CN104720070A - Microemulsion preconcentrate and microemulsion and method for preparing same - Google Patents

Abstract

The present invention discloses a microemulsion system consisting essentially of coconut oil and polysorbate 80 in a specific weight ratio. The present invention also discloses a microemulsion preconcentrate and a microemulsion containing a lipophilic functional ingredient prepared with the microemulsion system. The present invention also discloses methods for preparing the microemulsion preconcentrate and the microemulsion.

Description

Microemulsion preconcentrate and microemulsion and method for preparing same

technical field

The present invention relates to a microemulsion system consisting essentially of coconut oil and polysorbate 80 in a specific weight ratio. The present invention also relates to a microemulsion preconcentrate and a microemulsion prepared with the microemulsion system and containing a lipophilic functional ingredient. The present invention also relates to the microemulsion preconcentrate and the preparation method of the microemulsion. The microemulsion can be used in the development and production of new health drinks.

Background technique

In recent years, many functional ingredients, such as xanthophyll, astaxanthin and coenzyme Q10 (co-enzymeQ10, CoQ10) in carotenoids, have been found to have health effects (healthcare effects). However, the water solubility of these functional ingredients is extremely poor, which limits the development of health care products containing these functional ingredients.

With people's emphasis on health and requirements for flavor, appearance and convenience of healthcare products, the development of healthcare products should not be limited to capsules, In the form of tablets or powder. Microemulsion technology (microemulsion technique) can effectively increase the solubility of fat-soluble compounds (liposoluble compounds) in water. If the use restriction of surfactants and cosurfactants can be overcome, microemulsified liposoluble functional ingredients can be added to drinks. It should help to develop new health drinks.

Coenzyme Q10 is a substance that exists in the human body. It belongs to liposoluble antioxidants (liposoluble antioxidants), and it will decrease with age. Coenzyme Q10 was a prescription drug used in the treatment of heart diseases in the early days. In recent years, it has become an emerging ingredient for health and nutrition due to its excellent anti-oxidation ability. In addition, due to the low in vivo availability of fat-soluble substances, most of the current research focuses on how to improve the bioavailability of coenzyme Q10.

The production methods of coenzyme Q10 can be divided into two types: microbial fermentation and chemical synthesis. At present, there is only PharmaEssence Pharmaceutical Co., Ltd. (13th Floor, Building F, No. 3 Yuanyuan Street, Nangang District, Taipei City, Taiwan, China) in Taiwan. ) to mass-produce coenzyme Q10 by chemical synthesis. On the other hand, there are currently water-soluble powders of coenzyme Q10 on the market, which can contain up to 40% coenzyme Q10, but the price of the product is much higher than that of coenzyme Q10 raw materials, and it needs to be imported from abroad. When developing new health care products, if the industry relies too much on foreign technology and imported raw materials, it will undoubtedly increase the production cost. From the perspective of long-term operation, it is not a long-term solution. Therefore, the industry must find appropriate technologies or raw materials to replace. If a liquid formulation can be developed so that the industry can use the coenzyme Q10 raw material to start manufacturing health drinks, it will help to improve the product competitiveness of the industry.

In order to improve the oral bioavailability (oral bioavailability) of coenzyme Q10, P.Thanatuksorn et al. studied 5 kinds of oils (fats), 4 kinds of emulsifiers (emulsifiers) and two kinds of water phases [with or without 8g/100gw/w skim milk (distilled water)], and found that the use of coconut oil (coconut oil), skim milk aqueous solution (skim milk aqueous solution) and stearoyl-2-calcium lactate (calcium stearoyl-2-lactate) lactate, CSL) to generate an optimal formulation. According to the experimental results, people such as P.Thanatuksorn prepared a model coenzyme Q10 product (model CoQ10product) emulsified with coconut oil, 8g/100gw/w skim milk aqueous solution and CSL, wherein the coenzyme Q10 product through the emulsification of 100g is obtained by the following formula Composition: 0.28g of CoQ10, 0.8g of CSL, 2.6g of coconut oil, 14g of sugar, 6.8g of skim milk and 75.52g of water. The size of the oil droplets formed immediately after emulsification (emulsification) was 2.37 ± 0.59 μm, and the oil droplets were partially converted into a cream-like phase after being stored at 4 ° C for 10 days. phase). The oral bioavailability of this model Coenzyme Q10 product was demonstrated to be slightly higher than that of a standard commercial CoQ10 product (HJB CoenzymeQ10 EX; Fujitex Co., Ltd., Japan) (P. Thanatuksorn et al. (2009), LWT-Food Science and Technology, 42:385-390). From this point of view, the model coenzyme Q10 product prepared by Thanatuksorn et al. has a larger particle size, and the storage time at 4°C is not long enough.

Junya Hatanaka et al. used solubilizing agents commonly used as food ingredients to prepare new formulations of coenzyme Q10, including a liquid formulation and a water-soluble powder formulation. The liquid formula is a nano-emulsion (nano-emulsion, NE) containing the following ingredients: 10.5% coenzyme Q10, 12.0% nonionic surfactants, 3% soybean Lecithin (soybean lecithin), 55% glycerol (glycerol), 15.0% deionized water and 4.5% medium chain triglycerides (medium chain triglycerides, MCT), in which non-ionic surfactant and Soy lecithin acts as an emulsifier, while MCT acts as an oily phase (Junya Hatanaka et al. (2008), International Journal of Pharmaceutics, 363:112-117). After investigation, the composition of the non-ionic surfactant and MCT is unknown. When preparing the nanoemulsion "CoQ10-NE", it is necessary to use a high amount of glycerin and two different components as emulsifiers, and it is necessary to use a homomixer (homomixer) and a high pressure homogenizer (high pressure homogenizer) to achieve the formula Complete emulsification may help CoQ10-NE to have an average particle size of 60nm, but it makes the process of CoQ10-NE complicated.

