LU87170A1 - DIETITIC COMPOSITIONS AND PROCESS FOR THEIR PREPARATION - Google Patents

Description

Ιΐ ”ϋώ ώ J

fi λΓ-7 i 7 Π GRAND-DUCHY OF LUXEMBOURG

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'\ ÿtfnfàjfa Minister of 18 ...... max.S ....... 1.9..8..8 .................. JpSjy ~ of the Ecohomie and the Middle Classes

Titm rlp.1 drunk. 3¾¾ Intellectual Property Service _ 1 Γ S 1VrS ....................................... ................. (= ¾¾) LUXEMBOURG \ ^ £ 3 ^ \ £ PA - \ \ \ peç ^ '· \

Patent Application for Inv0 ^ BM ^ h \ ....................................... .................................................. .................................................. .................................................. ........................................ „......... ................................. 1)

I. Application V

Caola ...... Ko.zme.-hikai ....... és ..... Hàztartàsvegyipari ...... Vàllalat, 90, ....... Bocskai (2) ut. ., ....... HB.ndap.est., ....... Hungary., ....... represented ...... by Mr Jean Waxweiler, 55 rue des Bruyères, Howald, acting in q ~ Y £ "£ | ~ gg ...... mânHatâîrë“ ............................. .................................................. .................................................. .................................................. .................................................. .................................................. .................................................. ............................... (3) deposit (s) this ....... nineteen hours ... rr ^^^ ..... one hundred guatre-vlngt-quatre ................................... ........................................ (4) to .1.5 ..., ., 0.0 ........... hours, to the Ministry of the Economy and the Middle Classes, in Luxembourg: 1. this request for obtaining a patent for an invention concerning:

Compositions ....... dié.ti..ti.qu.es ........ and ...... process ...... for ........ their ...... preparation ........... (5) 2. description in French ...... language ............... ...............................................of the' invention in triplicate: 3 ..................... / ...................... ........................ drawing boards, in triplicate; 4. the receipt of the fees paid to the Luxembourg Registration Office on ......... 18.03 .1988 ______________________________ 5. the delegation of power, dated ............ .................................................. ................................................ the. .................................................. .................................................. ...; 6. the successor document (authorization); declares (s) assuming responsibility for this declaration, that the inventor (s) is (are): (6) see annex .................. .................................................. ................................ ........... __ __ __ claim (s) for the above patent application the priority of one (or more) application (s) of (7) - patent —------------------------- ---------------------------------------------------------- ------------- filed (s) in (8) Hungary ............................ .....................

on (9) .- .. 1.8., .. tue s_JLâ & 2 __________________________________________________________________________________________________________________________________________________________________________________________________: ____________ under N ° (10) JUÙA. / 3.Z _____________________________________________________________________________________________________________________________________________________________________________ in the name of (11) Caola Kozmetikai és Hàztartàsvegyipari Vàllit her (his) ___ ) and, if appointed, for its representative, in Luxembourg__________________________________________________ ..5..5 ._- r..ue ...... de.s ...- Bruy.èr.es. # ..... ..Howald _______________________________________________________________________________________________________________ (12) requests) the grant of a patent for the invention for the subject described and represented in the abovementioned appendices, with postponement of this grant to 'Ln ____________ i..gl _____________________ ______________________________________________________________month. (13)

The authorized representative: .....................................___________________________________________________________________ (14) Π. Deposit Minutes

The above patent application ^ âaKijjhion has been filed with the Ministry of the Economy and the Middle Classes, Property Service ME ^ "iiêAS'à € i} ^^^) Ourg, dated: 18.03.1988 / a Vf : \ Pr. The Minister of Economy and the Middle Classes, at 15., .. 0.0 — hours I | j I p. d.

\% \ xc / d The head of the intellectual property department, ie, / ’A 68007_____ EXPLANATIONS RELATING TO THE DEPOSIT FORM.

