TW201943426A - Composition, in the form of a soft capsule, comprising a combination of extracts from olive fruit, Red Yeast Rice and Crocus Sativus L. and method of preparing the same - Google Patents

Abstract

A stable non-aqueous composition comprising the unique combination of hydroxytyrosol, monacolin K and crocin, contained in standardized extracts of olive fruits, Red Yeast Rice and Crocus Sativus L., respectively and a method for preparing the same. This composition is suitable for the preparation of a nutritional supplement in the form of a soft capsule for the protection of blood lipids from oxidative stress.

Description

   Composition in combination of olive fruit, red yeast rice and saffron extract in soft capsule form and preparation method thereof   

The present invention relates to a stable non-aqueous composition containing a unique combination of three water-soluble extracts from olive fruit, red yeast rice and saffron stigma, and a preparation method thereof. This composition is suitable for encapsulation in soft capsules and is standardized with certain amounts of base tyrosol, erythromycin K, and crocus glycosides, where these ingredients work synergistically to protect blood lipids against oxidative stress.

Hydroxytyrosol (HT) is a phenolic compound that occurs naturally in olive fruits and olive oil, and was first found in and extracted from the waste water produced during the washing of green olives during the manufacture of olive oil. Some studies have revealed the antioxidant and anti-diabetic effects of olive oil polyphenols including hydroxytyrosol. Recent studies in rats following a diet-induced metabolic syndrome model on high carbohydrate and fat rats have shown that treatment with hydroxytyrosol reduces obesity, improves glucose and insulin intolerance, and improves endothelial function. Systolic pressure.

Establish a list of permitted health declarations made on food in accordance with Commission Regulation (EU) No. 432/2012, which consumes at least 5 mg of hydroxytyrosol and its derivatives (e.g., oleuropein) daily (oleuropein complex and tyrosol), olive oil polyphenols can help protect blood lipids against oxidative stress. If these amounts are provided by an appropriate amount of olive oil, they can be eaten in the context of a balanced diet (for example, 20 grams of olive oil per day). However, considering the inconsistent concentrations of the polyphenols in olive oil, the amount ingested has not been standardized. Therefore, there is a need for a composition capable of providing a prescribed amount of hydroxytyrosol every day.

Red yeast rice is a rice product fermented by Monascus purpureus yeast. The active ingredient in red yeast rice is erythromycin K. The erythromycin K belongs to the statins family and shows similar properties to the known statin Lovastatin in regulating blood cholesterol concentration. More specifically, it inhibits hydroxymethylglutaryl-CoA (HMG-CoA) reductase in the liver to make cholesterol, thereby reducing its concentration in the blood. According to the list of permitted health claims made on food, a daily intake of 10 mg of erythromycin K from red yeast rice will help maintain blood cholesterol levels. Commercial products of red yeast rice are freely soluble in water and have a variable erythromycin K content, from 0.5% to more than 10%.

Saffron (saffron) is a perennial, spicy Iridaceae family herbaceous plant, which is characterized by a strong aroma, bitterness and orange-red pigment. These characteristics are due to more than 150 volatile (mainly terpene) and non-volatile (mainly carotenoid) active components, and mainly due to four major biologically active compounds, in other words, saffron Aldehydes, bitter saffron, saffron acid and saffron glycosides. Saffron is considered a tonic and antidepressant and has been used in many ancient cultures to strengthen digestion, soothe coughs, smooth menstruation, relax muscle spasms, calm anxiety and improve mood. The stigma of saffron spice is gradually gaining attention because it is more functional, such as in metabolic disorders, cardiovascular disease, depression, anxiety, and insomnia. Clinical studies in rats have revealed the hypolipidemic effect of saffron on pancreatic lipase activity, making it a suitable candidate for use in hypolipidemic treatment.

