WO2016146802A1 - Astaxanthin compositions (ii) - Google Patents

Abstract

The invention relates to astaxanthin compositions for use in foods, food supplements or animal feed or as a medicament. Astaxanthin compositions, which contain at least 80 wt.%, in particular at least 90 wt.%, especially at least 95 wt.%, relative to the total weight of astaxanthin and astaxanthin derivatives in the composition, a monoester of the astaxanthin having an aliphatic, unbranched C₁₈-C₂₂-monocarboxylic acid, have a particularly high bioavailability. They are therefore particularly suitable for use in foods, food supplements or animal feed and for therapeutic use as a medicament and as an ingredient for medical preparations or pharmaceutical agents.

Description

 Astaxanthin Compositions (II)

The present invention relates to astaxanthin compositions for use in

 Food, dietary supplements or feed or as a medicament.

Astaxanthin (3,3'-dihydroxy-ß, ß-carotene-4,4'dione) is a red carothinoid dye from the group of xanthophylls, which is described by the following formula (shown is the all-trans isomer).

Astaxanthin, hereinafter also AXT, has an asymmetric center in the 3 'and 3' position and can therefore be used as a mixture of diastereomers of (3R, 3'R) -, (3S, 3'S) - and (3S, 3'R) - Isomers, as a racemate of (3R, 3'R) and (3S, 3'S) are present in the form of pure isomers or. Synthetic AXT is often a mixture of diastereomers (3S, 3'S), (3R, 3'S) and

 (3R, 3'R). Natural extracted AXT can be in nearly pure (3S, 3'S) or (3R, 3'R) form, depending on the natural source. Similarly, enantiomerically pure astaxanthin is accessible by total synthesis.

Astaxanthin is produced predominantly synthetically - see G. Britton, S. Liaanen- Jensen, H. Pfander (Editor), Carotenoids, Vol. 2, Birkhäuser Verlag, Basel, 1996, in particular S. 1 1, pp. 267 et seq Pp. 281 ff. And references cited therein; B. Schäfer, natural products of the chemical industry, Academic Publishing House, Heidelberg, 2007, p. 427 et seq. And references cited therein; EP 1 197483, EP 1285912. In addition to synthetic astaxanthin production, astaxanthin can also be obtained on an industrial scale from the blood rain algae (Haematococcus pluvialis) (EA Johnson, GH An, Crit Rev. Biotechnol., 1991, 1: 297-326). , This gives a complex mixture of mono- and difatty acid esters of astaxanthin - see also D. Breithaupt, J. Agric. Food. Chem. 2004, 52: 3870-3875.

Astaxanthin is approved as a feed additive and is primarily referred to as

 Feed ingredient used for various animals, especially for salmon and

Trout. Thus, AXT has a vitamin-like effect has a positive effect on the fertility and the immune defense of fish in breeding facilities and leads to an attractive pigmentation of the meat. Astaxanthin is also used as an additive for dietary supplements, used as a cosmetic additive with antioxidant properties or as a food colorant. AXT can protect the skin from the stress caused by UV radiation and in this function has a much stronger effect than vitamin E. AXT complements the protective effect of sunscreen and is not washable.

More recently, it has been reported that AXT is basically suitable for the treatment of a number of different disorders - see, for example, B.J.H. Weisburger, Am. J. Clin. Nutr. 1991, 53: 226S-237S; M. Guerin, Trends in Biotechnology, 2003, 21: 210-216; Ghazi Hussein et al., J. Nat. Prod., 2006, 69: 443-449, Astaxanthin and Human Health - Literature Survey: http: //www.astapure- algatech.com/Data/Sub2_1/Files/algatechnologies.pdf, each with additional evidence.

Thus, in vivo studies on animal models suggest that AXT lowers blood sugar levels and improves various parameters of the metabolic syndrome (Uchiyama K., Redox., Rep. 2000, 7 (5): 290-3, G. Hussein et al 2007, 100 (Suppl. 1): 176p, M. Ikeuchi et al., Biosci, Biotechnol., Biochem., 2007, 71: 893-9, Naito, Y., K. Uchiyama, et al.

Biofactors 2004, 20 (1): 49-59).

In high blood pressure models, AXT increases blood flow and vascular tone - see, eg, B. Yanai et. al. (2008) Integrated Blood Pressure Control 1: 1-3.

Epidemiological studies suggest that carotenoids such as astaxanthin have beneficial effects on heart disease - D.A. Cooper et al., Nutr. Rev. 1999, 57: 210-214, J. Krappi et. al., Int. J. Nutr. Res. 2006, 77 (1): 3-1 1. Due to its antioxidant activity, in particular its effect to inhibit the oxidation of low-density lipoproteins, carotenoids such as astaxanthin are proposed for the prevention of arteriosclerosis - see T. Iwamoto et al. , J. Atheroscler. Thromb. 2000, 7: 216-222.

Furthermore, it has been reported on several occasions that the administration of AXT reduces the risk of cancer - see J.H. Weisburger, Am. J. Clin. Nutr. 1991, 53: 226S - 237S. In vivo

 Studies in mice show that astaxanthin slows or even inhibits tumor growth, in particular of breast cancers, bladder carcinomas and lung carcinoma - see B.P. Chew et al., Anticancer Res. 1999, 19: 1849-1853, T. Tanaka et al. Carcinogenesis 1994, 15: 15-19 and D.A. Cooper et al., Nutr. Rev. 1999, 57: 133-145. In addition, AXT appears to promote the formation of connexin 43 and therefore has a chemoprotective effect against other cancers (see A. L. Vine et al., Nutr., Cancer 52 (1) (2005), 105-1 13).

Astaxanthin also plays a role in modulating the immune system - see H.

Jyonouchi et al. J. Nutr. 1995, 125: 1570-1573, - and has anti-inflammatory activity J. Park, et al. Nutr. Metab. 2010, 7: 18-27, Kurashige et al. Physiol. Chem. Phys. Med. 1990, NMR22: 27-38, K. Ohgami et al. Investigative Ophthalmology & Visual Sei. 2003, 44 (6): 2694-2701 and Y. Suzuki et al. Exp. Eye Res. 2006, 82 (2): 275-281. It was also used to treat

Autoimmune diseases such as Crohn's disease have been proposed.

Furthermore, astaxanthin is proposed for the treatment of joint diseases, in particular for improving the symptoms of inflammatory joint diseases - see Y. Nir, G. Spiller C. Multz C. Effect of an astaxanthin-containing product on carpal tunnel syndrome. American College of Nutrition Annual Meeting, San Antonio, Texas, October 2002, Y. Nir, G. Spiller. Los Altos, California: Health Research and Studies Center 2002. Y. Nir, G. Spiller. J Am Coli Nutr, 2002, 21.

In animal models it has been shown that the administration of AXT favorably influences the course of bacterial infections, in particular inflammation of the gastrointestinal tract, caused by Helicobacter pylori infections - see M.

Bennedsen et al., Immunol. Lett. 1999, 70: 185-189.

Further, astaxanthin is proposed for the prevention of ocular diseases such as damage to the lens and retina by UV radiation, macular degeneration, cataract and glaucoma to improve male fertility, memory and attention and physical performance - K. Sawaki et al. Journal of Clinical Therapeutics & Medicines, 2002, 18: 73-88.

Astaxanthin can significantly help to delay skin aging and reduce the appearance of wrinkles, age spots and freckles - Suganuma K et al., Jichi Medical University Journal. 2012, 35: 25-33; K. Tominaga K et al., Acta Biochim Pol.

