 ml steel autoclave under inert conditions with 680 ml of methanol. The autoclave is closed, the mixture is stirred at 350 rpm and heated to 110 ° C. Once the desired internal temperature (110 ° C) is reached, the solvent is distilled off at a flow rate of 1.4 ml / min for 7 hours (meaning that 588 ml of methanol is distilled off). After that, the mixture is cooled to 25 ° C and diluted with 170 ml of methanol. The crystals are filtered off, washed with 150 ml of methanol and dried in a drying oven for 16 hours at 80 ° C under 20 mbara. 117.2 g of dry astaxanthin are obtained containing 11 mg / kg of dichloromethane and 140 mg / kg of methanol. In principle it is possible to carry out example 1 or 2 as described above also at any other temperature in the range from 80 to 140 ° C instead of 105 ° C and 110 ° C, respectively. These other temperatures are, e.g. e.g. 80 ° C, 85 ° C, 90 ° C, 95 ° C, 100 ° C, 115 ° C, 120 ° C, 125 ° C, 130 ° C, 135 ° C, 140 ° C and any other temperature in between. Examples 1 and 2 can be repeated especially at a temperature of 115 ° C.

Examples 3-6: powder forms

Example 3: Microsphere Shape of 5% Astaxanthin

10 g of purified crystalline astaxanthin as obtained in Example 1 and 1.7 g of dl-α-tocopherol are dissolved in an appropriate solvent. This solution is added with stirring to a solution of 97.7 g of modified food starch (eg Capsul HS), 25.0 g of glucose syrup (eg Glucidex IT 47), 3.3 g of sodium ascorbate and 240 g of water at a temperature of 50 to 60 ° C. This pre-emulsion is homogenized with a rotorestator homogenizer for 20 minutes. Finally, the emulsion is homogenized with a high pressure homogenizer. In the Next step, the remaining solvent is distilled off and the solvent-free emulsion is dried by a standard dust capture process. 140 g of microspheres are obtained with an astaxanthin content of 5.7%.

Example 4: Microsphere Shape of 5% Astaxanthin

Example 3 can be repeated using purified crystalline astaxanthin as obtained in Example 2 instead of the purified crystalline astaxanthin as obtained in Example 1.

Example 5: Microsphere Shape of 10% Astaxanthin

20 g of crystalline astaxanthin purified as obtained in Example 1 and 1.7 g of dl-α-tocopherol are dissolved in an appropriate solvent. This solution is added with stirring to a solution of 81.7 g of modified food starch (eg Capsul HS), 13.3 g of glucose syrup (eg Glucidex IT 47), 8.3 g of sodium ascorbate and 230 g of water at a temperature of 50 to 60 ° C. This pre-emulsion is homogenized with a rotorestator homogenizer for 20 minutes. Finally, the emulsion is homogenized with a high pressure homogenizer. In the next step, the remaining solvent is distilled off and the solvent-free emulsion is dried using a standard dust capture process. 140 g of microspheres are obtained with an astaxanthin content of 12.0%.

Example 6: Microsphere Shape of 10% Astaxanthin

Example 5 can be repeated using purified crystalline astaxanthin as obtained in Example 2 instead of the purified crystalline astaxanthin as obtained in Example 1.

Examples 7-8: Oily Suspensions

Example 7: 10% Astaxanthin Fluid Suspension

A coarse suspension containing 60 g of purified crystalline astaxanthin as obtained in Example 1, 5.5 g of dl-α-tocopherol and 480 g of safflower oil is prepared by mixing at 45 ° C. For particle size reduction, this coarse suspension is continuously pumped through a stirred ball mill (diameter of zirconium dioxide beads: 0.4 mm, Dispermate SL C12 ball mill; VMA-Getzmann GmbH, Germany ) until the desired mean particle size is achieved (<2 microns). After 140 minutes of milling time, 450 g of an oily suspension are obtained with an astaxanthin content of 10.7% and an average particle size of 1.8 microns (measured with the Malvern Mastersizer 3000, presentation by Fraunhofer ).

Example 8: 10% Astaxanthin Fluid Suspension

Example 7 can be repeated using purified crystalline astaxanthin as obtained in Example 2 instead of the purified crystalline astaxanthin as obtained in Example 1.