EP 2170090 relates to a nutritional and dietary product which is used as a source of hydroxytyrosol to prevent or treat cardiovascular disease, plaque buildup in arteries, high arterial pressure and metabolic syndrome. The present invention also relates to a method for preparing a reinforced oil-containing product containing olive extract, that is, a method for preparing a so-called functional food. This method consists of mixing an aqueous solution of olive extract with olive oil in the presence of an emulsifier. Then, the mixture was left to stand for at least 72 hours and the water phase was decanted to obtain the reinforced rich oil. Furthermore, the above-mentioned emulsion of olive extract and edible oil in liquid form is used to prepare soft gel capsules. Due to the separation step of the water phase from the oil phase, the aforementioned method of making edible oil rich in hydroxytyrosol is time consuming.

WO 2010/069951 relates to a pharmaceutical formulation for oral administration comprising omega-3 and omega-6 fatty acids and natural or semi-synthetic statins. The two active ingredients remain isolated from each other within the same dosage unit. The fatty acid is encapsulated in a soft gelatin capsule, which is further atomized with a suspension including statins and other active ingredients. According to a specific example of the invention, the final product includes 500 mg of omega-3 fatty acids and 200 mg of fermented red rice in each capsule, which corresponds to 3 mg of statins on the capsule coating.

WO 2012114133 relates to a method for enriching olive oil with biologically active substances obtained by extracting saffron (saffron) plant powder and stigmas with alcohol or water. All the enriched solutions exhibit higher antioxidant capacity than the original, thus revealing a synergistic effect of the combination of the active ingredients from the dried extract of saffron and olive oil. However, the content of active ingredients (saffonin, saffron acid, saffron aldehyde) in the saffron extract and therefore in the enriched olive oil is not specified.

A stable non-aqueous composition consisting of three water-soluble extracts, in other words, a unique combination of olive fruit extract, red yeast rice extract, and saffron extract, was not reported in the aforementioned technique. The composition is standardized with individual hydroxytyrosol, erythromycin K, and crocus glycosides, all dispersed in edible vegetable oil.

The present invention is based on the discovery that the three water-soluble extracts provide a synergistic effect in terms of the antioxidant efficacy of the active ingredients contained in the extract.

However, stable non-aqueous compositions suitable for inclusion in soft capsules should meet certain criteria. It is therefore important that the composition is stable and provides a uniform distribution of reactive ingredients in, for example, soft capsules. The applicant in this case has conducted a meaningful study for this purpose. However, following conventional wisdom, it has been shown to be difficult to avoid the formation of large agglomerates of the active ingredient in a suspension in edible oil (see the experimental section of this application).

Therefore, a first object of the present invention is a nutritional product suitable for oral administration in the form of soft capsules, which provides a unique combination of the active ingredients hydroxytyrosol, erythromycin K, and crocetin. The composition of the present invention combines the unique properties of the three components, which can work synergistically to maintain the subject's blood cholesterol concentration by protecting blood lipids against oxidative stress.

The second object of the present invention is a non-conventional but feasible method for preparing a non-aqueous homogeneous composition containing hydroxytyrosol, erythromycin K, and crocus glycoside. In this context, the present invention addresses the problem of keeping active ingredients isolated from each other in the same formulation.

The present invention relates to a nutritional product suitable for oral administration in the form of soft capsules, which provides a unique daily combination of the active ingredients hydroxytyrosol, erythromycin K, and crocetin.

In a preferred embodiment, the hydroxytyrosol is in the form of an olive fruit extract, which has been standardized to at least 7% hydroxytyrosol and the like. This extract is commercially available and can be extracted from olive fruit and olive fruit wastewater by known methods. The analysis of hydroxytyrosol in standardized olive fruit extracts was performed at 280 nm with the assistance of high performance liquid chromatography (HPLC).

In a preferred embodiment, the erythromycin K is in the form of a red yeast rice extract, which has been standardized to at least 4% erythromycin K. A water-soluble red yeast rice extract system comprising up to 25% erythromycin K is known in the prior art and is commercially available. The analysis of rubidin K in standardized red yeast rice extract at 237 nm was assisted by high performance liquid chromatography (HPLC).

