Coenzyme Q10 self-emulsifying solution, and preparation process and equipment thereof

Abstract

The invention discloses a coenzyme Q10 self-emulsifying solution as well as a preparation process and equipment thereof, and belongs to the technical field of fine chemical engineering. The coenzyme Q10 self-emulsifying solution is prepared from the following components in parts by weight: 5 to 30 parts of coenzyme Q10, 0 to 30 parts of oil phase, 0 to 50 parts of essence, 1 to 2 parts of Tween 80, 29 to 59 parts of surfactant, 1 to 10 parts of cosurfactant, 0 to 5 parts of polyglycerol monopalmitate and 0 to 0.02 part of antioxidant. A self-emulsifying solution of the coenzyme Q10 is prepared through a three-roller grinding machine and an emulsifying vacuum tank, and the self-emulsifying solution is not prone to being oxidized during preparation. The prepared self-emulsifying solution of the coenzyme Q10 is small in particle size, good in stability and high in bioavailability, can be prepared into microcapsules, soft capsules, hard capsules, oral liquid, emulsion or suspension, and is wide in application range.

Description

Technical Field

[0001] The invention belongs to the technical field of fine chemical industry, and in particular relates to a coenzyme Q10 self-emulsifying solution, a preparation process and equipment thereof. Background Art

[0002] Coenzyme Q10 is an active ingredient that can protect the heart, resist fatigue, and delay skin aging, but it is a fat-soluble substance and is difficult to be absorbed by the human body. As the concentration of surfactant increases, the oil-water interfacial tension of the coenzyme Q10 self-emulsifying solution gradually decreases. When a certain concentration is reached, due to the effect of the co-emulsifier, mixed adsorption occurs, and negative interfacial tension appears, so that the system spontaneously disperses into fine droplets. When it enters the gastrointestinal tract and encounters an aqueous medium, it can spontaneously emulsify to form an emulsion under slight stirring and gastrointestinal peristalsis. The rapid spontaneous emulsification and high dispersion of the coenzyme Q10 self-emulsifying solution at the absorption site can effectively improve the oral absorption of the water-insoluble active ingredient (coenzyme Q10). Compared with the traditional self-emulsifying drug delivery system, the self-emulsifying solution adds flavor ingredients to effectively improve the taste of the product, increase the aroma of the product, promote consumer appetite, and increase the added value of the product.

[0003] Generally, coenzyme Q10 has the following functions: scavenging free radicals, anti-tumor, acting as a non-specific immune enhancer to enhance immunity, activating metabolism, acting as a cofactor in cell energy conversion, anti-oxidation, enhancing cardiac hypoxia tolerance, etc. It has a wide range of functions, including anti-aging, anti-oxidation, enhancing immunity, anti-tumor, protecting the skin and other physiological activities. It has great application potential in many industries such as medicine, food and cosmetics. It is a rare substance that combines medicine, nutrition and health care.

[0004] The amount of coenzyme Q10 required by the human body is relatively small in daily diet, and most of it is synthesized by the human body itself. The synthesis of coenzyme Q10 varies in different organs, and the concentration is higher in tissues and organs such as the heart, liver, kidney, and pancreas. The human body's ability to synthesize coenzyme Q10 reaches its peak at around the age of 20, and then the synthesis amount gradually decreases with age. For the elderly and people with medical conditions, endogenous coenzyme Q10 alone cannot meet the body's needs. In this case, it is necessary to increase the dose of exogenous supplements. my country's health food raw material catalog recommends a daily dosage range of 30-50mg for coenzyme Q10.