2012; 59 (1): 43-7; E. Yamashita, Carotenoid Science. 2006; 10: 91-5; Satoh et al. Oyo Yakuri Pharmacometrics, 201 1, 80 (1/2): 7-1 1.

Basically astaxanthin is therefore of interest for the production of medicines as well as for feed, food and nutritional supplements, especially those for human nutrition. However, it proves to be particularly problematical that astaxanthin is poorly absorbed by the human or animal organism when administered orally, and that the serum levels achieved in the blood or lymph serum are only slight. B.R.M. Clark et al. Lipids 2000, 35: 803-806; J. Mercke Odeberg et al., Europ. J.

Pharm. 2003, 19: 299-304, M. Osterlie et al., J. Nutr. Biochem, 2000, 1: 482-490. Another problem is the low solubility of astaxanthin in excipients suitable for the preparation of nutritional supplements and medicaments. Although this problem can be partially solved by esterification of astaxanthin with fatty acids. However, surprisingly, the diesters of astaxanthin with fatty acids show comparable properties with respect to the achievable serum levels as unesterified astaxanthin - see DA White et al., Aquacult. Res. 2002, 33: 343-350, Odeberg et al., Eur. J. Pharmac. Sciences 2003, 19: 299-304, Miyazawa et al., Biosci Biotechnol Biochem, 201 1, 76: 1856-1858, Osterlie et al., J. Nutr. Biochem., 11, 2000: 482-490,, Okada et al., Biosci.

Biotechnol. Biochem., 2009, 73: 1928-32 ,. Coral-Hinostroza et al., Comparative Biochemistry and Physiology, Part C, 139, 2004: 99-1 10. It is known that absorption of astaxanthin is by passive diffusion into the intestinal epithelium - which requires some amount of fat and therefore can be promoted by fats in food (see GN Coral-Hinostroza et al., Comp. Biochem.

Physiol. Part C 2004, 139: 99-1 10 with further evidence). J. Mercke Odeberg et al., Europ. J. Pharm. 2003, 19: 299-304, describe that the oral bioavailability of

Astaxanthin can be improved by special fat-based formulations, wherein the emulsifiers used here have a strong influence on the bioavailability. The improvement of oral bioavailability by formulations, however, limits and limits the potential applications of astaxanthin.

Our own investigations have shown that the "natural astaxanthin", a complex astaxanthin-fatty acid ester mixture derived from the blood rain algae {Haematococcus pluvialis), has a higher content compared to astaxanthin or difatty acid esters of the

Astaxanthin has improved oral bioavailability. However, the commercial availability of natural astaxanthin is very limited. Due to the complexity of such a mixture, it is not very attractive for pharmaceutical applications.

It is therefore an object of the present invention to overcome the disadvantages of the prior art, and in particular to provide astaxanthin derivatives or compositions which, on the one hand, have better oral bioavailability and which, moreover, are more readily accessible than the natural derived from the rain algae {Haematococcus pluvialis) astaxanthin ".

The older European patent application 14184483.7 describes the production of

Difatty acid esters of astaxanthin by esterification of astaxanthin with fatty acid chloride in the presence of a tertiary amine base. If, instead of the acid chloride, the free acid is used, predominantly the monofatty acid ester is formed, which can be obtained from the reaction mixture by removal of unreacted astaxanthin. In addition, it is possible to obtain the monofatty acid esters by using substoichiometric amounts of acid chloride in admixture with unreacted astaxanthin and difatty acid esters. The monoester can be isolated from the mixture, for example by chromatography.

It has now surprisingly been found that astaxanthin compositions containing at least 80 wt .-%, in particular at least 90 wt .-%, especially at least 95 wt .-%, based on the total weight of astaxanthin and astaxanthin derivatives in the

Composition, a monoester of astaxanthin with an aliphatic, unbranched Ci8-C22 monocarboxylic acid, have a particularly good bioavailability. The invention therefore relates to the use of astaxanthin compositions in foods, dietary supplements or animal feed, wherein the

Astaxanthin compositions at least 80 wt .-%, in particular at least 90% by weight, especially at least 95 wt .-%, based on the total weight of astaxanthin and astaxanthin derivatives in the composition, a monoester of astaxanthin with an aliphatic, unbranched Ci8-C22 monocarboxylic acid contain.

The invention also relates to those described here and below

Astaxanthin compositions for therapeutic use as a medicament and as an ingredient for medical preparations or pharmaceutical agents. Accordingly, the invention also relates to a medicament which is an inventive

Astaxanthin composition and at least one suitable for pharmaceutical purposes adjuvant.

The present invention also relates to additives for foods comprising the astaxanthin composition of the invention and at least one food additive, d. H. at least one food grade adjuvant. The present invention further relates to additives for feed comprising the astaxanthin composition of the invention and at least one additive suitable for feed, d. H. at least one feed suitable for feed.

The present invention also relates to dietary supplements comprising the astaxanthin composition of the invention and at least one supplement suitable for dietary supplements, i. H. at least one adjuvant suitable for dietary supplements.

It is understood that the aforementioned food additives, feed additives,

Nutritional supplement and pharmaceutical composition contain the astaxanthin according to the invention as the sole, astaxanthin-containing ingredient and in particular that they contain no further, unesterified astaxanthin or other derivatives of astaxanthin.

The invention has a number of advantages. For one thing, the

Compositions according to the invention have a better oral bioavailability than unesterified astaxanthin or corresponding diesters and the serum levels of astaxanthin in the blood plasma are several times higher. Surprisingly, the oral bioavailability of the astaxanthin compositions according to the invention is even better than that of the "natural astaxanthin." In addition, the compositions are synthetically readily available, not least because of their better oral bioavailability Compositions of the invention are also particularly attractive for pharmaceutical applications.

In particular, the astaxanthin compositions according to the invention are for the

Prevention and treatment of a variety of diseases and disorders suitable, such as

 Prevention and treatment of joint diseases, in particular inflammatory joint diseases such as rheumatoid arthritis, osteoarthritis and the carpal tunnel syndrome, prevention and treatment of eye diseases such as damage to the lens or retina, z. B. for the prevention of macular degenerata, the cataract or the

Glaucoma and the protection of the lens and the retina from UV rays,

 Prevention and treatment of skin diseases and for prevention and

 Reduction of skin aging, in particular for the prevention and reduction of skin folds, age spots and freckles,

 Prevention and treatment of heart disease, in particular for the prevention of myocardial infarction and for the improvement of convalescence after a heart attack,

 Prevention and treatment of type 2 diabetes and related

 Concomitant diseases, for example prevention and treatment of the metabolic syndrome, for lowering the blood sugar level in insulin-resistant individuals or for the treatment and prevention of diabetic nephropathy,

 Prevention and treatment of tumor diseases, in particular

 Cervical carcinoma, bladder cancer, breast and lung carcinoma, prevention and treatment of diseases of the blood vessels such as arteriosclerosis, - treatment of bacterial infections, in particular to improve the course of diseases of the gastrointestinal tract, which are caused by infection with Helicobacter pylori,

 Prevention and treatment of inflammatory diseases, in particular of

Autoimmune diseases such as Crohn's disease,

- Prevention and treatment of degenerative nerve disorders, such as Parkinson's,

 to improve male fertility,

 to improve the general condition,

 to improve memory and attention,

 to improve physical performance,

- to strengthen the immune system.

A treatment according to the invention includes not only the treatment of acute or chronic signs, symptoms and / or dysfunctions but also a preventive treatment (prophylaxis), in particular as a recurrence or phase prophylaxis. The treatment may be symptomatic, for example as symptom suppression. she can be carried out on a short-term, medium-term basis, or it may also be a long-term treatment, for example in the context of maintenance treatment.

