DE19936831A1 - Reduction of cholesterol oxides by n-3-PUFA and vitamin E - Google Patents

Abstract

The invention relates to the use of n-3-PUFA and/or vitamin E for reducing the formation of cholesterol oxides.

Description

The invention relates to the use of polyunsaturated Fatty acids (PUFA) of the type n-3-PUFA (or ω-3-PUFA) and / or Vi tamine E to reduce cholesterol oxide formation in human or animal body.

Unsaturated fatty acids are divided into 3 families (n-9, n-6 and n-3) divided, this division at the position of the first ten double bond oriented from the methyl end. Fatty acids with more than one double bond are considered to be polyunsaturated Designated fatty acids (poly-unsaturated fatty acids, PUFA). The mentioned fatty acid families can not be converted into one another become.

Cholesterol oxides are increasingly found in the human body in artherosclerotic lesions. In addition, both in vitro as well as in vivo studies of their high angiotoxicity and atherogenic activity determined (Peng, S.K., et. al., J. Clin. Lab. Anal. (1991); 5: 144-152; Imai, H., Science (1980); 207: 651-653). The source of endogenous cholesterol oxides is the cholesterino oxidation in vivo. It also releases cholesterol oxides through the Nah tion, in particular through the consumption of egg products (Jacobson, M.S., The Lancet (1987); 8560: 656-658).

Recommended due to the atherogenic effect described above the American Health Association eating healthy adults Limit eggs to 3-4 meals a week.

By Simopoulos, A.P., et al. (Am. J. Clin. Nutr. (1992); 55: 411-414) has already been proposed, long chain, multiple accumulate saturated fatty acids in egg yolk and in this form Baby food, such as B. infant formula, to add. The However, this proposal is questionable insofar as the generally known, easy oxidizability polyunsaturated fatty acids (PUFA) an increased formation of cholesterol Oxidation products are expected in chicken eggs. So report Marshall, A.C., et al., In Journal of Food Science (1994), 59, 3: 561-563 that after feeding polyunsaturated fatty acids containing fish oil on chickens increases lipid oxidation products were found in egg yolk. Successful use of PUFA for the targeted reduction of cholesterol oxides could not expected here.

It was therefore an object of the present invention to find a way find the content of atherogenic cholesterol oxides in humans lichen or animal body or in food animal Reduce origin. This should make prevention possible for cholesterol oxide-mediated atherosclerotic lesions or cholesterol oxide-mediated angiotoxic or atherogenic Effects are created.

Surprisingly, this task was solved by the inventor According to the finding that when administered certain multiple unsaturated fatty acids, namely n-3-PUFA (ω-3-PUFA) and / or vitamin E significantly reduce the cholesterol oxide content is cash.

A first object of the invention therefore relates to the use of n-3 PUFA and / or vitamin E for the manufacture of a veterinary medicinal medicine or a feed for reducing cholesterol oxide formation in the animal body or in the near means of animal origin, such as. B. eggs and egg products. To this end, animals such as pigs, rabbits, Fi like, e.g. B. trout, salmon, and especially poultry, such as Ducks, geese and especially chickens, specially prepared feed agent or medication. These preparations are formulated to include an uptake of n-3 PUFA in one dose in the range of about 0.1 to 2000 mg / kg body weight and / or the Intake of vitamin E in a dose in the range of about 0.1 to Ensure 1000 mg / kg body weight by the animal body most.

Suitable veterinary medicines contain n-3-PUFA in a proportion of about 10 to 1000 mg per dose unit and / or Vitamin E in an amount of about 5 to 1500 mg per dose Ness.

Suitable feed contains n-3-PUFA in a proportion of about 0.1 to 10 wt .-% and / or vitamin E in a proportion of about 5 to 2000 mg / kg of feed.

