A coenzyme Q10 oil preparation and its preparation method and application

Abstract

The present invention belongs to the field of coenzyme Q10 technology and relates to a coenzyme Q10 oil, a preparation method thereof, and an application thereof. The coenzyme Q10 oil contains the following components in percentage by mass: 20-40% coenzyme Q10, 45-65% mixed oil, 10-15% biphasic emulsifier, and 0-3% optional antioxidant; the coenzyme Q10 in the coenzyme Q10 oil exists in a molecular form above 0°C; the mixed oil contains both saturated fatty acids (esters) and unsaturated fatty acids (esters); the biphasic emulsifier contains both a hydrophilic emulsifier and a lipophilic emulsifier. The coenzyme Q10 in the coenzyme Q10 oil provided by the present invention can still stably exist in a molecular form at high content, and has high bioavailability.

Description

Technical Field

[0001] The present invention belongs to the technical field of coenzyme Q10, and in particular relates to a coenzyme Q10 oil preparation and a preparation method and application thereof. Background Art

[0002] Coenzyme Q10 (CoQ10) is a biopharmaceutical that is essential for energy production in the human body. Found in the cell membranes of various organs, it can improve myocardial metabolism and enhance cardiac function. Coenzyme Q10 also possesses excellent antioxidant and free radical scavenging properties, preventing lipid peroxidation in blood vessel walls, preventing atherosclerosis, and boosting immunity. As a fat-soluble vitamin, Coenzyme Q10's insolubility in water makes it difficult for the human body to digest and absorb. While it can be diluted and dissolved in oil, its limited solubility in oil and its crystalline state make it ineffective, often requiring excessive Coenzyme Q10 dosage to achieve the desired effect.

[0003] Most Coenzyme Q10 soft capsules currently on the market use relatively simple vegetable oils, such as soybean oil, corn oil, and sunflower oil, as a dissolving agent. This not only has limited efficacy, but Coenzyme Q10 itself has low solubility in vegetable oils and is prone to crystallization, which limits its content in the product. Furthermore, Coenzyme Q10 in existing Coenzyme Q10 soft capsules is primarily crystalline, with extremely poor water solubility and low bioavailability in the human body. To achieve the desired effect, large amounts of Coenzyme Q10 must be supplemented, which is uneconomical. Summary of the Invention

[0004] The present invention aims to overcome the defects of existing coenzyme Q10 products, such as the tendency of coenzyme Q10 to precipitate in a crystalline state, making it impossible to use it at high concentrations and having poor bioavailability, and to provide a new coenzyme Q10 oil preparation and its preparation method and application. The coenzyme Q10 in the coenzyme Q10 oil preparation can still exist stably in a molecular form at high concentrations and has high bioavailability.

[0005] During the wet grinding process, the common practice in the art is to grind the crystals to a particle size as small as possible to facilitate their dissolution in the solvent. However, the inventors of the present invention surprisingly discovered during their research that the particle size of coenzyme Q10 crystals is not necessarily the smaller the better, and that the particle size does not show a positive proportional relationship with the dissolution effect of the oil. When the particle size of coenzyme Q10 crystals is ground to D 50When the particle size is 50-120nm, its dissolution effect in the solvent is the best. When the particle size is further reduced, the dissolution effect is significantly worse. After in-depth and extensive research, the inventors of the present invention also found that compared with a single oil, the compounding of saturated fatty acids (esters) and unsaturated fatty acids (esters) can not only promote the disappearance of coenzyme Q10 crystals under negative pressure conditions, so that it exists in molecular form, but also the mixed oil and coenzyme Q10 can produce unexpected synergistic effects in anti-aging, which is more conducive to the biological activity of coenzyme Q10. In addition, the use of a two-phase emulsifier can give the coenzyme Q10 oil both hydrophilic and lipophilic properties, thereby changing the inherent water-insoluble and slightly oil-soluble properties of coenzyme Q10, so that coenzyme Q10 can be stably dispersed in both water and oil systems, thereby further expanding the application range of coenzyme Q10, so that it can be used in various foods, cosmetics, health products or medicines. In summary, the coenzyme Q10 crystals are ground to D 50 The invention was completed based on the specific particle size range of 50-120 nm. The mixed oil and biphasic emulsifier dissolves the coenzyme Q10 in a negative pressure solution, achieving molecular dissolution at temperatures below the melting point while maintaining stability and preventing crystallization. This results in a high-content, stable, non-crystallizable, molecularly stable coenzyme Q10 oil with high bioavailability.

[0006] Specifically, the present invention provides a coenzyme Q10 oil, which contains the following components in percentage by weight: 20-40% coenzyme Q10, 45-65% mixed oil, 10-15% biphasic emulsifier, and 0-3% optional antioxidant; the coenzyme Q10 in the coenzyme Q10 oil exists in molecular form above 0°C; the mixed oil contains both saturated fatty acids (esters) and unsaturated fatty acids (esters); and the biphasic emulsifier contains both a hydrophilic emulsifier and a lipophilic emulsifier.

[0007] The present invention also provides a method for preparing the coenzyme Q10 oil, which comprises grinding coenzyme Q10 crystals in the presence of an oil mixture I and a two-phase emulsifier to reduce the particle size D of the coenzyme Q10 crystals to 0. 50 The particle size is reduced to 50-120 nm, and then the obtained fine grinding liquid and oil mixture II are mixed evenly under negative pressure to obtain coenzyme Q10 oil; the oil mixture I and oil mixture II are both mixtures of mixed oils and optional antioxidants.

[0008] The preparation method of the coenzyme Q10 oil provided by the present invention relies on the dual regulation of the dissolution-promoting ability of the mixed oil and the interaction between the components, and the size effect brought about by the specific particle size, so that the crystals of coenzyme Q10 disappear, so that it exists stably in molecular form, thereby giving full play to its biological activity. In the coenzyme Q10 oil provided by the present invention, coenzyme Q10 is in a molecular state, its molecules are arranged in a disordered manner, and the lattice energy overcome during the dissolution or dissolution process is relatively low, which is conducive to entering the body fluids of the human body and enhancing bioavailability. In addition, the molecular state of a simple drug is only short-lived, and crystals are easily precipitated after a period of time. The present invention stabilizes the molecular state of coenzyme Q10 from the formula and preparation method, thereby prolonging its crystallization precipitation.

