CZ293046B6 - Foods supplement exhibiting activity on plasma lipids and blood antioxidant capacity - Google Patents

Abstract

The present invention relates to a foods supplement exhibiting activity on plasma lipids and blood antioxidant capacity comprising as active components a mixture of 10 to 90 percent by weight of Cardui mariae fructus extractum siccum and 90 to 10 percent by weight of at least one vegetable oil containing n-3 and n-6 polyunsaturated fatty acids, whereby the active components are mixed with up to 20 multiple weight amount of a physiologically acceptable vehicle.

Description

Technical field

The invention relates to a dietary supplement having an effect on plasma lipids and the antioxidant capacity of blood. Its beneficial physiological effect is manifested in lowering total cholesterol concentration, increasing high density lipoprotein concentration and increasing total antioxidant blood capacity. It is intended for preventive protection of the cardiovascular system against atherosclerotic changes.

A dietary supplement to combinations of herbal substances that have beneficial anti-atherogenic and antioxidant effects and is suitable for all age and some risk groups of the population and which does not have undesirable side effects.

The combination consists of the seeds of Milk Thistle (Cardui mariae fructus extractum siccum) and vegetable oil having a suitable ratio of n-3 and n-6 polyunsaturated fatty acids.

BACKGROUND OF THE INVENTION

A preventive anti-atherogenic effect is characterized by dietary supplements containing substances of plant origin affecting either lipid metabolism, such as artichoke extract (Cynara scolymus L.), plant sterols (stanols), vegetable oils containing mono- and n-3 / n-6 polyunsaturated fatty acids and dietary fiber (indigestible residues of plant origin) or contain low molecular weight antioxidants that increase the antiooxidative capacity of blood and prevent the formation and action of free radicals such as tocopherols, carotenoids, ascorbic acid, natural phenolic acids and flavonoids.

A disadvantage of these formulations is that none of them is a combination of herbal substances that is suitably supplemented in both effects. Food supplements with positive effects on lipid metabolism do not significantly affect the formation of active oxygen species (so-called free oxygen radicals), but some may increase the possibility of lipoperoxidative damage to cell membranes and lipoproteins. In contrast, low-molecular-weight antioxidants have no effect on total cholesterol or the proportion of lipoproteins of different density circulating in the bloodstream.

In the literature, the inhibitory effect of a mixture of quarcetine and catechin on the formation of lipoperoxidation products in rats fed poly / monounsaturated fatty acids has been described (Fremont et al., 1998). However, no detailed pharmacological studies have been conducted with both flavonoids.

Silybum marianum (L.) Gaertner (Milk Thistle, Asteraceae) has been used for several centuries in European traditional medicine for its hepatoprotective effects. Its roots, leaves and seeds were treated as food (Morazzoni and Bombardelli, 1995). The name silymarin is used for the extract of S. marianum seeds (Cardui mariae fructus extractum siccum), which contains 70 to 80% of the silymarin complex, ie a mixture of flavonolignans standardized for silibinin and 30 to 20% of the chemically undefined fraction.

S. marianum extract and silibinin protect the liver from the action of hepatotoxic agents (see DE-A19 23 082 and DE-A 35 37 656).

Extract 5. Marianum and silibinin inhibit copper ion-induced oxidation of human LDL lipoproteins in vitro (Škottová et al., 1999).

S. marianum extract and flavonolignans, particularly silibinin bishemisuccinate, are effective in supportive therapy in the treatment of cytostatics (Lentzen et al., 1998).

In the Czech Republic, S. marianum extract is the active ingredient of drugs classified as hepato5 protective agents, such as FLAVOBION®, SILYGAL®, LAGOSA® or LEGALON® (the extract content in the tablet is 100 to 204 mg, that is 70 to 150 mg silymarin complex), in S1MEPAR® the extract of S. marianum is combined with vitamins of complex B, in HEPABEN® with Fumaria officinalis extract and in HEPATOFAKL® PLANTA with Chelidonium majus extract. In these products, their indication is extended by cholecinetic and choleretic effect.

