Oil-soluble composition as well as preparation method and application thereof

Abstract

The invention provides an oil-soluble composition as well as a preparation method and application thereof. The oil-soluble composition according to the present invention comprises: a functional component in an amount of 25 parts by weight or less; phospholipid, the content of which is 1-10 parts by weight; and an unsaturated fatty acid, in which the functional component has an unsaturated olefin and an electron withdrawing group.

Description

Technical Field

[0001] The invention belongs to the field of food, and in particular relates to an oil-soluble composition with high stability and high absorption rate. Background Art

[0002] In applications such as health care products, effective ingredients with unsaturated olefins and electron-withdrawing groups have low solubility and high freezing points, are difficult to convert into micelles in the human body, have low absorption, and are prone to precipitate crystals at room and low temperatures, limiting their application in dosage forms such as soft capsules and gels.

[0003] Taking coenzyme Q10 as an example, the conventional processes for preparing coenzyme Q10 soft capsules include melting method and dispersion method. Conventionally prepared coenzyme Q10 soft capsules are difficult to convert into micelles during intestinal digestion and have low absorption in the human body. The content of coenzyme Q10 that can be carried by the melting method is relatively small. When the content of dissolved coenzyme Q10 exceeds 1%, crystals will precipitate at room temperature and the low-temperature stability is poor. The coenzyme Q10 soft capsules prepared by the dispersion method have also precipitated after cooling after high temperature, and have poor thermal stability.

[0004] Patent CN116036060A discloses a coenzyme Q10 oil preparation: coenzyme Q10 20-40%, mixed oil 45-65% (containing both saturated fatty acids (esters) and unsaturated fatty acids (esters)), and two-phase emulsifier 10-15% (including emulsifiers such as Tween).

[0005] Patent CN101022786A discloses a food additive formulation for oral release: (a) CoQ10; (b) a mixture of one or more monoesters of long-chain fatty acids with carbon chain lengths of C6 to C24 and short-chain alcohols with carbon chain lengths of C1 to C4 or one or more medium-chain monoesters or diesters or combinations thereof; and (c) one or more emulsifiers. All of the CoQ10 is in a completely dissolved form.

[0006] There is a need in the art for an oil-soluble composition system that is more compatible with different functional ingredients and easier to digest and absorb. Summary of the invention

[0007] The present invention provides an oil-soluble composition, which comprises: an effective component, the content of which is less than 25 parts by weight; a phospholipid, the content of which is 1-10 parts by weight; and an unsaturated fatty acid, wherein the effective component has an unsaturated olefin and an electron-withdrawing group.

[0008] In one embodiment, the content of phospholipids is 2-8 parts by weight or 1-5 parts by weight.

[0009] In one embodiment, the active ingredient is selected from coenzyme Q10, astaxanthin, lutein, beta-carotene, fucoxanthin, vitamin K2 and dihydroquercetin.

[0010] In one embodiment, the content of the effective ingredient is 1-25 parts by weight, 1-20 parts by weight, 1-15 parts by weight or 1-10 parts by weight.

[0011] In one embodiment, the weight percentage of the effective ingredient is 25% or less or 23% or less.

[0012] In one embodiment, the phosphatidylcholine content of the phospholipids is 40-70% and the phosphatidylethanolamine content is less than 20%.

[0013] In a preferred embodiment, the phosphatidylcholine content of the phospholipids is 45-65%.

[0014] In a preferred embodiment, the phosphatidylcholine content of the phospholipids is 55-65%.

[0015] In a preferred embodiment, the phosphatidylethanolamine content in the phospholipids is 5-15% or 5-10%.

[0016] In one embodiment, the unsaturated fatty acid has a degree of unsaturation of 3-7.

[0017] In one embodiment, the degree of conjugation of the unsaturated fatty acid is 0 or 1.

[0018] In one embodiment, the content of unsaturated fatty acids is 65-97 parts by weight, 72-90 parts by weight, or 75-80 parts by weight.

[0019] In one embodiment, the unsaturated fatty acid is selected from monostearin, arachidic acid, hexadecatrienoic acid, nervonic acid, linoleic acid (e.g., conjugated linoleic acid, 9c, 11t-conjugated linoleic acid), arachidonic acid (e.g., conjugated arachidonic acid) and docosahexaenoic acid (e.g., conjugated docosahexaenoic acid).

[0020] In one embodiment, the oil-soluble composition further comprises an additive selected from the group consisting of flavors, pigments, antioxidants, nutritional enhancers, colloids and syrups.

[0021] In a preferred embodiment, the additive is selected from the group consisting of pyrroloquinoline quinone, rosemary extract, curcumin and xanthan gum.

[0022] In a preferred embodiment, the additive is present in an amount not exceeding 20% ​​of the phospholipid content.

[0023] In a preferred embodiment, the oil-soluble composition does not contain an emulsifier, the emulsifier being Tween (eg, polysorbate 80).

[0024] In another aspect, the present invention provides a method for preparing the oil-soluble composition disclosed herein, comprising heating the effective ingredient, phospholipids and unsaturated fatty acids at 55-75° C. and mixing them thoroughly.

[0025] In one embodiment, the method further comprises passing the resulting mixture oil solution through a homogenizer,

[0026] In one embodiment, the method further comprises adding the additive to the obtained oil system.

