GB2203043A - Dietary composition - Google Patents

Description

P Al 3 2 2 9 3 -> C4.

1 - 1 7'rAP)' "MPC.STT!7-IN ANED PROCESS FOR FREPP'-FING SAME Thlis Invention relates to dietary ccmpositions.

In an other aspect of the invention, there is provided @-process for preparing these compcsitions.

It is known that the C 18-22 c;-r-l unsaturated fattv acids possess advantageous biological properties. Amongst these substances, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are outstanding; the importance and multip-le biological effects of both acids have been discussed by Dve:1Derg et al. /-The Lancet 15, 117 (19- lis'),7.

The effects, connected with the important ro-le of the pclyunsaturated fatty acids, mainly EPA and DHA, in the hyperlipidaemia and thrombotic: diseases hae been reviewed by Goodnight et al. /-Arterios--lerosLs 2, 87 (1982)7.

Ine active components of the fish-cil, eicosapentaenoic acid (IEPA) and docosahexaenoic acid (DHA). are precursors of the biosynthesis of the PG3 series and simultaneously they are competitive inhibitors of harmful metabolites such as TXA2 and TXB2 arising from the so-called "arachidonic acid cascade" which is a chain of complicated biochemical processes starting from arachidonic acid.

In addition to many preferably effects, a drawback of the polyunsaturated fatty acids consists in the fact that they represent a possible source of the most harmful malondialdehyde Mn DA) resulting from radical peroxidation processes whereby the so-called "ceroidal lipc..Luscinoe-is" can be induced in the central nervous system.

- 2 The ut-'Ll'Lzat-icn of EPA for alimentary purposes in the fcrw.. of a cyc'L-.dextrin inclusion complex has been deE:ri-bed in the French pate-,,t specification No. 2,550,445.

Marschall et al. /-Am. J. Clin. Nutr. 38, 895 (1983)7 studied the role of Ci-r-3 polyunsaturated fatty acids- in the synthesis of d--linclenic acid and prostaglandins as well as in the dietary alimentation.

In addition to EPA and DHA, the fish-oils contain high amcints of saturated and lowly saturated fatty acids as well as ncnhydrolyzable components the removal of which is very ir-portant since the -It-. riglyceride level of blood and the calory intake are sensitively enhanced by the increase in the dietary dose. Furthermore, stercids which are harmful from a dietetic point of view, e.g. cholesterol as well as vitamin A, both liable to v L min D (its prec.,rsc-r and in the human crganism, can also be present amiong the nonhydrolyzable constituents.

The dietary effects of the ci-r-3 polyunsaturated fatt acids and mainly of EPA and DHA in relation to their manifold physiological connections are discussed in a high number of other papers /-see e.g. U. Barcelli: Thromb. Res. 39, 307 (1985); J.J. Jurkowski: iNCI 74, 1145 (1985); A. Lembke: Milchwissenschaft 40, 329 (1985)7.

It is also known that algae have from time immemorial been used by the mankind for the purpose of nutrition and feeding. Thus, algae are mainly consumed by the peoples of the Far East; recently, however, they are utilized in dry fcrm or in the form of talClets in the developed countries, tc- 11 1 lgae are the carriers of highly valua::,le nutriti\e L -1 LI materials 5ince thleir drIed form contains in high. ccnc;-::n4Lration substances which are essential for a healthy life such as vitamins, proteins, complexes of proteins with microelements, 5accharides, polyunsaturated fatty acids and the 1 i k e.

A general and detailed rev iew on algae is found e.g. in the book of Zajic.. "Properties and Products of Aligae" (Edition Planum, New York, 1970).

The investigation on the biological effects of microelements and trace elements has been started in the last decades. Thus, it has been recognized 'that selenium is one of the most important, essential substance of life. The preferable action of selenium mainly lies in the activation of the glutathione-peroxidase enzyme, more precisely in the activation of the prosthetic group of the enzyme which is the most important endogenic inhibitor of the damaging dation processes. Selenium is not accumulated in the peroxL I - human croanism; thus, it has continuously to be suppiemonter-,'. Up to the present, selenium has been supplied in the -form of inorganic compounds, mainly as selenium dioxide or sodium selenite.

Selenium in itself has hypotensive effect, improves the ischaemic, hypoxic and infarction states of the heart and inhibits the ceroidal lipofuscinosis of the central nervous system; it also exerts a beneficial effect on periodontitis and proved to diminish the probability of the development of cancer diseases; furthermore, it is considered to be a agent. A number Of alterations Cr respectively, such as liver necrosis, oestruction of the erythr-.--yte membrane, interstitial laesions, STelevation in the ECG, kwashiorkor syndrome (prctein malnutrition) and multiplex sclerosis proved to be induced by selenium deficiency.