(1) if applicable "Application for certificate of addition to the main patent, to the main patent application No ............ of .......... .. ”- (2) enter the surname, first name, profession, address of the applicant, when the latter is an individual or company name, legal form, address of the head office, when the applicant is a legal person - (3) enter Λ l the surname, first name, address of the professional representative, industrial property attorney, with special powers, if applicable: "represented by ............ acting in quality of representative ”A4 OJ d - (4) date of filing in full - (5) title of invention - (6) enter the names, first names, addresses of the inventors or the indication" (see) separate designation (will follow ) ", when the designation is made or will be made in a separate document, or the indication" not to mention ", when the inventor signs or signs a non-mention document to be attached to a designation L - 3> Z.2-3>

List of inventors

György BAKTAY, 10, Eotvôs u., H-1153 Budapest

Dr. Péter LITERATI-NAGY, 38, VII u., H-1172 Budapest

Dr. Lajos György NAGy 24, Elnôk u., H-1089 Budapest

Dr. György BLASKÖ, 32-34, Zöldlomb u., H-1025 Budapest

Miklôs GRÔSZ, 42., Major u., H-1119 Budapest

Dr. Jànos PALINKÂS, 12, Allende park, H-1119 Budapest

Dr. Mària BOROSS, 4, Pauler u., H-1013 Budapest

Dr. Miklôs FABIAN, 17, Lukàcs Gy. U., H-1039 Budapest

Erzsébet PAKO, 16, Népezinhàz u., H-1081 Budapest

Dr. Làszlô BOGDANY, 36, Kerêk u., H-1035 Budapest Gàbor BOZOKI, 88 / b, Vâci ut, Hl-133 Budapest (i PRIORITY REUENOICftTIQN Filing of the patent application in Hungary from March 18, 1987 UNDER number 1174 / 87

DESCRIPTIVE MEMORY FILED IN SUPPORT OF A PATENT INVENTION APPLICATION IN THE GRAND DUCHY OF LUXEMBOURG

by; Caola Kozmetikai és Hàztartàsvegyipari Vàllalat 90, Bocskai ut Budapest Hungary for; Dietitic compositions and process for their preparation.

* * *

The present invention relates to dietetic compositions.

According to another aspect of the invention, a method is provided for the preparation of this composition.

5 We know that des-3 unsaturated fatty acids in Cjg_22 have advantageous biological properties. Eicosapentaenolic acid (EPR) and docosahexaenoic acid (DHR) are remarkable among these. Dyerberg et al. [The Lancet 15, 117 (1978)] emphasized the importance and the multiple biological effects of the two acids.

The effects associated with the important role of polyunsaturated fatty acids, in particular EPR and DHR in hyperpidemia and thrombotic diseases, have been summarized by Goodnight et al. [Rrteriosclerosis 2, 87 (1982)].

The active components of fish oil, for example EPR and DHR, are precursors of biosynthesis of the PG-3 series and simultaneously, they inhibit by competition harmful metabolites like TXRg and TXB2, originating from the so-called "arachidonic acid cascade", which is a chain of 20 complicated biological processes starting from arachidonic acid.

In addition to their many favorable effects, polyunsaturated fatty acids have a disadvantage in that they represent a possible source of highly harmful maIondiaIdehyde (FIDR) resulting from radical peroxidation processes, which can induce the so-called "cerium lipofuscinosis" in the central nervous system.

The use of EPR for food comments in the form of a cyclodextrin inclusion complex has been described in the French patent specification Ho. 2,550,145. Darshall et al. [Rm. J. Clin. Nutr. 38, 895 (1983) 3 have studied the role of ω-3 polyunsaturated fatty acids in the synthesis of olefinic acid and prostaglandins, as well as in dietetic food.

In addition to EPR and DHR, fish oils contain large amounts of saturated fatty acids and weakly saturated t 2 fatty acids as well as non-hydrolyzable components, the elimination of which is very important, since the blood triglyceride level and calorie intake are significantly increased by increasing the dietary dose. In addition, dietary harmful steroids, for example cholesterol, as well as uitamine D (its precursor) and vitamin R, both of which may accumulate in the human body, may also be present among the non-hydrolyzable constituents.

