EP1713746A2

EP1713746A2 - Method for producing dry powders of one or several carotenoids

Info

Publication number: EP1713746A2
Application number: EP05707139A
Authority: EP
Inventors: Jesper Feldthusen-Jensen; Helmut Auweter; Andreas Habich; Erik LÜDDECKE; Angelika-Maria Pfeiffer
Original assignee: BASF SE
Current assignee: BASF SE
Priority date: 2004-02-06
Filing date: 2005-02-02
Publication date: 2006-10-25
Also published as: WO2005075385A3; CN1942106A; JP2007521812A; CA2552931A1; DE102004006106A1; US20070173547A1; NO20063962L; WO2005075385A2

Abstract

The invention relates to a method for producing dry powders of one or several carotenoids, said method being characterised in that a) one or several carotenoids are suspended in an aqueous molecularly dispersed or colloidally dispersed solution of a mixture consisting of trehalose and at least one protein-containing protective colloid and b) the obtained suspension is transformed into a dry powder by separation of water and, optionally, additionally used solvents and by subsequent drying, optionally in the presence of a coating material.

Description

Process for the preparation of dry powders of one or more carotenoids

description

The invention relates to a process for the preparation of dry powders of one or more carotenoids, preferably xanthophyll-containing dry powders, in particular xanthophylls, selected from the group consisting of astaxanthin, canthaxanthin, lutein, zeaxanthin, citranaxanthin and β-apo-8'-carotenic acid - ethyl ester.

The class of carotenoids is classified into two main groups, the carotenes and the xanthophylls. In contrast to the carotenes, which are pure polyene hydrocarbons, such as, for example, β-carotene or lycopene, oxygen functions such as hydroxyl, epoxy and / or carbonyl groups also occur in the xanthophylls. Typical representatives of this group include Astaxanthin, canthaxanthin, lutein and zeaxanthin.

The oxygen-containing carotenoids also include citranaxanthin and ß-apo-8'-carotenic acid ethyl ester.

Oxygenated carotenoids are widespread in nature and include in corn (zeaxanthin), in green beans (lutein), in peppers (capsanthin), in egg yolks (lutein) as well as in crayfish and salmon (astaxanthin), giving these foods their characteristic color.

These polyenes, which are both synthetically accessible and isolable from natural sources, represent important color bodies for the food and animal feed industries and for the pharmaceutical sector and, as in the case of astaxanthin, are active ingredients with provitamin A activity in salmon.

Both carotenes and xanthophylls are insoluble in water, while only a low solubility is found in fats and oils. This limited solubility as well as the high sensitivity to oxidation stand in the way of direct application of the relatively coarse-grained products obtained by chemical synthesis in the coloring of food and animal feed, since the substances in coarse-crystalline form do not provide storage stability and only give poor coloring results. These effects, which are disadvantageous for the practical use of the xanthophylls, have an effect in particular in the aqueous medium.

Improved color yields can only be achieved in the direct coloring of foods only through specifically produced formulations in which the active ingredients are present in finely divided form and, if appropriate, protected against oxidation by protective colloids. len. In addition, these formulations used in animal feed lead to a higher bioavailability of the carotenoids or xanthophylls and thus indirectly to better coloring effects, for example in egg yolk or fish pigmentation.

To improve the. Color yields and to increase the resorbability or bioavailability, various processes have been described, all of which have the aim of reducing the crystallite size of the active ingredients and bringing them to a particle size range of less than 10 // m.

Numerous methods, including described in Chimia 21, 329 (1967), WO 91/06292 and WO 94/19411, use the grinding of carotenoids by means of a colloid mill and thus achieve particle sizes of 2 to 10 μm.

There are also a number of combined emulsification / spray drying processes, e.g. in DE-A-12 11 911 or in EP-A-0410236.

According to European patent EP-B-0 065 193, finely divided, powdered carotenoid preparations are prepared by dissolving a carotenoid in a volatile, water-miscible organic solvent at elevated temperatures, optionally under increased pressure, by mixing the carotenoid with a precipitates aqueous solution of a protective colloid and then spray dried.

An analogous process for the production of finely divided, powdered carotenoid preparations is described in EP-A-0 937412 using water-immiscible solvents.

