DE2124972A1 - Food and feed additive - Google Patents

Description

Food and feed additive

The invention relates to food and putter additives. In particular, the invention relates to food and putter additives, their effect in an inhibition or a delay of numerous biochemical and sub-cellular ones There are reactions that normally occur during biodegradation as a result of the aging process. " The invention also relates to food and putter additives that have a preventive or inhibiting effect exercise on incipient lung diseases by protecting the lung membranes.

Aging is understood to mean gradual changes that occur over time in cells * tissues, organs or Organisms run off. Primarily, the aging process leads to a gradual loss of puncture capacity, which ultimately leads to the death or death of the cells or the organism. Obviously that begins Aging process »if there is a loss of information ·

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Transmission in the DNA / RNA synthetase protein sequence makes noticeable. The DNA molecule (deoxyribonucleic acid) forms part of every cell nucleus. Though about the the exact mechanism is not yet in agreement, the DNA molecule ultimately contains the program for life, aging and death. DNA is believed that it forms the genetic substance. In this role he inevitably has two functions. It has to be contained in a chemical code information about the development of the cell according to its genetic make-up Furthermore, it must be reproducible (true to the original) in order to transfer this genetic material to future generations transfer. The RNA molecule (ribonucleic acid) occurs mainly in the cytoplasm of the cells and only to a limited extent in the nucleus and forms a determining factor Pactor in protein synthesis.

When it comes to the DNA / RNA synthetase protein sequence too If an information span comes, the RNA synthetase changes, whereby the RNA molecule formed from it also undergoes a change and no longer an exact one The image of the parent molecule is. The protein formed from the modified RNA molecule is therefore incorrect synthesized because the amino acid components used were incorrectly selected or by the Massenger RNA molecule have been misread. If the proteins produced deviate sufficiently from the norm, the will notice them Bodies as free bodies and attacks them with antibodies. At the same time they are used to maintain the body required correct proteins not formed in the required way. The body therefore tries increase the speed of protein synthesis.

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to produce the necessary "protein building blocks", Instead of forming the right protein building blocks, however, there is more and more wrong formation synthesized or incorrect proteins.

Research has shown that port striding the aging process via an accumulation of a protein / Llpid complex, fluorescent pigment can be traced in the aging body cells. This pigment is optimally called lipofuscin or simply called "aging pigment". It has long been the doctrine that the aging process is genetically programmed according to an exact Mechanism takes place and that the change in RNA synthetase is purely time-dependent. This rigid reasoning does not explain an acceleration of the Aging as a result of stress-like phenomena, e.g. as a result of anxiety and other emotional stimuli, retirement, Disease, avitaminosis and the like.

For some time, attempts have been made to explain aging using the so-called "free radical theory". Free radical reactions are so called because in the course of chemical reactions at times highly reactive intermediate products, known as free radicals are known to occur. The high chemical reactivity of free radicals is due to the given freedom of choice to return. Free radicals can be found in very low concentrations on their own prove magnetic moment. Free radical reactions often occur in daily life. Examples of this are the formation of smog, the rancidity of butter and other fats, the reaction of oxygen with fuel

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substances, like gasoline in a car engine, drying of oil-based paints and the manufacture of common plastics as already mentioned, a high chemical reactivity, so that from these free radical reactions, which are almost unchanged irreversible, the most varied Products can emerge.

In biological systems, therefore, those introduced by free radicals are likely to be more or less arbitrary and irreversible reactions after numerous harmful reactions and conversions, as expected pull yourself «Various research results have confirmed this. The damage done here is likely at a given rate for the initiation of the reaction expected to be proportional to the duration of the Chain reaction increase. At a given start-up speed, the typical free radial reaction can be achieved between molecular oxygen and organic compounds by the following equation:

Ou
RH + O ₂ ■ »R. + HO ₂

reflect in which the amount of RH converted into other compounds depends on the number of repeated propagation steps, i.e. on the duration of the chain reaction. The complete reaction can be, in a simplified Form, represented by the following equations:

Cu
Introduction . RH + O ₂ > R.

Reproduction R. + Q ₂

RO ₂ + RH> R * + ROOH

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Aborted reaction R '+ R * ■ -> R: R

In the given equations, RH means an organic one Compound, while Cu stands for a copper catalyst. The "free radical theory" of the old remains, in spite of the fact that it brings the various opinions and theories up to now under a single hypothesis, the proof guilty that aging is a genetically programmed, species-specific series of events acts. Although certain diet supplements have already been developed to inhibit the aging process, so far this has been possible it has not yet been established that these are fully or at least largely effective distinguish.

The invention was thus primarily based on the object of developing food and putter additives that an effective inhibition or delay of a substantial part of the normal aging process able to bring about adherent biodegradation. In particular, these additives are intended to break down the RNA synthetase slow down, prevent the accumulation of incorrectly synthesized cells and proteins in the body and prevent the appropriate Decrease antibody response. Furthermore, with the help of these additives, the aging-accelerating Have the effects of stress and stress-like factors effectively combated. Furthermore, through this Additives effectively reduce and / or delay the build-up of lipofusoin or aging pigment can be achieved in aging body cells. Another task of such additions is to be the tolerance

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of the body against radiation and the efficiency of the Increase oxygen utilization. Furthermore, these additives are supposed to help fight under control in the body abnormal nitrogen balance and poor tissue formation require proper protein synthesis to get going and maintaining it. These additives should also reduce the free radical reactions inhibit in the body and keep the body largely free of free radicals formed. In the end These additives are supposed to keep the cell membranes from collapsing as a result of free radical attack on cells.

It has now been found that the tasks outlined can be solved with the aid of a food and feed additive let, of the four critical components, viz Antioxidants consisting of vitamin E and mixtures thereof with a synthetic lipid antioxidant; the trace element selenium contains a sulfur-containing amino acid and a membrane stabilizer.

Examples of suitable membrane stabilizers are antihistaraine, Salicylates, corticosteroids, antihistamine-like compounds, and vitamin C.

It is essential that the said critical Components of the body at the same time and continuously to provide.