Here and below means a feed for a means for the nutrition of non-human beings, especially non-human mammals but also of fish. A feed additive is accordingly understood to mean a formulation, eg. B. in powder or liquid form, which can be incorporated in the manufacture of a feed in the feed. Here and below is understood by a food a nutrient-containing agent for human nutrition, which serves primarily to absorb nutrients such as fats, proteins and carbohydrates. Accordingly, a food additive is understood to mean a formulation, e.g. In powder or liquid form, which can be incorporated in the preparation of a foodstuff in the food.

Here and below, a nutritional supplement is a formulation suitable for oral administration, which is taken in addition to the conventional diet of humans with the primary aim of administering active ingredients, here of astaxanthin or a derivative, in order to improve the

General condition or general well-being.

 Dietary supplements are located at the interface between food and medicines and are governed by EU Directive 2002/46 / EC.

The prefix C _n -C _m used herein for generic terms such as monocarboxylic acid or fatty acid indicates a range of the number of carbon atoms that a member of the group designated by the generic term may have.

The astaxanthin compositions according to the invention contain predominantly, i. H. at least 80% by weight, in particular at least 90% by weight, especially at least 95% by weight, based on the total weight of astaxanthin and astaxanthin derivatives in the

 Composition, a monoester of astaxanthin with an aliphatic, unbranched Ci8-C22 monocarboxylic acid. In addition, the inventive

Astaxanthinzusammensetzungen also contain unesterified astaxanthin and / or one or more diesters of astaxanthin, wherein the proportion thereof according to the invention 20 wt .-%, in particular 10 wt .-%, especially 5 wt .-%, based on the total weight of astaxanthin and astaxanthin derivatives in the Composition, does not exceed. The

But astaxanthin composition can also exclusively or almost exclusively, ie more than 95 wt .-% consist of the monoester of astaxanthin with an aliphatic, unbranched Ci8-C22 monocarboxylic acid. Preferably, the monoester is uniform, ie it is essentially, ie at least 80 wt .-%, in particular at least 90 wt .-% of the monoester exactly one aliphatic, unbranched Ci8-C22 monocarboxylic acid. The term "exactly one" means in this

Context that it is the monoester of a specific aliphatic, unbranched Ci8-C22 monocarboxylic acid, d. H. an aliphatic, unbranched C 18 -C 22 -monocarboxylic acid having the same empirical formula. In the case of the unsaturated aliphatic, unbranched C 18 -C 22 monocarboxylic acids, a specific aliphatic unsaturated C 12-22 monocarboxylic acid comprises both the mixtures of the various double bond isomers and the cis- and trans-isomer mixtures. If the composition also contains diesters of astaxanthin, the diesters are generally the diester with the aliphatic, unbranched C 18 -C 22 -monocarboxylic acid, which also contains the diester

Monoester forms.

The aliphatic, unbranched C 18 -C 22 monocarboxylic acids may be saturated or unsaturated. Unsaturated, aliphatic, unbranched Ci8-C22 monocarboxylic acids may contain one or more, for. B. 1, 2, 3, 4, 5 or 6 ethylenic double bonds. These may have an ice or trans configuration with respect to the particular double bond. The

Aliphatic, unbranched Ci8-C22 monocarboxylic acids are typically non-functionalized, i. H. in addition to the two oxygen atoms of the carboxyl group, they have no further heteroatoms.

Examples of saturated aliphatic, unbranched C 18 -C 22 -monocarboxylic acids are, in particular, even-numbered acids, such as stearic acid, arachic acid and behenic acid. Examples of unsaturated aliphatic, unbranched C 18 -C 22 monocarboxylic acids are, in particular, monounsaturated C 18 -C 22 -monocarboxylic acids, such as oleic acid and the like

 Double bond isomers of petroselinic acid, elaidic acid and vaccenic acid (C18-1 acids), C20-1 acids such as losenoic acid and gadoleic acid, C22-1 acids such as cetoleic acid and erucic acid.

- polyunsaturated Ci8-C22 monocarboxylic acids such as linoleic acid (C18-2 acid), the

C18-3 acids alpha-linolenic acid, gamma-linolenic acid, calendic acid, punicic acid, alpha-elaeostearic acid and beta-elaeostearic acid, the C20-4 acid arachidonic acid, the C20-5 acids timnodonic acid (= eicosapentaenoic acid) and clupanodonic acid, the C22-5 Acid docosapentaenoic acid and the C22-6 acid cervonic acid.

Preferred C 18 -C 22 -monocarboxylic acids are selected from mono- or polyunsaturated aliphatic, unbranched C 18 -C 22 monocarboxylic acids. In particular, the at least monounsaturated C 18 -C 22 monocarboxylic acid is selected from C18-1, C18-2, C18-3 and C18-4 fatty acids. Specifically, it is a C18-1 fatty acid. Preferred among the astaxanthin compositions according to the invention are those in which at least 90% by weight of the monoester of astaxanthin is a monoester of astaxanthin with one, in particular exactly one aliphatic, unbranched cis-monocarboxylic acid, this cis-monocarboxylic acid especially under C18-0-, C18 C1-, C18-2, C18-3 and C18-4 fatty acids, including monoesters of cis / trans mixtures

unsaturated aliphatic, unbranched cis-monocarboxylic acid and mixtures of the double bond isomers of this unsaturated aliphatic, unbranched cis-monocarboxylic acid. Among the astaxanthin compositions according to the invention, those are particularly preferred in which at least 90% by weight of the monoester of astaxanthin is a monoester of astaxanthin having one, in particular exactly one aliphatic, unbranched C 18 -C 22 -monocarboxylic acid, which is monosubstituted or polysubstituted, eg. B. 1-, 2-, 3-, 4-, 5- or 6-fold unsaturated, including monoesters of cis / trans mixtures of these unsaturated aliphatic, unbranched Ci8-C22 monocarboxylic acid and mixtures of double bond isomers of these unsaturated aliphatic, unbranched CI8-C22 monocarboxylic acid. In this case, it has proven particularly advantageous if not more than 60%, in particular not more than 40% and especially not more than 30% of the unsaturated C 18 -C 22 -monocarboxylic acid are present as trans-C 18 -C 22 -monocarboxylic acid, ie. H. not more than 60%, in particular not more than 40% and especially not more than 30% of all double bonds in the Ci8-C22 monocarboxylic acid residue are present in the transform.

Among the astaxanthin compositions according to the invention, preference is given in particular to those in which at least 90% by weight of the monoester of astaxanthin is a monoester of astaxanthin having one, in particular exactly one aliphatic, unbranched C 18 -C 22

Monocarboxylic acid is selected from C18-1, C18-2, C18-3 and C18-4 fatty acids. It has proven to be particularly advantageous if in the monoester not more than 60%, in particular not more than 40% and especially not more than 30% of the C18-1, C18-2, C-18-3 and C- 18-4 fatty acids are present as trans fatty acids, d. H. not more than 60%, in particular not more than 40% and especially not more than 30% of all double bonds in the fatty acid radical of the monoester are present in the transform.