[0005] Coenzyme Q10 is a water-insoluble macromolecular substance, which is difficult to use directly. It is slowly absorbed and rarely absorbed orally, and has a very low bioavailability. At present, the existing clinical preparation types of coenzyme Q10 are mainly soft capsules, tablets and water-soluble injections. However, oral soft capsules and tablets have very low absorption efficiency due to poor solubility. Therefore, a coenzyme Q10 self-emulsifying solution, a preparation process and equipment thereof are developed to solve the technical problems of poor stability of coenzyme Q10 in solution, low bioavailability and lack of supporting antioxidant preparation equipment in the prior art. Summary of the invention

[0006] The purpose of the present invention is to provide a coenzyme Q10 self-emulsifying solution, a preparation process and equipment thereof, so as to solve the technical problems in the prior art that coenzyme Q10 has poor stability in solution, low bioavailability and lacks supporting antioxidant preparation equipment.

[0007] In order to achieve the above object, the present invention adopts the following technical solutions:

[0008] The coenzyme Q10 self-emulsifying solution comprises the following components in parts by weight: 5-30 parts of coenzyme Q10, 0-30 parts of oil phase, 0-50 parts of flavor, 1-2 parts of Tween 80, 29-59 parts of surfactant, 1-10 parts of cosurfactant, 0-5 parts of polyglycerol monopalmitate and 0-0.02 parts of antioxidant.

[0009] Preferably, the coenzyme Q10 self-emulsifying solution comprises the following components in parts by weight: 10-25 parts of coenzyme Q10, 10-30 parts of oil phase, 20-45 parts of flavor, 1 part of Tween 80, 32-39 parts of surfactant, 1-8 parts of co-surfactant, 1-5 parts of polyglycerol monopalmitate and 0.005-0.01 parts of antioxidant.

[0010] Furthermore, the oil phase is a mixture of linseed oil, medium-chain fatty acid glycerides, oleic acid and olive oil, and the mass ratio of medium-chain fatty acid glycerides, linseed oil, oleic acid and olive oil is 2:(0.5-1):(0.5-1):(0.5-1); the flavor is one or more of sweet orange oil flavor, peppermint oil, rosemary oil, lemon flavor, lemongrass oil, and lemon terpenes; the surfactant is one or more of phospholipids, citric acid fatty acid glycerides, polyglycerol laurate, polyglycerol myristate and polyglycerol oleate; the co-surfactant is one or more of polyethylene glycol 400, ethanol, and glycerol; the antioxidant is one or more of ascorbic acid, calcium ascorbate, sodium ascorbate and natural vitamin E.

[0011] The preparation method of linseed oil comprises the following steps:

[0012] (1) Pretreatment: After flax seeds are shelled and peeled, they are placed in a forced air drying oven to dry to obtain dry and clean flax seeds, the dry and clean flax seeds are crushed and sieved to obtain flax seed powder, the flax seed powder is weighed and added to distilled water, and after being mixed evenly, a flax seed mixed liquid is obtained, which is placed in an ultrasonic cleaning instrument for ultrasonic treatment to obtain a flax seed pretreatment liquid;

[0013] (2) Enzymatic hydrolysis: adjusting the pH value and temperature of the flax seed pretreatment solution, adding alkaline protease for enzymatic hydrolysis, and after the enzymatic hydrolysis is completed, raising the temperature of the constant temperature water bath to inactivate the enzyme, and after the end, obtaining a flax seed enzymatic hydrolyzate;

[0014] (3) Centrifugal separation: centrifuging the flaxseed hydrolysate to obtain an upper layer of clear oil I, a middle layer of emulsion I and a lower layer of precipitate I, discarding the lower layer of precipitate I, centrifuging the obtained emulsion I again to obtain an upper layer of clear oil II, a middle layer of emulsion II and a lower layer of precipitate II, discarding the lower layer of precipitate II, freezing the obtained emulsion II, centrifuging it and separating it to obtain an upper layer of free clear oil III;

[0015] (4) Combining and drying: The upper layer of clear oil I, the upper layer of clear oil II and the upper layer of free clear oil III are combined and dried until the mass is constant to obtain linseed oil.