US20060073176A1 (corresponding to TWI321989B) discloses a water-soluble composition containing coenzyme Q10, which contains: (A) 5-40% by mass of coenzyme Q10, (B) 5-30% by mass of poly Monoester (monoester) composed of glycerol (polyglycerol with averaged polymerization degree of 10) and fatty acid having 18 carbon atoms (fatty acid having 18 carbon atoms), (C) 1-18% by mass and having an average polymerization degree of 3- Mono-, di-, tri-orpenta-ester (mono-, di-, tri-orpenta-ester) of polyglycerol with 18 carbon atoms and (D) water. The water-soluble composition containing Coenzyme Q10 is claimed to have an average particle diameter of 110 nm or less. Although it is mentioned in the disclosure of US 20060073176 A1 that no solvent such as oil is required to dissolve or disperse high-concentration coenzyme Q10 when preparing the water-soluble composition containing coenzyme Q10, this case not only requires the use of two surfactants To make this water-soluble composition containing coenzyme Q10, in some embodiments, the fifth ingredient must also be used, namely (E) cosolvent (solubilizer), including glucose-fructose liquid sugar (glucose-fructoseliquid sugar) , gum arabic, reducing starch sugar, and in some embodiments even palm oil or sucrose acetate/isobutyric acid ester (SAIB) ) as an oil component to form an oil phase with coenzyme Q10. In addition, in the manufacturing process of the water-soluble composition containing coenzyme Q10, it is necessary to use a homomixer and a high-pressure homogenizer to achieve complete emulsification of the formula, which increases the demand for production equipment.

US 20070259034 A1 discloses a crystal-free coenzyme Q10 composition (crystal-free coenzymeQ10 composition), which comprises coenzyme Q10, a solvent and a carrier oil. According to US 20070259034 A1, the solvent can be conjugated linoleic acid (CLA), flaxseed oil, ethyl ester marine lipids, citrus oils ) or a combination of them. According to US 20070259034 A1, the carrier oil can be linseed oil, organic linseed oil containing linoleic acid (alpha linoleic acid, ALA), soybean lipids, borage lipids or marine organisms Lipid. Marine lipids are concentrates of ethyl ester EPA/DHA and can be 50% to 90% EPA/DHA combined. According to US 20070259034 A1, the coenzyme Q10 composition further comprises capric and caprylic glycerides, or vegetable monoglycerides, or a mixture of vegetable monoglycerides and diglycerides (a mixture of vegetable monoglycerides and diglycerides). According to US 20070259034 A1, the coenzyme Q10 composition will be encapsulated in a softgel for oral administration. From this point of view, the coenzyme Q10 composition disclosed in US 20070259034 A1 is not suitable for manufacturing health products in liquid form, especially health drinks.

US 20080145411 A1 discloses a composition for oral administration, which comprises an oxidized coenzyme Q10 (oxidized coenzymeQ10), a lysolecithin (lysolecithin) and an oil and fat (oil and fat), wherein the lysolecithin is relatively oxidized The weight ratio of coenzyme Q10 is not less than 0.7. Lysolecithin is a high priced chemical and its use adds to the cost of manufacture. Furthermore, it appears from all the examples of US 20080145411 A1 that the composition for oral administration is not suitable for the manufacture of health products in liquid form, especially health drinks.

US 20080248013 A1 (corresponding to TW I351925 B) discloses a liquid composition containing coenzyme Q10 by dispersing and emulsifying coenzyme Q10 in a glycerin and a water-soluble substance (water- soluble substance) in the aqueous liquid (aqueous liquid), the water-soluble substance is composed of octenyl succinate starch (octenylsuccinate starch) and dextrin (dextrin). The liquid composition can be dried to form a solid composition containing Coenzyme Q10. After investigation, it is necessary to use a high-pressure homogenizer to achieve complete emulsification of the formula when preparing the liquid composition, which increases the demand for production equipment. Furthermore, the liquid composition produced in the examples of US 20080248013 A1 has a particle size not less than 0.3 μm, which cannot meet the appearance requirements of beverage production.

US 20040152612 A1 discloses microemulsion preconcentrates and microemulsions containing coenzyme Q10. The microemulsion pre-concentrate comprises a mixture consisting of: (a) a mixture of a medium and long chain tri(acid)glyceride and an omega-9 fatty acid and/or an omega-6 fatty acid; ( b) a surface-active component (surface-active component), which contains a polyoxyethylene type (polyoxyethylene type) surfactant; and (c) a therapeutic active ingredient (therapeutic) from the ubiquinone family (ubiquinone class) active ingredient), especially coenzyme Q10. In the embodiment 1 of US 20040152612 A1 prepared 3 microemulsion pre-concentrates, wherein component (a) is 812(a1) and oleic acid (oleic acid) (a2) (which is an emulsifier or co-solvent), component (b) is Tween80(b), component (c) is coenzyme Q10(c1), and additionally Add vitamin E (c2) or polyoxyethylene castor oil (CremophorEL) (b2) (it is a co-solvent), and the weight ratio of component (b) and component (a) is about 1:1 or 9 :7.

US 20040126367 A1 (corresponding to TW I334862 B) discloses a solution containing reduced coenzyme Q10 (reduced coenzymeQ10), wherein reduced coenzyme Q10 is coated with liposome (liposome) or is dissolved or dissolved with a surfactant Emulsified to maintain reduced CoQ10 from oxidation. The substance used to form the liposome may be phospholipid or glycolipid. The surfactant is preferably a nonionic surfactant, more preferably a polysorbate surfactant such as Tween80 or polyoxyethylene hardened castor oil such as HCO60. ). In Example 1 of US 20040126367 A1, three kinds of lecithins were used to evaluate the oxidative stability of liposomes for reduced coenzyme Q10. In Example 2 of US 20040126367 A1, Tween 80 and HCO60 (1wt% or 0.1wt% aqueous solution) were used to evaluate the oxidation stability of surfactants for reduced coenzyme Q10. The preparation example 2 of US 20040126367 A1 provides an emulsion comprising the following ingredients: Tween 80, 1.0wt%; glycerin, 12.5wt%; phosphatidylcholine (phosphatidylcholine), 1.2wt%; reduced coenzyme Q10, 0.1wt%; purified water (purified water), added to 100.0wt%.

US 20100284983 A1 (corresponding to TW 200715995 A) discloses a water soluble composition (water soluble composition) containing coenzyme Q10, which contains coenzyme Q10, a hydrophilic polyglycerol fatty acid ester (hydrophilic polyglycerol fatty acid ester), a parent Oily sucrose fatty acid ester (lipophilic sucrose fatty acidester) and an aqueous phase component (aqueous phase component). The hydrophilic polyglycerol fatty acid ester is a decaglycerol mono-saturated fatty acid ester composed of a fatty acid residue containing 12 or more carbon atoms, more preferably selected from At least one selected from the group consisting of laurate ester, myristate ester and palmitate ester. The lipophilic sucrose fatty acid ester is preferably an ester composed of higher fatty acid (higher fatty acid) and acetic acid (acetic acid), more preferably sucrose palmitate, sucrose stearate and their acetylated products (acetylation product). Relative to 100 parts by weight of coenzyme Q10, the added amount of the lipophilic sucrose fatty acid ester is preferably 1 to 200 parts by weight, more preferably 5 to 150 parts by weight, and more preferably 10 to 100 parts by weight parts, particularly preferably 30 to 100 parts by weight. The aqueous phase component contains a polyhydric alcohol and/or water. The polyol is preferably glycerin and sorbitol. It has been found that when manufacturing the water-soluble composition containing coenzyme Q10, heating must be carried out at a specific temperature (50-70° C.) to dissolve the components used, and a high-pressure homogenizer must be used for emulsification.