[0009] In addition, the present invention also provides the use of the coenzyme Q10 oil in the preparation of cosmetics, health products or medicines.

[0010] The beneficial effects of the present invention are as follows:

[0011] (1) The coenzyme Q10 oil provided by the present invention has a high coenzyme Q10 content, which can reach up to 40%. Even at such a high content, it can still remain stable. Coenzyme Q10 crystallization will not occur above 0°C, which is conducive to digestion and absorption. It does not need to be melted again when used, which is particularly conducive to the preparation and storage of soft capsules. After being prepared into soft capsules as contents, solid crystals will not precipitate due to changes in the environment, causing difficulties in human absorption.

[0012] (2) In the coenzyme Q10 oil provided by the present invention, the mixed oil has a good solubility for coenzyme Q10, and the combination of coenzyme Q10 and the mixed oil in a certain proportion can exert an unexpected synergistic effect. Compared with a single oil, the anti-aging effect is more significant. The combination of the two is stable, does not cause chemical reactions, has no adverse reactions, and is safe and feasible.

[0013] In a preferred embodiment, when the grinding method comprises mixing the coenzyme Q10 crystals with the oil mixture I and then performing a first stage grinding, the particle size D of the coenzyme Q10 crystals is reduced to 50 The particle size of the coenzyme Q10 crystals in the initial grinding solution is reduced to 0.2-1 μm, and then the initial grinding solution is mixed with a two-phase emulsifier and the second stage of grinding is carried out to reduce the particle size D of the coenzyme Q10 crystals in the initial grinding solution to 0.2-1 μm. 50 On the one hand, this method forms a gentle and efficient crystallization refinement effect through two-stage low-temperature grinding, which solves the problem of difficulty in preparation caused by electrostatic adsorption and low melting point, and can reach the required particle size range in a shorter grinding time, which can shorten the grinding time from more than 7 hours in a conventional single-cycle grinding to less than 3 hours; on the other hand, the timing of adding emulsifier is grasped, and the particle size D of coenzyme Q10 crystallization is reduced to 50-120nm. 50After the particle size is reduced to 0.2-1 μm, a two-phase emulsifier is added separately, which is beneficial to improving the emulsification and embedding effects. This method can achieve secondary embedding of coenzyme Q10 by the emulsifier, and further protect the crystallization. It can not only avoid crystallization caused by collision of materials due to high-speed mechanical movement during the grinding process, but also be more conducive to reducing the coenzyme Q10 crystals to the target particle size. It can also enable coenzyme Q10 to exist stably in molecular form for a long time, prolong the time of crystallization precipitation, and be more conducive to its biological activity. DETAILED DESCRIPTION

[0014] In the present invention, the coenzyme Q10 oil contains coenzyme Q10, mixed oils and fats, and a two-phase emulsifier, and may further contain an antioxidant. Based on the total weight of the coenzyme Q10 oil, the content of coenzyme Q10 is 20-40%, such as 20%, 22%, 25%, 28%, 30%, 32%, 35%, 38%, 40% or any value therebetween; the content of the mixed oil is 45-65%, such as 45%, 48%, 50%, 52%, 55%, 58%, 60%, 62%, 65% or any value therebetween; the content of the two-phase emulsifier is 10-15%, such as 10%, 11%, 12%, 13%, 14%, 15% or any value therebetween; the content of the antioxidant is 0-3%, such as 0, 0.1%, 0.5%, 0.8%, 1%, 1.5%, 2%, 2.5%, 3% or any value therebetween.

[0015] In the present invention, the coenzyme Q10 in the coenzyme Q10 oil exists in a molecular form at a temperature above 0° C., that is, the coenzyme Q10 is completely dissolved in the oil and exists in an amorphous form.

[0016] In the present invention, the mixed oil contains saturated fatty acids (esters) and unsaturated fatty acids (esters) at the same time. The term "saturated fatty acids (esters)" refers to saturated fatty acids and / or saturated fatty acid esters. The term "unsaturated fatty acids (esters)" refers to unsaturated fatty acids and / or unsaturated fatty acid esters. In a preferred embodiment, the mass ratio of saturated fatty acids (esters) to unsaturated fatty acids (esters) in the mixed oil is 1:(1-2.5), such as 1:1, 1:1.2, 1:1.5, 1:1.8, 1:2, 1:2.2, 1:2.5 or any value therebetween. In a preferred embodiment, the mass ratio of saturated fatty acids (esters), monounsaturated fatty acids (esters) and polyunsaturated fatty acids (esters) in the mixed oil is 1:(0-1.5):(1-1.5). Based on 1 part by weight of the saturated fatty acid (ester), the content of the monounsaturated fatty acid (ester) is 0-1.5 parts by weight, such as 0, 0.2, 0.5, 0.8, 1, 1.2, 1.5 parts by weight, or any value therebetween; the content of the polyunsaturated fatty acid (ester) is 1-1.5 parts by weight, such as 1, 1.1, 1.2, 1.3, 1.4, 1.5 parts by weight, or any value therebetween. The inventors of the present invention have discovered that when the oil is compounded and used in the above manner, it is not only more conducive to promoting the dissolution of coenzyme Q10 crystals, allowing them to exist stably in molecular form, but also more conducive to the biological activity of coenzyme Q10.

[0017] In the present invention, the saturated fatty acid (ester) is preferably a saturated fatty acid glyceride, such as at least one of palmitic triglyceride, stearic acid glyceride, caprylic acid glyceride, capric acid glyceride, caprylic acid glyceride, and lauric acid glyceride. Specific examples of the monounsaturated fatty acid (ester) include, but are not limited to, at least one of oleic acid, myristoleic acid, and palmitoleic acid. Specific examples of the polyunsaturated fatty acid (ester) include, but are not limited to, at least one of α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, conjugated linoleic acid, γ-linolenic acid, and arachidonic acid.