In the nanoparticulate active substance dispersions of xanthophylls prepared according to EP-B-0065 193, however, the following phenomena can often be observed.

The aqueous, xanthophyll-containing active ingredient dispersions are often colloidally unstable, particularly when concentrated. Due to flocculation of the active ingredient particles, which partially sediment, partially cream, a further transfer of the dispersion into a dry powder is no longer possible.

Thus, the high requirements for formulations containing xanthophyll in terms of color effect and bioavailability due to the problems described with the above-mentioned. Procedures are not always met.

Another disadvantage of gelatins is their strong adhesive properties. With the usual drying methods for liquid systems such as spray drying, it can when using gelatin-containing products, thread formation or caking occur.

In addition, consumer acceptance of products containing gelatin is becoming less and less.

Only relatively low concentrations of fat-soluble substances can often be embedded in other frequently used protective colloids such as gum arabic, starch, dextrins, pectin or tragacanth. In addition, gum arabic in particular was not always available in sufficient quality in the past due to poor harvests.

Synthetic colloids such as polyvinylpyrrolidone or partially synthetic polymers such as cellulose derivatives also have a limited emulsifying capacity and are not always accepted, especially in the food sector.

DE-A-44 24 085 describes the use of partially degraded soy proteins as protective colloids for fat-soluble active ingredients. The soy proteins disclosed here have a degree of degradation of 0.1 to 5%. The color strength of the formulations produced using these protective colloids is not always satisfactory.

German Offenlegungsschrift DE-A-101 04494 describes the production of carotenoid dry powders using soy proteins together with lactose as protective colloids. Despite improved cold water redispersibility and increased coloring power of the carotenoid preparations disclosed here, the storage stability of these formulations, especially when the active ingredient content is high, is not always satisfactory.

The object of the present invention was therefore to propose processes for the preparation of carotenoid-containing dry powders, in particular dry powders of oxygen-containing carotenoids, which do not have the above-mentioned disadvantages of the prior art and which enable a high carotenoid content in the preparation to achieve.

This object was achieved according to the invention with a method for producing dry powders of one or more carotenoids, characterized in that

a) suspending one or more carotenoids in an aqueous molecularly disperse or colloidally disperse solution of a mixture of trehalose and at least one protective colloid containing protein and b) the suspension formed is separated into a dry powder by separating off the water and, if appropriate, additionally used solvents and subsequent drying, if appropriate in the presence of a coating material.

Protective colloids containing protein are:

Gelatin, for example pork or fish gelatin, in particular acidic or basic degraded gelatin with Bloom numbers in the range from 0 to 250, very particularly preferably gelatin A 100 and A 200, and low molecular weight, enzymatically degraded gelatin types with the Bloom number 0 and molecular weights of 15,000 up to 25,000 D such as Collagel A and Gelitasol P (Stoess, Eberbach) and mixtures of these types of gelatin;

Casein and / or a caseinate, for example sodium caseinate;

Plant proteins such as soybean, rice and / or wheat proteins, these plant proteins being partially degraded or in undegraded form.

Casein or a caseinate or mixtures thereof are used as preferred protective colloids in the context of the present invention. Sodium caseinate is a particularly preferred protective colloid.

A preferred embodiment of the above. The process is characterized in that the suspension produced in process step a) is ground into a dry powder before being transferred. In this case, the active ingredient [the carotenoid (s)] is preferably suspended in crystalline form before the grinding process.

The grinding can be carried out in a manner known per se, e.g. done with a ball mill. Depending on the type of mill used, grinding is carried out until the particles have an average particle size D [4.3], determined via Fraunhofer diffraction, of 0.1 to 100 μm, preferably 0.2 to 50 μm, particularly preferably 0.2 to 20 μm , very particularly preferably 0.2 to δμm, in particular 0.2 to 0.8 microns. The term D [4,3] denotes the volume-weighted mean diameter (see manual for Malvern Mastersizer S, Malvern Instruments Ltd., UK).

More details about the grinding and the equipment used for it can be found, among others. in Ullmann's Encyclopedia of Industrial Chemistry, Sixth Edition, 2000, Electronic Release, Size Reduction, Chapter 3.6 .: Wet Grinding and in EP-A-0498824.