Another object of the invention relates to the use of n-3-PUFA and / or vitamin E for the manufacture of a medicament or a dietary supplement, supplements, or treats secured food, to reduce cholesterol oxide levels dung in the human body. These preparations are formulated that they take up n-3 PUFA at a dose in the range of about 10 to 2000 mg / kg body weight and / or the intake of  Vitamin E in a dose in the range of about 5 to 2000 mg / kg Ensure body weight through the human body.

Suitable drugs contain n-3-PUFA in a proportion of approximately 20 to 2000 mg per dose unit and / or vitamin E in one batch part of about 10 to 2000 mg per dose unit.

Suitable dietary supplements contain n-3-PUFA in one Proportion of about 10 to 1000 mg / kg and / or vitamin E in one part of about 5 to 400 mg / kg.

Suitable fortified foods contain n-3-PUFA in one Percentage of about 10 to 500 mg per serving and / or Vitamin E in a proportion of about 5 to 100 mg per consumer portion.

Examples of foods that can be enriched with n-3-PUFA and / or vitamin E are suitable as bakery products special bread, cereals, milk, milk products, such as in particular Yogurt, chocolate, chocolate bars and the like.

The invention relates in particular to the use of n-3-PUFA and / or vitamin E for the manufacture of a medicament, a food supplement / supplement or fortified Food as defined above for cholesterol prevention oxide-mediated atherosclerotic lesions or cholesterol Oxide-mediated angiotoxic or atherogenic effects in People.

Within the scope of the present invention, individual n-3 PUFAs can be used as Pure substance alone or in a mixture with other n-3 or n-6-PUFA can be used. There is also the possibility Mixed preparations or extracts of vegetable or animal origin to use jump, which has a high n-3-PUFA content sen.

Examples can be given here: Mixtures, out chooses marine extracts, dry preparations or homogenates Cellular organisms, fish extracts or oils and plant extracts or oils, and especially fish oil, linseed oil, hemp oil, rapeseed oil and soy bean oil and from marine unicellular organisms, such as phytoplankton and algae, extracted oils.

In the context of the invention, n-3 PUFAs are as free acid or as physiologically acceptable salt or especially as organic logically degradable esters or usable as phospholipids. Before pulled esters include alkyl esters, the alkyl portion being one to  six carbon atoms, or mono-, di- or triglyce ride.

According to a preferred embodiment, the poly-unsaturated n-3 fatty acid with 18 to 22 carbon atoms or a mixture of substances containing at least one polyunsaturated n-3 fatty acid with 18 to 22 carbon atoms is used as n-3-PUFA. The polyunsaturated n-3 fatty acid is particularly preferably selected from α-linolenic acid (C18: 3n-3) (α-LNA), eicosapentaenoic acid (C20: 5n-3) (EPA); Docosa pentaenoic acid (C22: 5n-3) (DPA) and docosahexaenoic acid (C22: 6n-3) (DHA). N-3-PUFA mixtures which can be administered particularly preferably include EPA and DHA; α-LNA and EPA; or α-LNA and DHA. The following mixing ratios are preferably present in these n-3-PUFA mixtures:
EPA: DHA = 5: 95% to 95: 5% by weight; such as B. 15: 85 wt% to 60: 40 wt%;
α-LNA: EPA = 5: 95% by weight to 95: 5% by weight;
α-LNA: DHA = 5: 95% by weight to 95: 5% by weight;

The vitamin E used in the invention includes the To copherols α, β, γ, and δ and the tocotrienols α, β and γ individually or in a mixture, such as. B. a mixture of tocopherol α and γ.

In a further preferred embodiment, the inven relates the use of a combination of n-3 PUFA or one biodegradable esters thereof and vitamin E to the above named purposes.

According to a further preferred embodiment, one or several n-3 PUFA or one or more biodegradable Esters of which are used without the addition of vitamin E.