[0027] In another aspect, the present invention provides a soft capsule comprising the oil-soluble composition disclosed herein.

[0028] In another aspect, the present invention provides a gel comprising the oil-soluble composition disclosed herein and a gelling agent.

[0029] In one embodiment, the gelling agent is selected from the group consisting of xanthan gum, gum arabic, konjac gum, guar gum, carrageenan, locust bean gum, pectin and gelatin.

[0030] In one embodiment, the gel is an oleogel or a gel candy.

[0031] In another aspect, the present invention provides the use of the oil-soluble composition disclosed herein, the soft capsule disclosed herein or the gel disclosed herein in food, medicine or cosmetics. In one embodiment, the food is a health food. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 A comparison chart showing the severity of crystallization of oil solution samples after refrigeration is shown.

[0033] Figure 2 A comparison of the severity of delamination after simulated digestion of oil solution samples is shown.

[0034] Figure 3 An exemplary softgel capsule product prepared from a sample of a Coenzyme Q10 oil solution is shown.

[0035] Figure 4 Shows oil solution samples with different active ingredients, from left to right: lutein, astaxanthin, and coenzyme Q10 oil solutions. DETAILED DESCRIPTION

[0036] the term

[0037] "Unsaturation" refers to the saturation strength of carbon atoms in organic molecules. In this application, the calculation formula of unsaturation is: Unsaturation (Ω) = (2C + 2-H) / 2,

[0038] Where: C- number of carbon atoms, H- number of hydrogen atoms

[0039] Conjugation refers to the overlap of p orbitals separated by a σ bond. A conjugated system is a system with alternating single-double bonds, where the p orbitals of the double bonds are connected to each other by electron delocalization, which usually reduces the overall energy of the molecule and increases its stability. The number of conjugated systems a compound has is called the "degree of conjugation".

[0040] In the present application, the term "unsaturated olefin" refers to a hydrocarbon group containing a carbon-carbon double bond.

[0041] In the present application, "electron withdrawing group" refers to a group that reduces the electron cloud density on the benzene ring when a substituent replaces the hydrogen on the benzene ring.

[0042] Oil soluble composition

[0043] Provided herein is an oil-soluble composition comprising an effective ingredient in an amount of less than 25 parts by weight, a phospholipid in an amount of 1-10 parts by weight, and an unsaturated fatty acid, wherein the effective ingredient has an unsaturated olefin and an electron-withdrawing group.

[0044] In the oil-soluble composition of this article, phosphatidylcholine and phosphatidylethanolamine are present in a specific amount in phospholipids. In some embodiments, the phosphatidylcholine content in phospholipids is 45-65%, for example 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%. In some embodiments, the phosphatidylethanolamine content in phospholipids is below 20%, for example 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%.

[0045] In the oil-soluble composition herein, the content of phospholipids is 1-10 parts by weight, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 parts by weight.

[0046] In the oil-soluble composition herein, the effective ingredients may be selected from coenzyme Q10, astaxanthin, lutein, β-carotene, fucoxanthin, vitamin K2 and dihydroquercetin.

[0047] In the oil-soluble composition of the present invention, the content of the effective ingredient is less than 25 parts by weight, for example, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 part by weight.

[0048] In the oil-soluble composition of the present invention, the weight percentage of the effective ingredient in the oil-soluble composition may be less than 25% or less than 23%, for example, 25%, 24.5%, 24%, 23.5%, 23%, 22.5%, 22%, 21%, 20% or less.

[0049] In the oil-soluble composition herein, the unsaturation degree of the unsaturated fatty acid may be 3-7, for example, 2, 3, 4, 5, 6, 7.

[0050] In the oil-soluble composition herein, the degree of conjugation of the unsaturated fatty acid may be 0 or 1.

[0051] In the oil-soluble composition of the present invention, the content of unsaturated fatty acids can be 65-97 weight parts, for example, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97 weight parts.

[0052] In the oil-soluble composition herein, the unsaturated fatty acid may be selected from glyceryl monostearate, arachidic acid, hexadecatrienoic acid, nervonic acid, linoleic acid (e.g., conjugated linoleic acid, 9c, 11t-conjugated linoleic acid), arachidonic acid (e.g., conjugated arachidonic acid) and docosahexaenoic acid (e.g., conjugated docosahexaenoic acid).

[0053] In one embodiment, the oil-soluble composition further comprises an additive selected from the group consisting of flavors, pigments, antioxidants, nutritional enhancers, colloids and syrups.

[0054] In a preferred embodiment, the additive is selected from the group consisting of pyrroloquinoline quinone, rosemary extract, curcumin and xanthan gum.

[0055] In a preferred embodiment, the additive is present in an amount not exceeding 20% ​​of the phospholipid content.

[0056] In a preferred embodiment, the oil-soluble composition does not contain an emulsifier, which may be Tween (eg, polysorbate 80).

[0057] Preparation method

[0058] Provided herein is a method for preparing the oil-soluble composition disclosed herein, which comprises heating the effective ingredient, phospholipids and unsaturated fatty acids at 55-75° C. and mixing them thoroughly and uniformly.

[0059] In one embodiment, the method further comprises passing the resulting mixture oil solution through a homogenizer,

[0060] In one embodiment, the method further comprises adding the additive to the obtained oil system.