US 20060051462 A1 discloses self emulsifying compositions for delivery of lipophilic coenzyme Q10 and other dietary ingredients. After investigation, more than 2 oil components and/or more than 2 emulsifiers are used in the solution formulation (solution formulation) exemplified in the examples of US 20060051462 A1, which will undoubtedly increase the manufacturing cost. Furthermore, the properties of these solution formulations disclosed in US 20060051462A1 are unknown.

Many liquid nanoemulsion concentrates (liquid nanoemulsion concentrates) are exemplified in the examples of US 20090317532 A1, and their formulations require the use of at least one oil component, at least one emulsion stabilizer (emulsion stabilizer), at least one surfactant, It is even necessary to add a co-surfactant, which will undoubtedly increase the manufacturing cost. Furthermore, the preparation of the oil phase and the water phase must be heated at 60°C to make the components used be miscible, and a high-pressure homogenizer is required for emulsification.

Contents of the invention

Thus, in a first aspect, the present invention provides a microemulsion preconcentrate comprising a lipophilic functional ingredient which forms an aqueous medium when diluted with an aqueous medium. Oil-in-water (o/w) microemulsion, and the microemulsion pre-concentrate is basically composed of the following (consist essentially of):

A microemulsifying system (microemulsifying system) made of coconut oil and polysorbate 80 (Polysorbate 80), wherein the weight ratio (weight ratio) of coconut oil relative to polysorbate 80 is 1:4 to 1:9 ,as well as

A lipophilic functional ingredient dissolved in the microemulsion system, wherein the weight ratio of the lipophilic functional ingredient relative to the microemulsion system is not greater than 10.

In a second aspect, the present invention provides an oral oil-in-water microemulsion (o/w microemulsion for oral administration) prepared by diluting a microemulsion preconcentrate as described above with an aqueous medium given.

In the third aspect, the present invention provides a health drink, which contains an oil-in-water microemulsion as described above.

In a fourth aspect, the present invention provides a method for preparing a microemulsion preconcentrate as described above, comprising:

Use coconut oil to evenly mix a lipophilic functional ingredient, and then mix evenly with polysorbate 80,

in:

The weight ratio of coconut oil to polysorbate 80 is 1:4 to 1:9, and

The weight ratio of the lipophilic functional ingredient to the sum of coconut oil and polysorbate 80 is not more than 10.

In a fifth aspect, the present invention provides a method for preparing an oil-in-water microemulsion as described above, comprising:

uniformly mixing a lipophilic functional ingredient with coconut oil, followed by uniform mixing with polysorbate 80, so that a microemulsion preconcentrate is formed, and

Dilute the microemulsion preconcentrate with an aqueous medium,

in:

The weight ratio of coconut oil to polysorbate 80 is 1:4 to 1:9, and

The weight ratio of the lipophilic functional ingredient to the sum of coconut oil and polysorbate 80 is not more than 10.

The beneficial effects of the present invention are: when mixing coconut oil and polysorbate 80 with a specific weight ratio, the formed boundary/oil mixture can form a stable oil-in-water microemulsion with an aqueous medium, or with Lipophilic functional ingredients such as coenzyme Q10 can prepare stable microemulsion pre-concentrate without adding any co-surfactants (such as short-chain acids, alcohols or fatty acids commonly used in the art), and without using high-pressure equalizers. It can be emulsified by a mass machine, that is, it can evenly disperse lipophilic functional ingredients such as coenzyme Q10 in an aqueous medium at room temperature and form a stable microemulsion, which has the advantages of easy operation and low cost.

Description of drawings

Figure 1 shows Tween80 as the surfactant, coconut oil as the oil phase and deionized water as the water phase, at a boundary/oil ratio of 9/1 (left, T91) or 8/2 (right, T82), The test samples prepared by adding deionized water to a total weight of 5g with 0.5, 1.0 or 1.5g of the interface/oil mixture respectively will form a transparent and clear oil-in-water microemulsion (clear and transparent o/w) after uniform mixing microemulsion);

Fig. 2 is a three-phase diagram of a microemulsification system established according to the present invention, wherein the oil phase used to establish this microemulsion system is coconut oil, surfactant is Tween 80 and water phase is deionized water, and oblique line Area (hatched area) is microemulsion area (microemulsion region);

Fig. 3 shows that the pH value change of water phase does not have obvious impact on the microemulsion system established according to the present invention, wherein the oil phase used to establish the microemulsion system is coconut oil, surfactant is Tween 80, and water The phases are phosphate buffer at pH 2.0, 0.1M citric acid-sodium citrate buffer at pH 3, 4, 5 or 6, or phosphate buffer at pH 8.0; lotion area;

Fig. 4 shows the storage stability of a microemulsion system according to the present invention at different temperatures (room temperature, 37° C. and 55° C.), wherein the oil phase used to establish the microemulsion system is coconut oil, and the surfactant is Tween80, And the water phase is deionized water; T91-10X means the boundary/oil ratio=9/1, and the dilution factor is 10 times; T91-50X means the boundary/oil ratio=9/1, and the dilution factor is 50 times; T91-100X means Boundary/oil ratio=9/1, dilution factor is 100 times; T82-10X means boundary oil ratio=8/2, dilution factor is 10 times; T82-50X means boundary/oil ratio=8/2, dilution factor is 50 times; and T82-100X means boundary/oil ratio=8/2, the dilution factor is 100 times;

Fig. 5 shows the oil-in-water microemulsion containing coenzyme Q10 generated using the microemulsion system of the present invention, wherein the liquid in the sample bottle on the right is the product prepared in Example 2, and the liquid in the sample bottle on the left It is a 10-fold dilution of the product;

Fig. 6 shows the appearance of two kinds of microemulsion samples prepared in embodiment 3 before and after ultrahigh temperature sterilization treatment, wherein the water phase that is used to form the microemulsion sample in the left picture is deionized water; The aqueous phase used to form the microemulsion samples in the picture on the right was commercially available green tea;

Fig. 7 shows the coenzyme Q10 concentration (ppm) measured in the blood plasma of rats fed with the formula of the present invention containing coenzyme Q10 or the formula of comparative example at different time points;

Figure 8 shows an oil-in-water microemulsion containing curcumin generated using the microemulsion system of the present invention; and

Fig. 9 shows an oil-in-water microemulsion containing β-carotene produced by using the microemulsion system of the present invention.