In dietary supplements, the amount of extract per tablet is 15 to 100 mg, i.e. 10 to 70 mg of the silymarin complex.

N-3 / n-6 polyunsaturated fatty acids have been shown to have a beneficial effect in preventing the development of 15 cardiovascular diseases; n-3 polyunsaturated fatty acids also have a very beneficial effect on the progress of progressive polyertritis. Their side effect is a potential increase in the risk of forming lipoperoxidation products. Polyunsaturated fatty acids are an active ingredient in a number of dietary supplements (Zadák, 1999).

SUMMARY OF THE INVENTION

A novel dietary effect against the prior art has a dietary supplement having an effect on plasma lipids and the antioxidant capacity of blood, which comprises as active ingredients 25 a mixture of 10 to 90 percent by weight of dry extract of Milk Thistle (Cardui mariae fructus extractum siccum) and 90 up to 10% by weight of at least one vegetable oil comprising n-3 and n-6 polyunsaturated fatty acids, wherein the active ingredients are mixed up to a 20-fold by weight amount of a physiologically acceptable vehicle.

Preferably, blackcurrant seed oil (Ribes nigrum) or a mixture of evening primrose (Oenothera bienis) or borage (Borago officinalis) seed oils is used as the vegetable oil.

In a preferred formulation, the physiologically acceptable vehicle comprises 5 to 50% by weight of 35% by weight of polyethylene propylene glycol copolymers, 1 to 20% by weight of silica and 5 to 50% by weight of A-acetyl-D-glucosamine.

In an alternative preferred embodiment, the physiologically acceptable vehicle comprises 5 to 50 weight percent cellulose, 1 to 10 weight percent silica, 1 to 5 weight percent magnesium stearate, 10 to 55 weight percent sorbitol, and 1 to 30 weight percent A-acetyl- D-glucosamine.

The advantages of the present invention include that eicosamoids resulting from n-3 unsaturated acids act anti-inflammatory, anti-aggregation and vasodilatory. Most vegetable oils contain linoleic acid and γ-linolenic acid, both of which belong to the group of n-6 unsaturated fatty acids, n-6 Unsaturated acids are metabolised in humans to arachidonic acid and to eicosanoids, which act pro-inflammatory, vasoconstrictor and pro-aggregation. Which metabolic pathway is preferred is determined by competition for the same desaturation and elongation enzyme system.

Only at a suitable ratio of n-3 and n-6 acids can α-linolenic acid (n-3) be metabolized to eicosanpentaenoic and docosahexaenoic acids, which are further metabolized to eicosamnoids with cardioprotective effect. This requirement for the content of n-3 acids is perfectly met by blackcurrant seed oil (Ribes nigrum) with a ratio of n-3 and n-6 acids of about 1: 4.

In other cases, the desired ratio of the two components may be adjusted by mixing two types of oils, 55 using borage seed oil (Borago officinalis).

-2GB 293046 B6

The extract of S. marianum consists of a mixture of low-molecular substances, the so-called silymarin complex (silymarin) in the content of 70 to 80% and 30 to 20% of the mixture of high-molecular substances. Low molecular weight substances are sibilinin, isosilibinin, silycristin, silydianin, dehydrosilibinin, taxifoline and other minor flavonoids. High-molecular-weight substances are chemically unidentified polyphenols and their oxidized forms.

DETAILED DESCRIPTION OF THE INVENTION

Specific examples of the invention are presented below.