[0061] In a specific embodiment, the method of the present invention may include:

[0062] (1) Mix the active ingredients, phospholipids or emulsifiers, and oils according to the weight ratio disclosed herein, and heat at 55-75° C. to mix thoroughly;

[0063] (2) The resulting mixed oil solution is then passed through a homogenizer to obtain a uniform oil system;

[0064] (3) According to the scheme disclosed in this article, add or not add additives to the oil system and stir it thoroughly.

[0065] Other preparations or uses

[0066] The present invention provides a soft capsule comprising the oil-soluble composition disclosed herein.

[0067] The present invention provides a gel comprising the oil-soluble composition disclosed herein and a gelling agent.

[0068] In one embodiment, the gelling agent is selected from the group consisting of xanthan gum, gum arabic, konjac gum, guar gum, carrageenan, locust bean gum, pectin and gelatin.

[0069] In one embodiment, the gel is an oleogel or a gel candy.

[0070] In another aspect, the present invention provides the use of the oil-soluble composition disclosed herein, the soft capsule disclosed herein or the gel disclosed herein in food, medicine or cosmetics. In one embodiment, the food is a health food.

[0071] Example

[0072] The embodiments of the present application will be described in detail below in conjunction with the examples. It will be appreciated by those skilled in the art that the following examples are only used to illustrate the present application and should not be considered as limiting the scope of the present application. If the specific conditions are not specified in the examples, they are carried out according to the conditions recommended by normal conditions or manufacturers. If the manufacturers are not specified in the reagents or instruments used, they are all conventional products that can be obtained commercially. If not specifically indicated, the amounts listed are all based on the gross weight and described in parts by weight. The application should not be construed as being limited to the specific embodiments described.

[0073] 1. Materials and Equipment

[0074] materials

[0075] Effective ingredients: Coenzyme Q10, astaxanthin, lutein esters

[0076] Emulsifier: lecithin (containing different proportions of PC and PE according to the examples below), monoglyceride, soybean polysaccharide, polysorbate 80, modified starch, sucrose ester

[0077] Oils: conjugated linoleic acid, monostearate, arachidic acid, hexadecanoic acid, nervonic acid, arachidonic acid, docosahexaenoic acid,

[0078] Additives: Rosemary extract, PQQ (pyrroloquinoline quinone)

[0079] equipment

[0080] Water bath, homogenizer, rotational viscometer, high performance liquid chromatography, UV spectrophotometer

[0081] 2. Preparation method

[0082] The preparation method comprises the following steps:

[0083] (1) The active ingredients, phospholipids or emulsifiers, and oils are mixed according to the weight ratio of the following examples, and heated at 55-75°C to mix thoroughly;

[0084] (2) The resulting mixed oil solution is then passed through a homogenizer to obtain a uniform oil system;

[0085] (3) According to the specific formula of the following example, add additives to the oil system and stir thoroughly.

[0086] 3. Test Methods

[0087] 3.1 Low temperature stability evaluation

[0088] After the sample is refrigerated at 4°C for 8 hours, observe the appearance of the sample. Observe the severity of its crystallization, such as Figure 1 As shown, the degree of precipitation increases from right to left.

[0089] The evaluation indicators are as follows (from left to right):

[0090] - No crystal precipitation, clear and bright;

[0091] + A small amount of crystals precipitated, slightly turbid;

[0092] ++ A lot of crystals precipitated, turbid.

[0093] 3.2 Viscosity determination method

[0094] Refrigerate the sample at 4°C for 8 hours and then measure the viscosity. The viscometer measurement steps are as follows:

[0095] 1. Adjust the level of the viscometer and check the zero position;

[0096] 2. Select the appropriate rotor for installation according to the viscosity range, and then adjust the rotor height to ensure that the rotor can cover the measuring scale line;

[0097] 3. Adjust the speed of the viscometer, observe the torque and readings. When the torque percentage is close to 50%, the viscosity of the measured liquid is measured.

[0098] 3.3 Testing of effective ingredient content

[0099] 3.3.1 Coenzyme Q10

[0100] The HPLC method (Pharmacopoeia General Chapter 0512) was used for determination. The chromatographic conditions and system suitability test were as follows: octadecylsilane bonded silica gel was used as filler; methanol-anhydrous ethanol (1:1, V / V) was used as mobile phase; the column temperature was 35°C; and the detection wavelength was 275nm. Take appropriate amounts of coenzyme Q10 reference substance and coenzyme Q9 reference substance, dissolve and dilute with anhydrous ethanol to make a mixed solution containing about 0.2 mg of each in 1 mL, take 20 μL and inject into the liquid chromatograph. The separation degree of coenzyme Q9 peak and coenzyme Q10 peak should be greater than 4, and the number of theoretical plates calculated based on the coenzyme Q10 peak should be no less than 3000.

[0101] Determination method: Take 20 mg of the prepared sample, weigh it accurately, add about 40 mL of anhydrous ethanol, shake it in a 50°C water bath to dissolve, cool it, transfer it to a 100 mL volumetric flask, dilute it to the scale with anhydrous ethanol, and shake it well. As the test solution, accurately measure 20 μL, inject it into the liquid chromatograph, and record the chromatogram; take an appropriate amount of coenzyme Q10 reference substance and determine it in the same way. Calculate the peak area according to the external standard method to obtain the content of coenzyme Q10, which is recorded as W1. Draw a standard curve of coenzyme Q10 and peak area, and substitute the peak area determined by high-performance liquid chromatography into the standard curve to calculate W1.