[0016] The preparation method of linseed oil in the prior art is generally extracted by squeezing or mixed solvent leaching, which usually requires a large amount of solvent consumption and has a low extraction rate, and the residual solvent and impurity content are high. The present application obtains linseed oil by ultrasonic treatment combined with alkaline protease hydrolysis and multiple centrifugal separations. Ultrasonic treatment can reduce the size of linseed particles and destroy the cell wall structure through the cavitation effect and mechanical effect of ultrasound, thereby accelerating the release of oil and effective ingredients, which can not only improve the extraction rate of linseed oil, but also shorten the extraction time, reduce solvent consumption, and reduce production costs. Alkaline protease can degrade the macromolecular protein in linseed protein into small molecular peptides and amino acids, making it easier to be digested and absorbed by the human body, reducing the allergy and antigenicity of the protein, and applying it to the coenzyme Q10 self-emulsifying solution not only makes the solubility of the coenzyme Q10 dosage form better, easier to be digested and absorbed by the human body, but also reduces allergy, and has a better application prospect.

[0017] The linseed oil obtained by the preparation method of the present application has a residual solvent of ≤10 mg / kg and an impurity content of ≤0.1% after testing, and the extraction rate of linseed oil exceeds 98.8%, which is improved to a certain extent compared with the linseed oil extraction method in the prior art and is suitable for industrial production.

[0018] Furthermore, in step (1), the temperature of the blast drying oven is 70-75° C., the drying time is 4-6 hours, the flax seed mesh size is 80-200 mesh, the solid-liquid ratio of the flax seed mixture is 1:5-6 g / mL, the intensity of the ultrasonic treatment is 400-450 W, the ultrasonic time is 40-60 min, and the ultrasonic temperature is 50-55° C.; in step (2), the pH is adjusted to 9-11 with a sodium hydroxide solution, the temperature is 42-45° C., the enzymatic hydrolysis time is 2.5-3 hours, the constant temperature water bath is heated to 95-100° C., and the enzyme is inactivated for 8-10 minutes; in step (3), the centrifugal speed is 8000-10000 rpm, the centrifugal time is 25-30 minutes, the freezing temperature is -18° C., and the freezing time is 24-26 hours; and in step (4), the drying temperature is 55-60° C.

[0019] The present invention also provides a preparation process of a coenzyme Q10 self-emulsifying solution, comprising the following steps: uniformly mixing other auxiliary materials except the coenzyme Q10 powder according to weight parts, heating to 60-70° C., slowly adding the coenzyme Q10 powder after the other auxiliary materials are dissolved, grinding with a three-roll grinder to obtain a mixed liquid, putting the mixed liquid into an emulsifying vacuum tank, filling it with nitrogen, stirring until the coenzyme Q10 is completely dissolved, and emulsifying at a temperature of 10-12 hours to obtain a coenzyme Q10 self-emulsifying solution.

[0020] The present invention also provides a preparation device for a coenzyme Q10 self-emulsifying solution, which is applicable to the preparation process of the coenzyme Q10 self-emulsifying solution, and includes a three-roller grinder and an emulsifying vacuum tank;

[0021] The multi-roller grinder is used to grind the material of the coenzyme Q10 self-emulsifying solution, and includes a frame, on which a plurality of rollers are rotatably mounted, and a plurality of motors are mounted on the frame, the number of the plurality of motors being consistent with the number of the plurality of rollers, and when the plurality of motors are running, they will respectively drive the corresponding rollers to rotate and make the plurality of rollers operate asynchronously with each other to grind the material of the coenzyme Q10 self-emulsifying solution; the multi-roller grinder also includes a scraping device movably arranged on the frame, and the scraping device can contact the rotating roller to scrape the material attached to the circumferential surface of the roller;

[0022] The emulsifying vacuum tank is used for self-emulsifying the ground coenzyme Q10 self-emulsifying solution material, and comprises a fixing frame, a sealing cover is installed through the top surface of the fixing frame, a driving motor is installed on the sealing cover, a shaft is installed on the power output shaft of the driving motor, and a stirring rod is installed on the shaft; a slidable and rotatable transparent tank is arranged in the fixing frame, and the transparent tank and the sealing cover can be plugged in and matched.