[0018] In the present invention, the biphasic emulsifier contains both a hydrophilic emulsifier and a lipophilic emulsifier. The weight ratio of the hydrophilic emulsifier to the lipophilic emulsifier is preferably (1.5-4):1, such as 1.5:1, 1.8:1, 2:1, 2.2:1, 2.5:1, 2.8:1, 3:1, 3.2:1, 3.5:1, 3.8:1, 4:1, or any value therebetween. When the hydrophilic and lipophilic emulsifiers are compounded and used in the above preferred manner, the water- and oil-soluble properties of Coenzyme Q10 can be well balanced, which is more conducive to the stable dispersion of Coenzyme Q10 in both oil-water systems and has broader application prospects.

[0019] In the present invention, specific examples of the hydrophilic emulsifier include, but are not limited to, at least one of sucrose esters with an HLB value of 13-16, Tween, polyglycerol fatty acid esters, and poloxamers. The Tween may be at least one of Tween 20, Tween 40, Tween 60, and Tween 80. The polyglycerol fatty acid ester may be at least one of polyglycerol ester ML-500, polyglycerol ester CR-200, and polyglycerol ester ML-750. The poloxamer may be at least one of poloxamer 124, poloxamer 168, and poloxamer 188.

[0020] In the present invention, specific examples of the lipophilic emulsifier include, but are not limited to, at least one of sucrose esters with an HLB value of 3-6, phospholipids, Span, and monoglycerides. The phospholipids include, for example, at least one of lecithin, soybean lecithin, and hydrogenated lecithin. The Span includes, for example, at least one of Span 20, Span 40, Span 60, and Span 80. The monoglyceride includes, for example, at least one of glyceryl monostearate, monoglyceryl lactate, monoglyceryl succinate, monoglyceryl citrate, monoglyceryl oleate, and diacetyltartaric acid monoglyceride.

[0021] In the present invention, the antioxidant can be any of the existing substances that can effectively prevent the active ingredients from being oxidized, and specific examples thereof include but are not limited to at least one of vitamin E, tocopherol, rosemary extract, and tea polyphenol extract.

[0022] The preparation method of the coenzyme Q10 oil provided by the present invention comprises grinding the coenzyme Q10 crystals in the presence of an oil mixture I and a two-phase emulsifier to reduce the particle size D of the coenzyme Q10 crystals to 0. 50 The particle size is reduced to 50-120 nm, and then the obtained fine grinding liquid and oil mixture II are mixed evenly under negative pressure to obtain coenzyme Q10 oil; the oil mixture I and oil mixture II are both mixtures of mixed oils and optional antioxidants.

[0023] Coenzyme Q10 crystal particles are large, and a temperature higher than the melting point of coenzyme Q10 is required to achieve molecular dissolution. However, a high processing temperature is not only not conducive to protecting the activity of coenzyme Q10, but also coenzyme Q10 is prone to agglomeration due to uneven heating at high temperatures, which is not conducive to improving its bioavailability. 50Within the particle size range of 50-120nm, molecular dissolution can be achieved under negative pressure at a temperature below the melting point of Coenzyme Q10. This not only reduces the burden on equipment and saves energy, but also reduces the damage to the material caused by high temperatures. Furthermore, Coenzyme Q10 crystals have strong oil absorption capacity and soft crystal hardness. Using a mixed oil as a dispersant achieves excellent dissolution and dispersion effects, preventing Coenzyme Q10 from agglomerating during the grinding process, maintaining the relative stability of the dispersed system, and preventing it from tightly adhering to the inside of the grinder, causing wasteful feeding and difficult cleaning.

[0024] Coenzyme Q10 crystals have strong electrostatic adsorption, high viscosity, are easily adsorbed on the surface of utensils or auxiliary materials, and have a low melting point (the melting point of coenzyme Q10 crystals is 48°C). Using conventional pulverization methods will easily cause part of the coenzyme Q10 to melt and stick due to the heating of the equipment, causing production difficulties and bringing many inconveniences. Conventional pulverization methods are difficult to reduce the particle size of coenzyme Q10 crystals to D 50 The present invention adopts the following staged grinding method to perfectly solve the above problems.

[0025] In a preferred embodiment, the grinding method comprises the following steps:

[0026] S1. Mix the coenzyme Q10 crystals with the oil mixture I and then grind them in the first stage to reduce the particle size of the coenzyme Q10 crystals to D 50 Reduced to 0.2-1 μm, the primary grinding fluid was obtained;

[0027] S2, after the primary grinding liquid is mixed with the two-phase emulsifier, the second stage of grinding is carried out to reduce the particle size of the coenzyme Q10 crystals in the primary grinding liquid to D 50 Reduced to 50-120nm, a fine grinding liquid was obtained.

[0028] In a preferred embodiment, the method for preparing the coenzyme Q10 oil comprises the following steps:

[0029] S1', stirring and mixing saturated fatty acids (esters), unsaturated fatty acids (esters) and optional antioxidants, and then dividing the resulting oil mixture into two parts: oil mixture I and oil mixture II;

[0030] S2`, after briefly stirring and dispersing the coenzyme Q10 crystals and the oil mixture I, perform the first stage grinding in a ball mill to reduce the particle size of the coenzyme Q10 crystals to D 50 Reduced to 0.2-1 μm, the primary grinding fluid was obtained;

[0031] S3', after the initial grinding liquid and the two-phase emulsifier are simply stirred and dispersed, the second stage of grinding is carried out in a ball mill to reduce the particle size of the coenzyme Q10 crystals in the initial grinding liquid to D 50Reduced to 50-120 nm, a fine grinding solution was obtained;

[0032] S4`, the lapping liquid and the oil mixture II are mixed evenly under negative pressure to obtain the coenzyme Q10 oil.