[0102] 3.3.2 Astaxanthin

[0103] Accurately weigh an appropriate amount of sample (containing about 1 mg of astaxanthin) into a 100 mL brown volumetric flask, add 80 mL of acetic acid-dimethyl sulfoxide solution (2.5:97.5, V / V), keep warm at 70°C for 5 minutes, cool, and dilute to scale. Filter with filter paper, discard the initial filtrate, take 5 mL of the filtrate, dilute to 20 mL with acetic acid-dimethyl sulfoxide solution, and use this solution for testing.

[0104] The solution to be tested was placed in a 1 cm optical path cuvette, and acetic acid-dimethyl sulfoxide solution was used as a blank control. The absorbance value A was measured at a wavelength of 489 nm.

[0105] The content of total astaxanthin X is calculated as follows:

[0106]

[0107] Where:

[0108] X: astaxanthin content, mg / g;

[0109] A489: Absorption value of the sample;

[0110] V: constant volume of the sample, mL;

[0111] 1908: Extinction coefficient;

[0112] m: mass of the sample, g.

[0113] 3.3.3 Lutein esters

[0114] Weigh an appropriate amount of sample accurately and put it into a 50mL centrifuge tube, add 10mL of water, vortex for 5min to disperse the sample, add 15mL of extractant n-hexane-acetone-toluene-anhydrous ethanol (10:7:7:6, V / V), vortex for 5min, let stand for stratification (or centrifuge), draw the upper organic phase into a flat-bottom flask, repeat the extraction twice, merge the organic phase into the same flask, vacuum concentrate to dryness in a 50℃ water bath, accurately add n-hexane: ethyl acetate (7:3, V / V) 25.0mL, ultrasonically dissolve; accurately measure 1mL and put it into a 10mL volumetric flask, add n-hexane to the mark, shake well, and the sample solution to be tested is obtained. Use n-hexane as the blank solvent, measure the absorbance of the sample solution to be tested at 445nm, and calculate.

[0115] Calculation results:

[0116]

[0117] In the formula,

[0118] X: the content of lutein esters in the sample, in mg / g;

[0119] A: absorbance value of sample solution;

[0120] B: Sample dilution multiple (10 times in the above steps);

[0121] M: sample mass, g;

[0122] 1394: Molar absorption coefficient.

[0123] 3.3.4 β-Carotene

[0124] Determined by high performance liquid chromatography (GB 5009.83).

[0125] 3.3.5 Fucoxanthin

[0126] The chromatographic conditions and system suitability test were as follows: chromatographic column: Diamonsil Plus 5μm C18, 4.6×150mm; mobile phase: acetonitrile: water (80:20); flow rate: 0.8mL / min; column temperature: 25℃; detection wavelength: 450nm; injection volume: 10μL.

[0127] Accurately weigh an appropriate amount of the mixed sample (containing about 2 mg of fucoxanthin) into a 50 mL brown volumetric flask, add 3 mL of water, and ultrasonically treat for 5 minutes. Then add about 30 mL of anhydrous ethanol and ultrasonically extract again for 10 minutes. Cool to room temperature, dilute to the mark with anhydrous ethanol, and shake well. Accurately pipette 1 mL of the above solution, dilute to 20 mL with anhydrous ethanol, shake well, and filter through a 0.45 μm filter membrane.

[0128] The standard working solution and sample solution were measured and the chromatograms were recorded according to the above instrument conditions. The standard solution and sample solution were injected into the high performance liquid chromatograph respectively, and the standard working curve was drawn with the peak area of ​​the standard solution versus the mass concentration. The fucoxanthin was qualitatively determined according to the retention time, and the peak area of ​​the sample solution was compared with the standard curve for quantitative determination.

[0129] 3.3.6 Vitamin K2

[0130] Determined by high performance liquid chromatography (GB 5009.290).

[0131] 3.4 Detection methods of phospholipid components

[0132] Phosphatidylcholines (PC) and phosphatidylethanolamines (PE) in phospholipids were determined by high performance liquid chromatography (General Rule 0512).

[0133] Chromatographic conditions: silica gel was used as filler (chromatographic column Alltima Sillica, 250mm×4.6mm×5µm), column temperature was 40°C; methanol-water-glacial acetic acid-triethylamine (85:15:0.45:0.05, V / V) was used as mobile phase A, and n-hexane-isopropanol-mobile phase A (20:48:32, V / V) was used as mobile phase B; flow rate was 1 mL per minute; gradient elution was performed as shown in the table below, and mobile phase chromatographic conditions are shown in Table 1; the detector was an evaporative light scattering detector (reference conditions: drift tube temperature was 72°C; carrier gas flow rate was 2.0 mL per minute).

[0134] surface Mobile phase for phospholipid PC and PE detection

[0135]

[0136] Take appropriate amount of PC and PE reference substances, dissolve them in chloroform-methanol (2:1, V / V) to prepare a mixed solution containing 50µg, 100µg and 200µg of the above reference substances per 1mL. Take 20µL of the above solution and inject it into the liquid chromatograph. The components are eluted in the above order. The separation degree of each component should meet the requirements. The number of theoretical plates calculated for PC and PE should not be less than 1500.