Among the astaxanthin compositions according to the invention, particular preference is given to those in which at least 90% by weight of the monoester of astaxanthin is a monoester of astaxanthin with C18-1-fatty acid, in particular of oleic acid or cis / trans isomeric mixture of oleic acid. In the monoesters of C18-1 fatty acid preferably not more than 60%, in particular not more than 40% and especially not more than 30% of the double bonds in the C18-1 fatty acid radical are present in the transform. Among the astaxanthin compositions according to the invention, particular preference is also given to those in which at least 90% by weight of the monoester of astaxanthin is present

Monoester of astaxanthin with an unbranched C18-0 fatty acid. In a group of embodiments are at least 40 wt .-%, in particular at least 60 wt .-% or at least 80 wt .-% of the monoester, in particular the monoester of unsaturated aliphatic, unbranched Ci8-C22 monocarboxylic acid, particularly preferably the monoester of C18 -0-, C18-1, C18-2, C18-3 and C18-4 fatty acid and especially the monoester of oleic acid as the monoester of all-E-astaxanthin.

In a further group of embodiments, 20 to 90% by weight, in particular 30 to 80% by weight or 40 to 70% by weight, of the monoester, in particular of the monoester of unsaturated aliphatic, unbranched C 18 -C 22 -monocarboxylic acid, are particularly preferred the monoester of C18-0, C18-1, C18-2, C18-3 and C18-4 fatty acids and especially the monoester of oleic acid as monoester of all-E-astaxanthin and 10 to 80% by weight, in particular 20 to 70 wt.% or 30 to 60 wt.% as one or more Z isomers, e.g. Example, as a 9-Z, 13-Z or 15-Z isomer or as a mixture of two or three of these Z-isomers. In a further group of embodiments, at least 80% by weight, in particular at least 90% by weight, of the monoester, in particular of the monoester of unsaturated aliphatic, unbranched C 18 -C 22 -monocarboxylic acid, more preferably of the monoester of C 18-0, C 18- 1, C18-2, C18-3 and C18-4 fatty acid and especially the monoester of oleic acid as monoester of the 3S, 3'S enantiomer of astaxanthin.

In a further group of embodiments, at least 80% by weight, in particular at least 90% by weight, of the monoester, in particular of the monoester of unsaturated aliphatic, unbranched C 18 -C 22 -monocarboxylic acid, more preferably of the monoester of C 18-0, C 18- 1, C18-2, C18-3 and C18-4 fatty acids and especially the monoester of oleic acid as the monoester of the 3R, 3'R enantiomer of astaxanthin.

In a further group of embodiments, the monoester, in particular the monoester of the unsaturated aliphatic, unbranched C 18-22 monocarboxylic acid, particularly preferably the monoester of C 18-0, C 18-1, C 18-2, C 18-3 and C18-4 fatty acid and especially the monoester of oleic acid to the monoester of a

Mixture of the 3S, 3'S-enantiomer, the 3R, 3'S-meso-form and the 3R, 3'R-enantiomer of astaxanthin, in particular the statistical mixture of these Astaxanthinformen.

According to a group of embodiments of the invention, the astaxanthin compositions according to the invention or the corresponding monoesters are described in US Pat

 Food additives or feed additives used. This food or

 Feed additive contains the astaxanthin composition according to the invention and at least one excipient or auxiliaries suitable for foods or feedstuffs.

A suitable for food or feed excipient is understood in the context of the invention, a substance approved for animal and / or human nutrition.

Suitable auxiliaries are, in particular, those which comprise incorporation of the additive into

Foods in which they make the astaxanthin composition to a better dilute manageable concentration in the additive. These include, in particular, support materials, in particular liquid support materials such as vegetable oils and organic solvents, but also solid support materials such as fats, fatty acids, waxes, fatty alcohols and fatty acid esters of fatty alcohols, carbohydrates, sugar alcohols, and inorganic fillers, which are used for the production of food or feed allowed are.

Examples of solvents are:

 C 1 -C 6 -alkanols, such as, for example, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2-methyl-1-propanol, 3-methyl-1-butanol, 1-pentanol and mixtures thereof;

C 1 -C 4 -alkyl esters of aliphatic C 1 -C 4 -carboxylic acids, such as, for example, the methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-butyl or isobutyl esters of formic acid, of acetic acid , propionic acid or butyric acid such as methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate, isobutyl acetate, ethyl formate and mixtures thereof; such as

aliphatic, in particular non-cyclic, ketones having 3 to 6 C atoms, such as acetone,

 Methyl ethyl ketone, isobutyl methyl ketone and mixtures thereof; such as

 Mixtures of the abovementioned solvents from various classes of the abovementioned solvents. Suitable carbohydrates include mono-, di-, oligo- and polysaccharides. examples for

 Monosaccharides and disaccharides are mainly glucose, fructose, galactose, mannose, maltose, sucrose and lactose. Suitable polysaccharides are starch and oligomeric starch degradation products (dextrins) as well as cellulose powder. Suitable sugar alcohols are especially sorbitan and glycerol.

Suitable fats and oils may be of synthetic, mineral, vegetable or animal origin. Examples of oils are vegetable oils such as soybean oil, sunflower oil, corn oil,

 Linseed oil, rapeseed oil, thistle oil, wheat germ oil, rice oil, coconut oil, almond oil, apricot kernel oil, palm oil, palm kernel oil, avocado oil, jojoba oil, hazelnut oil, walnut oil, peanut oil, pistachio oil, triglycerides of medium-chain (= Cs-C-io) vegetable fatty acids (so-called MCT oils ) and PUFA oils (PUFA = polyunsaturated fatty acids such as

Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and α-linolenic acid), furthermore semisynthetic triglycerides, e.g. Caprylic acid / capric acid triglycerides such as the miglyol types, paraffin oil, liquid hydrogenated polyisobutenes, squalane, squalene, furthermore animal oils and fats such as fish oils including mackerel, sprat, tuna, halibut, cod and salmon oil. Preference is given to vegetable oils and oils of animal origin which are liquid at 40 ° C., in particular vegetable oils such as soybean oil, sunflower oil, thistle oil,

Corn oil, olive oil, linseed oil, rapeseed oil, rice oil, coconut oil, peanut oil, palm oil, palm kernel oil, PUFA oils, MCT oils, and fish oils, and mixtures of these oils. In contrast to oils, fats usually have a melting point above 30 ° C. Examples of fats are:

 saturated fatty acids having 12 to 30 carbon atoms (saturated C 12 -C 30 -fatty acids), in particular 14 to 28 C-atoms (saturated C 4 -C 28 -fatty acids) and especially 16 to 24

C atoms (saturated C 16-24 fatty acids) such as myristic acid, palmitic acid,

 Margarine acid, stearic acid, arachidic acid, behenic acid, cerotic acid, melissic acid and lignoceric acid and mixtures thereof;

 Fatty acid esters of saturated fatty acids having 14 to 30 carbon atoms, in particular 14 to 28 carbon atoms and especially 16 to 24 carbon atoms, such as the esters of palmitic acid,

 Margarine acid, stearic acid, arachidic acid, behenic acid, cerotic acid, melissic acid and lignoceric acid and mixtures thereof, in particular the mono-, di- and

 Triglycerides of the aforementioned fatty acids and mixtures thereof (hereinafter referred to as fatty acid glycerides), in particular the aforementioned saturated fatty acids and especially those saturated fatty acids having 14 to 28 carbon atoms and especially 16 to 28

C-atoms, and esters of the aforementioned saturated fatty acids having preferably 14 to 28 carbon atoms and especially 16 to 28 carbon atoms, with Cio-C3o-fatty alcohols, in particular with Ci4-C28 fatty alcohols. The abovementioned esters of saturated fatty acids may contain up to 10% by weight, based on the fatty acid content in the ester, of one or more polyunsaturated fatty acids in esterified form. In particular, the proportion of unsaturated fatty acid constituents in these esters is less than 5% by weight, based on the total fatty acid constituents in the ester;

The oils and fats can be raffinate oils or crude oils or crude fats, which still contain origin-specific impurities such as proteins, phosphate, (alkaline earth) metal salts and the like in conventional amounts.