[0033] In a preferred embodiment, the conditions of the first stage grinding include a working temperature of 0°C-10°C (such as 0°C, 2°C, 4°C, 6°C, 8°C, 10°C or any value therebetween), 70% of the ball particle size is between 0.7-0.9 mm (such as 0.7 mm, 0.8 mm, 0.9 mm or any value therebetween) and 30% is between 0.4-0.6 mm (such as 0.4 mm, 0.5 mm, 0.6 mm or any value therebetween), and the grinding time is 60-90 min (such as 60 min, 65 min, 70 min, 75 min, 80 min, 85 min, 90 min or any value therebetween).

[0034] In a preferred embodiment, the conditions for the second stage grinding include a working temperature of 10°C-20°C (such as 10°C, 12°C, 14°C, 16°C, 18°C, 20°C or any value therebetween), a ball particle size between 0.1-0.3 mm (such as 0.1 mm, 0.2 mm, 0.3 mm or any value therebetween), and a grinding time of 30-90 min (such as 30 min, 35 min, 40 min, 45 min, 50 min, 55 min, 60 min, 65 min, 70 min, 75 min, 80 min, 85 min, 90 min or any value therebetween).

[0035] In a preferred embodiment, the conditions for uniformly mixing the lapping liquid and the oil mixture II under negative pressure include a temperature of 35°C to 40°C, such as 35°C, 36°C, 37°C, 38°C, 39°C, 40°C, or any value therebetween; a pressure of -0.07MPa to -0.1MPa, such as -0.07MPa, -0.06MPa, -0.05MPa, -0.04MPa, -0.03MPa, -0.02MPa, -0.1MPa, or any value therebetween; and a time of 15-25min, such as 15min, 18min, 20min, 22min, 25min, or any value therebetween. In the present invention, the pressure refers to the gauge pressure.

[0036] In a preferred embodiment, the usage ratio of the oil mixture I and the oil mixture II is (65%-95%):(5%-35%), such as 65%:35%, 70%:30%, 75%:25%, 80%:20%, 85%:15%, 90%:10%, 95%:5% or any value therebetween.

[0037] In addition, the present invention also provides the use of the coenzyme Q10 oil in the preparation of cosmetics, health products or medicines.

[0038] The present invention will be described in detail below through examples.

[0039] Example 1 Coenzyme Q10 oil and its preparation method

[0040] (1) The raw materials of the coenzyme Q10 oil in this embodiment are as follows:

[0041] raw material Content (wt%) Coenzyme Q10 crystals 21 Medium chain triglycerides (caprylic / capric triglyceride) 21 Myristic acid 21 Conjugated linoleic acid 21 Soy lecithin 4 Twain-80 2 Polyglycerol Ester ML-500 4 Polyglycerol Ester CR-200 4 Vitamin E 2

[0042] (2) The preparation method of the coenzyme Q10 oil in this embodiment is as follows:

[0043] S1`, stirring and mixing medium chain triglycerides, myristic acid, conjugated linoleic acid and vitamin E to obtain a fat mixture.

[0044] S2', 65% of the oil mixture obtained in step S1' and the coenzyme Q10 crystals were briefly stirred and dispersed, and then added to a ball mill for the first stage of grinding. The ball particle size was 70% between 0.7-0.9 mm and 30% between 0.4-0.6 mm. The working temperature was 10 ° C, and the ball milling time was 60 min to obtain coenzyme Q10 crystal particles with a particle size of D 50 It is the initial grinding liquid of 0.5μm.

[0045] S3', adding soybean lecithin, Tween-80 and polyglycerol ester to the initial grinding liquid of step S2', and then entering the ball mill for the second stage of grinding, the ball particle size is between 0.1-0.3mm, the working temperature is 10℃, and the ball milling time is 45min, to obtain coenzyme Q10 crystal particles with a particle size of D 50 It is a 101nm fine grinding liquid.

[0046] S4`, stirring the grinding liquid and the remaining 35% oil mixture at 38°C and -0.08MPa under negative pressure for 20 minutes until evenly mixed, and then cooling to room temperature to obtain coenzyme Q10 oil, which is encapsulated in soft capsules.

[0047] Example 2 Coenzyme Q10 oil and its preparation method

[0048] (1) The raw materials of the coenzyme Q10 oil in this embodiment are as follows:

[0049] raw material Content (wt%) Coenzyme Q10 crystals 31 Medium chain triglycerides (caprylic / capric triglyceride) 26 Conjugated linoleic acid 31 Soy lecithin 4 Twain-80 2 Polyglycerol Ester ML-750 5 Vitamin E 1

[0050] (2) The preparation method of the coenzyme Q10 oil in this embodiment is as follows:

[0051] S1`, stirring and mixing medium chain triglycerides, conjugated linoleic acid and vitamin E to obtain a fat mixture.

[0052] S2', 80% of the oil mixture obtained in step S1' and the coenzyme Q10 crystals were briefly stirred and dispersed, and then added to a ball mill for the first stage of grinding. The ball particle size was 70% between 0.7-0.9 mm and 30% between 0.4-0.6 mm. The working temperature was 5 ° C, and the ball milling time was 70 minutes to obtain coenzyme Q10 crystal particles with a particle size of D 50 It is the initial grinding liquid of 0.8μm.

[0053] S3', adding soybean lecithin, Tween-80 and polyglycerol ester to the initial grinding liquid of step S2', and then entering the ball mill for the second stage of grinding, the ball particle size is between 0.1-0.3mm, the working temperature is 10℃, and the ball milling time is 55min, to obtain coenzyme Q10 crystal particles with a particle size of D 50 It is a 115nm fine grinding liquid.

[0054] S4`, stirring the grinding liquid and the remaining 20% ​​oil mixture at 37°C and -0.08 MPa under negative pressure for 25 minutes until evenly mixed, and then cooling to room temperature to obtain coenzyme Q10 oil, which is encapsulated in soft capsules.