A likewise preferred variant of the method according to the invention is characterized in that the suspension in stage a) contains the following steps: ai) dissolving one or more carotenoids in a water-miscible organic solvent or in a mixture of water and a water-miscible organic solvent or

a ₂ ) dissolving one or more carotenoids in a water-immiscible organic solvent and

a ₃ ) Mixing the solution obtained according to aj) or a ₂ ) with an aqueous molecularly disperse or colloidally disperse solution of a mixture of trehalose and at least one protein-containing protective colloid, the hydrophobic phase of the carotenoid being formed as a nanodisperse phase.

The water-miscible solvents used in stage ai) are above all water-miscible, thermally stable, volatile solvents containing only carbon, hydrogen and oxygen, such as alcohols, ethers, esters, ketones and acetals. Such solvents are expediently used which are at least 10% water-miscible, have a boiling point below 200 ° C. and / or have less than 10 carbons. Methanol, ethanol, n-propanol, isopropanol, 1,2-butanediol-1-methyl ether, 1,2-propanediol-1-n-propyl ether, tetrahydrofuran or acetone are particularly preferably used.

In the context of the present invention, the term “a water-immiscible organic solvent” stands for an organic solvent with a water solubility at normal pressure of less than 10%. Possible solvents include halogenated aliphatic hydrocarbons, e.g. Methylene chloride, chloroform and carbon tetrachloride, carboxylic acid esters such as dimethyl carbonate, diethyl carbonate, propylene carbonate, ethyl formate, methyl, ethyl or isopropyl acetate and ethers such as methyl tert. butyl ether in question. Preferred water-immiscible organic solvents are the following compounds from the group consisting of dimethyl carbonate, propylene carbonate, ethyl formate, ethyl acetate, isopropyl acetate and methyl tert. butyl ether.

The process according to the invention is preferably the production of dry powders of oxygen-containing carotenoids, particularly preferably compounds, selected from the group consisting of astaxanthin, canthaxanthin, lutein, zeaxanthin, citranaxanthin and ß-apo-δ'-carotenic acid ethyl ester, very particularly preferred around astaxanthin and canthaxanthin.

The above-mentioned dry powders are advantageously produced by at least one of the carotenoids in a water-miscible organic solvent at temperatures above 30 ° C., preferably between 50 ° C. and 240 ° C., in particular whose 100 ° C to 200 ° C, particularly preferably 140 ° C to 180 ° C, optionally under pressure, dissolves.

Since exposure to high temperatures may all-trans isomer content may reduce the desired high, dissolving the / the carotenoid (s) as quickly as possible, for example in the seconds range, for example in 0.1 to 10 seconds, particularly ^■ preferably in less than 1 second , For the rapid preparation of the molecularly disperse solution, the use of elevated pressure, for example in the range from 20 bar to 80 bar, preferably 30 to 60 bar, can be advantageous.

The molecularly disperse solution thus obtained is then mixed directly with the optionally cooled aqueous molecularly disperse or colloidally disperse solution of the mixture of trehalose and at least one protein-containing protective colloid in such a way that a mixture temperature of about 35 ° C. to 80 ° C. is established.

The solvent component is transferred into the aqueous phase and the hydrophobic phase of the carotenoid (s) is formed as a nanodisperse phase.

With regard to a more detailed description of the process and apparatus for the above-mentioned dispersion, reference is made to EP-B-0065 193 at this point.

The invention also relates to a method for producing an astaxanthin dry powder, characterized in that

a) dissolves astaxanthin in a water-miscible organic solvent or a mixture of water and a water-miscible organic solvent at temperatures above 30 ° C.,

b) the solution obtained is mixed with an aqueous molecularly disperse or colloidally disperse solution of a mixture of trehalose with casein or a caseinate or a mixture of trehalose with casein and a caseinate and

c) the suspension formed is transferred to a dry powder.

This is very particularly preferably a method for producing astaxanthin-containing dry powder using a mixture of trehalose and casein and / or sodium caseinate, in particular from trehalose and sodium caseinate.

The conversion into a dry powder can be carried out, inter alia, by spray drying, spray cooling, freeze drying or drying in a fluidized bed, if appropriate also in a presence of a covering material. Suitable coating agents include corn starch, silica or tricalcium phosphate.