Suitable fatty alcohols are in particular saturated aliphatic alcohols having 8 to 30 C atoms (hereinafter also referred to as Cs-Cso fatty alcohols), for example cetyl alcohol, stearyl alcohol, nonadecanol, arachidyl alcohol, behenyl alcohol, lignoceryl alcohol,

Ceryl alcohol, myricyl alcohol and melissyl alcohol.

Waxes are, in particular, natural waxes of plant or animal origin, such as beeswax, candelilla wax, shellac wax, sheathing fat and carnauba wax.

Hydrocarbon waxes, such as paraffin waxes, ceresin, sasol waxes, ozokerite and

Micro-axis into consideration.

Examples of inert, food-grade inorganic fillers are inorganic materials in powder form (inorganic fillers), e.g. For example, oxides such as alumina,

Silica, titania, silicates such as sodium silicate, magnesium silicate, talc, calcium silicate, zinc silicate, aluminum silicates such as sodium aluminum silicate, potassium aluminum silicate,

Calcium aluminum silicate, bentonite, kaolin and sodium chloride. The excipients which are suitable for foodstuffs and animal feeds furthermore include dispersants, including lipophilic dispersants for dispersing the astaxanthin compositions in lipophilic carriers and protective colloids for dispersing the novel tablets

Astaxanthin compositions in hydrophilic carriers such as water, further antioxidants (oxidation stabilizers) and food approved dyes.

Examples of antioxidants are tocopherols such as α-tocopherol, α-tocopherol palmitate, α-tocopherol acetate, tert.-butylhydroxytoluene, tert-butylhydroxyanisole, ascorbic acid, their salts and esters such as. Sodium ascorbate, calcium ascorbate, ascorbyl phosphate ester and ascorbyl palmitate and ethoxyquin. The antioxidants are, if desired, in the

Additives according to the invention typically in amounts of from 0.01 to 10 wt .-%, based on the total weight of the additive.

Examples of preservatives include benzoic acid and its salts, especially its sodium, potassium and calcium salts, 4-hydroxybenzoic acid (PHB) and its salts,

especially their sodium, potassium and calcium salts, the salts of PHB alkyl esters such as the sodium salt of PHB methyl ester, the sodium salt of PHB ethyl ester and the sodium salt of PHB propyl ester, sorbic acid and its salts, in particular its sodium, potassium and calcium salts, salts of propionic acid, in particular its sodium, potassium and

Calcium salts, boric acid and lactic acid and their salts. Preservatives, if desired, are typically included in the additives in amounts of from 0.001 to 2% by weight, based on the total weight of the additives.

Typical lipophilic dispersants are ascorbyl palmitate, polyglycerol fatty acid esters such as polyglycerol-3-polyrizinoleate (PGPR90), sorbitan fatty acid esters, in particular sorbitan-Cio-C28-fatty acid esters such. B. mono- and di-Cio-C28-fatty acid esters of sorbitan such as

Sorbitan monolaurate, sorbitan monooleate and sorbitan monostearate (SPAN60), ethoxylated sorbitan fatty acid esters such as PEG (20) sorbitol monooleate, monoesters of lactic acid with saturated C24-C24 fatty acids, sugar esters of saturated C16-C28 fatty acids, propylene glycol fatty acid esters and phospholipids such as lecithin. Lipophilic dispersants, if desired, are typically included in the additives in amounts of from 0.01% to 10% by weight, based on the total weight of the additives.

Protective colloids are polymeric substances suitable for dispersing water-insoluble solids in aqueous compositions. Suitable protective colloids approved for food and feed include, for example

 1) proteinaceous protective colloids,

 2) lignosulfonic acids, their salts, in particular their sodium salts and potassium salts,

3) oligo- and polysaccharides, including modified polysaccharides such as dextrins, cellulose and cellulose derivatives such as methylcellulose, carboxymethylcellulose and their salts, hydroxyethylcellulose, hydroxypropylcellulose and

 Hydroxypropylmethylcellulose, gum arabic, pectins,

4) polyvinyl alcohol, including partially saponified polyvinyl alcohol, 5) polyvinylpyrrolidone and

 Mixtures of the aforementioned protective colloids.

The proteinaceous protective colloids of group 1) is a water-soluble or swellable polymeric substance which is composed of amino acids and

optionally having glycosidic constituents. The proteinaceous protective colloid is usually of plant or animal origin. Examples of proteinaceous protective colloids of group 1) are caseins and caseinates, including as, ots2, β and κ casein and mixtures thereof, prolamins, d. H. Storage proteins from cereal seeds such as gliadin, secalin,

Avenalin, Hordein, Zein, Oryzin and Kafirin, whey proteins such as beta-lactoglobulin, alpha-

Lactalbumin, serum albumin, proteose peptone, immunoglobulins and mixtures thereof, gelatin such as beef, pork and fish gelatin, in particular acidified gelatin such as

Gelatin A100 and A200, alkaline degraded gelatin such as gelatin B100 and B200 and enzymatically degraded gelatin types such as those available under the trade names Gelita® Collagel A, Gelita® Sol DA, Gelita® Sol PA and Gelita® Sol LDA (DGF Stoess), and soy protein and partially hydrolyzed soy protein and lupine protein. Lupine protein is understood to be plant proteins derived from lupine. According to one

preferred embodiment, the powdered composition contains at least one proteinic protective colloid of group 1), optionally in combination with an oligo- or polysaccharide of group 3). The molecular weight (weight average) of the proteinaceous

Protective colloid is typically in the range of 10,000 to 250,000 daltons, more preferably in the range of 15,000 to 200,000 daltons and especially in the range of 20,000 to 180,000 daltons. Preferred protective colloids are casein, caseinates z. B. Na-caseinate, soy protein,

partially hydrolyzed soy protein, prolamine and lupine protein.

According to a preferred group of embodiments of the invention, the food or feed additives is a solution or suspension of the

Astaxanthin composition according to the invention in an oil or fat suitable for food or feed. The concentration of astaxanthin in such additive formulations is generally in the range of 0.01 to 30 wt .-%, in particular in the range of 0.1 to 10 wt .-%, based on the total weight of the additive. In the case of a solution lies the

Concentration preferably in the range of 0.01 to 3 wt .-%, in particular in the range of 0.1 to 2 wt .-%. In the case of a suspension, the concentration of astaxanthin is in the range of 1 to 30 wt .-%, in particular in the range of 2 to 20 wt .-%. The concentration of astaxanthin indicated the total concentration of astaxanthin in the form of the monoester, the optional diester and the unesterified astaxanthin. In addition to the suitable for food or feed oil, the solution may contain the aforementioned additives such as lipophilic dispersants and / or antioxidants and / or dyes, preferably in the aforementioned amounts. In the case of suspensions of the invention

As a rule, astaxanthin compositions have at least 80% by weight, in particular at least 90% by weight, of the particles of the astaxanthin composition

Particle diameter below 100 μηη, especially below 70 μηη and especially below 50 pm up. Frequently, the particles of the astaxanthin composition in the suspension have a volume-average particle diameter (D4.3 value) in the range from 0.2 to 50 μm, in particular in the range from 0.3 to 30 μm and especially in the range from 0.5 to 20 μm on. The volume-average particle diameter is understood to mean the volume-average particle diameter determined by means of Fraunhofer diffraction on a dilute 0.01 to 0.1% strength by weight, especially 0.05% strength by weight suspension.

The additives for food and feed according to the invention may also be powders. These powders generally have in addition to the invention

Astaxanthinzusammensetzung also other powder ingredients on. Which includes

especially flow aids and fillers.