Detailed ways

In order to provide a microemulsion composition suitable for health drinks, the applicant has found through experiments that when coconut oil and polysorbate 80 are mixed in a specific weight ratio, the formed oil/oil mixture can be mixed with an aqueous The medium forms a stable oil-in-water microemulsion. The applicant further found that the oil-in-water microemulsion containing a lipophilic functional ingredient formulated with a microemulsion system composed of coconut oil and polysorbate 80 has a particle size not greater than 100nm, and is transparent and clear Appearance. In addition, during the process of preparing the oil-in-water microemulsion, the emulsification process can be carried out at normal temperature and pressure, and there is no need to use a high-pressure homogenizer. The microemulsion technology developed by the applicant in the present invention has the advantages of simple operation and low cost, and is very suitable for the development and production of health drinks containing lipophilic functional ingredients.

Therefore, the present invention provides a microemulsion preconcentrate containing a lipophilic functional ingredient, which microemulsion preconcentrate forms an oil-in-water microemulsion when diluted with an aqueous medium, and the microemulsion preconcentrate It basically consists of the following:

A microemulsion system consisting of coconut oil and polysorbate 80, wherein the weight ratio of coconut oil to polysorbate 80 is 1:4 to 1:9, and

A lipophilic functional ingredient dissolved in the microemulsion system, wherein the weight ratio of the lipophilic functional ingredient relative to the microemulsion system is not greater than 10.

The present invention also provides a method for preparing a microemulsion preconcentrate as described above, comprising:

Use coconut oil to evenly mix a lipophilic functional ingredient, and then mix evenly with polysorbate 80,

in:

The weight ratio of coconut oil to polysorbate 80 is 1:4 to 1:9, and

The weight ratio of the lipophilic functional ingredient to the sum of coconut oil and polysorbate 80 is not more than 10.

Coconut oil is an edible oil extracted from the pulp (meat) or kernel (kernel) of the mature coconut (matured coconut) of the coconut palm (cocosnucifera L.). The main components of coconut oil are: 44.6% lauric acid, 16.8% myristic acid, 8.2% palmitic acid, 8% caprylic acid and 6% oleic acid.

Polysorbate 80 is a nonionic surfactant and emulsifier derived from polyethoxylated sorbitan and oleic acid. Brand names of polysorbate 80 include Tween, Alkest, and Canarcel.

As used herein, the term "lipophilic substance", "lipophilic compound" or the like means a substance that is not easily soluble in an aqueous solution but is miscible with a lipid. In the present invention, the terms "lipophilic" and "oil-soluble" are used interchangeably.

As used herein, the term "functional ingredient" includes physiologically or pharmacologically active substances intended for the treatment, prevention, diagnosis, cure or mitigation of disease or illness, or for A substance that, when administered to an animal, provides some degree of nutritional or therapeutic benefit to the animal.

According to the present invention, the lipophilic functional ingredients include, but are not limited to: coenzyme Q10 (including oxidized coenzyme Q10, reduced coenzyme Q10, etc.), curcumin, carotenoids (for example, β-carotene, lutein ), astaxanthin, lycopene, resveratrol, DHA, etc., or their combination.

In a preferred embodiment of the present invention, the lipophilic functional ingredient is coenzyme Q10. In another preferred embodiment of the present invention, the lipophilic functional ingredient is curcumin. In yet another preferred embodiment of the present invention, the lipophilic functional ingredient is β-carotene.

As used herein, the term "aqueous medium" means a liquid medium containing a substantial amount of water in terms of a unit volume of the liquid medium. Aqueous media suitable for the present invention include, but are not limited to, those suitable for making commercially available beverages or health drinks, such as pure water, deionized water, mineral water, fruit juice, vegetable juice, soda, cola, root beer, Milk, yogurt, soy milk, beverage tea, sports drinks, etc.

In a preferred embodiment of the present invention, the aqueous medium is deionized water. In another preferred embodiment of the present invention, the aqueous medium is green tea drink (green teadrink).

In a preferred embodiment of the present invention, the weight ratio of coconut oil to polysorbate 80 is 1:4. In another preferred embodiment of the present invention, the weight ratio of coconut oil to polysorbate 80 is 1:9.

According to the present invention, the weight of the lipophilic functional ingredient relative to the microemulsion system preferably falls within the range of 1:10000 to 1:10, more preferably falls within the range of 1:1000 to 1:10, More preferably, it falls within the range of 1:250 to 1:10, and more preferably, it falls within the range of 1:150 to 1:10. In a preferred embodiment of the present invention, the weight ratio of the lipophilic functional component to the microemulsion system is 1:30. In another preferred embodiment of the present invention, the weight ratio of the lipophilic functional component to the microemulsion system is 1:60. In yet another preferred embodiment of the present invention, the weight ratio of the lipophilic functional component to the microemulsion system is 1:250.

In a preferred embodiment of the present invention, the lipophilic functional ingredient is coenzyme Q10, and the weight ratio of coenzyme Q10 to the microemulsion system is 1:30.

In another preferred embodiment of the present invention, the lipophilic functional ingredient is curcumin, and the weight ratio of curcumin to the microemulsion system is 1:60.

In yet another preferred embodiment of the present invention, the lipophilic functional ingredient is β-carotene, and the weight ratio of β-carotene to the microemulsion system is 1:250.

The present invention also provides an oral oil-in-water microemulsion obtained by diluting a microemulsion preconcentrate as described above with an aqueous medium.

The present invention also provides a method for preparing an oil-in-water microemulsion as described above, comprising:

uniformly mixing a lipophilic functional ingredient with coconut oil, followed by uniform mixing with polysorbate 80, so that a microemulsion preconcentrate is formed, and

Dilute the microemulsion preconcentrate with an aqueous medium,

in:

The weight ratio of coconut oil to polysorbate 80 is 1:4 to 1:9, and

The weight ratio of the lipophilic functional ingredient to the sum of coconut oil and polysorbate 80 is not more than 10.