In a preferred embodiment, the saffron glycosides are in the form of a saffron (saffron) extract, which has been standardized to at least 25% saffron glycosides. GR 1008908 indicates a method for producing stable water-soluble extracts from saffron stigmas, which are rich in saffron glycosides and suitable for preventing atherosclerosis. This patent is incorporated herein by reference in its entirety. Evaluation of saffron glycosides in standardized extracts from saffron stigmas at 440 nm was assisted by high performance liquid chromatography (HPLC).

In a preferred embodiment, the dosage unit is for a soft capsule having a weight between 600 and 1200 mg, the capsule comprising a stable non-aqueous composition comprising: 5-8% w / w which has been standardized to at least 7% hydroxytyrosol olive fruit extract, 10-30% w / w red yeast rice extract standardized to at least 3% erythromycin K, 10-20% w / w standardized to at least 25 % Saffron saffron dry extract, 25-50% w / w edible oil and suitable emulsifier.

In a preferred embodiment, the amount of the olive fruit extract that has been standardized to 7% hydroxytyrosol ranges from 30 to 70 mg per dosage unit, which corresponds to 2 to 5 mg of pure hydroxytyrosol per dosage unit.

In a preferred embodiment, the amount of the olive fruit extract that has been standardized to 7% hydroxytyrosol is 35 mg per dosage unit, which corresponds to 2.5 mg of pure hydroxytyrosol per dosage unit.

In a preferred embodiment, the amount of the red yeast rice extract standardized to 4% erythromycin K ranges from 50 to 200 mg per dosage unit, which is equal to 2 to 8 mg of erythromycin per dosage unit. K accordingly.

In a preferred embodiment, the amount of the red yeast rice extract standardized to 4% erythromycin K is 125 mg per dosage unit, which corresponds to 5 mg of erythromycin K per dosage unit.

In a preferred embodiment, the amount of the saffron extract that has been standardized to 25% saffron glycosides ranges from 70 to 200 mg per dosage unit, which corresponds to 17.5 to 50 mg of crocus glycosides per dosage unit.

In a preferred embodiment, the amount of the saffron extract that has been standardized to 25% saffron glycosides is 100 mg per dosage unit, which corresponds to 25 mg of saffron glucosides per dosage unit.

In a preferred embodiment, the olive fruit extract, red yeast rice extract, and saffron extract are dispersed in an edible vegetable oil selected from the group consisting of coconut oil, corn oil, cottonseed oil, olive oil, and palm oil. , Peanut oil, rapeseed oil, safflower oil, sesame oil, soybean oil and sunflower oil.

In a preferred embodiment, the dispersion of the olive fruit extract, red yeast rice extract, and saffron extract occurs in edible vegetable oil, and the amount ranges from 200 mg to 400 mg per dosage unit, and more preferably Dosage unit 240 mg.

In a preferred embodiment, the olive fruit extract, red yeast rice extract and saffron extract are dispersed in polyphenols and will work synergistically with the three extracts mentioned above to protect blood lipids against oxidative stress. In olive oil.

In a preferred embodiment, the composition further comprises a suitable emulsifier, preferably lecithin, in an amount ranging from 80 mg to 160 mg per dosage unit, more preferably 100 mg per dosage unit.

In a preferred embodiment, the dosage unit is in the form of a soft capsule. Each capsule contains a capsule shell component and encapsulates the composition of the present invention, wherein the composition contains 2.5 mg of hydroxytyrosol and 5 mg of red tincture. Myctinol K, 25 mg crocetin, 240 grains of edible oil and 100 grains of lecithin.

In a preferred embodiment, the dosage unit is in the form of a soft capsule, and each capsule contains a capsule shell component and encapsulates the composition of the present invention, wherein the composition contains 35 mg of olive fruit extract and 125 mg of red Yeast rice extract and 100 mg saffron extract, 240 grains of cooking oil and 100 grains of lecithin.

The invention also relates to a method for preparing a stable non-aqueous composition comprising a unique combination of dried olive fruit extract, red yeast rice extract and saffron dry extract, wherein the composition is used to regulate the blood cholesterol concentration of a subject There is a synergy effect.