10 The dietary effects of ω-3 polyunsaturated fatty acids and especially EPR and OHR in relation to their numerous physiological relationships, are discussed in a large number of other articles [see for example U. Banceli i: Thromb. Res. m, 307 (1985); J.J. Jurkomskiî JNCI 71, 1145 (1985); R. 15 Lembke ·. Hi Ichmissenschaft 40, 329 (1985).

We also know that algae have been used since time immemorial by mankind for nutrition and food. Seaweed is therefore mainly consumed by the peoples of the Far East; in recent times, however, they are widely used in dry form or in tablet form also in developed countries.

Algae are extremely interesting nutrient carriers since their dried form contains in high concentrations substances which are essential for a healthy life, such as vitamins, proteins, protein complexes with microelements, saccharides, polyunsaturated fatty acids and the like.

General and detailed information concerning algae is described for example in the work of Zajic:; 30 "Properties and Products of Rlgae" (Edition Planum, Mem-York, 1970).

This last decade, we began to study the biological effects of microelements and microelements. It has thus been learned that selenium is one of the most important and most essential substances for life. Beneficial action

H

3 of 3éléniua rests especially 3ur the activation of the enzyme glutathione peroxidase, more precisely 3ur the activation of the prosthetic group of the enzyme which is the most important endogenous inhibitor of the harmful processes of peroxidation. Selenium · 5 is not accumulated in the organist, so it must be supplied continuously. Until now, selenium was introduced into the organist under the influence of inorganic cototes, mainly selenium dioxide · or sodium selenite.

The selenium itself has a hypotensive effect, it improves the ischetic, hypoxic and infarcted states of the heart and it inhibits cereal Iipofuscinosis of the central nervous system] moreover, it has a beneficial effect on periodontitis and it has It has been shown that it decreases the probability of the development of cancerous diseases], moreover, it is considered to be an agent inhibiting mutagenesis. Numerous changes or diseases, respectively, such as liver necrosis, yonecrosis, destruction of the erythrocyte membrane, interstitial lesions, elevation of ST in the ECG, Kvashiorkor syndrome (sub- protein diet) and multiple sclerosis are induced by selenium deficiency.

A report on the biological effects of selenium has been published by Thressa et al. [Hutrition Revie * 35, 7 (1977)], Shamberger [J. of Approx. Path. and Tox. 4, 305 (1980)], as well as 25 flasukata et al I. [Experlentia 39, 405 (1983)].

The aim of the present invention is to develop a new dietary composition which eliminates the disadvantageous biological effects of the consumption of polyunsaturated fatty acids, which combines the advantageous properties of DHR, EPR, algae and selenium, and which is able, thanks to its composition, to at least partially compensate for an unhealthy lifestyle and poor eating habits.

The invention is based on the finding that the above object can be perfectly achieved by a food composition which comprises an alga containing selenium with s 4 polyunsaturated fatty acids.

The present invention therefore relates to a dietary composition which comprises 0.5 to 50% by mass of acute containing selenium as well as 99.5 to 50% by mass of Cjg_22 unsaturated fatty acids containing at least two unsaturated bonds or derivatives thereof, with additives commonly used in the food industry and possibly an antioxidant.

Furthermore, the invention relates to a process for preparing the above dietary composition, which comprises mixing 0.5 10 to 50X by mass of algae containing selenium as well as · 99.5 to 50X by mass of unsaturated C | q-22 fatty acids containing at least two unsaturated bonds or derivatives thereof, with additives commonly used in the food industry and possibly an antioxidant.

The acute selenium-containing is prepared according to the procedure which is described in the Applicant's patent application filed at the same time as the present application and which corresponds to Hungarian patent application No. 575/88.

As starting material, unsaturated ω-3 fatty acids serving as active components of the composition, the oils obtained from various sea or freshwater fish, especially mackerel, cod, herring oils, may be used. , sardines, squid, as well as oils from the liver of these fish, for example cod liver oil and shark liver oil.

The Chlorella or Scenedesmus strains are suitably used as algae which are not only useful for human consumption but also have their own beneficial biological action.

The composition is sensitive to oxidation. It is therefore suitable to use an active preservative, for example (X-tocopherol (vitamin E), glutathione or a traditional antioxidant such as butyihydroxytoluene.