[0055] Example 3 Coenzyme Q10 oil and its preparation method

[0056] (1) The raw materials of the coenzyme Q10 oil in this embodiment are as follows:

[0057] raw material Content (wt%) Coenzyme Q10 crystals 31 Medium chain triglycerides (caprylic / capric triglyceride) 10 Glyceryl Laurate 6 Palmitoleic acid 16 Docosahexaenoic acid (DHA) 8 Conjugated linoleic acid 16 Sucrose esters (HLB=3-6) 3 Sucrose esters (HLB=13-16) 5 Poloxamer 168 4 Vitamin E 1

[0058] (2) The preparation method of the coenzyme Q10 oil in this embodiment is as follows:

[0059] S1`, stirring and mixing medium chain triglycerides, laurin, DHA, palmitoleic acid, conjugated linoleic acid and vitamin E to obtain a fat mixture.

[0060] S2', 85% of the oil mixture obtained in step S1' and the coenzyme Q10 crystals were briefly stirred and dispersed, and then added to a ball mill for the first stage of grinding. The ball particle size was 70% between 0.7-0.9 mm and 30% between 0.4-0.6 mm. The working temperature was 5 ° C, and the ball milling time was 65 min to obtain coenzyme Q10 crystal particles with a particle size of D 50 It is the initial grinding liquid of 1.0μm.

[0061] S3', add sucrose ester (HLB = 3 ~ 6), sucrose ester (HLB = 13 ~ 16) and poloxamer 168 to the initial grinding liquid of step S2' and then put it into the ball mill for the second stage of grinding, the ball particle size is between 0.1-0.3mm, the working temperature is 10 ° C, the ball milling time is 55min, and the coenzyme Q10 crystal particle size D 50 It is a 120nm fine grinding liquid.

[0062] S4`, stirring the grinding liquid and the remaining 15% of the oil mixture at 40°C and -0.1MPa under negative pressure for 20 minutes until evenly mixed, and then cooling to room temperature to obtain coenzyme Q10 oil, which is encapsulated in soft capsules.

[0063] Example 4 Coenzyme Q10 oil and its preparation method

[0064] (1) The raw materials of the coenzyme Q10 oil in this embodiment are as follows:

[0065] raw material Content (wt%) Coenzyme Q10 crystals 40 Palmitic acid triglyceride 16 Oleic acid 8 α-linolenic acid 4 Conjugated linoleic acid 20 Span-80 2 Twain-80 2 Polyglycerol Ester ML-750 6 Vitamin E 2

[0066] (2) The preparation method of the coenzyme Q10 oil in this embodiment is as follows:

[0067] S1`, stirring and mixing palmitic triglyceride, oleic acid, α-linolenic acid, conjugated linoleic acid and vitamin E to obtain a fat mixture.

[0068] S2', 95% of the oil mixture obtained in step S1' and the coenzyme Q10 crystals were briefly stirred and dispersed, and then added to a ball mill for the first stage of grinding. The ball particle size was 70% between 0.7-0.9 mm and 30% between 0.4-0.6 mm. The working temperature was 5 ° C, and the ball milling time was 85 min to obtain coenzyme Q10 crystal particles with a particle size of D 50 It is the initial grinding liquid of 0.6μm.

[0069] S3', add Span-80, Tween-80 and polyglycerol ester ML-750 to the initial grinding liquid of step S2' and then put it into the ball mill for the second stage of grinding. The ball particle size is between 0.1-0.3mm, the working temperature is 15℃, and the ball milling time is 55min to obtain coenzyme Q10 crystal particles with a particle size of D 50 It is a 76nm fine grinding liquid.

[0070] S4`, stirring the grinding liquid and the remaining 5% oil mixture at 40°C and -0.07MPa under negative pressure for 25 minutes until evenly mixed, and then cooling to room temperature to obtain coenzyme Q10 oil, which is encapsulated in soft capsules.

[0071] Comparative Example 1

[0072] (1) Same as the recipe of Example 1.

[0073] (2) Preparation method of coenzyme Q10 oil:

[0074] A coenzyme Q10 oil was prepared according to the method of Example 1, except that in step S4, the mixing of the lapping solution and the oil mixture was performed at room temperature (25° C.) and normal pressure. The remaining conditions were the same as in Example 1. The resulting coenzyme Q10 oil was orange-red and opaque, and the coenzyme Q10 therein was in crystalline form.

[0075] Comparative Example 2

[0076] (1) Same as the recipe of Example 1.

[0077] (2) Preparation method of coenzyme Q10 oil:

[0078] S1`, stirring and mixing medium chain triglycerides, myristic acid, conjugated linoleic acid and vitamin E to obtain a fat mixture.

[0079] S2', 65% of the oil mixture obtained in step S1', coenzyme Q10 crystals, soybean lecithin, Tween-80 and polyglycerol ester were simply stirred and dispersed into a ball mill, with the ball particle size between 0.1-0.3mm, the working temperature was 10℃, and the ball milling time was 105min to obtain coenzyme Q10 crystal particles with a particle size of D 50 The polishing liquid is 2375nm.

[0080] S3`, stirring the grinding liquid and the remaining 35% oil mixture at 38°C and -0.08MPa negative pressure for 20 minutes until evenly mixed, and then cooling to room temperature to obtain a coenzyme Q10 oil solution, which is orange-red and opaque, and the coenzyme Q10 therein still exists crystals.

[0081] Comparative Example 3

[0082] (1) Same as the recipe of Example 1.

[0083] (2) Preparation method of coenzyme Q10 oil:

[0084] S1`, stirring and mixing medium chain triglycerides, myristic acid, conjugated linoleic acid and vitamin E to obtain a fat mixture.

[0085] S2', 65% of the oil mixture obtained in step S1', coenzyme Q10 crystals, soybean lecithin, Tween-80 and polyglycerol ester were simply stirred and dispersed and then put into a ball mill for the first stage of grinding, with 70% of the ball particle size between 0.7-0.9 mm and 30% between 0.4-0.6 mm, the working temperature was 10 ° C, and the ball milling time was 60 min to obtain coenzyme Q10 crystal particles with a particle size of D50 It is the initial grinding liquid of 1.5μm.