It has been proven to follow a procedure common to the first-mentioned technique, that is, by preparing a blend of three water-soluble solid extracts, followed by dispersing the solid blend with stirring or agitation aid and optionally with heating aid It is difficult to prepare a uniform dispersion into a hydrophobic matrix. Experiments were performed following well-accepted procedures, which together mixed dried extracts of olive fruit, red yeast rice, and saffron, and blended the mixture for 120 minutes using a 50-liter drum mixer at a rotation speed of 7 rpm. The homogeneity test of the blend was performed on 3 samples from different locations of the drum mixer. In particular, the major homogeneity deviations in the final blend were observed with respect to hydroxytyrosol analysis even after 240 minutes of blending time (Tables 1 and 2).

It is assumed that these deviations are reduced during agitation with heating assistance and dispersion of the blend into edible oils in the presence of emulsifiers. In this context, 24 kg of edible oil and 10 kg of lecithin were mixed in an enamel reactor at 600 rpm and 60 ° C. A blend of the three extracts was gradually added to the above oily suspension and all were mixed under the same conditions. However, it formed large agglomerates in the oily suspension, which became uneven even after stirring for 120 minutes and after passing through a colloid mill (300 long tons / hour).

It has been surprisingly found that a non-aqueous, oily, homogeneous and stable dispersion consisting of extracts from olive fruit, red yeast rice and saffron can be obtained by following these steps:

a) Each of the dried extracts is sieved through a 60-mesh sieve to obtain a particle size of less than 250 microns.

b) The screened olive fruit extract is mixed with an edible oil and an emulsifier at a temperature range of 45 ° C to 75 ° C.

c) Dispersing the screened red yeast rice extract in the oily mixture of the second step, followed by stirring at the same temperature for a period of 1 to 3 hours.

d) cooling the oily mixture in the third step to a temperature range between 25 ° C and 35 ° C, and then homogenizing through a colloid mill (300 long tons / hour).

e) Disperse the screened saffron dry extract in the homogeneous oily dispersion of the third step, and then stir at a temperature between 25 ° C and 35 ° C for a period of 1 to 3 hours.

f) The final oily non-aqueous mixture is cooled to room temperature, more preferably at 25 ° C and further homogenized through a colloid mill (300 long ton / hour).

A homogeneity test was performed to prove that the final oily non-aqueous composition was homogeneous. Table 3 shows the amount of active ingredient of each extract in the blend and its analysis in each sample.

The uniformity test summarized in Table 3 shows that the composition obtained following steps a) to f) is homogeneous and the percentage of the active ingredient is completely retained, in other words, hydroxytyrosol, erythromycin K and Saffron glycosides, such as those evaluated by high pressure liquid chromatography (HPLC). The composition of the present invention remains stable after storage for 3 and 6 months under normal and accelerated temperature and relative humidity conditions.

The stable non-aqueous composition of the present invention comprises a unique combination of dry solid extracts from olive fruit, red yeast rice and saffron stigma, which are suitable for encapsulation in soft capsules and can be used as a dietary supplement for oral administration edible.

In a preferred embodiment, the soft capsule shell is manufactured from gelatin, a plasticizer, preferably glycerin and pure water according to a method known in the art. The method for producing gelatin comprises mixing the components in a vacuum at a high temperature, preferably between 60 ° C and 80 ° C, for a period of 3 to 4 hours, preferably 4 hours.

In a preferred embodiment, the soft capsule shell is manufactured from non-animal ingredients according to known methods and includes water-soluble polysaccharides, cellulose, microcrystalline starch derivatives and / or carrageenan extracts. The soft capsules as prepared are intended for use by subjects who follow a vegetarian diet.

The gelatin or non-gelatin-derived soft capsules can be shaped into a variety of forms, selectively oval, or long oval, or spherical.