The invention was also based on the object of developing such additives, the lung mera protect by preventing the vitamin A it contains extensive oxidation by air pollution

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maintain"

It has been found that this problem can be solved with one food and feed additive, of the three critical components, namely vitamin E, vitamin C and a synthetic lipid antioxidant, such as butylated hydroxytoluene, in synergistic Contains quantities. It is essential that these critical components meet the Bodies are made available simultaneously and continuously.

The monoacid, polyunsaturated lipid components of the lung tissue are broken down into free radicals _{by air pollutants such as NO 2 and O ,,.} This degradation obviously consists in an auto-oxidation of monounsaturated and polyunsaturated compounds. Naturally occurring vitamin A is considered critical for healthy metabolism and the growth of epithelial cells in the lung caverns. The oxidizing air pollutants usually contained in the air actually destroy vitamin A. Ingesting the antioxidants, vitamin E, vitamin C and a synthetic lipid antioxidant, in synergistic amounts helps to protect the natural source of vitamin A against the usual, oxidizing air pollutants.

All of the objects underlying the invention

can be achieved by using a food and feed additive solve the 5 critical components,

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namely vitamin E, vitamin C, a synthetic lipid antioxidant that contains the trace element selenium and a sulfur-containing amino acid. Together with vitamin C can also other membrane stabilizers are concomitantly ₀ However, it is essential that the critical ingredients mentioned provided to the body simultaneously and continuously to Verfigung.

In the case of agents or compounds, the cell membranes from collapse as a result of an attack on the cells preserve by free radicals, they are membrane stabilizers. These membrane stabilizers protect cells from attack by free Radicals, which would otherwise lead to a breakdown or decomposition of the membrane; latter Phenomenon leads to leakage of liposomal enzymes, which also leads to damage to the DNA molecule leads. Examples of membrane stabilizers are as already mentioned, antihistamines, vitamin C, salicylates, Corticosteroids and antihistamine-like compounds. Per day and 45.4 kg body weight should be about 0.1 to about 500 mg membrane stabilizer should be taken.

Examples of antihistamines that are symptomatic because of their antagonistic effects on histamines Used to relieve allergic phenomena are antazoline phosphate, carbinoxamine maleate, chlorcyclizine hydrochloride, Chlorothene citrate, chlorpheniramine maleate, diphenhydramine hydrochloride, polyamine succinate, methaphenilene hydrochloride, Methapyrilene hydrochloride, pheniramine maleate, promethazine hydrochloride, pyrathiazine hydrochloride, pyrilamine

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maleate, pyrrobutamine phosphate, thonzyl hydrochloride, triple amino nitrate and triple naraine hydrochloride. . Examples of other antihisamines are cyclizine hydrochloride, cyclizine lactate, dimenhydrinate, and meelizine hydrochloride and hydroxyzine hydrochloride.

Examples of suitable corticosteroids are cortisone, hydrocortisone, prenisolone, cortisone acetate, fluoroortisone, Deoxycorticosterone acetate, hydrocortisone acetate, fluorine " cortisone acetate, hydrocortamate hydrochloride, hydrocortlson « cyclopentyl propionate, hydroeortisone suecinate, sodium salt, Methylprednisolone, prednisolone acetate, prednisolone butyl acetate and prednisone. As a rule, the corticosteroids are the glucocorticoid or 11,17-xysteroid compounds.

Examples of salicylates are acetylsalicylic acid (aspirin), Methyl ester of acetylsalicylic acid, benzyl ester of acetylsalicylic acid and calcium acetyl salicylate. The expression "salicylate" is intended to include the acids and esters mentioned and metal salts are understood.

Examples of antihistamine-like agents or compounds are polyvinylpyrrolidone, enzymes such as trypsin and chymotrypsin as well as pulmonary medicines such as adensin-5-monophosphate. Polyvinylpyrrolidone is a solid with an average molecular weight of 25,000 and corresponds to the formula

I.
CH

CH.

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The vitamin C, which is contained in the lung tissue Grease against oxidation by air pollutants, such as NÖg and 0, protects, acts as a protective antioxidant . In the additives according to the invention, pro 45 * 4 kg body weight contain 50 to 500 mg vitamin C. be. Vitamin C is L-ascorbic acid the formula:

HIGH
CH ₂ OH

Ascorbic acid is soluble in water and solid at room temperature. Its melting point is 190 ° to 192 ⁰ C. It also does not "toxic salts, esters and derivatives can be used vitamin C. Vitamin C forms stable metal salts such as sodium ascorbate. DLese can also be used. Sodium asorbate is prepared, for example, by the process described in U.S. Patent 2,442,005. In terms of vitamin C activity, 120 mg sodium ascorbate corresponds to 100 mg ascorbic acid. Sodium ascorbate is water-soluble and solid at room temperature. Ascorbyl palmitate can also be used.

Finally, mixtures of the cell membrane stabilizers can also be used get used.

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The cell membrane stabilizers specified below are the preferred stabilizers. Furthermore, the following is also the preferred daily dose for the individual in the food and feed additive stabilizers used:

Cell membrane daily dose

stabilizer

Aspirin 0.25 - 25 grains / 45 * 4 kg body weight

Hydrocortisone 0.5 - 50 mg / "

Polyvinylpyrrolidone 1 - 100 mg / "

Vitamin C 0.2-0.3 g / "

The vitamin E component can be found in the diet and Feed additive in the form of the pure compound, preferably in the form of od-tocopherol, may be included. The vitamin E component can also be used in the form of an active vitamin Ε compound, e.g. as acetate, succinate or other esters can be used. All active, isomeric forms can be used, including the dl and d forms of the compounds mentioned, as well as numerous naturally occurring materials and extracts to be used with vitamin E activity, The amount of respective vitamin E source is chosen so that for. an average body weight of 45.4 - 54.4 kg the desired dosage (based on a unit dose) is administered. Because the body has any excess Vitamin E either excretes or stores, there is no theoretical upper limit for the amount of vitamin E. As a practical matter, the unit dose should typically be about 10 micrograms (0.01 I.U.) to 1.0 g

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(1000 IU) or even up to 10 g (10000 IU).