For the use according to the invention, n-3-PUFA and / or vitamin E, either as individual active ingredients or as mixtures with others ren therapeutic agents, in the form of suitable human or veterinary medicines are administered. In there them as mixtures of the active ingredients with suitable pharmaceutical Carriers or diluents. The agents can be taken orally or administered parenterally, but preferably they are administered in given oral dosage forms.  

The type of pharmaceutical and pharmaceutical Carrier or diluent depends on the desired administration type of delivery. Oral agents can be used, for example, as tablets or capsules and can contain conventional excipients, such as binders (e.g. syrup, acacia, gelatin, sorbitol, tragacanth or polyvinylpyrrolidone), fillers (e.g. lactose, sugar, Corn starch, calcium phosphate, sorbitol or glycine), lubricants (e.g. magnesium stearate, talc, polyethylene glycol or silicon dio xid), disintegrating agents (e.g. starch) or wetting agents (e.g. B. sodium lauryl sulfate). Oral liquid preparations can be in the form aqueous or oily suspensions, solutions, emulsions, Siru pen, elixirs or sprays, etc. are present or can be as Troc ken powder for reconstitution with water or another egg suitable carrier. Such liquid preparations can be used Liche additives, such as suspending agents, flavor substances, diluents or emulsifiers. For the parenteral administration can be done with solutions or suspensions use usual pharmaceutical carriers.

The agents according to the invention can be given to a human or a Animal in doses from about 0.1 mg to about 2000 mg per kg of body weight weight per day. You can in a single dose or administered in multiple doses.

For the use according to the invention, n-3-PUFA and / or vitamin E also in the form of suitable supplements / food supplements be administered. Examples can be given with n-3-PUFA and / or vitamin E enriched fat emulsions, which one z. B. in a conventional manner from soybean oil or fish oil Egg lecithin as an emulsifier. Advantageously used egg lecithin obtained from egg from laying hens, which longer with n-3-PUFA and / or vitamin E-rich feed Time, such as B. 3 to 6 weeks were fed.

n-3-PUFA and / or vitamin E can still be considered special enriched foods are formulated, which like the mentioned supplements or food supplements within the framework of egg enteral nutritional therapy can be used. As examples for suitable foods z. B. dietary foods, such as B. nutritionally defined drinking food, sports food, slide called beta-food or baby or premature food become.

Are n-3 PUFA and / or vitamin E individually or in combination in Feed is administered, the active compounds as Pure substance or mixtures of substances or liquid or solid extracts administered together with common feed ingredients. At  Common feed ingredients are: corn, barley, white zen, oats, rye, tritikale, sorghum, rice and bran, semolina bran and flours of these cereals, soybeans, soy products such as soybean meal, rapeseed, rapeseed meal, cotton seeds and extraction meal, sunflowers, sunflower extracts tion meal, linseed, linseed meal, oilseed expeller ten, field beans, peas, gluten, gelatin, tapioca, yeast, sin gle cell protein, meat bone meal, meat meal, blood meal, Fish meal, salts, minerals, trace elements, vitamins, amino acids, feed fat and the like.

The present invention will now be explained in more detail by the following example and with reference to the accompanying FIG. 1.

Fig. 1 shows the concentration curve of various cholesterol oxides in fresh egg yolk (black symbols) or after 4 weeks of storage of the ice at room temperature (bright symbols), each after 4 weeks of feeding a 1.5 wt .-% fish oil and different amounts (mg / kg) feed containing vitamin E on laying hens.

example 1

Examination of cholesterol oxide formation in egg yolk when feeding n-3 PUFA and various amounts Vitamin E.

a) The following basic mix (Table 1) for a laying hen alone lining was made:  

Table 1

Basic feed mix

The basic feed showed the following nutrient, vitamin and traces element content (Table 2) on:  