[0137] Determination method: Weigh an appropriate amount of PC and PE reference substances respectively, weigh accurately, dissolve with chloroform-methanol (2:1, V / V), and draw a standard curve. Accurately measure 20µL of each of the above reference substance solutions and inject it into the liquid chromatograph, record the chromatogram, and calculate the regression equation with the logarithm of the concentration of the reference substance solution and the logarithm of the corresponding peak area. Accurately weigh about 15mg of this product, place it in a 50mL volumetric flask, add chloroform-methanol (2:1, V / V) to dissolve and dilute to the scale. Take 20µL of the test solution and inject it into the liquid chromatograph, record the chromatogram, and calculate the content of PC and PE by the regression equation.

[0138] 3.5 Micellar conversion experiment

[0139] By simulating the digestion and absorption in the oral cavity and gastrointestinal tract, the digestion and absorption of the oil solution containing effective ingredients in the body, namely the micelle conversion rate, is evaluated.

[0140] The specific operation is as follows: sterilize the oil solution sample at 90℃ for 30min, weigh a sample containing 50mg of the active ingredient, add purified water to 5g to prepare the test solution; prepare simulated saliva (SSF), gastric juice (SGF) and intestinal juice (SIF), and add the corresponding enzymes, namely oral mucosal protein (saliva); pepsin (gastric juice); and pancreatic enzyme, pancreatic lipase, bile salt (intestinal juice). Adjust the pH of saliva to 6.8, the pH of gastric juice to 3.0, and the pH of intestinal juice to 7.0, and activate at 37.2℃ for one hour before use. The test solution was added to 4 mL of simulated saliva to simulate the oral digestive environment pH of 6.8. Oral digestion was completed by constant temperature oscillation at 37°C for 10 min. 8 mL of simulated gastric juice was added to the digestive solution after simulated saliva digestion, the pH of the simulated gastric digestive environment was 3.0, the temperature was constantly controlled at 37°C, and the incubation time was 1 h, which completed the simulated gastric digestion. 16 mL of simulated intestinal juice was added to the digestive solution after simulated gastric digestion, the pH of the simulated intestinal digestive environment was 7.0, and the incubation time was 2 h. During this period, the pH value was dynamically adjusted to maintain the pH at 7.0, which completed the simulated intestinal digestion. Finally, the reaction was terminated in an ice bath, and the upper clear liquid was obtained by centrifugation at 14,000 rpm for 30 min, which was the micelle layer.

[0141] The content before digestion is the actual content of the active ingredient before the in vitro digestion experiment; the content before digestion and in the micellar layer are both tested according to the method in 3.3.

[0142] surface Digestive juice formula

[0143]

[0144] Calculation formula:

[0145] Micellar conversion rate = content of active ingredients in the micelle layer / content of active ingredients before digestion * 100%

[0146] The content in the formula is expressed as the amount of the substance of the effective ingredient. Multiple effective ingredients can be superimposed, and the unit is mol.

[0147] 3.6 Effects on intestinal digestion

[0148] The sample was digested by the method of 3.5, and the state (severity of stratification) after two hours of intestinal digestion was the intestinal digestion effect. Figure 2 As shown, the degree of division increases from the left to the right.

[0149] The evaluation indicators are as follows: Figure 2 From left to right):

[0150] *: Indigestible, severe stratification;

[0151] **: Incomplete digestion, with floating oil;

[0152] ***: Complete digestion.

[0153] 3.7 Peroxide value determination method

[0154] The peroxide value is measured according to the first method of GB 5009.227. Weigh 2-3 g of the sample (accurate to 0.001 g), place it in a 250 mL iodine volumetric flask, add 30 mL of chloroform-glacial acetic acid (2:3, V / V) solution, and fully dissolve it. Accurately add 1.00 mL of saturated potassium iodide solution, plug the bottle cap tightly, shake gently for 0.5 min, and place it in the dark for 3 min. Take it out and add 100 mL of water. After shaking well, immediately titrate the precipitated iodine with sodium thiosulfate standard titration solution. When the titration reaches light yellow, add 1 mL of starch indicator, continue titration and shake vigorously until the blue color of the solution disappears as the end point. Perform a blank experiment at the same time. The volume of sodium thiosulfate standard titration solution consumed in the blank test shall not exceed 0.1 mL.

[0155] Calculation formula: X1=(V-V0)*c*0.1269*100 / m

[0156] X1: peroxide value, in g / 100g;

[0157] V: sodium thiosulfate standard titration solution consumed by the sample, in mL;

[0158] V0: volume of sodium thiosulfate standard solution consumed in blank test, in mL;

[0159] c: concentration of sodium thiosulfate standard titration solution, in mol / L;

[0160] 0.1269: The mass of iodine equivalent to 1.00 mL of sodium thiosulfate, in g / mmol;

[0161] m: sample mass, in g;

[0162] 100: Conversion factor for 100g sample.

[0163] Example 1: Effects of different saturation oils on coenzyme oil solution

[0164] Samples were prepared according to the formula in Table 3 (in parts by weight, where the percentages of PC and PE in phospholipids are mass percentages), using oils with different saturations to evaluate the low temperature stability, viscosity, micelle conversion rate, and peroxide value of the amorphous coenzyme Q10 oil solution.