The homogenized composition can be included in food products, tablets, capsules and the like.

5

The term "dental product" here includes all useful products which can be administered orally or parenterally. The product administered orally may be contained in an article of the pastry or confectionery industry (for example 5 chocolates, cakes), compositions of the meat or butchery industry, spices, margarine , milk, butter or fatty products, oils and the like.

The main advantages of the composition according to the present invention can be summarized as follows: a) The individual components of the composition have in themselves important biological and dietary effects and combine the preferable properties of EPR and DHR as well as selenium and algae.

b) The risk of the appearance of "ceroidal ipofuscinosis" by consumption of polyunsaturated fatty acids is eliminated.

c) The use of a continuous diet is not required by consumption of the composition of the invention, since it does not contain the harmful components of fish oil described above (saturated fatty acids, cholesterol, 20 vitamins fl and D).

d) Selenium is present in a natural form enriched in algae, that is to say as a material of natural origin.

e) The composition is useful for the preventive treatment of apoplexic and thromboembolic states of the cardiovascular system, therefore for inhibiting the development of infarction and apoplexy as well as for preventing atopic or atopically related disorders. The use of the composition is strongly preferred also in declared states.

The invention is illustrated in detail by the following nonlimiting examples. The preparation of the components used as starting materials is shown in Examples 1, 2 and 3, while the preparation of the compositions is illustrated in the other Examples.

6

Example 1 10 kg of sardine oil are added at a temperature of 50 to 60 ° C to a solution containing 2 kg of eodium hydroxide in 70 liters of 952 ethanol. The mixture is heated to 5 reflux under nitrogen for 2 hours and then cooled to 10 ° C with stirring. The crystalline sodium salt of saturated fatty acid is filtered and diluted with a little ethanol. The ethanolic filtrate is evaporated and then 20 liters of boiling water are added to the residue. Non-hydrolyzable compounds such as cholesterol are completely removed by extraction with 5 liters of hexane. The extracted aqueous phase is acidified to pH 2 by addition of dilute sulfuric acid and again extracted with 15 liters of hexane. The organic phase is washed with water, dried over anhydrous sodium sulfate and evaporated to give 3.2 kg of oily concentrate having a DHR content of 36.8% and an EPR content of 31.82. This oil is brown and smells like fish. The oily concentrate is therefore mixed with fuller's earth, heated under nitrogen at 105 ° C for 10 minutes and filtered hot. The deodorization is completed by steam distillation under vacuum at 170 ° C / 1.3 bar for 3 hours, which gives 1.6 kg of an odorless, light yellow, flavorless oil of substantially unchanged composition.

Example 2 24 kg of cod liver oil are dissolved in 16 25 liters of methanol at 60 ° C., then the solution is added dropwise of 8 kg of sodium hydroxide solution at 402, between 50 and 60 ° C with stirring. The mixture was stirred at 60 ° C for an additional 45 minutes. Then 20 kg of 152 hydrochloric acid is added to the solution at about 60 ° C. After separation of the phases, the organic phase is extracted with 10 kg of 152 hydrochloric acid and then washed with 180 liters of hot tap water until neutral. The phases are separated, then 100 liters of acetone are added to the oily phase. The mixture is heated to about 45 ° C, then a solution of 3.8 kg of lithium hydroxide monohydrate in 30 liters of water is added. After 30 7 • while stirring, the mixture is left to stand overnight, then filtered and the acetone filtrate is evaporated. The residue is acidified by addition of 8 kg of hydrochloric acid at 15X, extracted 3 times with hexane and evaporated. A nitrogen atmosphere is used during the whole purification operation. 6.4 kg of purified fish oil are thus obtained having an iodine number of 258 and an acid number of 160.

One kg of norue liver oil purified as described above is added dropwise at 60 ° C to a solution containing 3 kg of urea in 9 liters of ethanol. The mixture is stirred at the temperature for 2 hours, after cooling, it is left to stand at -18 ° C. overnight in a refrigerator, then filtered and the filtrate is evaporated. 2.5 liters of hydrochloric acid (concentrated acid diluted to 15 i: i with water) are added to the residue and the mixture is stirred for 15 minutes, after extraction with hexane, the hexane phase is washed with with water until neutral, dried over anhydrous sodium sulfate and evaporated to give 0.34 kg of ω-3 fatty acids having an iodine number of 315, containing 24X of ERfl and 42X of DHfl.