Vitamin E known as a lipid antioxidant reduces the biological need for oxygen in the body. This vitamin increases the efficiency of oxygen transfer in the body and decreases the amount of im Body stored free oxygen as it prefers the other body parts with free oxygen reacted. Therefore, the vitamin E can be used as a "preservative" for body components, such as for example red blood cells and arterial wall lipids, because - it prefers with free Oxygen or other oxidizing compounds that would otherwise attack the named body components, reacted. According to the invention is the fact that vitamin E with the organic selenium complex known as factor 3 a unique and vital synergistic Effect unfolds, of the greatest importance and highly critical.

The vitamin E can be mixed in the usual way with a vegetable oil, in particular with a seed oil, e.g. with wheat germ oil, safflower oil, corn oil, soybean oil and the like., can be added.

Knowledge of the importance of the trace element selenium as a micronutrient, it has developed rapidly over the past 10 years. In the mode of action In the body, selenium is partly similar to vitamin E in that it is biochemical as a lipid and antioxidant Acts as a water soluble free radical scavenger. The practical application of basic nutritional science Findings on the selenium made a rapid one

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Underwent development; this element has been used in the diet of numerous animals such as sheep, cattle and dogs, became very important. The most essential and critical function of selenium is according to the invention in the formation of the organic complex known as factor 3. It has now been found that the factor together with vitamin E unfolds a synergistic catalytic effect, namely in being highly successful Point the reaction equilibrium towards destruction of the wrongly synthesized protein shifts.

Although the exact structure of factor 3 is not known

Füt ve approximately
Biax tests in animals have shown that a minimum amount of selenium is required until a factor 3 activity is reached, and that there is also a maximum selenium concentration beyond which no further increase in factor 3 activity is recorded and free selenium is detectable is. In this way it was determined that the optimal daily selenium intake from all available sources per 45.4-54.4 kg body weight should be about 5-10 mg (in the form of the oxide). Concentrations at which a factor 3 activity is established without excess free selenium being formed are 1 microgram - 500 mg (in the form of the oxide).

The selenium can be used in elemental form, as an oxide or as another organic or inorganic selenium compound . It occurs naturally in various amounts in a wide variety of foods and is also preferred as an impurity

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sulfur-containing amino acids, ζ.Β «in methionine as Selenomethionine. The latter is due to the fact that the chemical behavior and the Reactivity of sulfur and selenium to one another so are similar in that it is extremely difficult, if not impossible, to obtain selenium from sulfur-containing compounds remove completely.

For example, in food-grade sulfur-containing amino acids is usually the appropriate one Contain selenoamino acid, so that the selenium in the specified amounts is absorbed. For example, when analyzing a gram of a commercially available, Food grade cysteine about 75 wt .- ^ (750 mg) cysteine and about 0.1 wt .- ^ (1 mg) Selenocysteine found. The latter was incinerated, one containing about 0.65 mg of selenium as the oxide. ash incurred. Even in the case of analytically pure sulfur-containing amino acids, it cannot be avoided that they contain contains small amounts of selenoamino acids.

Thus, so the vitamin E, the most £ borrowed ^m aem organic selenium complex "factor j5 ^M Some researchers unfolds a synergistic effect, preferably in an Mindestdiätkonzentratlon to give optimal synergy. Suggest that this synergism on the formation of a possible factor 3 / vitamin E-KoBiplexes. Similar diet experiments with mice, rats and miniature pigs have shown that for the development of the greatest synergistic effect with the factor j3 again minimum and maximum concentrations

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of vitamin E are required. These attempts have extrapolated kg 54.4 shows that 5-100 Microgramra vitamin E must be supplied in the diet for optimal effect synergistisehen daily - an average body weight of 45, ¹ I-.

Sulfur-containing amino acids are cysteine, cystine, an amino acid of the formula

and methionine; according to the invention they are used in amounts of at least 1 mg per unit dose. Here too there is no theoretical upper limit as the amino acids are foods. According to the invention However, amounts of preferably up to 10g are used. Because of the methyl group present methionine represents a sulfur-containing amino acid preferred according to the invention; Methionine is particularly suitable to combat stress-related mechanisms that contribute to accelerating the aging process. The above-mentioned amino acids form sulfur suppliers in the body and reduce the influence of one Irradiation on the aging process. ·

Parts of the vitamin E component can be replaced by 1 or Replaced several synthetic lipid antioxidant (s) tien will. These antioxidants have a catalytic effect in the sense of inhibition or inhibition an autoxidation of fats, lipids, polymers and the like. Their main effect is a termination the free radical chain reaction, a suppression electron mobility, a sequestration of

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Traces of metal and a free radical trap. In vivo 'the antioxidants lower the lipoxidase capacity, i.e. the capacity of an enzyme to act in vivo by inducing free radical chain reactions causes an autoxidation by transferring electrons or hydrogen residues to the enzyme Peroxide-free, free lipid radicals located on the enzyme surface protonate or the formation of free ones Inhibit radicals. A preferred synthetic antioxidant is butylated hydroxytoluene. He- According to the country, other known synthetic MpId- * antioxidants, such as butylated hydroxyanisole, 2-mercaptomethylamine, Ν, Ν'-diphenyl-p-phenylenediamine, Ammonium diethyldithiocarbamate, 1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline, Ethoxyquin, aminoethylisothyromium, aromatic phenols, aromatic amines and the like. Can be used. Get when using them the synthetic antioxidants in an amount of up to at 200 mg per unit dose used; however, usually smaller amounts can also be used will. The reactions of synthetic antioxidants are similar to those of vitamin E, but with the essentials Exception that no synergism or no complex formation takes place with the Paktor 3. For this reason it is critical that, per unit dose, at least 5 micrograms and preferably at least 100 micrograms of vitamin E can be used.

The optimal daily doses of the individual ingredients are:

0.5 - 1 * 0 g (500 - 1000 I.E.) vitamin E, 5 - 100 micrograms selenium in the form of the oxide, 1 - 2 g sulphurous

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Amino acid, e.g. methionine, 1 - 100 g membrane stabilizer. When using form 10-300 micrograms · synthetic antioxidants such as butylated hydroxytoluene, the optimum daily dose "Other vital components can also in the unit dose, such as lecithin in an amount from .1 to 0.5 g or vitamin B ₁ ρ in an amount 1-2 micrograms can be added.