[0165] The results showed that among fatty acids with 3-7 unsaturations, the oil solution of coenzyme Q10 had high micelle conversion rate and low temperature stability.

[0166] Under a specific composition, the intermolecular forces reach a balanced state, thus obtaining a stable coenzyme Q10 oil solution system without precipitation crystals. For saturated fatty acids and fatty acids with an unsaturation index of less than 3, there are no sp hybrid orbitals or the number of sp hybrid orbitals is insufficient to accept electrons from the coenzyme and phospholipids, and the intermolecular forces cannot be balanced. The instability of the system makes it impossible for coenzyme Q10 to be effectively converted into micelles in the intestines, inhibiting the absorption of coenzyme Q10. Due to the low solubility of coenzyme Q10 in oils and fats, crystals will precipitate in oil solutions with unbalanced intermolecular forces, which is manifested as poor low-temperature stability, low micelle conversion rate, and increased viscosity and peroxide value.

[0167] In the oil-soluble system of coenzyme Q10, fatty acids with an unsaturation degree of 3-7 have enough sp hybrid orbitals to accept electrons from coenzyme Q10 and phospholipids, so that the intermolecular forces of the entire oil-soluble system reach a balanced state, thereby improving the efficiency of converting the coenzyme Q10 oil solution into micelles. The unsaturated bonds also play a synergistic role in the energy conversion during the digestion process, promoting the absorption of coenzyme Q10 in the small intestine. The balance of intermolecular forces in the oil system also greatly reduces the freezing point of coenzyme Q10, improving its stability at low temperatures, which is manifested in high low-temperature stability and micelle conversion rate, and reduced viscosity and peroxide value.

[0168] surface Effects of different saturation oils on coenzyme oil solution

[0169]

[0170] Example 2: Effect of the conjugation number of unsaturated oil on coenzyme oil solution

[0171] Samples were prepared according to the formula in Table 4 (in parts by weight, where the percentages of PC and PE in phospholipids are mass percentages), using unsaturated oils with different conjugation numbers, to evaluate the low temperature stability, viscosity, micelle conversion rate, and peroxide value of the coenzyme Q10 oil solution.

[0172] The results showed that in non-conjugated fatty acids (conjugation number is 0) or conjugated fatty acids with a conjugation number less than 2, the oil solution of coenzyme Q10 has a high micelle conversion rate and low-temperature stability.

[0173] In the composition, the intermolecular force balance is achieved under the unsaturated oil composition with a specific conjugation number. When the unsaturated oil is conjugated, the energy of the electron transition is low, the distance between the energy levels of the large π bond is close, and the electron is easily excited. When the conjugation number is greater than 1, it is difficult for the unsaturated oil and coenzyme and phospholipid to form an intermolecular force balance effect. The instability of the system makes it impossible for coenzyme Q10 to be effectively converted into micelles in the intestine, inhibiting the absorption of coenzyme Q10. Due to the low solubility of coenzyme Q10 in oil, crystals will precipitate in the oil solution with unbalanced intermolecular forces, which is manifested as poor low-temperature stability, low micelle conversion rate, and increased viscosity and peroxide value.

[0174] In the oil-soluble system of coenzyme Q10, the sp hybrid orbitals and π bonds of unsaturated fatty acids with a conjugation number of 0-1 can accept electrons from the coenzyme and phospholipids, so that the intermolecular forces of the entire oil-soluble system reach a state of equilibrium, thereby improving the efficiency of the conversion of the coenzyme Q10 oil solution into micelles and promoting its absorption. The stability of the intermolecular forces of the entire system greatly reduces the freezing point of coenzyme Q10, allowing the system to remain in a precipitation-free state at low temperatures, which is manifested in high low-temperature stability and micelle conversion rate, and reduced viscosity and peroxide value.

[0175] surface Effects of different oils and fats on coenzyme oil solution

[0176]

[0177] Example 3: Effect of different emulsifier ratios on coenzyme oil solution

[0178] Samples were prepared according to the formula in Table 5 (in parts by weight, where the percentages of PC and PE in phospholipids are in mass percentages), using different types of emulsifiers, and the low temperature stability, viscosity, micelle conversion rate, and peroxide value of the coenzyme Q10 oil solution were evaluated.

[0179] The results show that common emulsifiers, such as monoglycerides, polysaccharides, polysorbate 80, modified starch, and sucrose esters, cannot make the oil-soluble system of coenzyme Q10 produce high micelle conversion rate and low-temperature stability. This shows that the composition of the present application is not a simple emulsification or self-emulsification effect. The use of the above common emulsifiers shows poor low-temperature stability, low micelle conversion rate, and increased viscosity and peroxide value.

[0180] Phospholipids are rich in unsaturated bonds. In the oil-soluble system of coenzyme Q10, they have sufficient sp hybrid orbitals to maintain the balance of intermolecular forces, improve the efficiency of converting coenzyme Q10 oil solution into micelles, promote its absorption, and enhance its stability under low temperature conditions, which is manifested in high low-temperature stability and micelle conversion rate, and reduced viscosity and peroxide value.