Aqueous media suitable for the preparation method of the present invention include, but are not limited to, those described above.

According to the present invention, a minimum amount of aqueous medium can be used to dilute the microemulsion preconcentrate, and the formed oil-in-water microemulsion can be further diluted with a larger amount of aqueous medium without affecting the microemulsion present in the microemulsion. The particle size of the nanoparticles. According to the present invention, the minimum amount of the aqueous medium is about 2 times the weight of the microemulsion preconcentrate.

According to the present invention, the aqueous medium has a pH value of 2-8, preferably has a pH value of 5-8. In a preferred embodiment of the present invention, the pH value of the aqueous medium is an acceptable pH value for oral beverages, for example, the pH value is 7.

When the preparation method of the present invention uses an aqueous medium suitable for making commercially available beverages or health drinks, the formed oil-in-water microemulsion can be made into health drinks.

The preparation method of the invention can be carried out under normal temperature and pressure, and uniform mixing of all components can be achieved without using a high-pressure homogenizer.

Example

The present invention will be further described with reference to the following examples, but it should be understood that the examples are for illustrative purposes only and should not be construed as limitations on the implementation of the present invention.

Experimental Materials:

Unless otherwise specified, the water used in the following examples is all deionized water (de-ionized water).

The following materials were purchased from Sigma-Aldrich Co.LLC., USA: coconut oil (coconut oil), sodium citrate (sodium citrate tribasic dehydrate), β-carotene (β-carotene), and carboxymethylcellulose sodium salt (sodiumcarboxymethylcellulose, CMC).

The 1% (w/v) CMC solution used in the following examples was prepared with deionized water.

The following materials were purchased from Taiwan Merck Co., Ltd. (6th Floor, No. 89, Section 2, Tiding Avenue, Neihu District, Taipei City, Taiwan): Tween60, Tween80, methanol (methanol), ethanol (ethanol), hexane (hexane) , isopropylether, phosphoric acid, sodium dihydrogen phosphate, and disodium hydrogen phosphate.

Citric acid was purchased from Zhenfang Co., Ltd. (Zhenfang Building, No. 116, Section 1, Xinsheng South Road, Taipei City, Taiwan, China).

Unless otherwise specified, the 0.1M citric acid-sodium citrate buffer (citric acid-sodium citrate buffer) with pH 3.0～6.0 used in the following examples is according to the pH value to be prepared, and a certain amount of The ratio of citric acid and sodium citrate was added to deionized water and mixed evenly, and finally confirmed with a pH meter.

Phosphoric acid buffer (phosphoric acid buffer) with pH 2.0 is based on the desired pH value, adding a certain proportion of phosphoric acid and sodium dihydrogen phosphate into deionized water and mixing evenly, and finally confirming with a pH meter.

Phosphate buffer with a pH of 8.0 is prepared according to the desired pH value, adding a certain proportion of sodium dihydrogen phosphate and disodium hydrogen phosphate to deionized water and mixing evenly, and finally measured with a pH meter. confirm.

Oil-soluble coenzyme Q10 (product model: ) was purchased from PharmaEssin Pharmaceutical Co., Ltd. (13th Floor, Building F, No. 3 Yuanyuan Street, Nangang District, Taipei City, Taiwan, China).

Curcumin (curcumin) was purchased from Dengsheng Enterprise Co., Ltd. (9th Floor, No. 189, Gangchao Road, Neihu Science Park, Taipei City, Taiwan, China).

Embodiment 1. use coconut oil to set up the microemulsification system of the present invention (Establishment of microemulsifying systems of this invention using coconut oil as oil phase) as oil phase

For setting up the microemulsion system according to the present invention, the present embodiment uses coconut oil as the oil phase (oil phase), and investigates the kind of surfactant (surfactant) and the pH value of the water phase (the aqueous phase's pH value) for the microemulsion Formation (the formation of microemulsion), also explore the impact of temperature on the storage stability (storage stability) of the microemulsion system established by the present invention, and analyze the viscosity (viscosity) and particle size of the microemulsion system established by the present invention diameter (particle size).

A. The influence of surfactant upon the microemulsifying system of this invention according to the microemulsifying system of the present invention

In this experiment, coconut oil is used as the oil phase, Tween60 or Tween80 is used as the surfactant, and deionized water is used as the water phase to find out the components that can form microemulsions and their dosage ratio range.

experimental method:

Coconut oil is mixed with a selected surfactant at a specified interface/oil ratio (surfactant/oil ratio) (9/1, 8/2, 7/3, 6/4, 5/5, 4/6, 3/7, 2/8 or 1/9, w/w, with a total weight of 50g) into a container, and use a magnetic stirrer (Corning PC-420D) to evenly mix the mixture at a stirring rate of about 800rpm Surfactant/oil mixture in container.

For each well-mixed oil/oil mixture, remove a specified amount (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0 or 4.5 g) and place in an empty sample bottle , Then add deionized water until the total weight of the test sample (test sample) in the sample bottle reaches 5g. Use the same magnetic stirring method as above to stir the test sample in each sample bottle and observe its appearance change, that is, whether there is a microemulsion formed. A ternary phase diagram is drawn according to the interface/oil ratio of coconut oil and surfactant, the dilution ratio (dilution ratio) of the interface/oil mixture relative to the water phase, and whether the test sample has formed a microemulsion.

Experimental results:

The applicant found that: when coconut oil was used as the oil phase and Tween60 was used as the surfactant, the formed phase/oil mixture at various phase/oil ratios could not be uniformly mixed with the water phase at different dilution factors to form a transparent Clear microemulsion. On the contrary, when coconut oil is used as the oil phase and Tween80 is used as the surfactant, as shown in Figure 1, the interface/oil mixture formed under the interface/oil ratio of 9/1 or 8/2 can be mixed with the water phase Mix evenly to form a transparent and clear microemulsion.

The applicant draws a three-phase diagram as shown in Figure 2 according to the results of whether coconut oil and Tween80 will form microemulsions with the water phase at various boundary/oil ratios and different dilution ratios, in which there will be areas where microemulsions form is the hatched area between the two dilution lines at the initial boundary/oil ratio of 8/2 and 9/1.