20

Example 3 40 mg of sodium selenite are added to 8 liters of Knop-Pringsheim culture medium introduced into a glass vial of algae culture having a volume of 10 liters. The 25 e3t system sterilized at 1221 ° C under a 1 bar overpressure for 30 minutes. The sterile solution is cooled and inoculated with a pure algae culture of selenium resistant Scenedesmus obtisiusculus. Sterile air containing 5X by volume of carbon dioxide is bubbled through the culture medium at 25 ° C, while the system is illuminated with an electric discharge tube working with 4000 lux at a length of wave from 440 to 520 and from 640 to 700 μ ”, after a culture period of H days, the alga is separated from the culture medium. The mass of algae thus obtained is decomposed by ultrasound and dried carefully at a temperature below 65 ° C to give 6 g of an algae powder having a "k 8" selenium content of 1200 pg / g.

EXAMPLE 4 100 g of algae containing selenium · (content of 5 selenium ": 260 pg / g of algae powder) are stirred with 150 g of" liver oil "enriched at 65X (containing 221 of EPR and DHFI 43X). After hoiogenization, the mixture is preserved by adding 0.2X in a cup of vitamin E.

10 Exeiole 5

Preparation of a cotiment of nargarine al lienta ire Eight grams of norue liver oil enriched with 65X (containing 22% of EPA and 43% of 0ΗΑ) and 1 g of seaweed containing selenium "(with a selenium concentration of 260 pg / g of algae powder) are "mixed with 250 g of" argarine "olle, then the" mixture is hoiogenized.

Exeiole 6

The process described in Example 4 is followed, except that the following quantities of starting materials are used: 400 g of norue liver oil enriched with 65% (containing 22% of EPR and 43X of DHR) ; 70.6 g of seaweed powder containing 1200 pg / g of selenium "; and 0.4 g of Vitamin E.

The hoaogenate thus obtained is introduced into soft gelatin capsules or soft gelatin pearl capsules having a capacity of 500 μg and then included in a package. alveoli.

30

Exeaole 7

Conpriae having the following conposition are prepared with devices and according to known pharmaceutical methods: ψ 4 9

Aorue liver oil enriched in EPfl and DHA, containing 0.1% of vita E coaae preservative (43X of DHfi and 22% of EPfl) 200 ag

Seaweed containing selenium 5 (selenium concentration: 380 pg / g seaweed powder 86 ag

Lactose 140 ag

Ab i don 60 ag

Polyvinylpyrrolidone 3.5 ag 10 Aagnésiua stearate 3.5 ag

The coapriae are optionally coated with sugar in a suitable Bachine.

4

Claims (5)

1. Dietetic composition, characterized in that it comprises 0.5 to 501 by mass of algae containing selenium as well as 99.5 to 50X by mass of unsaturated fatty acids Cjg_22 containing at least two unsaturated bonds or derivatives thereof, mixed with additives commonly used in the food industry and possibly an antioxidant. 2. Composition according to claim 1, characterized in that it comprises esters, alkaline earth metal lethal salts or amine salts as derivatives of fatty acids. 3. Composition according to Claim 1 or 2, characterized in that it comprises i'ac i of 5,8,11, H, 17-eicosapentaenoic acid and 4,7,10,13,16, 19-docosahexaenoic as unsaturated fatty acids. 4. Composition according to Claim 1, characterized in that it comprises gra3 acids obtained from sea fish oil as unsaturated fatty acids. 5. Process for the preparation of a food composition according to claim 1, characterized in that it comprises the mixture of 0.5 to 50X by mass of algae containing selenium as well as 99.5 to 50X in bulk of unsaturated C | 0-22 fatty acids containing at least two unsaturated bonds or derivatives thereof, with additives commonly used in the food industry and possibly an antioxidant.