[0086] S3', the initial grinding liquid of step S2' is directly subjected to the second stage of grinding, the ball particle size is between 0.1-0.3mm, the working temperature is 10℃, the ball milling time is 45min, and the coenzyme Q10 crystal particle size D is obtained. 50 It is a 253nm fine grinding liquid.

[0087] S4`, stir the polishing liquid and the remaining 35% oil mixture at 38°C and -0.08MPa under negative pressure for 20 minutes until evenly mixed, then cool to room temperature to obtain an orange-red transparent uniform coenzyme Q10 oil.

[0088] Comparative Example 4

[0089] (1) Same as the recipe of Example 1.

[0090] (2) Preparation method of coenzyme Q10 oil:

[0091] Coenzyme Q10 oil was prepared according to the method of Example 1, except that the ball milling time in step S3 was changed to 370 min, and the particle size of coenzyme Q10 crystal particles was obtained. 50 The remaining conditions were the same as those in Example 1, and an orange-red, transparent, and uniform coenzyme Q10 oil was obtained.

[0092] Comparative Example 5

[0093] (1) Same as the recipe of Example 1.

[0094] (2) Preparation method of coenzyme Q10 oil:

[0095] Coenzyme Q10 oil was prepared according to the method of Example 1, except that the ball milling time in step S3 was changed to 780 min, and the particle size of the coenzyme Q10 crystal particles was obtained. 50 The remaining conditions were the same as those in Example 1, and an orange-red, transparent, and uniform coenzyme Q10 oil was obtained.

[0096] Comparative Example 6

[0097] (1) Same as the recipe of Example 1.

[0098] (2) Preparation method of coenzyme Q10 oil:

[0099] Coenzyme Q10 oil was prepared according to the method of Example 1, except that the ball milling time in step S3 was changed to 20 min, and the particle size of the coenzyme Q10 crystal particles was obtained. 50The remaining conditions were the same as those in Example 1, and an orange-red, transparent, and uniform coenzyme Q10 oil was obtained.

[0100] Comparative Example 7

[0101] (1) Myristic acid and conjugated linoleic acid were replaced by medium-chain triglycerides in equal parts by weight, and the rest of the formula was the same as in Example 1.

[0102] (2) Preparation method of coenzyme Q10 oil:

[0103] Coenzyme Q10 oil was prepared according to the method of Example 1, except that in step S1, myristic acid and conjugated linoleic acid were replaced by medium-chain triglycerides. The remaining conditions were the same as in Example 1, and an orange-red opaque coenzyme Q10 oil was obtained.

[0104] Comparative Example 8

[0105] (1) The medium-chain triglyceride was replaced with myristic acid in equal parts by weight, and the rest of the formula was the same as in Example 1.

[0106] (2) Preparation method of coenzyme Q10 oil:

[0107] Coenzyme Q10 oil was prepared according to the method of Example 1, except that in step S1, medium-chain triglycerides were replaced with the same weight portion of myristic acid. The remaining conditions were the same as in Example 1, and an orange-red opaque coenzyme Q10 oil was obtained.

[0108] Comparative Example 9

[0109] (1) Tween-80, polyglycerol ester ML-500, and polyglycerol ester CR-200 were all replaced by soybean lecithin in equal parts by weight, and the rest of the formula was the same as in Example 1.

[0110] (2) Preparation method of coenzyme Q10 oil:

[0111] Coenzyme Q10 oil was prepared according to the method of Example 1, except that in step S3, Tween-80, polyglycerol ester ML-500, and polyglycerol ester CR-200 were replaced with soybean lecithin. The remaining conditions were the same as in Example 1, and an orange-red opaque coenzyme Q10 oil was obtained.

[0112] Comparative Example 10

[0113] (1) Soybean lecithin was replaced with Tween-80 in the same amount by weight, and the rest of the ingredients were the same as those in Example 1.

[0114] (2) Preparation method of coenzyme Q10 oil:

[0115] Coenzyme Q10 oil was prepared according to the method of Example 1, except that in step S3, soybean lecithin was replaced with Tween-80 in the same amount by weight. The remaining conditions were the same as in Example 1, and an orange-red opaque coenzyme Q10 oil was obtained.

[0116] Test Example 1 Thermal Stability of Coenzyme Q10 Oil

[0117] The oils prepared in Examples 1-4 and Comparative Examples 1-10 were subjected to thermal stability testing to observe whether the oils exhibited phase separation, turbidity, and precipitation at different temperatures. The oils from Examples 1-4 and Comparative Examples 1-10 were stored in thermostats at 0°C, 25°C, and 45°C. After one week, the samples were visually inspected to determine the stability of the oil systems. (When Coenzyme Q10 was in molecular form, the oil systems appeared clear, transparent, and homogeneous. When Coenzyme Q10 crystallized, the oil systems exhibited phase separation, turbidity, or precipitation.) The results are shown in Table 1 below.

[0118] Table 1

[0119]

[0120]

[0121] As can be seen from the results in Table 1, the coenzyme Q10 oil provided by the present invention can remain stable over a wide temperature range, and the transparency of the oil system remains good, without phase separation, turbidity, or crystal precipitation.

[0122] Test Example 2 Anti-aging properties of coenzyme Q10 oil

[0123] Sample 1: Coenzyme Q10 oil prepared in Example 1.

[0124] Sample 2: Coenzyme Q10 oil prepared in Example 2.

[0125] Sample 3: Coenzyme Q10 oil prepared in Example 3.

[0126] Sample 4: Coenzyme Q10 oil prepared in Example 4.

[0127] Reference sample 1: The coenzyme Q10 in the formula of Example 1 was replaced with soybean oil of equal mass. The remaining components and preparation method were consistent with those of Example 1 to prepare an oil preparation, which is reference sample 1.

[0128] Reference sample 2: The mixed oil in the formula of Example 1 is replaced with soybean oil of equal mass. The remaining components and preparation method are the same as those in Example 1 to prepare an oil preparation, which is reference sample 2.