A flow aid, which is also referred to as an anti-agglomeration agent, is understood to mean a solid, powdery substance which reduces sticking of the powder particles to one another or to container walls. The anti-caking agents are typically inert, food-grade solid inorganic materials in powder form, e.g. For example, oxides such as alumina, silica, in particular in the form of finely divided silica such as fumed silica or silica gel (E 551), or titanium dioxide (E 171), phosphates such

Tricalcium phosphate, hydroxides such as aluminum hydroxide, carbonates and bicarbonates such as sodium carbonate (E 500), sodium bicarbonate, potassium carbonate (E 501),

Magnesium carbonate (E 504) and calcium carbonate (E 170), or silicates such as sodium silicate (E 550), magnesium silicate (E 553a), talc (E 553b), calcium silicate (E 552), zinc silicate (E 557), aluminum silicates such as sodium aluminum silicate (E. 554), potassium aluminum silicate (E 555), calcium aluminum silicate (E 556), bentonite (E 558), kaolin (E 559), sodium chloride, and / or inert, food grade solid organic materials in powder form, such as

For example, crystalline mono-, di- and higher polysaccharides such as lactose, sugar

(Sucrose), cellulose powder, stearic acid or stearates such as magnesium stearate (E 572), ammonium stearate (E 571) and aluminum stearate (E 573). Preferably, the

Flow aids on particle sizes that are below the particle size of the powder. Preferably, the particles of the flow aid have volume-average particle diameters in the range of 1/100 to 1/2 of the volume-average particle diameter of the powder particles of the astaxanthin derivative. The proportion of flow aids will generally not exceed 10% by weight and, if present, is typically 0.1 to 10% by weight, preferably 0.2 to 5% by weight, in particular 0.3 to 3% by weight. -%, based on the total weight of the powdery additive.

The powdery additive compositions contain, in addition to

Astaxanthin composition one or more other powder ingredients. In addition to the aforementioned flow aids, these include, in particular, other organic and inorganic substances which are suitable for foods and which are preferably a solid at 50 ° C., in particular at 80 ° C. These include in particular the aforementioned fillers, protective colloids, antioxidants and preservatives. In the invention powdery compositions generally have at least 90 wt .-% of

Powder particles have a particle diameter below 500 μηη, in particular a maximum of 200 μηη. The powder particles generally have an average particle size (particle diameter, volume average, D4.3 value) in the range from 0.5 to 300 μm, in particular in the range from 0.5 to

In a group of embodiments of inventive powdered food and feed additives, the powdery formulation comprises at least one protective colloid.

These compositions are dispersible in water. The weight ratio of

Protective colloid to the astaxanthin constituents of the astaxanthin composition is typically in the range of 50: 1 to 1: 5, more preferably in the range of 20: 1 to 1: 2, and especially in the range of 10: 1 to 1: 1.

In preferred embodiments of powdered food and feed additives, the powdered formulation comprises at least one proteinaceous protective colloid. According to a first group, the proteinaceous protective colloid is in particular a soy protein or a

Mixture of soy protein and another proteinic protective colloid, eg. As a mixture of soy protein and a prolamine, a mixture of soy protein and a lupine protein, a mixture of soy protein and a casein and / or caseinate, a mixture of

Soy protein and soy protein hydrolyzate. In particular, the soy protein forms the

 Main component of the proteinaceous protective colloid, the proportion of the protective colloid is at least 50 wt .-%, in particular at least 80 wt .-% or at least 90 wt .-%. According to a second group, the proteinaceous protective colloid is especially one

partially hydrolyzed soy protein or a mixture of partially hydrolyzed soy protein and another proteinaceous protective colloid, e.g. Example, a mixture of partially hydrolyzed soy protein and a prolamine, a mixture of partially hydrolyzed soy protein and a lupine protein, a mixture of partially hydrolyzed soy protein and a casein and / or caseinate.

In particular, the partially hydrolyzed soy protein forms the main constituent of the proteinaceous protective colloid, the proportion of the protective colloid is at least 50% by weight, in particular at least 80% by weight or at least 90% by weight. By partially hydrolyzed soy protein is meant a soy protein which has undergone partial enzymatic degradation with a protease. The degree of degradation DH of such a partially hydrolyzed soy protein is generally at least 1%, in particular at least 5%, z. In the range of 1 to 20% and especially in the range of 5 to 16%. By the degree of degradation DH is meant the

Ratios of the number of hydrolyzed peptide bonds to the total number of

Peptide bonds in the starting protein. The degree of degradation can be determined according to the so-called "pH-stat method" as described by CF Jacobsen et al. in Methods of Biochemical Analysis, Vol. IV, pp. 171-210, Interscience Publishers Inc., New York 1957. Commercially available soya protein isolates and concentrates with protein contents of generally 70 to 90% by weight are usually used as soya proteins for the preparation of the formulations according to the invention, but also for the preparation of the partially hydrolyzed soya proteins remaining 10 to 30 wt .-% represent more or less undefined other plant constituents.

In preferred embodiments of powdered food and feed additives, the pulverulent formulation comprises at least one protective colloid from the group of

 Lignosulfonates, especially Na-lignosulfonate, optionally in combination with other protective colloids, in particular those from group 3). In particular, that forms

Lignosulfonate in this embodiment, the main component of the protective colloid, the proportion of the protective colloid is at least 50 wt .-%, in particular at least 80 wt .-% or at least 90 wt .-%.

The invention also relates to foods which are an inventive

Astaxanthin composition containing the concentration of

 Astaxanthin composition corresponds to the food-approved content of astaxanthin in the food. Typically, the concentration of the composition according to the invention, calculated as astaxanthin, is in the range from 1 to 500 mg / kg of the respective foodstuff.

Examples of foods which according to the invention with the inventive

Compounds include fatty foods such as sausage, cheese,

 Edible oils, nutritional supplements, protein food, power bars, functional drinks such as sports and wellness drinks and high calorie beverages, astronaut diets, tube feeding and the like. The invention also relates to feedstuffs comprising an inventive

Astaxanthin composition containing the concentration of

Astaxanthin composition corresponds to the approved for the respective feed content of astaxanthin in the feed. Typically, the concentration of the composition of the invention, calculated as astaxanthin, is in the range of 1 to 500 mg / kg of the respective feed.

Typical constituents in feedstuffs are carbohydrate sources, in particular cereal flours such as wheat or maize flour, soybean meal, but also sugars and sugar alcohols, furthermore proteinaceous constituents such as soy concentrate, fish meal, glutens such as maize or corn

Wheat gluten, oils and fats, e.g. As the aforementioned edible oils, but also other edible fats of plant or animal origin, continue nutraceuticals such as free

Amino acids, their salts, vitamins and trace elements, and optionally

Processing aids, eg. As lubricants, antiblocking agents, inert fillers and the like, and optionally preservatives. Typical fish food compositions contain e.g. As cereal flour in an amount of, for example, 3 to 20 wt .-%, gluten, z. In an amount of from 1 to 30% by weight, one or more protein sources, e.g. B. soya concentrate and / or Fishmeal, z. In a total amount of 10 to 50 wt .-%, fats and / or oils in an amount of for example 10 to 50 wt .-%, optionally one or more vitamins in a total amount, for example, 0.1 to 2 wt. % and optionally amino acids in an amount of, for example, 0.1 to 5 wt .-%, each based on the total amount of feed ingredients.

The production of food or animal feeds is achieved by the addition of

Food with a food or feed additive of the invention in the desired amount. The additives can be added during the preparation of the food or feed or by adding to the food or feed ingredients in the production of the food or feed.