Table 2

calculated nutrient, vitamin and trace element content

b) This basic feed mixture was mixed with 1.5 percent by weight fish oil (containing 11.5% by weight of eicosapentaenoic acid (EPS) and 8% by weight of docosahexanoic acid (DHA)). In addition, the amounts of vitamin E given in FIG. 1 (0, 5, 10, 20, 160 mg / kg of feed) were added to the feed. White laying hens (age 35 weeks) were divided into different test groups of 12 animals each (control group 36 animals) and fed ad libitum with the differently supplemented feed compositions. A control group received unsupplemented feed. The feeding phase was four weeks. In the fifth week, the eggs were collected and analyzed. The analysis of the total cholesterol as well as the cholesterol oxidation products was carried out according to the method described by Se vanian A., et al. in Free Radic. Biol. Med. (1994); 17: 397-409. The analyzes were carried out on both fresh and stored eggs (four weeks at room temperature). The analysis of vitamin E was carried out by HPLC, such as. B. described by Wahle, et al., J. Sci. Food Agric (1993), 61, 463; the analysis of n-3-PUFA was carried out by gas chromatography (Simopoulos et al., loc. cit.).

c) The content of n-3-PUFA in egg yolk rose to values of about 10 mg / g, mostly in the form of DHA. Take with you the vitamin E content in the feed also decreased from the vitamin E content 5.33 +/- 1.54 nmol / g to 11.63 +/- 2.96 nmol / g, determined by HPLC, too.

While the cholesterol content in yolk remained constant during the course of the feeding of vitamin E or during storage, it was surprisingly observed that with increased administration of vitamin E fewer cholesterol oxidation products accumulated (cf. FIG. 1). The sum of the detectable cholesterol oxidation products in the egg yolk (ie sum of cholest-5-en-3β, 7β-diol, cholest-5-en-3β-ol-7-one and cholest-5-en-3β, 25 -diol) was 266 +/- 49 nmol / mg egg yolk in the control group and was reduced by 20% by feeding n-3-PUFA and by feeding Vita min E (20 mg / kg feed) by a further third. A further increase in vitamin E intake above 20 mg / kg feed did not lead to a further reduction in the cholesterol oxidation products.

In summary, it can thus be stated that enrichment of chicken egg with n-3 PUFA and vitamin E the cholesterol content Oxide in egg yolk reduces and thus the production of chicken egg with lower atherogenic properties.

Claims (8)

1. Use of n-3-PUFA and / or vitamin E for the production a veterinary drug or feed means to reduce cholesterol oxide formation in tieri body or in foods of animal origin. 2. Use of n-3-PUFA and / or vitamin E for the production a drug, a dietary supplement / Supplements or fortified foods for reducing cholesterol oxide formation in the human body. 3. Use of n-3-PUFA and / or vitamin E for the production a drug, a dietary supplement / supplement ment or fortified food for prevention Chole steric oxide mediated atherosclerotic lesions or Cholesterol oxide-mediated angiotoxic or atherogenic Effects in humans. 4. Use according to any one of the preceding claims, wherein n-3-PUFA or a biodegradable ester thereof and Vita min E can be used in combination. 5. Use according to any one of the preceding claims, wherein as n-3-PUFA at least one polyunsaturated n-3 fatty acid with 18 to 22 carbon atoms or at least one polyunsaturated n-3 fatty acid with 18 to 22 carbon mixture of substances containing fatomas is used. 6. Use according to claim 5, wherein the polyunsaturated n-3 fatty acid selected from α-linolenic acid (C ₁₈ : 3n-3), egg cosapentaenoic acid (C ₂₀ : 5n-3); Docosapentaenoic acid (C ₂₂ : 5n-3) and Docosahexaenoic acid (C ₂₂ : 6n-3). 7. Use according to claim 5, wherein the mixture of substances is selected is mari under extracts, dry preparations or homogenates single cell, fish extracts or oils and plant extracts ten or oils. 8. Use according to claim 7, wherein the mixture of substances is selected is among fish oil, linseed oil, hemp oil, rapeseed oil and soybean oil and oils obtained from marine unicellular organisms.