It has been shown that RNA synthetase is altered due to at least two related mechanisms. In addition to the highly reactive intermediate compounds consisting of free radicals, the change can also be caused by excited oxygen dimers. Oxygen is absorbed by all living cells and retained in them; this oxygen can natural radiation, including cosmic, & i, f i> -,) ^ - and X-rays to take and singlet excited Singlet- or to form singlet-triplet Dimerezustände. In the normal state, oxygen is in the triplet form, but irradiation can cause triplet-triplet absorption, with some of the oxygen molecules undergoing an intersystem crossing to form the metastable singlet form. The excited dimer is stable for up to 4-5 minutes; its energy is enough to change RNA synthetase and neurons. Removal of excess, available, free oxygen from the body cells reduces the formation of the stimulated oxygen by natural or other radiation, whereby the RNA synthetase is preserved. Vitamin E and the antioxidants that can be used according to the invention reduce the acidity

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Uptake of substances by body cells and consequently increase the body's tolerance to radiation. Further the antioxidants inhibit the rate of formation of free radicals, especially in those reactions in which molecular oxygen plays a role.

As already stated, the vitamin E / factor 3 has synergism or complex has a catalytic effect, with their help, the equilibrium shifted in the direction of a breakdown of incorrectly synthesized protein will. The catalyst accelerates reactions in which the sulfhydryl groups of the proteins are involved; in particular the catalyst accelerates the formation and breaking of the disulphide bridges and between the peptide chains and thus offers an opportunity to quickly split incorrect bridges. Considering From the foregoing, it will be understood that the body's antibody response to incorrectly synthesized Proteins is considerably reduced or completely prevented. The sulfur-containing amino acids serve as a source for the sulfhydryl groups, which replace the ones lost during the aging process, slightly oxidized disulfide bridges required are.

Stress-like mechanisms are partially counteracted by the methyl group donor methionine (for choline biosynthesis), whereby an accumulation of degradation products due to Neuro-Bi © synthesis and harmful free radicals is prevented. Free radicals have been isolated from the nervous system. It is most likely a by-product of the electrochemical nerve impulse. Thus, stress and nervous activity increase and accelerate the formation of free radicals

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thus the aging process. The onset and progression of the aging process can be seen in People through autopsy, life cycle assessment and the appearance of primary aging characteristics, such as Chase (poor) wound healing, facial wrinkles, loss of patience and graying of hair. That Study of the occurrence of primary aging characteristics is preferred as it is in volunteer test subjects can be easily monitored.

In an experiment with volunteers, a group of them were given one capsule of the food additive per day administered according to the invention as described in Example 1; another Group was given vitamin E alone; a third smaller group were given the usual vitamin tablets (of the "one per day" type) administered as a neutral agent. The trial was designed as a single blind trial carried out because the experimental conditions did not permit a double-blind experiment.

The groups to which the food additive according to the invention was administered and the group to which only consumed vitamin E showed significantly improved patience; this was done with puzzles and time-limited patience experiments determined with basketballs.

The group to which the food additive according to the invention had been administered was the only one which also showed improvements with regard to the other categories mentioned. Real improvements on all of the preferred observed aging indicators were in one or more individual

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(Individuals) taking the food additive had consumed (s), observe. In a (male) individual, the (original) Hair color back on. Furthermore, the lines or wrinkles on the face became less in this subject. Furthermore she was characterized by greater patience. Eventually one healed in this subject

10 cm wound is better. In another (female) individual there was an astonishing increase in wound healing to observe. This was a comparison of their recent birth of a child with a previous birth at normal healing rates. Both births required surgery. After the previous one At birth, the surgical incisions healed normally with the formation of scar tissue. The recent birth took place after the female test person took one capsule (daily) after the preparation for about 6 months had consumed according to Example 1. The surgical cuts healed in about 2/3 the time it took to heal lasted at the first birth. Furthermore, the the latter case practically no scar tissue. Finally, after healing, the surgical area was clear better condition than the operating area after the surgical wound has been cleared after the first birth.

en
In addition, all test subjects who had consumed the food additive according to the invention * showed a significant increase in mental agility, significantly calmer sleep, significantly better well-being, better circulation and reduced heart rates.

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The form of a nutrient or food additive geihäö the irfihduhgi which the Pulmonary membrane through scamming the natural Vitafnin Ä-Quöile in the Iiurigeh against iihe general oxidation protects by i & ftverünreihigiingen * contains vitamin E * Vitamin C and a synthetic lipid antioxidant. It is a syhergistic one Combination ^ examples of common catfish ^ oxidizing iAiftverühreiniguflgeni against those of the food or Putter means additional according to the invention to apply Schützß ■ tfe'rmägi are ozone Ötiekstoffoxid, carbon monoxide and

The amount of vitamin E should be between about 5 and about 2000 mg * diö amount of vitamin G between about 1Ό and 5000 mg lind the amount of synthetic lipid antioxidants between about one microgram and about 100 mg * The preferred synthetic lipid antioxidant is butylated hydroxytoluene. The preferred preparation based on a daily The dose per 45/4 kg of body weight contains 500 mg Vitamin E, JOO mg Vitamin G and 100 mg butylated Hydroxytoluene.

The following examples illustrate optimal and preferred ones Nutrition and feed additives according to Invention. In each case the preparation was made according to their manufacture depending on their final quantity in one or more gelatin capsules in size 0 or. Bottled larger * In all examples it was Sulfur-containing amino acid ^ unless otherwise stated * pure from analysis. Also mean in all

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Example, unless ahde "rs ähgegibeh * parts üiiä prozehtähgäbeni Weight division and weight approval V.