A specific embodiment of this feed relates to feed pellets, especially

Feed pellets for fish feed, which can be obtained with the solution according to the invention of the

Astaxanthin derivative are loaded. Such pellets contain the inventive

 Astaxanthin composition typically in an amount of 10 to 200 ppm, based on the total weight of the feed and calculated as astaxanthin. The preparation of such pellets is generally carried out by spraying conventional pellets with a solution of the astaxanthin composition according to the invention, preferably under reduced pressure, wherein the spraying can be carried out continuously or preferably discontinuously.

 For example, one may place the conventional pellets in a suitable vessel, evacuate the vessel, and then spray a solution of the astaxanthin composition into a food-grade oil while mixing the pellets and then aerating. In this way one achieves a uniform penetration of the oily solution into the pellets. If necessary, you can create vacuum again and again the solution of

Astaxanthin composition in a food-grade oil in the manner described above spray. In this way one obtains pellets which contain in the core the oil and the astaxanthin composition according to the invention. The invention also relates to dietary supplements. These dietary supplements contain the astaxanthin composition of the invention in formulated form, i. H. In addition to the astaxanthin composition according to the invention, they comprise at least one excipient approved for food supplements. These include above all in the

Related to the food additives called excipients such as carriers,

Dispersants, antioxidants, preservatives and dyes and other, necessary for the preparation of the desired dosage form excipients.

Typical dosage forms for food supplements are powders, powders, granules, tablets, in particular film-coated tablets, lozenges, sachets, cachets, dragees, capsules such as hard and soft gelatine capsules, effervescent tablets and effervescent powder. The amount of astaxanthin composition in the dietary supplement is typically in the range of 0.5 to 100 mg, especially 1 to 50 mg per dose unit, calculated as astaxanthin. The invention relates to the astaxanthin compositions described herein for therapeutic use as a medicament and as an ingredient for a medicinal preparation (= pharmaceutical agent). Suitable indications in which the

Compositions according to the invention can be used are the above-mentioned indications.

The use according to the invention of the compounds described includes a process as part of the treatment. In this case, the subject to be treated, preferably a mammal, in particular a human, animal or pet, an effective amount of astaxanthin according to the invention, usually formulated according to the pharmaceutical and veterinary practice, administered. Whether such treatment is appropriate and what form it takes depends on the individual case and is subject to a medical judgment (diagnosis) of the signs, symptoms and / or dysfunctions present, risks, certain signs, symptoms and / or dysfunctions , and other factors.

The treatment is usually carried out by single or repeated daily administration, optionally together or in alternation with other active ingredients or active substance-containing preparations, so that an individual to be treated has a daily dose of preferably about 0.1 to 50 mg / kg body weight, in particular 0.5 to 10 mg / kg body weight, or 1 to 1000 mg, especially 2 to 200 mg, each calculated as astaxanthin, preferably by oral administration is supplied.

The invention also relates to the preparation of medicinal preparations, hereinafter also referred to as pharmaceutical agents, for the treatment of an individual, preferably a mammal, in particular a human, animal or pet. So will the

Astaxanthin compositions according to the invention are usually administered in the form of medicinal preparations containing a pharmaceutically acceptable excipient, i. H. an excipient, the astaxanthin composition of the invention and optionally one or more other active ingredients. These preparations are preferably administered by oral route.

Examples of suitable medical preparations include solid dosage forms, such as powders, powders, granules, tablets, in particular film-coated tablets, lozenges, sachets, cachets, dragées, capsules, such as hard and soft gelatine capsules, effervescent tablets, effervescent powder, semisolid

Pharmaceutical forms, such as ointments, creams, hydrogels, pastes or patches, as well as liquid

Pharmaceutical forms, such as solutions, emulsions, in particular oil-in-water emulsions, Suspensions, for example lotions, eye and ear drops. Furthermore, liposomes or microcapsules may also be used.

In the preparation of the medical preparations according to the invention

Astaxanthin compositions are usually mixed or diluted with an excipient. Excipients may be solid, semi-solid or liquid materials which serve as a vehicle, carrier or medium for the active ingredient. The compositions of the invention typically contain the astaxanthin composition in an amount equal to the daily dose or a fraction of the daily dose, e.g. B. half, a third or a quarter of

Daily dose corresponds. The amount of astaxanthin in the medical

Preparation is typically in the range of 0.5 to 200 mg, in particular 1 to 100 mg per dose unit, calculated as astaxanthin.

Suitable excipients are listed in the relevant pharmacographies. Further, the formulations may include pharmaceutically acceptable carriers or conventional adjuvants, such as lubricants;

Wetting agents; emulsifying and suspending agents; conserving agents; antioxidants;

Antiirritatives; chelating agents; coating aids; Emulsion stabilizers; film formers; gelling agents;

Odor masking agents; masking flavors; resins; Hydrocolloids; Solvents;

 Solubilizing agents; Neutralizing agents; permeation; pigments; quaternary ammonium compounds; Refatting and superfatting agents; Ointment, cream or oil bases; Silicone derivatives; spreading aids; stabilizers; Sterilanzien;

 suppository bases; Tablet excipients, such as binders, fillers, lubricants,

 Disintegrants or coatings; Propellant; Desiccant; Opacifiers; Thickener;

waxes; plasticizers; Include white oils. A related embodiment is based on expert knowledge, such as in Fiedler, H.P., Lexicon of excipients for

Pharmacy, cosmetics and related areas, 4th edition, Aulendorf: ECV Editio Kantor

Verlag, 1996, is shown.

For the following studies, the following astaxanthin compositions were used. The abbreviation FI .-% stands for the surface percentages determined by HPLC:

Astaxanthin monooleate with the following properties:

Content of astaxanthin monooleate> 91% by weight;

E / Z isomer distribution in the astaxane scaffold> 45 FI .-% all-E isomer;

Enantiomeric purity:> 95% ee 3S, 3'S enantiomer;

Proportion of trans fatty acid esters> 40% by weight.

Astaxanthin dioleate having the following properties:

Content of astaxanthin dioleate> 93% by weight;

E / Z ratio in the astaxane scaffold> 60 FI .-% all-E-l

Enantiomeric purity:> 95% ee 3S, 3'S enantiomer; Proportion of trans fatty acid esters 60% by weight.

Astaxanthin natural product

 Mixture of mono- and diesters of astaxanthin (predominantly 3S, 3'S enantiomer) with C 16 -C 22 fatty acids from blood rain algae (Haematococcus pluvialis) having the following composition (determined by HPLC-MS, data in area%)

 1 .6% Astaxanthin C18: 4-monoester

 9.7% astaxanthin-C18: 3-monoester

15.0% Astaxanthin C18: 2-monoester

28.7% Astaxanthin C18: 1 monoester

 5.3% Astaxanthin C18: 0 monoester

The remaining 39.7% is distributed over 77 unidentified peaks, each <2 FI .-%, but these are mainly mono- and diesters of astaxanthin.

Production Example 1: Preparation of astaxanthin monopalmitate

3 g (1: 1, 7 mmol) of palmitic acid were initially charged in 47.37 ml (53 g, 740 mmol) of dichloromethane.

At room temperature, 2.85 g (17.55 mmol) of 1,1'-carbonyldiimidazole (CDI) was added in three portions at intervals of 5 minutes each time. The mixture was stirred overnight and the next day 3.49 g (5.85 mmol) of astaxanthin (3S, 3'S enantiomer, ee> 95%) was added.