    [Example]    

In a preferred embodiment, the edible olive oil is heated to 50 ° C, and the emulsifier is added portion by portion under agitation. Under stirring, preferably at 600 rpm, maintaining the same temperature, the olive fruit extract, which has been standardized for hydroxytyrosol and sieved through a 60-mesh sieve, is gradually dispersed in the oily body. Subsequently, the red yeast rice extract which had been sieved through a 60-mesh sieve was gradually added, and the oily mixture was stirred for 120 minutes, and the temperature was maintained at 50 ° C. Then, the oily mixture was cooled to 30 ° C and passed through a colloid mill (300 long ton / hour). Then, the saffron extract which had been sieved through a 60-mesh sieve was added to the homogeneous mixture, and the oily mixture was stirred at 600 rpm at 25 ° C for an additional 2 hours. The final mixture consisting of the filling body of the soft capsule was passed through a colloid mill (300 long ton / hour) to optimally homogenize. Then, the mixture is encapsulated in an oval soft gelatin capsule, followed by drying in a rotating container with an air flow of 20 ° C and a low humidity environment, preferably 25% RH, and at the same time mechanical cleaning with a lint-free towel The lubricating oil (paraffin oil) of the capsule was about 24 hours.

Briefly describe the final composition and capsule shell components in the following list:

In a preferred embodiment, the edible olive oil is heated to 50 ° C, and the emulsifier is added portion by portion under agitation. Under stirring, preferably at 600 rpm, maintaining the same temperature, the olive fruit extract, which has been standardized for hydroxytyrosol and sieved through a 60-mesh sieve, is gradually dispersed in the oily body. Subsequently, the red yeast rice extract which had been sieved through a 60-mesh sieve was gradually added, and the oily mixture was stirred for 120 minutes, and the temperature was maintained at 50 ° C. Then, the oily mixture was cooled to 30 ° C and passed through a colloid mill (300 long ton / hour). Then, the saffron extract which had been sieved through a 60-mesh sieve was added to the homogeneous mixture, and the oily mixture was stirred at 25 ° C and 600 rpm for an additional 2 hours. The final mixture consisting of the filling body of the soft capsule was passed through a colloid mill (300 long ton / hour) for optimal homogenization. Then, the mixture is encapsulated in a spherical soft non-gelatin capsule, followed by drying in a rotating container with an air flow of 20 ° C and a low-humidity environment, preferably 25% RH, and at the same time mechanically cleaning with a lint-free towel The lubricating oil (paraffin oil) of the capsule is about 24 hours.

Briefly describe the final composition and capsule shell components in the following list:

The composition of the present invention provides a regulated delivery of three active ingredients, in other words, hydroxytyrosol, erythromycin K, and crocus glycoside, to a subject through a standardized dosage unit. Each dosage unit in the form of a single soft capsule includes 2.5 mg of hydroxytyrosol in the form of an olive fruit extract, 5 mg of erythromycin K in the form of red yeast rice, and 25 mg of saffron glycoside in the form of saffron extract . Consuming two soft capsules of Example 1 and / or 2 daily can provide the amount of hydroxytyrosol and erythromycin K claimed according to the Commission Regulation (EU) No. 432/2012, and further provide the enriched Fan Safflower extract, all of which show beneficial effects in maintaining blood cholesterol concentrations.

The amount of the extract can be adjusted within the ability of a skilled person and the composition according to the invention containing active ingredients of different strengths can be prepared.

Anti-radical scavenging activity test

The stable free radical 2,2-diphenyl-1-pictylhydrazine radical (DPPH) model is a widely used method to evaluate the antioxidant capacity of natural products, and it has been used in olive oil and other vegetable oils. And for individual antioxidants (Brand-Williams, W. et al. Lebensm.-Wiss.u.-Technol. 1995, 28, 25-30). The spectrophotometric method used to evaluate total antioxidant activity is to monitor DPPH in the presence of antioxidants. The reduction in the degree of absorption of free radicals is used as a benchmark. DPPH. Is characterized by a free radical that is stable due to the delocalization of excess electrons on the molecule. Therefore, the molecule cannot dimerize as other free radicals will occur. This delocalization causes a dark purple color, which is characterized by an absorption band at about 515 nanometers. When DPPH. When the solution is mixed with a substance that can supply hydrogen atoms, it produces a reduced form, which is accompanied by a loss of purple color.