' Example f ^; ■ " ^: ~ - ' ^{: i:} ~ ■ ■ -

1 g Methiönih was mixed with 1 mg Selehömethlonin, ν The resulting mixture was divided into 10 equal parts and gelatin capsules, each of which was 0.5 g ct-toeopherol, transferred each finished capsule contained about 0.1 g methionine * 60 micrograms selenium (as oxide) and 0.5 g <? <- Töeopheröi (5ÖÖ I * E. Vitamin E) * Such a capsule was taken every day by an * watch subject taken *

Example. & · '-

1 g methionine was combined with Öyi mg iSelenomethlohin and 0.2 g of butyiated hydroxytoluenes mixed. The received Mixture was divided into 10 equal parts and In into each Gelatin capsules containing 10 mg ^ -Tocopherol transferred * Each finished capsule contained approximately 0.1 g Methionine, 6 micrograms selenium (as oxide) V 2Ö mg bü * tylated hydroxytoluene and 10 mg ^ -Töeopherbl (10 I.E. Vitamin E). One such capsule was made every day taken from an adult subject.

Example 3

1 g methionine was with 0.1 mg selenomethiohin and 0.1 g butylated Hydroxytöiüols mixed. The received Mixture would be divided into 10 equal parts and empty Gelätihekapselh transferred * One 100 I.U. Vitamins Commercially available Ständäräpsel containing capsules would be too each capsule containing the dry ingredients admitted. This example illustrates that the

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viscous, liquid <χ -tocopherol from those in dry Form present components can be separated »to a possible interaction before the administration to avoid. Each finished capsule contained about 0.1 g methionine, 6 micrograms selenium (as oxide), 10 mg of butylated hydroxytoluene and "100 mg <* - tocopherol. One such capsule was made every day taken from an adult subject.

Example 4

A mixture consisting of 1 g methionine, 0.1 mg selenomethionine and 0.2 g butylated hydroxytoluenes was divided into 10 equal parts after its preparation, each of which was compressed into a tablet. Each tablet was placed in a gelatin capsule containing 0.5 g of tocopherol. Compression of the dry components to form a tablet contributes to an essential protection of these components against possible interaction with the liquid Οζ -tocopherol. Each finished capsule contained about 0.1 g methionine, 6 micrograms selenium (as oxide), 20 mg butylated hydroxytoluene and 0.5 g ^ -tocopherol (500 IU vitamin E). One such capsule was taken by an adult subject every day.

Example 5

In the manner described in Example 4, tablets were prepared from the dry ingredients which together with a commercially available 100 I.U. vitamin E. containing the standard capsule in a gelatin capsule

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were brought. The advantages of such an approach are that the dry ingredients in Tablet form have a lower mass than powder form and that the liquid and dry ingredients are completely separated from each other, so that any possible interaction is eliminated is. Each finished capsule develops about 0.1 g of methionine, 6 micrograms selenium (as oxide), 20 mg butylated hydroxytoluene and O ^ g (100 I.U.) vitamin E. One such capsule was taken every day by an adult subject.

Example 6

0.5 S "-x'-tocopherol was placed in a gelatin capsule and covered with a liquid gelatin layer which was then allowed to harden. The dry components, namely 0.1 g methionine, 10 micrograms selenium (as oxide) and 0.1 g of butylated hydroxytoluene added. The gelatin layer was used to separate the liquid and powder components. Such a capsule was taken every day from an adult subject.

Example 7

A mixture of r -, _ fi g methionine, Q1mg selenomethionine, 2 g of butylated hydroxytoluene and 2 g of ascorbic acid (Vitamin C) was divided into 10 equal parts, each of which was compressed into a tablet. Every Tablet was made into a 0.5 g <x -toopherol containing Gelatin capsule introduced. Each finished capsule contained about 0.1 g methionine, 6 micrograms selenium (as oxide),

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0.2 g of butylated hydroxytoluene, 200 mg of vitamin C and 0.5 g (50 ¹ LE.) Of vitamin E. Such a capsule was taken every day by an adult test person.

Example 8

A mixture of 1 g methionine, 0.1 mg selenium methionine,

1 g of butylated hydroxytoluene, 1 g of ascorbic acid (vitamin C), 1 g of lecithin and 20 micrograms of vitamin B ₁₂ were divided into 10 equal parts, each of which was compressed into a tablet. Each tablet was placed in a pre 0.4 g oc-tocopherol-containing gelatin capsule. Each finished capsule contained about 0.1 g methionine, 6 micrograms selenium (as oxide), 0.1 g butylated hydroxytoluene, 100 mg "vitamin C, 0.1 g lecithin,

2 micrograms of vitamin B ₁₂ and 0.4 g (400 IU) of vitamin E. Such a capsule was taken every day by an adult test person,

Example 9

A mixture of 1 g of cysteine, 0.1 mg of selenomethionine, 0.1 g of butylated hydroxytoluene and 0.5 g of ascorbic acid (vitamin C) was divided into 10 equal parts, each of which was compressed into a tablet. Each tablet was added to a gelatin capsule already containing 50 mg (50 IU) of vitamin E. Each finished capsule contained approximately 0.1 g of cysteine, 0.01 mg of selenomethionine which is equivalent to 6 micrograms of selenium (in the form of the oxide), 10 mg of butylated hydroxytoluene, 50 mg of vitamin C, and 50 mg (50 IU) of vitamin E. One such a capsule has been taken every day by an adult subject.

Example 10

A mixture of 2 g of cysteine, 0.1 mg of selenium oxide, 0.1 g of butylated hydroxyanisoles and 100 mg of Leoitol was divided into 10 equal parts, each of which was compressed into a tablet

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Each tablet was placed in a gelatin capsule already containing 0.3 g of vitamin E covered with a gelatin layer brought in. Each finished capsule contained about 0.2 g of cysteine, 10 micrograms of selenium (in the form of the oxide), 10 mg of butylated hydroxyanisol, 10 mg of lecithin, and 0.3 g, (300 I.U.) of vitamin E. One such capsule was each Day taken from an adult subject.

Example 11

A mixture of 0.5 g of nutritional cysteine and 100 micrograms of butylated hydroxytoluene was divided into equal parts, each making up one tablet was pressed. Each tablet was placed in a gelatin capsule already containing 500 mg (500 IU) of vitamin E. Each finished capsule contained approximately 0.05 g cysteine, 10 micrograms butylated hydroxytoluene, 32 micrograms Selenium (as oxide) and 5OO mg (5OO I.U.) of vitamin E. One such capsule was taken by an adult every day Test subject taken.