[0023] Among them, the scraping device includes a shovel plate, which is provided with a vertical part and an inclined part; a threaded cylinder and a threaded rod threadedly connected to the threaded cylinder are installed on the vertical part, a turntable is installed on the end of the threaded rod away from the frame, and the inclined part can contact with the roller.

[0024] The scraping device is further provided with two guide rods, which are fixedly arranged on the side surfaces of the frame and penetrate the vertical portion.

[0025] A multi-stage hydraulic cylinder is installed on the inner bottom surface of the fixing frame, and a push plate is installed on the extended end of the multi-stage hydraulic cylinder, and the push plate is fixedly connected to the bottom surface of the transparent tank. Slide grooves are provided on the inner walls of both sides of the fixing frame, and a pair of slide bars are pivotally connected to the two sides of the transparent tank, and the ends of each slide bar are movably accommodated in the slide grooves.

[0026] Among them, a vacuum pump and a pressure gauge are installed on the top surface of the sealing cover, the vacuum pump's exhaust end extends to the bottom of the sealing cover, and the pressure gauge's detection end also extends to the bottom of the sealing cover; a gas storage tank is also installed on the top surface of the sealing cover, the gas storage tank is used to store inert gas, a gas pipe is installed on the gas storage tank, the gas pipe extends to the bottom of the sealing cover, and a switch valve is installed on the gas pipe.

[0027] In summary, due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0028] 1. The present invention prepares a coenzyme Q10 self-emulsifying solution through multiple components such as coenzyme Q10, oil phase, essence, Tween 80, surfactant, cosurfactant, polyglycerol monopalmitate and antioxidant, and realizes efficient self-emulsification of coenzyme Q10. The components work synergistically to improve the stability and bioavailability of coenzyme Q10. At the same time, the coenzyme Q10 self-emulsifying solution has the characteristics of simple preparation, high stability, good emulsification effect, and easy absorption. Its self-emulsifying property enables the coenzyme Q10 self-emulsifying solution to be rapidly emulsified when encountering the aqueous environment of the gastrointestinal tract, forming a uniform and delicate emulsion, thereby improving the solubility and absorption efficiency of coenzyme Q10 in the body. The self-emulsifying solution of coenzyme Q10 can be prepared into microcapsules, soft capsules, hard capsules, oral liquids, emulsions or suspensions, and has a wide range of applications.

[0029] 2. The flaxseed oil prepared by the process of enzymatic hydrolysis and centrifugal separation of the present invention not only removes impurities and bad flavors, but also retains its rich nutrients and natural flavors. Flaxseed oil, as one of the main components of the oil phase, is rich in unsaturated fatty acids such as α-linolenic acid. Coenzyme Q10 is an important antioxidant and energy metabolism coenzyme. In the coenzyme Q10 self-emulsifying solution, flaxseed oil and coenzyme Q10 work together. The application of flaxseed oil to the coenzyme Q10 self-emulsifying solution not only makes the solubility of the coenzyme Q10 dosage form better, easier to be digested and absorbed by the human body, but also reduces allergies, and has better application prospects.

[0030] 3. In the coenzyme Q10 self-emulsifying solution preparation equipment of the present invention, the three-roller grinder is provided with three motors to drive the three rollers to rotate, and achieves a controllable and sufficient grinding effect through the extrusion and friction of the roller surfaces at different relative speeds, so that the mixed liquid is more delicate and smooth; and after the grinding is completed, the shovel plate is driven to move in the direction close to the frame, so that the inclined part of the plug plate contacts the roller, thereby shoveling off the mixed liquid on the roller, reducing the loss of the mixed liquid and reducing the difficulty of cleaning the three-roller grinder.