In the composition suitable for oral administration, the three active ingredients were measured, in other words, hydroxytyrosol from olive fruit extract, erythromycin K from red yeast rice extract, and saffron extract DPPH free radical scavenging activity of crocetin and its combination to reveal the synergistic effect of the three components.

Experimental method for DPPH free radical scavenging test

A 10 ^-3 M DPPH solution was prepared by dissolving 0.0394 g of DPPH radicals in 100 ml of methanol. The measuring flask was wrapped in foil and stirred with a vortex. The obtained solution had a dark purple color and was left in the refrigerator for 2 hours so that the absorbance was stabilized. A calibration curve of DPPH concentration versus absorbance was prepared as follows: Methanol was added to dilute a 10 ^-3 M DPPH solution to prepare a range of 5 to 1000 μM (10 ^-4 M, 5 × 10 ^-5 M, 10 ^-5 M, and 5 × 10 ^-6 M) DPPH solution. These solutions were vortexed, left in the dark and the UV-Vis spectrophotometer (Varian Cary 300) was used to measure their absorbance at λ _max = 515 nm and 630 nm.

The calibration curve of DPPH absorbance (Abs) versus concentration (Conc) is expressed by the following equation: λ = 515 nm: Abs = 0.00557 * Conc-0.00070; R = 0.99994

λ = 630nm: Abs = 0.00192 * Conc-0.00298; R = 0.99997

For the antioxidant test, all the extracts / compositions tested were dissolved in methanol at the corresponding concentrations (see Tables 1 and 2). Briefly, a storage solution of all extracts in methanol was prepared as follows: olive fruit extract 3.60 mg / ml, red yeast rice extract 11.60 mg / ml, and saffron extract 10.52 mg / ml. The final solution is a dilution from the storage solution. The olive fruit extract solution was prepared by diluting 1 ml of the corresponding storage solution to 5 ml with methanol, the red yeast rice extract solution was prepared by diluting 2 ml of the corresponding storage solution with methanol to 5 ml, and the saffron extract solution was prepared with Methanol was prepared by diluting 2 ml of the corresponding stock solution to 5 ml; and the olive fruit / red yeast rice / saffron extract composition was prepared by mixing 1, 2 and 2 ml of the corresponding stock solution. For methanol with a blank work, the absorbance (A ₀ ) of a 10 ^-4 M DPPH solution at t = 0 was measured. For each of the pure extracts / compositions tested, aspirate 50 microliters of its methanol solution into a photoanalyzer with a pipette, then add 3.0 ml of a 10 ^-4 M DPPH solution and gently mix the solution . After 60 minutes, the absorbance (A _T ) was measured (the value reached a stable level after 40 minutes). For each measurement, the corresponding extract / combined solution in methanol was used as a blank (50 microliters of the sample methanol solution was mixed with 3.0 ml of methanol). For each sample tested for its free radical scavenging activity, the% reduction in DPPH absorbance was estimated as (A ₀ -A _T ) * 100 / A ₀ .

The values in the table are expressed as the average of at least five determinations. All experiments were repeated in duplicate. For all experiments, SD is estimated to be less than 10%.

Table 2. DPPH absorbance at λ _max = 630 nm before and after adding olive fruit / red yeast rice / saffron extract composition and its biologically active composition.

Due to the high absorption of saffron extract at 515 nm, the DPPH anti-radical scavenging activity test was also performed at 630 nm, which also showed a linear calibration curve for DPPH within a concentration range of 5 to 1000 mM.

In this context, as compared to the sum of the% reduction in each DPPH, Table 1 shows the synergistic effect of the combination of olive fruit and red yeast rice extract, which is expressed by the% reduction in DPPH of the combination of the two extracts.