Example 12

Example 11 was repeated with the exception that 0.2 g of ascorbic acid (vitamin C) was added to the dry mixture made from food grade cysteine and butylated Hydroxytoluene was added. Each finished capsule contained consequently, in addition to the components of Example 11, an additional 20 mg of vitamin C. Such a capsule was taken every day by an adult test subject "

Example 13

Example 11 was repeated, but with the exception that each capsule of home made 500 mg of vitamin E in addition

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Contained 1 g of wheat germ oil. Such a capsule was made taken every day by an adult subject.

Example 14

A mixture of 0.5 g of nutritional cysteine and 100 micrograms of butylated hydroxytoluene was divided into 10 parts, each of which was compressed into a tablet. Each tablet turned into an already 5S Wheat germ oil containing gelatin capsule added. Each completed capsule contained approximately 0.05 S cysteine, 10 micrograms Selenium (as oxide) and 10 mg (10 IU) of vitamin E. This example illustrates the use of a naturally occurring material (wheat germ oil) as a source of vitamin Ε. One such capsule was made every day taken from an adult subject.

Example 15

A mixture of 1 g of cysteine, 0.1 mg of selenomethionine, 0.1 g of butylated hydroxytoluene and 5% aspirin was used in 10 divided equal parts, each of which was compressed into a tablet. Each tablet became one already 50 mg (50 I.E.) vitamin Ε-containing gelatin capsule added. Each finished capsule contained about 0.1 g of cysteine, 0.01 mg Selenomethionine, which is equivalent to 6 micrograms selenium (as oxide), 10 mg butylated hydroxytoluene, 0.5 grain Aspirin and 50 mg (50 IU) of vitamin E. One such capsule was taken every day from an adult subject.

Example 16

A mixture of 1 g cysteine, 0.1 mg selenomethionine, 0.1 g butylated hydroxytoluene and 5 mg hydrocortisone were divided into 10 equal parts, each of which made a tablet was pressed. Each tablet became one already 50 mg (50 I.E.) gelatin capsule containing vitamin E was added.

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Each finished capsule contained about 0.1 g of cysteine, 0.01 mg Selenomethionine, which is equivalent to β micrograms selenium (as oxide), 10 mg of bulleted hydroxytolu oil, 0.5 mg Hydrocortisone and 50 · mg (50 Ι · Ε.) Of vitamin E. One such Capsule was taken every day by an adult subject,

Example 17

A mixture of 1 g of cysteine, 0.1 mg of selenomethionine, 0.1 g of butylated hydroxytoluene and 15 mg of polyvinylpyrrolidone was divided into 10 equal parts, each of which was compressed into a tablet. Each tablet was added to a gelatin capsule already containing 50 mg (50 IU). Each finished capsule contained approximately 0.1 g of cysteine; 0.01 mg selenomethionine, the 6 micrograms of selenium are equivalent (as oxide), 10 mg butylated hydroxytoluene, 1.5 mg polyvinylpyrrolidone and 50 mg (50 IU) of vitamin E _n Such a capsule every day was taken from an adult subject.

Example 18

Example 9 was repeated with the exception that the butylated hydroxytoluene was omitted from the formulation. One such capsule was taken every day from taken from an adult subject.

Example 19

Example 15 was repeated with the exception that the butylated hydroxytoluene was omitted from the formulation. One such capsule was taken every day from taken from an adult subject.

Example 20 Example 16 was repeated with the exception that

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the butylated hydroxytoluene is omitted from the formulation became. One such capsule was taken every day by an adult test person,

Example 21

Example 17 was repeated with the exception that the butylated hydroxytoluene was omitted from the formulation became. One such capsule was taken by an adult subject every day.

Example 22

A mixture of 1g cysteine, 0.1 mg selenomethionine, 0.1 g butylated hydroxytoluene and 0.5 g of sodium ascorbate was divided into 10 equal parts, of which. Each to one Tablet was compressed. Each tablet became a gelatin capsule already containing 50 mg (50 IU) of vitamin E. admitted. Each finished capsule contained about 0.1 g of cysteine, 0.01 mg of selenomethionine, the 6 micrograms of selenium (as oxide) are equivalent, 10 mg butylated hydroxytoluene, 50 mg (50 I.U.) vitamin E and 50 mg sodium ascorbate. One such capsule was taken by an adult subject every day.

Example 23

A mixture of 1 g cysteine, 0.1 mg selenomethionine, 0.1 g of butylated hydroxytoluene and 12 grains of the methyl ester of acetylsalicylic acid was divided into 10 equal parts divided * each of which was compressed into a tabletEach tablet was made into an already 50 mg (50 I.U.) Vitamin Ε-containing gelatin capsule added. Every finished capsule contained about 0.1 g cysteine, 0.01 rag Selenomethionine, which is equivalent to 6 micrograms selenium (as oxide), 10 mg butylated hydroxytoluenes, 50 mg (50 I.E.) Vitamin Ξ and 1.2 grains of the methyl ester of Acetylsalicylic Acid * One such capsule was given every day taken from an adult subject

must / 1.18

Example 24

A mixture of 1 g of cysteine, 0.1 mg of selenomethionine and 35 mg of frednison was divided into 10 equal parts by each of which was compressed into a tablet. Each tablet became one already containing 50 mg (50 IU) of vitamin E. Gelatin capsule added. Each finished capsule contained about 0.1 g cysteine, 0.01 mg selenomethionine, the 6 micrograms of selenium (as oxide) are equivalent to 50 mg (50 I.Eo) of vitamin E "and 3.5 mg of prednisone. One such Capsule was taken every day by an adult subject.