[0181] The composition of the present application is not prepared by emulsification or self-emulsification technology, but by balancing the intermolecular forces between specific compositions so that the oil solution of coenzyme Q10 has a high micelle conversion rate and low-temperature stability.

[0182] surface Effects of different emulsifiers on coenzyme oil solution

[0183]

[0184] Example 4: Effect of different PC contents in phospholipids on coenzyme oil solution

[0185] Samples were prepared according to the formula in Table 6 (in parts by weight, where the percentages of PC and PE in phospholipids are mass percentages), wherein phospholipids with different PC contents were used to evaluate the low temperature stability, viscosity, micelle conversion rate, and peroxide value of the coenzyme Q10 oil solution.

[0186] The results showed that when the PC content of phospholipids was in the ratio of 45-65%, the oil solution of the coenzyme had a high micelle conversion rate and low-temperature stability.

[0187] Since PC contains unsaturated bonds, it is the main component in phospholipids that provides sp hybrid orbitals, which improves the efficiency of converting coenzyme Q10 oil solution into micelles and promotes its absorption. When the PC content of phospholipids reaches 45-65%, the balance of intermolecular forces is achieved, and the stability of the composition under low temperature conditions is enhanced, which is manifested in high low temperature stability and micelle conversion rate, and reduced viscosity and peroxide value.

[0188] surface Effects of phospholipids with different PC contents on coenzyme oil solutions

[0189]

[0190] Example 5: Effect of coenzyme oil solution at different PE contents

[0191] Samples were prepared according to the formula in Table 7 (in parts by weight, where the percentages of PC and PE in phospholipids are in mass percentages), wherein phospholipids with different PE contents were used to evaluate the low temperature stability, viscosity, micelle conversion rate, and peroxide value of the coenzyme Q10 oil solution.

[0192] The results showed that when the PE content of phospholipids was greater than 20%, the oil solution of coenzyme Q10 did not have high micelle conversion rate and low temperature stability. When the PE content of phospholipids was below 20%, the oil solution of coenzyme Q10 had high micelle conversion rate and low temperature stability.

[0193] Since PE does not have unsaturated bonds, its amino group is an electron-donating group, which is not conducive to the balance of electrons in the system. Therefore, when the PE content is too high, it is not conducive to the stability of the system, which is manifested in poor low-temperature stability, low micelle conversion rate, and increased viscosity and peroxide value.

[0194] When the PE content of phospholipids is below 20%, the oil solution of the coenzyme reaches a balance of intermolecular forces, has a high micelle conversion rate and low-temperature stability, which is manifested in high low-temperature stability and micelle conversion rate, and reduced viscosity and peroxide value.

[0195] surface Effects of different PE contents on coenzyme oil solution

[0196]

[0197] Example 6: Effects of different coenzyme ratios on coenzyme oil solution

[0198] Samples were prepared according to the formula in Table 8 (in parts by weight, where the percentages of PC and PE in phospholipids are mass percentages). The compositions used different coenzyme Q10 contents to evaluate the low temperature stability, viscosity, micelle conversion rate, and peroxide value of the coenzyme Q10 oil solution.

[0199] The results showed that at a specific coenzyme content, the coenzyme oil solution had low-temperature stability and high micelle conversion rate.

[0200] Because coenzyme Q10 has a long side chain composed of benzoquinone and isoprene units, its unsaturated bonds can achieve molecular balance with unsaturated fatty acids and phospholipids at a specific ratio, which is manifested as high low-temperature stability and micelle conversion rate, and reduced viscosity and peroxide value.

[0201] surface Effect of Coenzyme Q10 Oil Solution at Different Coenzyme Ratios

[0202]

[0203] Example 7: Effect of different phospholipid ratios on coenzyme oil solution

[0204] Samples were prepared according to the formula in Table 9 (in parts by weight, where the percentages of PC and PE in phospholipids are in mass percentages), wherein the low temperature stability, viscosity, micelle conversion rate, and peroxide value of the coenzyme Q10 oil solution were evaluated at different ratios of phospholipids (PC content 65%, PE content 10%).

[0205] The results showed that at a specific phospholipid content, the oil solution of the coenzyme had low-temperature stability and a high micelle conversion rate.

[0206] Only when the phospholipid content is at a specific ratio can the coenzyme oil solution achieve a balance of intermolecular forces and obtain a coenzyme Q10 oil solution system with high micelle conversion rate and low-temperature stability, which is manifested by high low-temperature stability and micelle conversion rate, and reduced viscosity and peroxide value.

[0207] surface Effects of different phospholipid ratios on coenzyme Q10 oil solution

[0208]

[0209] Example 8: Application of different functional ingredients

[0210] Samples were prepared according to the formula in Table 10 (in parts by weight, where the percentages of PC and PE in phospholipids are in mass percentages), in which different types of functional ingredients were included, and the low-temperature stability, viscosity, micelle conversion rate, and peroxide value of the oil solution were evaluated.

[0211] like Figure 4 As shown, the results show that astaxanthin, lutein, β-carotene, fucoxanthin, vitamin K2 and other effective ingredients rich in unsaturated olefins and electron-withdrawing groups can replace coenzyme Q10 to form an oil solution with high micelle conversion rate and low-temperature stability, which is manifested by high low-temperature stability and micelle conversion rate, and reduced viscosity and peroxide value.