[0129] Reference sample 3: Coenzyme Q10 oil prepared in Comparative Example 1.

[0130] Reference sample 4: Coenzyme Q10 oil prepared in Comparative Example 2.

[0131] Reference sample 5: Coenzyme Q10 oil prepared in Comparative Example 3.

[0132] Reference sample 6: Coenzyme Q10 oil prepared in Comparative Example 4.

[0133] Reference sample 7: Coenzyme Q10 oil prepared in Comparative Example 5.

[0134] Reference sample 8: Coenzyme Q10 oil prepared in Comparative Example 6.

[0135] Reference sample 9: Coenzyme Q10 oil prepared in Comparative Example 7.

[0136] Reference sample 10: Coenzyme Q10 oil prepared in Comparative Example 8.

[0137] Reference sample 11: Coenzyme Q10 oil prepared in Comparative Example 9.

[0138] Reference sample 12: Coenzyme Q10 oil prepared in Comparative Example 10.

[0139] The above 16 samples were subjected to animal experiments.

[0140] Modeling: 180 Wistar rats weighing 120.45 g ± 3.12 g, half male and half female, were randomly divided into 18 groups, with 10 rats in each group. Except for the blank control group, all other groups received a daily subcutaneous injection of 5% D-galactose (120 mg / kg) in the neck to establish an aging model.

[0141] Dosing: The oil preparations of Sample 1, Sample 2, Sample 3, Sample 4, Reference Sample 1, Reference Sample 2, Reference Sample 3, Reference Sample 4, Reference Sample 5, Reference Sample 6, Reference Sample 7, Reference Sample 8, Reference Sample 9, Reference Sample 10, Reference Sample 11, and Reference Sample 12 were added to normal saline to form a suspension at a concentration of 2.0 g / mL (2 g of oil preparation per mL of normal saline). Administration was continued by oral gavage for 30 days, starting on day 11 of modeling. The dosing volume for each group was 2 mL. The blank control group and the model control group were gavaged with the same volume of normal saline. After each administration, the subjects fasted for 24 hours but could not drink water. Blood was collected from the fundus of the eye and allowed to stand at room temperature until completely coagulated. The blood was then centrifuged and serum was separated for later use. Serum SOD activity, GSH-Px activity, and MDA content were measured using the xanthine oxidase method, the dithiodinitrobenzoic acid method, and the thiobarbituric acid spectrophotometry, respectively.

[0142] (1) Effects of samples on serum MDA content: The test samples were orally administered to mice for 30 consecutive days. The results of the detection of MDA content in serum, a product of lipid peroxidation degradation, are shown in Table 2.

[0143] Table 2

[0144]

[0145]

[0146] (2) Effects of the samples on the activity of SOD in mouse serum: The test samples were orally administered to mice for 30 consecutive days. The results of the detection of SOD activity in the serum are shown in Table 3.

[0147] Table 3

[0148] Group Number of animals SOD (U / mL) Increased (%, VS model control group) Blank control group 10 176.7±16.1 69.4 Model control group 10 104.3±19.3 -- Sample 1 group 10 170.1±16.4 63.1 Sample 2 10 176.2±15.9 68.9 Sample 3 groups 10 176.9±17.3 69.6 Sample 4 groups 10 182.4±12.8 74.8 Reference group 1 10 115.4±16.8 10.6 Reference group 2 10 152.1±11.7 45.8 Reference group 3 10 151.9±17.2 45.6 Reference group 4 10 149.5±13.3 43.3 Reference group 5 10 156.7±14.8 50.2 Reference group 6 10 163.4±13.6 56.7 Reference group 7 10 164.7±15.1 57.9 Reference group 8 10 162.9±13.9 56.2 Reference group 9 10 152.8±14.3 46.5 Reference 10 groups 10 152.4±15.5 46.1 Reference group 11 10 153.6±14.6 47.3 Reference group 12 10 154.1±13.8 47.7

[0149] (3) Effects of the samples on the activity of GSH-PX in mouse serum: The test samples were orally administered to mice for 30 consecutive days. The results of the detection of GSH-PX activity in the serum are shown in Table 5.

[0150] Table 5

[0151] Group Number of animals GSH-PX (U / mL) Increased (%, VS model control group) Blank control group 10 86.4±3.4 62.4 Model control group 10 53.2±4.8 -- Sample 1 group 10 84.6±2.7 59.0 Sample 2 10 86.5±2.5 62.6 Sample 3 groups 10 87.1±2.3 63.7 Sample 4 groups 10 89.6±2.1 68.4 Reference group 1 10 57.4±3.7 7.9 Reference group 2 10 74.8±4.8 40.6 Reference group 3 10 74.0±3.1 39.1 Reference group 4 10 73.3±3.9 37.8 Reference group 5 10 77.6±4.2 45.9 Reference group 6 10 79.2±3.4 48.9 Reference group 7 10 79.9±3.5 50.2 Reference group 8 10 79.0±3.8 48.5 Reference group 9 10 75.5±3.2 41.9 Reference 10 groups 10 75.1±3.7 41.2 Reference group 11 10 75.9±4.0 42.6 Reference group 12 10 76.2±4.5 43.2