Example 25

A mixture of 1 g of cysteine, 0.1 mg of selenomethionine and 0.5 g of diphenhydramine was divided into 10 equal parts, each of which was compressed into a tablet · each Tablet was added to a gelatin capsule already containing 50 mg (50 Ι ·.) Of vitamin E. Any finished capsule Contained about 0.1 g of cysteine, 0.01 mg of selenomethionine, which is 6 micrograms of selenium (as oxide equivalent, 50 mg (50 Ι · Εί ") Vitamin E" and 50 mg Diphenhydramine · One such Capsule was taken every day by an adult subject.

Example 26

A mixture of 1 g of cysteine, 0.01 mg of selenomethionine, and 0.4 g of pyrrobutamine phosphate was divided into 10 equal parts, each of which was compressed into a tablet. Each tablet was made into an already 50 mg (50 IU) Vitamin E-containing gelatin capsule added to each The finished capsule contained about 0.1 g of cysteine, 0.01 mg of selenomethionine, the equivalent of 6 micrograms of selenium (as oxide) are, 40 mg pyrrobutamine phosphate and 50mg (50 I · Ε ·) Vitamin S. One such capsule was replaced by one every day adult test subject taken »

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Example 27 2 I 24972

A mixture of 1 g · cysteine, 0.11 mg selenomethiönine and 0.75g chlorothene citrate was divided into 10 equal parts, each of which was compressed into a tablet · Each tablet became one already containing 50 mg (50 IU) of vitamin E Gelatin capsule added. Each finished capsule contained about 0.1 g of cysteine, 0.01 mg of selenomethiönine, the 6 micrograms of selenium (as oxide) are equivalent to 75 mg Chlorothene citrate and 50 mg (50 IU) of vitamin E. One such capsule was taken from an adult each day Test subject taken,

Example 28

A mixture of 1 g cysteine, 0.1 mg selenomethiönine, 0.1 g butylated hydroxytoluene and 0.2 ^ cyclizine lactate divided into 10 equal parts, each of which was compressed into a tablet. Each tablet became one 50 mg (50 I.E.) of vitamin E-containing gelatin capsules have already been added. Each finished capsule contained approximately 0.1 g Cysteine, 0.01 mg selenomethiönine, the 6 micrograms selenium (as oxide) are equivalent, 10 mg butylated hydroxytoluene, 20 mg cyclizine lactate and 50 mg (50 I.E.) vitamin E. One such capsule was taken every day by an adult subject,

Example 29

A mixture of 1 g cysteine, 0.1 mg selenomethiönine, 0.1 g butylated hydroxyanisol and 5 grains of aspirin were divided into 10 equal parts, each of which made a tablet was pressed. Each tablet became one already 50 mg (50 I.E.) gelatin capsule containing vitamin E was added. Each finished capsule contained about 0.1 g of cysteine, 0.01 mg of selenomethiönine, the equivalent of 6 micrograms of selenium (as oxide) are, 10 mg of butylated hydroxyanisol, 50 mg (50 I.U.) of vitamin E, and 0.5 gram of aspirin, one such Capsule was taken every day by an adult subject,

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Example 30

A mixture of 1 g methionine, 0.1 mg selenomethionine and

5 grains of aspirin were divided into 10 equal parts, each of which was compressed into a tablet, each tablet was added to a gelatin capsule already containing 50 mg (50 IU) of vitamin E. Each finished capsule contained about 0.1 g methionine, 0 ^ 01 mg selenomethionine, the

6 micrograms of selenium (as oxide) are equivalent to 50 mg (50 I.U.) Vitamin E and 0.5 grains of aspirin, such a capsule was taken every day by a single person.

Example 31

A mixture of 500 mg of vitamin E, 300 mg of vitamin C and 100 micrograms of butylated hydroxytoluene was divided into 10 equal parts, each making up one tablet was pressed. Each finished tablet contained approximately 50 mg (50 IU) vitamin E, 30 mg vitamin C and 10 micrograms Butylated hydroxytoluene, the vitamin C was used in the form of L-aseorfoic acid. Such a capsule was taken every day from an adult subject.

Example 32

A mixture of 500 mg of vitamin E, 300 mg of vitamin C and 100 micrograms of butylated hydroxytoluene was divided into 10 equal parts, each making up one tablet was pressed. Each finished tablet contained approximately 50 mg (50 IU,) vitamin E, 30 mg vitamin C and 10 micrograms butylated hydroxytoluene. The vitamin C was used in the form of sodium ascorbate. Such a capsule was taken every day by an adult subject

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A mixture of 500 mg of vitamin E, 300 mg of vitamin C and 100 micrograms of butylated hydroxytoluene was divided into 10 equal parts, each of which was compressed into a tablet. Each finished tablet contained about 50 mg (50 I ₀ E.) of vitamin E, 30 mg of vitamin C and 10 micrograms of butylated hydroxytoluene. The vitamin C was used in the form of ascorbyl palmitate. One such capsule was taken by an adult subject every day.

Example 34

A mixture of 500 mg of vitamin E, 300 mg of vitamin C and 100 micrograms of butylated hydroxyanisol was added in 10 divided equal parts, each of which was compressed into a tablet. Each finished tablet contained approximately 50 mg (50 IU) vitamin E, 30 mg vitamin C and 10 micrograms butylated hydroxyanisol. The vitamin C was in good shape of L-escorbic acid has been used. Such a one Capsule was taken every day by an adult subject.

Example 35

A mixture of 500 mg of vitamin E, 300 mg of vitamin C and 100 micrograms ammonium diethj ^ dithiocarbamate was added in Divided parts, each of which was compressed into a tablet. Each finished tablet contained approximately 50 mg (50 IU) Vitamin E, 30 mg of vitamin C and 10 micrograms of ammonium diethyldithiocarbamate The vitamin C was used in the form of L-ascorbic acid. Such a capsule was taken every day from an adult subject.

Example 36

A mixture of 500 mg of vitamin E, 300 mg of vitamin C and 100 micrograms Aminoäthylisothyrotnlum was in 10 equal

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3M

Parts divided, each of which is compressed into a tablet became. Each finished tablet contained about 50 rag (50 IU) of vitamin E, 30 mg of vitamin C and 10 micrograms of aminoethyl isothyromium. The vitamin C was used in the form of L-ascorbic acid. Such a capsule became everyone Day taken from an adult subject.