Example 1:

Dietary supplement with effect on plasma lipids and antioxidant capacity of blood containing Silybum marianum seed extract (Cardui mariae fructus extractum siccum) and polyunsaturated fatty acids of vegetable origin as active ingredients:

Extract of Silybum marianum Seed Oil Ribes nigrum Polyethylene-propylene glycol copolymer Silica N-acetyl-D-glucosamine ad 1.430 g 2.145 g 4,220 g 1,800 g 6,0 g

Example 2:

Dietary supplement with effect on plasma lipids and antioxidant capacity of blood containing Silybum marianum seed extract (Cardui mariae fructus extractum siccum) and polyunsaturated fatty acids of vegetable origin as active ingredients:

Milk Thistle (Silybum marianum) Seed Oil Bor ago officinalis Oil from Ribes seeds to nigros Cellulose Silica Magnesium stearate N-acetyl-D-glucosamine Sorbitol ad 1.430 g 1.430 g 0.715 g 1.502 g 0.501 g 0.100 g 2.502 g 5.0 g

Example 3:

Experimental hypercholesterolemia induced in an animal model has been shown to enhance the antihypercholesterolemic effect of Silybum marianum extract (Cardui mariae fructus extractum siccum) in combination with seed oil found LDL antioxidant effect of silibine in vivo. The results are shown in Table 1.

Example 4:

In a double-blind experiment, 17 volunteers were given a dietary supplement containing 286 mg of Silybum marianum extract (Cardui mariae fructus extractum siccum) and 100 mg of Ribes nigrum oil in one tablet, at a daily dose of 3 tablets, for 60 days. The control group formed

Healthy placebo-treated volunteers. Blood collection was performed at the beginning, 30 days and at the end of the study. Parameters relevant for evaluating the effect of the dietary supplement on lipid and liver metabolism and antioxidant blood capacity were determined. The results are shown in Tab. 2.

Industrial applicability

A health-optimizing dietary supplement is one of the recognized factors in prolonging active life 10 in an aging population and in groups at increased risk for chronic diseases. A dietary supplement with an effect on plasma lipids and the antioxidant capacity of blood can be used in the prevention of atherosclerosis risk factors, protection of the liver from the effects of toxic substances and in the period of convalescence after treatment of liver and cardiovascular diseases. Flavonolignans and the polymeric fraction of Silybum marianum extract and poly15 unsaturated vegetable oil are responsible for the favorable physiological effect.

-4GB 293046 B6

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Table 2. Effects of S. marianum extract on lipid and liver metabolism parameters and serum antioxidant capacity in healthy volunteers.