To increase the stability of the active ingredient against oxidative degradation, it is advantageous to use stabilizers such as α-tocopherol, t-butyl-hydroxy-toluene, t-butylhydroxyanisole, ascorbic acid, sodium ascorbate or ethoxyquin in a concentration of 2 to 10% by weight, preferably 3 to 7% by weight, based on the dry weight of the powder. They can be added to either the aqueous or the solvent phase, but they are preferably dissolved together with the active ingredients in the solvent phase.

To increase the stability of the active ingredient against microbial degradation, it may be appropriate to add preservatives such as e.g. Add methyl 4-hydroxybenzoate, propyl 4-hydroxybenzoate, sorbic acid or benzoic acid or their salts.

Under certain circumstances, it may also be advantageous to additionally use a physiologically approved oil such as, for example, sesame oil, corn oil, cottonseed oil, soybean oil or peanut oil and esters of medium-chain vegetable fatty acids in a concentration of 0 to 500% by weight, preferably, in the solvent phase 10 to 300% by weight, particularly preferably 20 to 100% by weight, based on the xanthophyll (s), which is then precipitated together with the active ingredients and the additives mentioned in extremely fine particles when mixed with the aqueous phase.

The ratio of protective colloid and trehalose to carotenoid is generally chosen so that an end product is obtained which contains 0.1 to 40% by weight, preferably 1 to 35% by weight, particularly preferably 5 to 30% by weight particularly preferably 10 to 25% by weight of at least one carotenoid, 1 to 40% by weight, preferably 2 to 30% by weight, particularly preferably 3 to 20% by weight, very particularly preferably 5 to 15% by weight at least one protective colloid and 10 to 80 wt .-%, preferably 20 to 75 wt .-%, particularly preferably 30 to 70 wt .-%, very particularly preferably 40 to 60 wt .-% trehalose, all percentages based on the dry weight of the Powder, and optionally small amounts of stabilizers and preservatives.

The invention also relates to dry powder of carotenoids, obtainable by one of the processes mentioned at the beginning.

These are preferably dry powders containing oxygen-containing carotenoids, selected from the group consisting of astaxanthin, canthaxanthin, lutein, zeaxanthin, citranaxanthin and ß-apo-8'-carotenic acid ethyl ester, particularly preferably canthaxanthin and astaxanthin, very particularly prefers astaxanthin. The astaxanthin content in the preparations according to the invention is preferably in the range from 10 to 25% by weight.

The dry powders according to the invention are distinguished, inter alia, by characterized in that they can be redispersed again without problems in aqueous systems while achieving a uniform fine distribution of the active ingredient in the grain size range less than 1 μm.

The use of a combination of trehalose and protein-containing protective colloids, in particular casein or sodium caseinate, as formulation auxiliaries has the advantage over other sugars, for example lactose or sucrose, that the carotenoid formulations produced therewith have a particularly high storage stability (see table).

The above-mentioned dry powders are particularly suitable as an additive for food and animal feed as well as an additive for pharmaceutical preparations. Typical areas of application for dry powder containing carotenoids in the animal feed sector are, for example, fish pigmentation in aquaculture and egg yolk and broiler skin pigmentation in poultry farming.

The implementation of the method according to the invention is explained in more detail in the examples below.

example 1

Preparation of an astaxanthin dry powder using a combination of trehalose and sodium caseinate

66 g of crystalline astaxanthin and 15 g of α-tocopherol were suspended in 496 g of an azeotropic isopropanol / water mixture at room temperature in a heatable receiver at a temperature of 30 ^° C. The active ingredient suspension was then heated to 90 ^C C and at a flow rate of 3.6 kg / h with further isopropanol / water azeotrope temperature of 220 ° C and a flow rate of 4.6 kg / h mixed, the astaxanthin at an established mixing temperature of 165 ° C at a pressure of 55 bar. This active ingredient solution was immediately mixed with an aqueous phase consisting of a solution of 29 g sodium caseinate and 166 g trehalose in 8724 g distilled water, in which the pH was adjusted to pH 9.5 with 1 M NaOH, at a flow rate of 55 kg / h mixed.