A review on the biological effects of selenium was published by Thressa et al. /-Nutrition Review 35, 7 '1977'7. R. I. Shamberger /-J. of Env. Path. and Tox. 4,3C5 (1960)7; as well as Masukawa et al. /_Experientia 39, 405 (198317.

The aim of the present invention is to develcp a dietary cow.pcsition, which eliminates the disadvantageous biological effects of the consumption of polyunsaturated fatty acids. provides the combination of the advantageous properties of EPA, DHA, algae and selenium, and is capable, on the basis of its cc,-..position, to counterbalance at least a part of unlealt;y life conduct and disadvantageous habits of alimentatiGn.

The invention is based on the recoonition that ihe abc,.e aims can cGmpletely be achieved by a fecd composition which comprises a seleniumcontaining alga together with pc'-y.unsaturated fatty acids.

Thus, the present invention relates to dietary compositions, which comprise 0.5 to 50% by mass of selenium-containing alga as well as 99.5 to 50% by mass of C18-22 unsaturated fatty acids containing at least two double bonds or their derivatives together with additives commonly used in the food industry and optionally with an antioxidant.

Furthermore the invention relates to a process for z S; r prepairi -c the ab--ve d i a tary r---.ripos i t ion, whiCh co-,p., i ses rr' xing 0. 5 to 5-0% tv mass of selenJLum-co.,n.tain;Lng alga as well as 99.5 to 50% by mass of C 18-22 unsaturated fatty acids containing at least two double bonds or their derivatives, with additives commonly used in the food industry and optionally wit-h an antioxidant.

The se-lepi, ur--- c or... t- a.1 n. ing algae car., be prepared by c., lltúJ'va',.-Lng algae on or in an aqueous mediur. contai-ning 10---7 to 2 X 10-3 moles per litre c-f' a sclul--le Gngan-ic and/or -Lnong-ar,2-lc seleniur cc.7,pound; preferably the algae used for cultivation is selected by treating a strain of al-ae and, the stlra--n on a prc:.p-a-ga±-'Lon and sell those that bc:"h. --'-n.c:c.:-pcrate w,, --a-re a h-gh grzwth rate. Preferred algae s-eciles incluie -n- 5 ar ue c:- green -a' gae, e.g. 'h'. c.?-c-2 a s p., S r en e mul s p.' cr S 1' r ul a s a_nd ine p a r -t -1 c ul a:- Aph an c c a p S a t h e r r... a 11 1 s, Chl cr e 11 a Chlorella fus a, Sce7-jedesn.js Scenedesr.-,-us M1 n. - 1 - - - c ----- 1 or Ns'Loc (as described in cur to F.u:n Way, in the c7F-an'.s7, of r-rie gno-wing a--gae.

ihe raw F...aterial of the C 18-22 Ci.Y-3 unsaturated fatty acids, serving as active ingredients of the composition,-may be the oils obtained from various marine or fresh-water fishes. mainly the oils from mackerel, cod-fish, herring, sardine and ink-fish as we'll as the oils which may be obtained from the liver of these fishes such as cod-liver oil and shark-liver oil.

As algae Chlorella or Scenedesmus strains are mainly used which are not only useful for human comsumption but also have own advantageous biological action.

POOR ' QUALITY ' 2 - Y1a - The corr.p-.sition is sensitive to oxidation. Thus, it is sui"t-.ab'Le to use an active preserving agent, e.g. d-tocc,nlhe-ol (vitamin E), glutathione or a traditional antioxidant such as bLtylhydroxytoluene.

The homogenized composition can be included in al'L,7ien'Lary products, tablets, capsules and the like. Here, the term "alimentary product" means all useful products tat Can orally or parenterally be administered. The orally ad,T.in.s4LereLrll product may be -contained in a confectionary 1 7 51 11 f 1 cr sweets incustry article (e.g. chocolates, cakesj'. Feat -i k o r 'L-,,u t che r i n du s 4. r v c omp o s i t i o n s, E- p i ce s, ma r g a r i n e, m. butter or fat products-, oils and the like.

The main advantages of the composition accordino to the invention can be summarized as follows. a) The individual components of the composition have in itself important biological and alimentation effects and combine the preferable properties of EPA and DHA as well as selenium and algae. It eliminates the possibility of "cercidal li-pe.fu5c.inosJLs" appearing on the consumption of polyunsaturated latty acids. c) The use of a continuous dietary regimen is not required by the consumption of the composition according to 'the invention since it does not contain the harmful fish-cil discussed above (saturated fatty acids, L chclestercl, vitamins A and D). Seienium is present in a natural form enriched in algae, i.e. as a material of native origin.

e) It is useful to prevent apoplectic and thromboembolic states of the cardiovascular system, thus to inhibit the development. of infarction and apoplexy as well as to prevent atopically related or atopic disturbances. The use of the composition is highly preferred in developed conditions, too.