After 6 hours, 133.8 μΙ acetic acid was added to the reaction mixture and stirred at room temperature overnight. After 20 hours, a sample was examined by thin-layer chromatography. (Silica gel, mobile phase cyclohexane / ethyl acetate = 1: 2). The

Thin-layer chromatogram showed that in part of the astaxanthin used for

 Astaxanthin monopalmitate had been implemented. Astaxanthine dipalmitate was detected only in very small amounts.

Separation of the astaxanthin monopalmitate from the reagents and the unreacted astaxanthin succeeds by chromatography of the reaction mixture

 Silica gel with cyclohexane / ethyl acetate in a volume ratio of 1: 2. Astaxanthin monopalmitate with a purity of> 80% by weight, in particular> 90% by weight, can be obtained in this way. In an analogous manner, it is possible to obtain astaxanthin monooleats having a purity of> 80% by weight, in particular> 90% by weight.

Studies on bioavailability The bioavailability study was carried out by determining the blood plasma level of astaxanthin in Göttingen minipigs. As a measure of the bioavailability, the integral plasma concentration in the blood serum was determined over 96 h (AUC). All astaxanthin derivatives were administered as solutions in olive oil:

 Formulation 1: astaxanthin monooleate, 4.2% by weight (calculated as free astaxanthin) in

 olive oil

 Formulation 2: Astaxanthin dioleate, 3.1% by weight (calculated as free astaxanthin) in

 olive oil

Formulation 3: Astaxanthin natural product, 2.4% by weight (calculated as free astaxanthin) in

 olive oil

The examination was carried out on three 4-5 months old, male Göttingen mini-pigs with a body weight of 9.5 - 10.5 kg. All minipigs were implanted with a catheter into the femoral vein to collect blood. Two of the mini-pigs (pig 2 and pig 3) also had a catheter implanted in the jugular vein. During the

Period, the catheters were rinsed daily with saline. During the non-treatment periods, the minipigs were fed a commercial diet for mini-pigs (SDS, Essex, UK). The diet was fed on weekday mornings and afternoons, and weekends early in the morning and just before noon.

On the day of treatment, the diet was supplemented with a high-fat diet enriched with 20% corn oil. For this purpose, 224 g of the commercial mini-pig diet were mixed with 54 g of corn oil. Pig 1 received 140 g of the high-fat diet immediately before the 1st and 2nd

 Treatment and 140 g immediately after the 1. and 2nd treatment and 140 g 2 h before the 3.

Treatment and 140 g 1 h after the 3rd treatment. Pigs 2 and 3 received 170 g each of the high-fat diet immediately before the 1st and 2nd treatment and 1 10 g immediately after the 1st. and 2 nd treatment and 170 g 2 h before the third treatment and 1 10 g 1 h after the third

Treatment.

There was a period of 1 week between treatments. The treatment scheme was as shown in Table 1:

Table 1: Treatment scheme

 I. Treatment 2. Treatment 3. Treatment

Pig 1 Formulation 3 Formulation 2 Formulation 1

Pig 2 Formulation 1 Formulation 3 Formulation 2

Pig 3 Formulation 2 Formulation 1 Formulation 3 For treatment, the formulation was administered to each pig by means of a nasogastric tube as a single dose. The single dose was 50 mg / kg astaxanthin. Immediately prior to administration and 2 h, 6 h, 7 h, 8 h, 9 h, 10 h, 1 h, 12 h, 1 h, 24 h, 32 h, 48 h, 56 h, 72 h and 96 h after administration, about 2 ml of blood was taken from the pigs via the femoral vein. The samples were stored on ice and within 30 min. after removal 10 min. centrifuged at 1500 g and 4-8 ° C. The plasma was placed in sterile, closable

 Polypropylene container (Micronic, Lelystadt) transferred and stored at temperatures below -75 ° C until analysis. The astaxanthin level in the blood plasma was determined by means of HPLC by WIL Research, Den Bosch NL. The results are shown in Table 2 below. The mean values for the three test pigs are given.

Table 2:

 tiast = time interval until falling below the detection limit

 tmax = time interval of the maximum serum level

 Cmax = maximum serum level

 Ciast = concentration before falling below the detection limit

 AUCiast = concentration integral up to the time before the detection limit is undershot AUCoo = extrapolated concentration integral

 ti 2 = half-life

Claims

Patent p

Use of astaxanthin compositions in foods,

 Dietary supplements or feeds, wherein the astaxanthin composition at least 80 wt .-%, based on the total weight of astaxanthin and

 Astaxanthinderivaten in the composition containing a monoester of astaxanthin with an aliphatic, unbranched Ci8-C22 monocarboxylic acid.

Use according to claim 1, wherein at least 80% by weight of the monoester of astaxanthin is selected from monoesters of exactly one aliphatic, unbranched C 18 -C 22 monocarboxylic acid.

Use according to claim 1 or 2, wherein at least 80 wt .-% of the monoester of astaxanthin is selected from monoesters of astaxanthin with exactly one at least monounsaturated aliphatic, unbranched Ci8-C22 monocarboxylic acid or with a cis / trans isomer mixture thereof exactly one aliphatic , at least monounsaturated, unbranched Ci8-C22 monocarboxylic acid.

Use according to one of the preceding claims, wherein the aliphatic, unbranched Ci ₈ -C ₂ 2-monocarboxylic acid with C18-0, C18-1 - is selected C18-2-, C18-3- C18-4- and fatty acids.

Use according to claim 4 wherein at least 90% by weight of the monoester of astaxanthin is the monoester with a C18-1 fatty acid.

Use according to any one of the preceding claims, wherein less than 60% by weight of the unsaturated fatty acids present in the monoester of astaxanthin are present as trans fatty acids.

Use according to any one of the preceding claims wherein at least 40% by weight of the monoester of astaxanthin is in the form of monoesters of all-trans-astaxanthin.

Use according to any one of the preceding claims, wherein at least 90% by weight of the monoester of astaxanthin is in the form of monoesters of astaxanthin which are in the asymmetric centers in position 3 and 3 ', either (S) or (R) respectively is.

A composition in the form of a food additive, feed additive or dietary supplement containing an astaxanthin composition according to any one of claims 1 to 8 and a food, feed or

Dietary supplement suitable adjuvant.

10. The composition of claim 9 selected from solutions and suspensions of the astaxanthin composition and a food or feed suitable oil or fat. 1 1. A composition according to claim 9 in the form of a powder comprising a

 Astaxanthin composition and a protective colloid.

12. The composition of claim 9 in the form of a dietary supplement for oral administration.

13. A foodstuff containing an astaxanthin composition according to any one of

 Claims 1 to 8, wherein the concentration of Astaxanthinzusammensetzung corresponds to the food-approved content of astaxanthin. 14. A feed comprising an astaxanthin composition according to any one of claims 1 to 8, wherein the concentration of the astaxanthin composition corresponds to the permitted content of feed for astaxanthin.

15. A process for producing a food or feed comprising the

 Additization of a conventional food or feed with a

Astaxanthin composition according to any one of claims 1 to 8.

16. Astaxanthin composition according to any one of claims 1 to 8 for therapeutic use as a medicament and as an ingredient for a medical preparation.

17. Astaxanthin composition according to claim 16 for the treatment or prevention of joint diseases, eye diseases, skin diseases, skin aging,

 Cardiac disorders, diseases of the blood vessels, inflammatory diseases, tumors, bacterial infections, type 2 diabetes and associated sequelae, and degenerative nerve disorders, to improve male fertility, memory, physical

 Efficiency and attention and strengthen the immune system.

18. A medical preparation containing an astaxanthin composition according to

 of claims 1 to 8 and at least one pharmaceutically acceptable adjuvant.