The applicant has also found that: when the boundary/oil ratio is 8/2, the water content (watercontent) of the test sample needs to be nearly 70% (w/w) or more to form a microemulsion; and the boundary/oil ratio is increased to 9 /1, the water content of the test sample is 60% (w/w) or above to form a microemulsion. As long as the water content reaches the minimum limit, the test sample prepared with the interface/oil mixture formed by these two interface/oil ratios can form a microemulsion, and the formed microemulsion can also be diluted with a large amount of water without affecting Nanoparticles present in microemulsions.

B. The influence of the pH value of the aqueous phase on the microemulsifying system according to the present invention (The influence of the aqueous phase's pH value upon the microemulsifying system of this invention)

In order to find out how wide the pH range of the water phase that coconut oil and Tween80 can form a microemulsion, this experiment uses the following buffered solutions (buffered solution) with different pH values as the water phase:

(1) Phosphate buffer solution of pH2.0;

(2) 0.1M citric acid-sodium citrate buffer solution with a pH value of 3, 4, 5 or 6; and

(3) Phosphate buffer solution of pH 8.0.

experimental method:

Coconut oil was prepared with Tween 80 as described in Section A above with different oil/oil ratios (9/1, 8/2, 7/3, 6/4, 5/5, 4/6, 3/7 , 2/8 or 1/9, w/w) of the oil/oil mixture. For each homogeneously mixed oil/oil mixture, remove a specified amount (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, or 4.5 g) into an empty vial, then add a selected The specified buffer solution until the total weight of the test sample in the sample bottle reaches 5g. Stir the test sample in each vial using the same magnetic stirring method as described in Section A above and observe its change in appearance, that is, whether a microemulsion is formed. According to the boundary/oil ratio of coconut oil and Tween80, the dilution ratio of the boundary/oil mixture relative to the water phase, and whether the test sample has formed a microemulsion, a three-phase diagram is drawn. Experimental results:

The applicant draws a three-phase diagram as shown in Figure 3 according to the results of whether coconut oil and Tween80 will form a microemulsion with the selected buffer solution at various boundary/oil ratios and different dilution ratios. As shown in Figure 3, when the pH of the aqueous phase was reduced to below 4, the microemulsion region (microemulsion region) was slightly reduced, but on the whole, the pH value change of the aqueous phase was not significant for the establishment of the microemulsion system according to the present invention. No noticeable effect.

C. The influence of temperature on the storage stability of the microemulsifying system according to the present invention (The influence of temperature upon the storage stability of the microemulsifying system of this invention)

This experiment investigates how temperature changes will affect the storage stability of the microemulsion system according to the present invention.

experimental method:

Tween 80 was uniformly mixed with coconut oil at a 9/1 or 8/2 (w/w) keratin/oil ratio to obtain a keratin/oil mixture as described in Section A above. Put an appropriate amount of oil/oil mixture into an empty sample bottle and dilute it 10 times, 50 times or 100 times with deionized water, and then use the same magnetic stirring method as described in Section A above to stir the sample bottle Test samples in the test until a microemulsion is formed. Afterwards, the vials were stored at room temperature, 37°C or 55°C. The microemulsion in the sample bottle was sampled at different time points (0, 1, 5, 7, 12, 16, 21 and 28 days) and carried out light penetration with a spectrophotometer (Merck SpectroquantPharo300) at 600nm Rate analysis (optical transmittance analysis). The experimental results obtained are shown in FIG. 4 .

Experimental results:

Referring to Fig. 4, Tween80 and coconut oil are mixed uniformly with the interface/oil ratio of 9/1 or 8/2 (w/w) and obtained interface/oil mixture is diluted 10 times, 50 times or 100 times with deionized water After the formed microemulsion was stored at room temperature or 37° C. for 28 days, the light transmittance of the test groups with a boundary/oil ratio of 9/1 or 8/2 did not change significantly. However, when the storage temperature increased to 55°C, the experimental group with a boundary/oil ratio of 8/2 would appear white turbidity as the storage period increased, and the lower the dilution rate, the higher the turbidity of the experimental group. This shows that the microemulsion system of the present invention has excellent storage stability at room temperature or at a temperature of 37° C., and is not affected by the interface/oil ratio of Tween80 and coconut oil and the dilution ratio of the interface/oil mixture relative to the water phase.

D. Viscosity and particle size analyzes of the microemulsifying system of this invention (Viscosity and particlesize analyzes of the microemulsifying system of this invention)

experimental method:

Tween 80 was uniformly mixed with coconut oil at a 9/1 or 8/2 (w/w) keratin/oil ratio to obtain a keratin/oil mixture as described in Section A above. Put an appropriate amount of oil/oil mixture into an empty sample bottle, and dilute it 10 times with deionized water, and then use the same magnetic stirring method as described in Section A above to stir the test sample in the sample bottle until there is microemulsion formation. Afterwards, analyze the microemulsion sample in each vial with a viscometer (Nameter vicometer 1810 SF) and a particle size analyzer (Beckman 440SX Delsa Laser Particle Measuring Device).

Experimental results:

The water content of the two microemulsion samples prepared in this experiment were both 90wt%. Referring to Table 1, they were found to have a viscosity of about 3.5-4 cP. Compared with the viscosity of pure water (1cP), the viscosity of these two microemulsion samples did not increase significantly. Regarding the particle size, the microemulsion sample with a boundary/oil ratio of 9/1 has an average particle size of about 1.9 nm, while the microemulsion sample with a boundary/oil ratio of 8/2 has an average particle size of about 3.73 nm. the average particle size. From this point of view, adding more surfactants can make the particle size of the dispersed phase (that is, nanoparticles dispersed in the microemulsion) smaller.

Table 1. Viscosity and particle size of microemulsion samples

Embodiment 2. preparation contains the oil-in-water microemulsion of coenzyme Q10 (Preparation ofCoQ10-containing o/w microemulsion)

In this embodiment, a microemulsion system according to the foregoing example 1 is used to prepare an oil-in-water microemulsion containing coenzyme Q10, wherein the microemulsion system uses coconut oil as the oil phase, Tween80 as the surfactant, and Deionized water was used as the water phase, and the Tween 80 relative to coconut oil had an 8/2 oil/oil ratio.

experimental method:

Using an ultrasonic vibration cleaning machine (Delta Ultrasonic Cleaner DC400), 1000mg of oil-soluble coenzyme Q10 was evenly dissolved in 6g of coconut oil by means of ultrasonic vibration. Alternatively, to quickly and uniformly disperse coenzyme Q10 in the oil phase (for example, coconut oil), a general magnetic stirrer can also be used to achieve.