The c-.mposition of the invention is illustrated in detail by the following non-11-miting Examples. The preparation of the components used as basic materials is shown in - 74 E x ar les 1, 2 and 3 wh JI Ist the prepara t -1 os-. of 11-he composi t 1 Cns. is described in the further Examples.

1xample 1 L- Ten kg of sardine-oil are added at a temperature of 50 to 60 0 C to a solution containing 2 kg of sodium hydroxide in 70 litres of 95% ethanol. The mixture is refluxed under nitrogen for 2 hours, then cooled to 10 0 C while stirring. The precipitated crystalline sodium salt of the saturated fatty acid is filtered and washed with a little etil.-,ano'L. The ethanolic filtrate is evaporated and then 20 litres of boiled-cut water are added to the residue. The nonhOrr--1y,able compounds such as cholesterol are removed by Extraction with 5 litres of hexane. The extracted aqueous phase is aCidif-ied to pH 2 by adding dilute sulfuric acid and it is again extracted with 15 litres of hexane. The crganic phase is washed with water, dried over anhydrous sodium sulfate and evaporated to give 3.2 kg of an oily concentrate with a CHA content of 36i8% and EPA content of 31.8%. This oil is brown and smells of fish. Thus, Fuller's earth is mixed to the oily concentrate which is then heated at 105 0 C under nitrogen for 10 minutes and filtered as hot.. The deodourization is carried out by steam distillation under reduced pressure of 1.3 bar at 170 OC for 3 hours to give 1.6 kg of a light yellow, odourless and tasteless oil with practically unchanged composition.

Y_.

1 "P - Exc-Tple 2 24 kc of ccd-li.er oil are dissclved in 16 litres of me-:ha,nol at 60 c C, then 6 kg of 40% sodium hyluroxide 0 rl are dropped to this solution at a temperature between 50 L, and 60 c C under stirring. The mixture is stirred at 60 0 c for additional 45 minutes. Then, 20 kg of 15% hydrochloric acid are added to the solution at about 60 0 C. After separating the phases, the organic layer is extracted with 10 kg of 15% hydroch-:oric acid and then washed with about 180 litres of hot tap water until neutral. The phases are separated, then 1GO litres cf acetone are added 'to the oily phase. The mixture is hea, "ed to about 45 0 C, then a solution containing 3.8 kg of lithIum hydroxide wicnohydrate in 30 litres of water is ad-ded. After stirring for 30 minutes, the mixture is left to stand ove-rn'Lah+. ",hen filtered and the acetone flt-ate . L I L, L is The residie is acidified by adding 8 kg of 15% hydrc2hl-.-ic acid, extracted three times with hexane and then ev2, cGrated. The whcle operation of purifying is carried out under nitrGgen. Thus, 6.4 kg of purified fish-oil are obtained with an iodine number of 258 and an acid number of 160.

One kg of the thus-purified cod-liver oil is dropwise added at 60 0 C to the solution of 3 kg of urea in 9 litres of methanol. The mixture is stirred at the same temperature for 2 hours. After cooling down, the mixture is left to stand in a refrigerator at -160C overnight, then filtered and the filtrate is evaporated. 2.5 litres of hyorochlcric acid (conCentrated acid diluted to 1:1 with water) are poured - 'n \0 -0-- to the:esidue and the mixture is stirred for 15 minctes. Afte: extracting with hexane, the organic phase is washed with water until neutral, dried over anhydrous sodium sulfate and evaporated to give 0.34 kg of wy-3 fatty acids with an iodine number of 315, EPA content of 24% and DHA content of 42%.