[0152] The serum MDA level of the animals in the model control group of this experiment was always higher than that in the blank control group and was statistically significant, indicating that the peroxidative damage model was successful and the results were credible. The samples of sample group 1, sample group 2, sample group 3, sample group 4, reference group 1, reference group 2, reference group 3, reference group 4, reference group 5, reference group 6, reference group 7, reference group 8, reference group 9, reference group 10, reference group 11, and reference group 12 were continuously gavaged into mice for 30 days. The content of MDA, a product of lipid peroxidation degradation, in the serum of the animals was significantly reduced compared with that in the model control group. The serum SOD levels of the animals in sample group 1, sample group 2, sample group 3, and sample group 4 were significantly increased compared with those in the model control group and were superior to those in the reference group. The serum GSH-PX levels of the animals in sample group 1, sample group 2, sample group 3, and sample group 4 were significantly increased compared with those in the model control group and were superior to those in the reference group. The results showed that sample group 1, sample group 2, sample group 3, and sample group 4 had excellent anti-aging functions. This shows that the coenzyme Q10 oil provided by the present invention can effectively enhance the body's ability to resist oxidation and scavenge free radicals, reduce the degree of tissue cell damage, and the indicators can basically be restored to the level before aging modeling. From the comparison of the results of sample group 1 with reference groups 4, 5, 6, 7, and 8, it can be seen that grinding coenzyme Q10 crystals to D 50 The Coenzyme Q10 oil, which is formulated within a specific particle size range of 50-120 nm and combined with the blended oil and biphasic emulsifier, exhibits superior anti-aging properties. Comparison of the results of Sample 1 with References 1, 2, 9, 10, 11, and 12 demonstrates that the combination of Coenzyme Q10 with the blended oil and biphasic emulsifier produces an unexpected synergistic anti-aging effect.

[0153] The coenzyme Q10 oil provided by the present invention is in a molecular state with disordered molecular arrangement. This reduces the lattice energy required to dissolve the coenzyme Q10 during dissolution, facilitating its entry into human body fluids and enhancing its bioavailability. Furthermore, the molecular state of the drug alone is only temporary, with crystals easily precipitating after a period of time. The present invention stabilizes the molecular state of coenzyme Q10 through its formulation and preparation, thereby prolonging its crystallization period.

[0154] Although the embodiments of the present invention have been shown and described above, it will be understood that the above embodiments are illustrative and are not to be construed as limitations on the present invention. A person skilled in the art may change, modify, replace and modify the above embodiments within the scope of the present invention without departing from the principles and purpose of the present invention.

Claims

1. A method for preparing a coenzyme Q10 oil, characterized in that: The coenzyme Q10 oil contains the following components by weight: 20-40% coenzyme Q10, 45-65% mixed oil, 10-15% biphasic emulsifier, and 0-3% optional antioxidant, wherein the biphasic emulsifier contains both a hydrophilic emulsifier and a lipophilic emulsifier; the method comprises grinding coenzyme Q10 crystals in the presence of oil mixture I and biphasic emulsifier to reduce the particle size of the coenzyme Q10 crystals to 0. 50 The particle size is reduced to 50-120 nm, and then the obtained polishing liquid and oil mixture II are mixed evenly under negative pressure to obtain a coenzyme Q10 oil solution; the oil mixture I and oil mixture II are both mixtures of mixed oils and optional antioxidants, and the mixed oils contain both saturated fatty acids (esters) and unsaturated fatty acids (esters); The grinding method comprises the following steps: S1. Mix the coenzyme Q10 crystals with the oil mixture I and then grind them in the first stage to reduce the particle size of the coenzyme Q10 crystals to D 50 Reduced to 0.2-1 μm, the primary grinding fluid was obtained; S2, after the primary grinding liquid is mixed with the two-phase emulsifier, the second stage of grinding is carried out to reduce the particle size of the coenzyme Q10 crystals in the primary grinding liquid to D 50 Reduced to 50-120nm, a fine grinding liquid was obtained.

2. The method for preparing the coenzyme Q10 oil according to claim 1, wherein: The conditions for the first stage grinding include a working temperature of 0°C-10°C, a ball particle size of 70% between 0.7-0.9 mm and 30% between 0.4-0.6 mm, and a grinding time of 60-90 min; the conditions for the second stage grinding include a working temperature of 10°C-20°C, a ball particle size between 0.1-0.3 mm, and a grinding time of 30-90 min.

3. The method for preparing the coenzyme Q10 oil according to claim 1, wherein: The conditions for uniformly mixing the lapping liquid and the oil mixture II under negative pressure include a temperature of 35° C. to 40° C., a pressure of -0.07 MPa to -0.1 MPa, and a time of 15 to 25 minutes.

4. The method for preparing the coenzyme Q10 oil according to claim 1, wherein: The usage ratio of the grease mixture I and the grease mixture II is (65%-95%):(5%-35%).

5. The method for preparing the coenzyme Q10 oil according to claim 1, wherein: The mass ratio of saturated fatty acid (ester) to unsaturated fatty acid (ester) in the mixed oil is 1:(1-2.5).

6. The method for preparing the coenzyme Q10 oil according to claim 1, wherein: The mass ratio of saturated fatty acid (ester), monounsaturated fatty acid (ester) and polyunsaturated fatty acid (ester) in the mixed oil is 1:(0-1.5):(1-1.5).

7. The method for preparing the coenzyme Q10 oil according to claim 6, characterized in that: The saturated fatty acid (ester) is a saturated fatty acid glyceride.

8. The method for preparing the coenzyme Q10 oil according to claim 6, characterized in that: The monounsaturated fatty acid (ester) is selected from at least one of oleic acid, myristic acid and palmitoleic acid.

9. The method for preparing the coenzyme Q10 oil according to claim 6, wherein: The polyunsaturated fatty acid (ester) is selected from at least one of α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, conjugated linoleic acid, γ-linolenic acid and arachidonic acid.

10. The method for preparing the coenzyme Q10 oil according to claim 1, wherein: The weight ratio of the hydrophilic emulsifier to the lipophilic emulsifier is (1.5-4):1; the hydrophilic emulsifier is selected from at least one of sucrose esters with an HLB value of 13-16, Tween, polyglycerol fatty acid esters and poloxamer; the lipophilic emulsifier is selected from at least one of sucrose esters with an HLB value of 3-6, phospholipids, span and monoglycerides.

11. The method for preparing the coenzyme Q10 oil according to claim 1, wherein: The antioxidant is selected from at least one of vitamin E, tocopherol, rosemary extract and tea polyphenol extract.

12. Coenzyme Q10 oil prepared by the method according to any one of claims 1 to 11.

13. Use of the coenzyme Q10 oil according to claim 12 in the preparation of food, cosmetics or medicines.

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