Then add 24g of Tween80 into the coenzyme Q10/coconut oil mixture by using a magnet stirring method, after completely uniform mixing, add 69g of deionized water and continue stirring with a magnet until there is no gel-like substance in the mixture exist. The obtained product was analyzed with a particle size analyzer. 10 g was taken out from the product, and diluted 10 times with deionized water, and then the change in appearance was observed.

Experimental results:

Referring to the sample bottle on the right side of Figure 5, the product obtained in this example is an orange oil-in-water microemulsion containing 10 mg/g coenzyme Q10, which is measured to have an average particle size of about 60.2 nm. The applicant found that the microemulsion can be diluted to any concentration with an aqueous medium, and the average particle size of the microemulsion is not affected by dilution. For example, the yellow liquid in the sample bottle on the left side of Figure 5 is the oil-in-water microemulsion containing 1mg/g coenzyme Q10 formed after diluting the product obtained in this embodiment 10 times with deionized water. The average particle size is about 60.2nm.

Embodiment 3. The influence of high temperature sterilization upon the microemulsifying system of the present invention (The influence of high temperature sterilization upon the microemulsifying system of this invention)

This example discusses whether high temperature sterilization will affect the oil-in-water microemulsion containing coenzyme Q10 produced by using the microemulsion system of the present invention.

experimental method:

Referring to Example 2, using an ultrasonic vibration cleaning machine (Delta UltrasonicCleaner DC400), 250 mg of oil-soluble coenzyme Q10 was evenly dissolved in 5 g of coconut oil in an ultrasonic vibration mode. Then add 20g of Tween80 into the coenzyme Q10/coconut oil mixture by magnetic stirring method, and then add 5000mL of deionized water or 4000mL of commercially available green tea after completely uniform mixing and continue stirring with a magnetic stone until there is no gelatinous substance in the mixture exist. Take out an aliquot (10mL/bottle) of the product, and carry out ultra-high temperature sterilization with a UHT/HTST sterilizer (a machine assembled by the applicant according to the technical disclosure of Taiwan New Patent No. 100960), The sterilization condition is 135°C for 3-5 seconds.

Experimental results:

In the production of beverages, ultra high temperature sterilization (UHT) or high temperature instant sterilization (ultra high temperature short time sterilization, HTST) is one of the common sterilization methods, and the sterilization conditions are generally 130 ~ 145 ° C Temperature and time of 2 to 5 seconds. Fig. 6 shows the appearance state of two kinds of microemulsion samples prepared by the present embodiment before and after ultrahigh temperature sterilization, wherein the water phase that is used to form the microemulsion sample in the left picture is deionized water, and The aqueous phase used to form the microemulsion samples in the right panel was commercially available green tea. From the results shown in Figure 6, the two microemulsion samples prepared in this embodiment did not produce obvious changes in appearance after ultra-high temperature sterilization, which shows that ultra-high temperature sterilization can be used to process microemulsions using the present invention. An oil-in-water microemulsion produced by a microemulsion system.

Embodiment 4. Rat feeding test (Rat feeding test)

This example discusses the oral absorption rate of the oil-in-water microemulsion type coenzyme Q10 formula generated by using the microemulsion system of the present invention.

Experimental Materials:

A. Feed samples:

The sample of the formula of the present invention is an oil-in-water microemulsion containing oil-soluble coenzyme Q10, which is prepared with reference to Example 2, and contains 10mg/g of oil-soluble coenzyme Q10, 8wt%Tween80, 2wt% coconut oil and The balance is deionized water.

The sample of the comparative formulation (comparative formulation) is a 1% CMC solution containing 10mg/mL oil-soluble coenzyme Q10.

B. Experimental animals:

Seven-week-old SLC:SD male rats (Japan SLC, Inc., Hamamatsu, Japan) were used in this animal experiment after being acclimatized for one week. During the domestication period, the rats were reared in an animal room (animal room) set to have the following conditions: temperature of 20-26°C, humidity of 40-70%, and lighting of 12 hours/day, and Solid food (CE-2, CLEA Japan, Inc., Tokyo, Japan) and tap water were allowed ad libitum.

experimental method:

Feeding dose: each rat is given a single dose of 60 mg coenzyme Q10/kg body weight, and each formula sample is tested with 3 rats.

Sampling time: before feeding and 0.5, 1, 2, 4, 8, 12, 24 hours after feeding, 0.5 mL of blood was collected from the tail artery and centrifuged, and then the obtained plasma samples were stored at -20°C.

Extraction method: The thawed (thawed) plasma sample (200 μL) was uniformly mixed with 200 μL ethanol, followed by uniform mixing with 200 μL hexane (Scientific Industries Vortex-Genie 2); after 5 minutes of ultrasonic (DeltaUltrasonic Cleaner DC400) vibration, The mixture was centrifuged (Heraeas Instruments Biofuge fresco, 12,000rpm, 10 minutes), and the organic layer was then dried under reduced pressure ( -215); the obtained dried product was redissolved in 300 μL of ethanol and analyzed by HPLC using a high performance liquid chromatography (Agilent, Series 1200).

HPLC conditions:

1. Column: Merck C-18 column (250X4mm, 5μm)

2. Mobile phase: methanol/isopropyl ether (85:15), isocratic elution

3. Analysis wavelength: 275nm

4. Eluting condition: 1mL/min

5. Sampling volume: 50μL

6. Column temperature: 35°C

Experimental results:

Referring to Fig. 7, compared with the formula of the comparative example, the formula of the present invention can rapidly increase the concentration of coenzyme Q10 in rat plasma. Table 2 shows the plasma pharmacokinetic coefficients (plasma pharmacokinetic coefficients) of rats after feeding 60mg/kg coenzyme Q10, wherein the maximum concentration (the peak plasma concentration, C _max ), and the area under the curve (area undercurve, AUC) were significantly higher than those of the rats fed with the comparative example. These experimental results show that the coenzyme Q10 formula prepared by the microemulsion system of the present invention can indeed improve the oral absorption rate of coenzyme Q10. It can be deduced from this that the microemulsion system according to the present invention can be used to prepare oil-in-water microemulsions containing oil-soluble bioactive substances to be used in health drinks.