Example 3

Eight litres of Knop-Pringsheimls culture medium are filled into an algacu1tiv2ting glass bottle of 10 litree volume and supplemented with 40 mg of sodium selenite. The system is sterilized at 121 OC under an overpressure cf 1 Or for 30 minutes. The sterile solution is inoculated with a pure alga culture of selenium-resistant Scenedespus citisiusculus. Sterile air containing 5% by volume of carbin dicxice is bubbled at 25 0 C through the culture megium under illurinaticn by an electric discharge lamp working with 4COC lux at a wavelength of 440 to 520 and 640 to 700 PM. After a cultivation period of 14 days the alga is separated from the Culture medium. The thus-obtained alga mass is decomposed by supersound and carefully dried at a temperature below 65 0 C to give 6 g of an alga powder with a selenium content of 1200 /ug/g.

jample 4 Hundred g of selenium-containing alga (with a selen concentration of 260 /ug/g of alga powder) are stirred to 150 g of an enriched cod-liver oil of 65% Containing 22% ium of EPA anc! 43% of D'r1AA. Al+er z rig, t'-e xture is prese-7ved by adding C. 2 % b ma 5 5 0 f \, JL t arn, i n E Example 5

Preparation of a dietary margarine composition Eight g of 65% cod-liver oil (containing 22% of EPA and 43% of DHA) and 1 g of selenium-containing alga (with a selenium concentration of 260 /ug/g of alga powder) are mixed to 250 9 of soft margarine, then the mixture is hommogenized.

Ex2-niple 6 The process described in Example 4 is followed, excent that the following of the starting materials are u s e d:

400 g of 65% enriched cod-liver oil (containling 22_% of L'-,px and 43% of DHA); 70.6 g of alga powder containing 1200 jug/g of seleniurin; and 0.4 g of vitamin E.

The thus-obtained homogenizate is filled into soft gelatin capsules or soft gelatin bead capsules with a capacity of 500 mg and then included into a blister package.

Example 7

Tablets with the following composition are prepared by using known pharmaceutical devices and process:

- 1 C-_;ld- I i, Er oil enr iched in EPA al-d CHA, 0.1% cf vitamin E as preserv- c nt a:L r-in g ing ape7t Selenium-containing alga Lactose Starch c,l,,.Jnllpyrrolicone 2C0 rg 43%; EPA content: 2 2 5-, ') 86 mg (seleniumconcentration: 380 /ug/g of alga powder) mg 6 0 m g 3.5 rg Magnes:jm stea-ate 3.5 mc b -1 - - If desired, the panning machine.

ta'-',lets are coated wilh sugar in a CI 1 a i m S 1. A dietary 0,5 to 50% by mass 9.5 to 50% by mass of containing at least 1 composition, which c o r, p r i s e s of selenium-containing alga as well as c 16-22 unsaturated fatty acids two double bonds or their derivatives, in admixture with additives commonly used in the food industry and optionally with an antioxidant.

2. A composition as claimed in claim 1, which comprises eEters, alkali earth salts or amine salts as fatty 2cid derivatives.

3. A composition as claimed in claim 1 or 22, which c o m p r i s e s 5,8, 11,14,17-eicosapentaenoic acid and 4,7,10,13,16,19-docosahexaenoi.c acid as unsaturated fatty acids.

4. A ccm.positiJon as claimed in claim 1, which com-Prises fCatty acids obtained from marine fish-oil as unsaturated fatty acids.

5. A proGess for the preparat,ion of a dietary composition as -claimed in claim 1, which c 0 m p r i S e S mixing 0.5 to 50% by mass of seleniumcontaining alga as well as 99.5 to 50% by mass of C 18-22 unsaturated fatty acids containing at least two double bonds or their derivatives, with additives commonly used in the food industry and optionally with an antioxidant.

- 1 6. 4 di etary c c -pc si t i c. n a^ Pae and one or more C 18-22 unsaturated a least two doutle bonds or adr,--lxture with edible substances or additives commonly used in the food industry and optionally an antioxidant.

7. A composition as claimed in claim 6, which contains based on the combined weight of the selenium-containing algae the C 18-22 unsaturated fatty acid(s) or derivatives thereof, to 5001p' of the seleniumcontaining algae and 50 to 99.5010' of c 18-22 unsaturated fatty acid(s) or derivatives thereof.

8. A process of preparing the dietary composition claimed claim 6 or claim 7 which comprises admixing the comPlcunds comprising fatty acids contai-ing derivatves thereof preferably t'ereef.

in any 10. A I E or 7, wherein dietary composition subst-anti ally as hereinbefor one of Examples 4 to 7.

com.position as claimed in any one of claims the "."atzy acids andi'or the algae have been prepared ty a process substantially as here-LInbefore described in Exam..Ple cr 2 or in Example 3, respectively.

il. A process as claimed in clair.r. 8, s,-,bstan',--a'j'_ly as he-e-'nbe-fore descrIbed -in any one of Examp'es 4 to 77 1. 3 Published 1988 at The Patent Office, State House, 66.71 High Holborn, London WC1R 4TP. Further copies may be obtained from The Patent Office, Sales Branch, St Mary Cray, Orpington, Kent BR5 3RD. Printed by Multiplex techniques ltd, St Mary Cray. Kent. Con. 1187.

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