The active ingredient particles formed in the mixture had a particle size of 130 nm in the isopropanol / water mixture, with an E1 / 1 value ¹⁾ of 117. The active ingredient suspension was then concentrated on a thin-film evaporator to a concentration of approximately 27.4% by weight dry matter and spray-dried. The dry powder had an astaxanthin content of 22.4% by weight. The dry powder redispersed in water had a particle size of 141 nm and had an E1 / 1 value of 120.

^{1) In} this context, the E1 / 1 value defines the specific extinction of a 0.5% aqueous dispersion of a 20% by weight dry powder in a 1 cm cell at the absorption maximum.

Example 2 (comparative example)

Preparation of an astaxanthin dry powder using a combination of lactose and sodium caseinate

83.5 g of crystalline astaxanthin and 20 g of α-tocopherol were suspended in 626 g of an azeotropic isopropanol / water mixture at room temperature in a heatable receiver at a temperature of 30 ° C. The active ingredient suspension was then heated to 90 ^C C and at a flow rate of 2.1 kg / h with further isopropanol / water azeotrope temperature of 220 ° C and a flow rate of 2.6 kg / h mixed, the astaxanthin at an established mixing ^temperature of 165 ^C C at a pressure of 55 bar. This active ingredient solution was immediately followed by an aqueous phase consisting of a solution of 83.5 g sodium caseinate and 177 g lactose in 20 580 g distilled water, in which the pH was adjusted to pH 9.5 with 1 M NaOH Flow rate of 60 kg / h mixed.

The active ingredient particles formed in the mixture had a particle size of 133 nm in the isopropanol / water mixture, with an E 1/1 value of 123.

The active ingredient suspension was then concentrated on a thin-film evaporator to a concentration of approximately 6.9% dry content and spray-dried. The dry powder had an astaxanthin content of 22.5% by weight. The dry powder redispersed in water had a particle size of 167 nm and had an E1 / 1 value of 123. Example 3 (comparative example)

Preparation of an astaxanthin dry powder using a combination of lactose and soy protein

83.5 g of crystalline astaxanthin and 20 g of α-tocopherol were suspended in 626 g of an azeotropic isopropanol / water mixture at room temperature in a heatable receiver at a temperature of 30 ^° C. The active ingredient suspension was then heated to 90 ° C. and, at a flow rate of 2.1 kg / h, was continuously mixed with further isopropanol / water azeotrope at a temperature of 220 ° C. and a flow rate of 2.6 kg / h, with astaxanthin at an established mixing temperature of 165 ° C at a pressure of 55 bar. This active ingredient solution was immediately followed by an aqueous phase consisting of a solution of 83.5 g soy protein and 177 g lactose in 11010 g distilled water, in which the pH was adjusted to pH 9.5 with 1 M NaOH Flow rate of 32.5 kg / h mixed.

The active ingredient particles formed in the mixture had a particle size of 107 nm in the isopropanol / water mixture, with an E 1/1 value of 124.

The active ingredient suspension was then concentrated on a thin-film evaporator to a concentration of approximately 23.7% dry content and spray-dried. The dry powder had an astaxanthin content of 23% by weight. The dry powder redispersed in water had a particle size of 317 nm and an E1 / 1 value of 101.

Example 4 (comparative example)

Production of an astaxanthin dry powder using a combination of dried glucose syrup (Glucidex ^® 47, Roquette Freres) and sodium caseinate

66 g of crystalline astaxanthin and 15 g of α-tocopherol were suspended in 496 g of an azeotropic isopropanol / water mixture at room temperature in a heatable receiver at a temperature of 30 ° C. The active ingredient suspension was then heated to 90 ° C. and, at a flow rate of 3.6 kg / h, was continuously mixed with further isopropanol / water azeotrope at a temperature of 220 ° C. and a flow rate of 4.6 kg / h, with astaxanthin at an established mixing temperature of 165 ° C at a pressure of 55 bar. Immediately afterwards, this active ingredient solution was adjusted with an aqueous phase consisting of a solution of 28.7 g sodium caseinate and 165.6 g Glucidex 47 in 8724 g distilled water, in which the pH was adjusted to 9.5 with 1 M NaOH was mixed at a flow rate of 56 kg / h. The active ingredient particles formed in the mixture had a particle size of 144 nm in the isopronal / water mixture, with an E1 / 1 value of 115.