Table 2. Plasma pharmacokinetic coefficients of rats fed with 60mg/kg coenzyme Q10

Embodiment 5. prepares the oil-in-water microemulsion (Preparation ofcurcumin-containing o/w microemulsion) containing curcumin

The present embodiment prepares an oil-in-water microemulsion containing curcumin with reference to Example 2. experimental method:

Using an ultrasonic vibration cleaning machine (Delta Ultrasonic Cleaner DC400), 500mg of curcumin was evenly dissolved in 6g of coconut oil by means of ultrasonic vibration. Then utilize the Tween80 of 24g to be added in the curcumin/coconut oil mixture by magnet stirring mode, wait to mix thoroughly and then add deionized water to a total of 100g and continue to stir with magnet until there is no colloidal substance in the mixture. The obtained product was analyzed with a particle size analyzer.

Experimental results:

Referring to Fig. 8, the product obtained in the present embodiment is an orange oil-in-water microemulsion containing 5mg/g curcumin, which is measured to have an average particle diameter of about 45.7nm. The curcumin-containing microemulsion obtained in this embodiment can also be diluted to any concentration with an aqueous base.

Embodiment 6. preparation contains the oil-in-water microemulsion of β-carotene (Preparation of β-carotene-containing o/w microemulsion)

In this example, an oil-in-water microemulsion containing β-carotene was prepared with reference to Example 2.

experimental method:

Using an ultrasonic vibration cleaning machine (Delta Ultrasonic Cleaner DC400), 120mg of β-carotene was evenly dissolved in 6g of coconut oil by means of ultrasonic vibration. Then add 24g of Tween80 into the β-carotene/coconut oil mixture by means of magnetic stirring, and then add deionized water to a total of 100g after mixing completely and uniformly, and continue stirring with a magnetic stone until there is no gelatinous substance in the mixture . The obtained product was analyzed with a particle size analyzer.

Experimental results:

Referring to Fig. 9, the product obtained in this embodiment is an orange oil-in-water microemulsion containing 1.2 mg/g β-carotene, which is measured to have an average particle size of about 47.1 nm. The microemulsion containing β-carotene obtained in this example can also be diluted to any concentration with an aqueous base.

All patent and literature data cited within this specification and references described therein are hereby incorporated by reference in their entirety. In case of conflict, the detailed description of this case (including definitions) shall prevail.

Although the invention has been described with respect to its specific embodiments, it will be appreciated that it can be further modified and that this application claims to cover any variation, use or adaptation of the invention which generally follows the The principles of the invention and including said modifications deriving from customary practice in the field to which the invention pertains and which may be employed with the essential features described above, fall within the scope of the claims of the present application.

Claims (19)

1. A microemulsion preconcentrate containing a lipophilic functional component, characterized in that: the microemulsion preconcentrate forms an oil-in-water microemulsion when diluted with an aqueous medium, and the microemulsion preconcentrate Things basically consist of: A microemulsion system consisting of coconut oil and polysorbate 80, wherein the weight ratio of coconut oil to polysorbate 80 is 1:4 to 1:9, and A lipophilic functional ingredient dissolved in the microemulsion system, wherein the weight ratio of the lipophilic functional ingredient relative to the microemulsion system is not greater than 10. 2 . The microemulsion pre-concentrate according to claim 1 , wherein the weight ratio of the lipophilic functional component to the microemulsion system is in the range of 1:10000 to 1:10. 3. The microemulsion pre-concentrate according to claim 1, characterized in that: the lipophilic functional components are coenzyme Q10, curcumin, carotenoids, astaxanthin, lycopene, resveratrol, DHA , or a combination of them. 4. The microemulsion pre-concentrate according to claim 1, wherein the weight ratio of coconut oil to polysorbate 80 is 1:4. 5. The microemulsion pre-concentrate according to claim 1, wherein the weight ratio of coconut oil to polysorbate 80 is 1:9. 6. An oil-in-water microemulsion for oral administration, characterized in that: the oil-in-water microemulsion is obtained by diluting the microemulsion preconcentrate as claimed in claim 1 with an aqueous medium. 7. The oil-in-water microemulsion according to claim 6, characterized in that: the aqueous medium is pure water, deionized water, mineral water, fruit juice, vegetable juice, soda, cola, beer root, milk, yogurt, Soy milk, beverage tea or sports drink. 8. A health drink, characterized in that: the health drink contains the oil-in-water microemulsion as claimed in claim 6. 9. A method for preparing a microemulsion preconcentrate containing a lipophilic functional component, characterized in that: the method comprises: Use coconut oil to evenly mix a lipophilic functional ingredient, and then mix evenly with polysorbate 80, Wherein the weight ratio of coconut oil to polysorbate 80 is 1:4 to 1:9, and the weight ratio of the lipophilic functional component to the sum of coconut oil and polysorbate 80 is not greater than 10. 10. The method according to claim 9, characterized in that the weight ratio of the lipophilic functional ingredient relative to the sum of coconut oil and polysorbate 80 falls within the range of 1:10000 to 1:10. 11. The method according to claim 9, characterized in that: the lipophilic functional ingredient is coenzyme Q10, curcumin, carotenoid, astaxanthin, lycopene, resveratrol, DHA or a combination thereof . 12. The method according to claim 9, characterized in that the weight ratio of coconut oil to polysorbate 80 is 1:4. 13. The method according to claim 9, characterized in that the weight ratio of coconut oil to polysorbate 80 is 1:9. 14. A method for preparing an oral oil-in-water microemulsion, characterized in that: the method comprises: uniformly mixing a lipophilic functional ingredient with coconut oil, followed by uniform mixing with polysorbate 80, so that a microemulsion preconcentrate is formed, and Dilute the microemulsion preconcentrate with an aqueous medium, Wherein the weight ratio of coconut oil to polysorbate 80 is 1:4 to 1:9, and the weight ratio of the lipophilic functional component to the sum of coconut oil and polysorbate 80 is not greater than 10. 15. The method according to claim 14, characterized in that the weight ratio of the lipophilic functional ingredient relative to the sum of coconut oil and polysorbate 80 falls within the range of 1:10000 to 1:10. 16. The method according to claim 14, characterized in that: the lipophilic functional ingredient is coenzyme Q10, curcumin, carotenoids, astaxanthin, lycopene, resveratrol, DHA or combinations thereof . 17. The method according to claim 14, characterized in that: the aqueous medium is pure water, deionized water, mineral water, fruit juice, vegetable juice, soda, cola, root root, milk, yogurt, soybean milk, beverage tea or energy drink. 18. The method of claim 14, wherein the weight ratio of coconut oil to polysorbate 80 is 1:4. 19. The method of claim 14, wherein the weight ratio of coconut oil to polysorbate 80 is 1:9.