Claims (7)

1. A process for the manufacture of food grade synthetic astaxanthin with a dichloromethane content <250 ppm, comprising the following steps: a) providing synthetic astaxanthin crystals containing dichloromethane; and b) adding methanol to synthetic astaxanthin in an amount to obtain a suspension of synthetic astaxanthin in methanol, whereby the amount of synthetic astaxanthin in said suspension is in the range of 5 to 50% by weight, based on the total weight of the suspension; and c) bringing the suspension obtained in step b) to a temperature in the range of 80 to 140 ° C, whereby the pressure is above atmospheric pressure; and d) maintaining the suspension at a temperature in the range of 80 to 140 ° C and at a pressure higher than atmospheric pressure, while the dichloromethane and methanol are separated by distillation until the amount of synthetic astaxanthin in said suspension is in the range from 25 to 75% by weight, based on the total weight of the suspension; with the proviso that the amount of synthetic astaxanthin in said suspension is greater than in the starting suspension obtained in step b); and e) cooling the synthetic astaxanthin suspension to a temperature in the range of 10 to 35 ° C; and f) optionally filtering the synthetic astaxanthin crystals; and g) drying the cooled synthetic astaxanthin suspension obtained in step e) or the filtered synthetic astaxanthin crystals obtained in step f); whereby during the process the synthetic astaxanthin is not completely dissolved in the methanol, and with which a synthetic astaxanthin of food grade with a content of dichloromethane <250 ppm is obtained. 2. The process according to claim 1, whereby in step c) the suspension is brought to a temperature in the range of 100 to 120 ° C, preferably to a temperature in the range of 105 to 115 ° C . 3. The process according to claim 1 or 2, wherein in step d) the dichloromethane and methanol are removed by distillation until the amount of synthetic AXN in said suspension is in the range of 35 to 65% in weight, preferably until the amount of synthetic AXN in said suspension is in the range of 45 to 55% by weight, based on the total weight of the suspension. 4. A process for the manufacture of food grade synthetic astaxanthin with a dichloromethane content <250 ppm, comprising the following steps: a) providing a synthetic astaxanthin solution containing dichloromethane; and b) adding methanol to the synthetic astaxanthin solution in an amount to obtain a suspension of synthetic astaxanthin in methanol, whereby the amount of synthetic astaxanthin in said suspension is in the range of 5 to 50% by weight, based on weight total suspension; and c) bringing the suspension obtained in step b) to a temperature in the range of 80 to 140 ° C, whereby the pressure is above atmospheric pressure; and d) maintaining the suspension at a temperature in the range of 80 to 140 ° C and at a pressure higher than atmospheric pressure, while the dichloromethane and methanol are separated by distillation until the amount of synthetic astaxanthin in said suspension is in the range from 25 to 75% by weight, based on the total weight of the suspension; with the proviso that the amount of synthetic astaxanthin in said suspension is greater than in the starting suspension obtained in step b); and e) cooling the synthetic astaxanthin suspension to a temperature in the range of 10 to 35 ° C; and f) optionally filtering the synthetic astaxanthin crystals; and g) drying the cooled synthetic astaxanthin suspension obtained in step e) or the filtered synthetic astaxanthin crystals obtained in step f); whereby during the process the synthetic astaxanthin is not completely dissolved in the methanol, and with which a synthetic astaxanthin of food grade with a content of dichloromethane <250 ppm is obtained. The process according to claim 4, wherein in step c) the suspension is brought to a temperature in the range of 100 to 120 ° C, preferably to a temperature in the range of 105 to 115 ° C. 6. The process according to claim 4 or 5, wherein in step d) the dichloromethane and methanol are removed by distillation until the amount of synthetic AXN in said suspension is in the range of 35 to 65% in weight, preferably until the amount of synthetic AXN in said suspension is in the range of 45 to 55% by weight, based on the total weight of the suspension. 7. The process according to claim 4, wherein after step a) and before step b) the following steps are performed: a2) optionally adding methanol to the synthetic astaxanthin solution from step a); and a3) removing dichloromethane by distillation; in the case that step a2) has been carried out by separating dichloromethane and methanol by distillation.