The active ingredient suspension was then concentrated on a thin-film evaporator to a concentration of approximately 19.4% dry content and spray-dried. The dry powder had an astaxanthin content of 23.6% by weight. The dry powder redispersed in water had a particle size of 623 nm and had an E1 / 1 value of 119.

Example 5 (comparative example)

83.5 g of crystalline astaxanthin and 20 g of α-tocopherol were suspended in 626 g of an azeotropic isopropanol / water mixture at room temperature in a heatable receiver at a temperature of 30 ° C. The active ingredient suspension was then heated to 90 ° C. and, at a flow rate of 3.6 kg / h, was continuously mixed with further isopropanol / water azeotrope at a temperature of 220 ° C. and a flow rate of 4.6 kg / h, with astaxanthin at an established mixing temperature of 165 ° C at a pressure of 55 bar. This active ingredient solution was immediately followed by an aqueous phase consisting of a solution of 83.5 g sodium caseinate and 177 g Glucidex 47 in 11010 g distilled water, in which the pH was adjusted to 9.5 with 1 M NaOH Flow rate of 56 kg / h mixed.

The active ingredient particles formed in the mixture had a particle size of 155 nm in the isopronal / water mixture, with an E1 / 1 value of 116.

The active ingredient suspension was then concentrated on a thin film evaporator to a concentration of approximately 25% dry content and spray-dried. The dry powder had an astaxanthin content of 22.3% by weight. The dry powder redispersed in water had a particle size of 179 nm and had an E 1/1 value of 117. Table: Storage stability of the Astaxanthin dry powder (heat test at 60 ° C)

Claims

claims:

1. A process for the preparation of dry powders of one or more carotenoids, characterized in that a) one or more carotenoids are suspended in an aqueous molecularly disperse or colloidally disperse solution of a mixture of trehalose and at least one protective colloid containing protein, and b) the suspension formed by separating off the water and optionally additionally used solvent and subsequent drying, optionally in the presence of a coating material, are converted into a dry powder.

2. The method according to claim 1, characterized in that the suspension produced in process step a) is ground before being transferred into a dry powder.

3. The method according to claim 1, characterized in that the suspension in step a) comprises the following steps: a ^ dissolving one or more carotenoids in a water-miscible organic solvent or in a mixture of water and a water-miscible, organic Solvent or a ₂ ) dissolving one or more carotenoids in a water-immiscible organic solvent and a ₃ ) mixing the solution obtained according to a or a ₂ ) with an aqueous molecular or colloidal solution of a mixture of trehalose and at least one protein-containing Protective colloid, the hydrophobic phase of the carotenoid being formed as a nanodisperse phase.

4. The method according to any one of claims 1 to 3, characterized in that casein or a caseinate or mixtures thereof are used as protective colloid.

5. The method according to any one of claims 1 to 4, characterized in that the carotenoids used are oxygen-containing carotenoids.

6. The method according to any one of claim 5, characterized in that the oxygen-containing carotenoids are compounds selected from the group consisting of astaxanthin, canthaxanthin, lutein, zeaxanthin, citranaxanthin and ß-apo-8'-carotenic acid ethyl ester ,

7. A process for producing an astaxanthin dry powder, characterized in that a) astaxanthin is dissolved in a water-miscible organic solvent or a mixture of water and a water-miscible organic solvent at temperatures above 30 ^° C., b) the resultant Mixing solution with an aqueous molecularly disperse or colloidally disperse solution of a mixture of trehalose with casein or a caseinate or a mixture of trehalose with casein and a caseinate and c) converting the suspension formed into a dry powder.

8. The method according to claim 7, characterized in that a mixture of trehalose and sodium caseinate is used as protective colloid in process step b).

9. Carotenoid-containing dry powder, obtainable by a process defined in accordance with one of claims 1 to 8.

10. Dry powder according to claim 9 with a carotenoid content of 0.1 to 40 wt .-%.

11. Dry powder according to claim 10, containing 10 to 25 wt .-% astaxanthin.

12. Use of the carotenoid-containing dry powder, defined according to one of claims 9 to 11, as an additive to foods, pharmaceuticals and / or animal feeds.