[0212] surface Application of different functional ingredients

[0213]

[0214] Example 9: Effect of additives on coenzyme oil solution

[0215] Samples were prepared according to the formulas in Tables 11-12 (in parts by weight, where the percentages of PC and PE in phospholipids are in mass percentages). Table 11 added PQQ, rosemary extract, curcumin, xanthan gum and other additives in addition to the functional ingredients. Table 12, based on the additive ratio in Table 11, adjusted the number of additives or reduced the number of phospholipids to evaluate the low temperature stability, viscosity, micelle conversion rate and peroxide value of the oil solution.

[0216] The results in Tables 11 and 12 show that additives such as PQQ, rosemary extract, curcumin, and xanthan gum can also form an oil solution with high micelle conversion rate and low-temperature stability through compound mixing with other ingredients, which is characterized by high low-temperature stability and micelle conversion rate, and reduced viscosity and peroxide value.

[0217] The results in Table 12 show that when the content of the additive does not exceed 20% of the phospholipid content, the oil solution of coenzyme Q10 has a high micelle conversion rate and low-temperature stability.

[0218] Lecithin is a two-way emulsifier that has a buffering and balancing effect on the forces between molecules in the system. When the amount of additives is increased or the amount of lecithin is reduced, the adjustment limit of lecithin is exceeded, and the intermolecular forces of the oil system cannot reach a balance, which manifests as poor low-temperature stability, low micelle conversion rate, and increased viscosity and peroxide value.

[0219] surface -12 Effect of additives on coenzyme oil solution

[0220] Table 11

[0221]

[0222] Table 12

[0223]

[0224] Although the present invention has been described with reference to illustrative embodiments, it will be appreciated by those skilled in the art that various other changes, omissions and / or additions may be made and that elements of the described embodiments may be substituted with substantial equivalents without departing from the spirit and scope of the present invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the present invention without departing from the scope of the present invention. Therefore, it is not intended herein to limit the present invention to the specific disclosed embodiments for carrying out the present invention, but rather it is intended that the present invention will include all embodiments within the scope of the appended claims.

Claims

1. An oil-soluble composition comprising: The effective ingredient has a content of 25 parts by weight or less; Phospholipids, in an amount of 1-10 parts by weight, preferably 2-8 parts by weight or 1-5 parts by weight; and Unsaturated fatty acids, in, The functional component has unsaturated olefins and electron-withdrawing groups.

2. The oil-soluble composition of claim 1, wherein the effective ingredient is selected from the group consisting of coenzyme Q10, astaxanthin, lutein, β-carotene, fucoxanthin, vitamin K2 and dihydroquercetin; Preferably, the content of the effective ingredient is 1-25 parts by weight, 1-20 parts by weight, 1-15 parts by weight or 1-10 parts by weight; Preferably, the weight percentage of the effective ingredient is less than 25% or less than 23%.

3. The oil-soluble composition according to claim 1 or 2, wherein the phosphatidylcholine content in the phospholipids is 40-70% and the phosphatidylethanolamine content is less than 20%; Preferably, the phosphatidylcholine content in the phospholipids is 45-65% or 55-65%, and / or the phosphatidylethanolamine content is 5-15% or 5-10%.

4. The oil-soluble composition according to any one of claims 1 to 3, wherein the degree of unsaturation of the unsaturated fatty acid is 3 to 7, and / or the degree of conjugation of the unsaturated fatty acid is 0 or 1, Preferably, the content of unsaturated fatty acids is 65-97 parts by weight, 72-90 parts by weight or 75-80 parts by weight; Preferably, the unsaturated fatty acid is selected from monostearin, arachidic acid, hexadecatrienoic acid, nervonic acid, linoleic acid (eg conjugated linoleic acid, 9c,11t-conjugated linoleic acid), arachidonic acid (eg conjugated arachidonic acid) and docosahexaenoic acid (eg conjugated docosahexaenoic acid).

5. The oil-soluble composition according to any one of claims 1 to 4, further comprising an additive selected from the group consisting of flavors, pigments, antioxidants, nutritional enhancers, colloids and syrups; Preferably, the additive is selected from pyrroloquinoline quinone, rosemary extract, curcumin and xanthan gum; Preferably, the content of the additive does not exceed 20% of the phospholipid content.

6. The oil-soluble composition according to any one of claims 1 to 5, which does not contain an emulsifier, and the emulsifier is Tween (eg polysorbate 80).

7. A method for preparing the oil-soluble composition according to any one of claims 1 to 6, comprising heating the effective ingredient, phospholipids and unsaturated fatty acids at 55-75° C. and mixing them thoroughly, Preferably, the method further comprises passing the obtained mixed oil solution through a homogenizer, Preferably, the method further comprises adding the additive to the obtained oil system.

8. A soft capsule comprising the oil-soluble composition according to any one of claims 1 to 6.

9. A gel comprising the oil-soluble composition according to any one of claims 1 to 6 and a gelling agent, preferably, the gelling agent is selected from xanthan gum, gum arabic, konjac gum, guar gum, carrageenan, locust bean gum, pectin and gelatin, Preferably, the gel is an oil gel or a gel candy.

10. Use of the oil-soluble composition according to any one of claims 1 to 6, the soft capsule according to claim 8 or the gel according to claim 9 in food, medicine or cosmetics; preferably, the food is a health food.

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