Example 37

Example 3I was repeated, but with the exception that instead of the 100 micrograms of butylated hydroxytoluene, 300 micrograms were used. Such a capsule was taken every day from an adult subject.

Example 38

A mixture of 500 mg of vitamin E, 300 mg of vitamin C, 1 g Wheat germ oil and 300 micrograms of butylated hydroxytoluene were divided into 10 equal parts, each of which became one Tablet was compressed. Each finished tablet contained 50 mg (50 IU) of vitamin E, 30 mg of vitamin C, 0.1 g of wheat germ oil and 10 micrograms of butylated hydroxytoluene, Das Vitamin C was used in the form of L-ascorbic acid.

Example 39

• A mixture of 500 mg (5001.E.) vitamin E (alpha- tocopheryl acetate), 1 g (0.21 cnr) wheat germ oil, "300 micrograms butylated hydroxytoluene, 300 mg vitamin C (ascorbic acid), 10 mg vitamin B ^ ( ThiaminhydrochlorId), TO mg of vitamin B _g (riboflavin), 2 mg of vitamin Bg (pyridoxine), 4 micrograms of vitamin B ^ ₂ (cyanocobalamin), 20 mg of panthenol (CalciumpantötlHiat) and 100 mg of niacinamit were divided into 4 equal parts, each of which was filled into a gelatin capsule and four capsules per day were taken by one adult.

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Example 4P

Example 39 was repeated, but with the exception that the butylated hydroxytolwol by an equal amount a 50:50 mixture by weight of butylated hydroxytoluene and butylated hydroxyanisol was replaced.

The preparations according to the invention are also suitable for administration to animals, including domestic animals, as Part of their daily feed The dosage is adjusted according to the body weight of the animal concerned,

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Claims (16)

- 56 - -patent claims d. \ Δ h ^ j I Z 1. Food and feed additive, characterized in that that the essential components are a) a sulfur-containing amino acid, b) selenium, c) an antioxidant, consisting of vitamin E or a mixture of vitamin E with a synthetic lipid antioxidant, wherein the amount of vitamin E in the antioxidant versus that needed to form a synergistic mixture with the amount of vitamin E required for organic selenium compounds is present in excess, and d) a membrane stabilizer contains. 2. Additive according to claim 1, characterized in that it is an antihistamine, a salicylate, as a membrane stabilizer Corticosteroid, vitamin C, an antihistamine-like agent or a mixture thereof. 5 x additive according to claim 2, characterized in that it contains as a membrane stabilizer acetylsalicylic acid in an amount of about 0.25 to about 25 grains per 45 ² I kg body weight. 4. Additive according to claim 2, characterized in that it is polyvinylpyrrolidone as an antihistamine-like membrane stabilizer in an amount from about 1 to about 100 mg per 45.4 kg of body weight contains. 5. Additive according to claim 2, characterized in that it is used as Corticosteroid membrane stabilizer hydrocortisone in an amount of 0.5 to about 50 mg per 45.4 kg of body weight contains. 6. Additive according to claim 2, characterized in that it acts as a membrane stabilizer at least 50 mg of vitamin C per 45.4 kg Contains body weight. 7. Additive according to claims 2 and 6, characterized in that that it is L-ascorbic acid as a vitamin G membrane stabilizer, Contains sodium ascorbate or ascorbyl palmitate. 10 9 8 5 0/1180 - 37 - 8. Additive according to claim 1, characterized in that it as the sulfur-containing amino acid cysteine, cystine, an amino acid of the formula GH ₂ ^ SCH ₂ CH (NH ₂ ) - COOHJ _g or methionine. 9. Additive according to claim 1, characterized in that it is a unit dose of 0.5 to 1,% vitamin E, 5 to 100 micrograms Selenium (calculated as oxide), 1 to 2 g of sulfur-containing amino acid, 0 to 300 micrograms of synthetic antioxidant and 0.2 to 0.3 g of vitamin C contains. 10. Additive according to claim 2, characterized in that it as a membrane stabilizer vitamin G and as an antioxidant a mixture of vitamin E with a synthetic one Contains lipid antioxidants, with vitamin C, the vitamin E and synthetic lipid antioxidant are present in such amounts as to make them a Vitamin A in the lung membranes protects against common, oxidizing air pollutants synergistic mixture form. 11. Additive according to claim 10, characterized in that it is butylated as a synthetic lipid antioxidant Hydroxytoluene, butylated hydroxyanisole, 2-mercaptomethylamine, NiN ^ -diphenyl-p-phenylenediamine, ammonium diethyldithiocarbamate, T, 2-dihydro-6-ftthoxy-2,2,4-trimethylquinoline, Contains ethoxyquin, aminoethylisothyromium, an aromatic phenol or an aromatic amine. 12. Food and feed additive, characterized in that it is essential components of a) vitamin C, b) vitamin E and c) contains a synthetic lipid antioxidant wherein a), b) and c) are present in such amounts that it rushes against the vitamin A in the lung membranes common oxidizing air pollutants form protective synergistic mixture. - 38 10 9850/11 SO 13. Additive according to claim 12, characterized in that it is used as synthetic lipid antioxidant butylated hydroxytoluene, butylated hydroxyanisole, 2-mercaptomethylamine, N, N ¹ -diphenyl-ρ-phenylenediamine, ammonium diethyldithiocafbamate, 1,2-dihydro-6-ethoxy 2,2,4-trimethylquinoline, ethoxyquin, amino-ethylisothyromium, an aromatic phenol or an aromatic amine contains. 14. Additive according to claim 13, characterized in that it as vitamin C membrane stabilizer L-ascorbic acid, sodium ascorbate or contains ascorbyl palmitate. 15 · Addition according to claim 13, characterized in that it additionally contains wheat germ oil. 16. Food and feed additive, characterized in that that it consists of a sulfur-containing amino acid, selenium and an antioxidant as essential ingredients of vitamin E or a mixture of vitamin E with a synthetic lipid antioxidant, wherein the amount of vitamin E in the antioxidant versus that used to form a synergistic mixture the organic selenium complex factor 3 required amount is contained in excess. 109850/1 180-