Most importantly, compared with the corresponding reduction of each extract, the typical specific example of the three extract combinations of the present invention greatly reduced the absorbance of the 10 ^-4 M DPPH solution, and furthermore, it appeared to be less than the three The combination of different extracts has greater performance. Therefore, this indicates the synergistic effect of the unique combination of olive fruit, red yeast rice and saffron extract on the DPPH absorption reduction, thus showing synergistic antioxidant activity .

literature

EP 2170090: hydroxytyrosol reinforced oil and its use

WO 2010/069951: Oral formulation comprising a combination of omega polyene fatty acids and natural or semi-synthetic statins

WO 2012114133: Manufacture of olive oil enriched with saffron (saffron) extraction and with increased antioxidant properties

GR 1008908: Cold extraction and manufacturing method of stable water-soluble solid extract from stigma of Greek saffron plant, the extract is used for preventing and / or treating arteriosclerosis.

Brand-Williams, W .; Cuvelier, M.E .; Berset, C. Use of a Free Radical Method to Evaluate Antioxidant Activity. Lebensm.-Wiss.u.-Technol., 28, 25-30 (1995).

Claims (12)

    A soft capsule suitable for oral administration, comprising a combination of hydroxytyrosol, erythromycin K and crocus glycoside as active ingredients, wherein the active ingredients are encapsulated in the soft capsule and uniformly distributed in a hydrophobic matrix in.         The soft capsule of claim 1, wherein the hydrophobic matrix comprises an edible oil.         The soft capsule of claim 1 or 2, wherein the edible oil is a vegetable oil selected from the group consisting of coconut oil, corn oil, cottonseed oil, olive oil, palm oil, peanut oil, rapeseed oil, safflower oil, sesame oil, soybean oil And sunflower oil.         The soft capsule of claim 1, wherein the vegetable oil is olive oil.         The soft capsule according to any one of claims 1 to 4, comprising edible olive oil in an amount ranging from 200 mg to 400 mg per dosage unit, more preferably 240 mg.         The soft capsule according to any one of claims 1 to 5, further comprising an emulsifier, preferably lecithin, and the amount per dosage unit is in the range of 80 mg to 160 mg, and more preferably 100 mg.         The soft capsule according to any one of claims 1 to 6, comprising an olive fruit extract in an amount ranging from 30 mg to 70 mg per dosage unit, more preferably 35 mg.         The soft capsule according to any one of claims 1 to 7, comprising a red yeast rice extract in an amount ranging from 50 mg to 200 mg per dosage unit, more preferably 125 mg.         The soft capsule according to any one of claims 1 to 8, comprising a saffron extract in an amount ranging from 70 mg to 200 mg per dosage unit, more preferably 100 mg.         A method for preparing a stable composition, wherein the composition contains hydroxytyrosol, erythromycin K and crocus glycoside as active ingredients and is uniformly distributed in a matrix, wherein the method includes the following steps: a) respectively Screen these solid active ingredients through a sieve to exclude particles with a particle diameter greater than 250 microns; b) mix the first active ingredient with edible oil and optionally an emulsifier at a temperature range of 45 ° C to 75 ° C; c ) Selectively dispersing the second active ingredient into the product obtained in step b) under the temperature range of 45 ° C to 75 ° C; d) cooling the product obtained in step c) to 25 ° C to A temperature range of 35 ° C, optionally followed by homogenizing the product through a mill; and e) a product obtained by dispersing the third active ingredient in step d) at a temperature range of 25 ° C to 35 ° C. in.         The method of claim 10, wherein the first and / or the second active ingredient is an extract of olive fruit or red yeast rice, and the third active ingredient is a saffron.         The method of claim 10 or 11, wherein the method comprises the following steps: a) screening the extract of olive fruit, red yeast rice and saffron as an active ingredient through a 60-mesh sieve; b) at a temperature of 45 ° C to 75 ° C The screened olive fruit extract, the edible olive oil, and the emulsifier are mixed at ℃; c) the screened red yeast rice extract is dispersed in the oily mixture of step b), and at the same temperature Under stirring; d) cooling the mixture of step c) to a temperature between 25 ° C and 35 ° C, followed by homogenization; e) dispersing the screened saffron extract into the homogeneous oily mixture of step d) And stirring at a temperature between 25 ° C and 35 ° C; f) cooling the mixture in step e) to 25 ° C and homogenizing through a colloid mill.