Metabolic Group Mean ± S.D. Statistical evaluation (1st group - 3rd group) parameter 1. sk 3. Sk. Mean ± S.D. proportion (%) Trends (%) Total cholesterol ESM 4.38 ± 0.58 4.43 1 0.75 + 0.07 ± 0.46 + 1.4 -3.5 (mM) Placebo 4.38 1 0.86 4.60 1 0.79 + 0.23 ± 0.55 + 4.9 TAG ESM 1.1710.65 1.1810.59 + 0.0510.37 + 4.6 -0.1 (mM) Placebo 1.06 ± 0.60 1.11 ± 0.44 + 0.05 ± 0.50 + 4.7 LDL-cholesterol ESM 2.56 ± 0.45 2.61 1 0.59 + 0.06 10.43 + 2.3 -4.4 (mM) Placebo 2.58 1 0.75 2.76 10.69 + 0.1910.35 + 6.7 HDL-cholesterol ESM 1.63 ± 0.22 1.5010.26 -0.13 ± 0.13 -8.2 + 3.4 (mM) Placebo 1.6710.30 1.4710.34 - 0.1910.21 -11.6 ApoAt ESM 1.3410.10 1.3410.13 -0.01 10.11 + 0.7 + 5.1 (g / 1) Placebo 1.3510.15 1.2910.18 -0.0610.12 -4.4 ApoB ESM 0.7510.15 0.7610.14 + 0.01 ± 0.09 + 1.1 -3.3 (g / 1) Placebo 0.7510.17 0.7910.18 + 0.03 1 0.09 + 4.4 Glucose ESM 5.1010.37 5.20 10.38 + 0.11 ± 0.36 + 2.1 + 2.0 (mM) Placebo 4.9410.41 4.95 10.60 + 0.003 + 0.62 + 0.1 Uric acid ESM 384.70 1 96.20 357.20 1 64.30 - 8.00 ± 34.65 -2.2 -4.4 (μΜ) Placebo 364.70 ± 66.90 373.00145.10 + 8.33151.58 + 2.2 ALT ESM 0.3310.18 0.34 10.12 + 10.11 + 2.7 -7.1 (pkat / l) Placebo 0.3910.14 0.43 ± 0.24 + 0.04 1 0.15 + 9.8 AST ESM 0.42 1 0.24 0.3710.12 -0.0410.13 -9.3 -2.9 (pkat / l) Placebo 0.3910.18 0.3710.12 0.03 ± 0.05 -6.4 GMT ESM 0.26 i 0.06 0.28 i 0.07 + 0.05 1 0.05 + 6.8 -5.9 tykat / l) Placebo 0.3610.17 0.41 ± 0.17 + 0.0510.11 + 12.7 CHS ESM 130.90122.10 132.60122.30 + 0.36 ± 9.05 + 0.3 + 2.3 (gkat / l) Placebo 143.20134.90 140.40133.30 - 2.8016.96 -2.0 AP ESM 1.5210.60 1.6010.59 + 0.0810.31 + 5.3 -6.0 (pkaVl) Placebo 1.2010.25 1.35 ± 0.29 + 0.15 + 0.23 + 11.3 Bilirubin ESM 16.91 ± 7.16 15.06 ± 9.59 - 1.2318.38 -7.3 -4.4 (μΜ) Placebo 18.0017.55 17.48 ± 7.04 - 0.51 1 7.75 -2.9 Total thiols ESM 0.51 i 0.04 0.72 ± 0.13 + 0.2210.15 + 30.4 + 1.8 (mM) Placebo 0.51 ± 0.05 0.7210.13 10.14 + 28.6 TBARS ESM 4.6210.62 4.79 1 0.65 + 0.1810.65 + 4.0 -2.9 (μΜ) Placebo 4.88 10.50 5.22 1 0.59 + 0.34 1 0.75 + 6.9 Ε » ESM 0.53 10.04 0.56 1 0.02 + 0.03 10.06 + 5.5 -2.7 (IN) Placebo 0.5410.02 0.5810.02 + 0.05 10.02 + 8.3 and.· ESM 14.34 11.60 15.51 ± 3.40 + 1.2512.41 + 8.1 + 10.0 * (A. 10 · ®) Placebo 14.9612.71 14.6712.031 12.32 - 1.9

* statistically significant (p <0.05)

Claims (4)

PATENT CLAIMS A dietary supplement having effect on plasma lipids and antioxidant capacity of blood, characterized in that it contains as active ingredients a mixture of 10 to 90% by weight of dry extract of Milk Thistle (Cardui mariae fructus extractum siccum) and 90 to 10% by weight of at least one vegetable oil. containing n-3 and n-6 polyunsaturated fatty acids, wherein the active ingredients are mixed with up to 20 times the amount of physiologically acceptable vehicle. Food supplement according to claim 1, characterized in that the vegetable oil used is blackcurrant seed oil (Ribes nigrum) or a mixture of oil of evening primrose (Oenothera bienis) or borage (Borago officinalis) seed. The dietary supplement of claim 1 or claim 2, wherein the physiologically acceptable vehicle is comprised of 5 to 50 percent by weight polyethylene propylene glycol copolymer, 1 to 20 percent by weight silica, and 5 to 50 percent by weight N-acetyl-D-glucosamine. . A dietary supplement as claimed in claim 1 or claim 2 wherein the physiologically acceptable vehicle is comprised of 5 to 50 weight percent cellulose, 1 to 10 weight percent silica, 1 to 5 weight percent magnesium stearate, 10 to 55 weight percent sorbitol and 1 to 30 weight percent of N-acetyl-D-glucosamine.