[0031] 4. In the coenzyme Q10 self-emulsifying solution preparation equipment of the present invention, the emulsifying vacuum tank is provided with a multi-stage hydraulic cylinder. During operation, the height of the transparent tank is adjusted by a push plate, so that the transparent tank and the sealing cover can be plugged in or separated, thereby facilitating the pouring out of the material in the transparent tank; by starting the vacuum pump, the air inside the transparent tank is extracted, so that the inside of the transparent tank is in a negative pressure state; after the inert gas is introduced through the gas pipe, the self-emulsifying solution is not easily oxidized. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0033] Figure 1 This is a particle size measurement diagram of the coenzyme Q10 self-emulsifying solution of Example 3 of the present invention;

[0034] Figure 2 This is the drug-time curve of the coenzyme Q10 self-emulsifying solution of Example 3 of the present invention;

[0035] Figure 3 The pseudo-ternary phase diagram of coenzyme Q10 in different excipients of the present invention;

[0036] Figure 4 A three-roll grinding machine according to the present invention;

[0037] Figure 5 It is a schematic diagram of the assembly mechanism of the frame, rollers and guide rods in the three-roller grinding machine of the present invention;

[0038] Figure 6 It is a schematic diagram of the assembly structure of the frame and the motor in the three-roller grinding machine of the present invention;

[0039] Figure 7 A three-dimensional diagram of a shovel plate and a threaded barrel in the present invention;

[0040] Figure 8It is a right side view of the shovel plate and the threaded barrel in the present invention;

[0041] Fig. 9 The three-dimensional structure of the emulsification vacuum tank in the present invention Figure 1 ;

[0042] Fig.10 The three-dimensional structure of the emulsification vacuum tank in the present invention Figure 2 ;

[0043] 10. Three-roller grinding machine; 101. frame; 102. mounting cavity; 103. roller; 104. motor; 105. shovel plate; 106. threaded cylinder; 107. threaded rod; 108. turntable; 109. guide rod; 111. vertical portion; 113. inclined portion; 200. emulsification vacuum tank; 201. fixed frame; 202. sealing cover; 203. driving motor; 204. shaft; 205. stirring rod; 206. transparent tank; 207. sliding rod; 208. slide chute; 209. barometer; 210. multi-stage hydraulic cylinder; 211. push plate; 212. vacuum pump; 213. gas storage tank; 214. gas pipe; 215. heating ring. DETAILED DESCRIPTION

[0044] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0045] Embodiment 1:

[0046] The coenzyme Q10 self-emulsifying solution of this embodiment contains the following components by weight: 5g coenzyme Q10, 2g medium-chain fatty acid glyceride, 0.5g linseed oil, 0.5g oleic acid, 1g olive oil, 1g Tween 80, 15g polyglycerol laurate, 14g polyglycerol oleate, 1g polyethylene glycol 400, 1g polyglycerol monopalmitate and 0.005g ascorbic acid.

[0047] The preparation of linseed oil comprises the following steps:

[0048] (1) Pretreatment: After flax seeds are shelled and peeled, they are placed in a forced air drying oven to dry at a temperature of 70° C. for 4 h to obtain dry and clean flax seeds. The dry and clean flax seeds are crushed through a 200-mesh sieve to obtain flax seed powder. 100 g of the flax seed powder is weighed and added to 500 mL of distilled water. After mixing evenly, a flax seed mixed solution is obtained. The flax seed mixed solution is placed in an ultrasonic cleaning apparatus for ultrasonic treatment at an intensity of 400 W, an ultrasonic time of 40 min, and an ultrasonic temperature of 50° C. to obtain a flax seed pretreatment solution.

[0049] (2) Enzymatic hydrolysis: The flax seed pretreatment solution was adjusted to pH = 9 with sodium hydroxide solution, the temperature was set to 42°C, alkaline protease was added for enzymatic hydrolysis, the enzymatic hydrolysis time was 2.5 h, the constant temperature water bath was heated to 95°C, the enzyme was inactivated for 8 min, and the flax seed enzymatic hydrolyzate was obtained;

[0050] (3) Centrifugal separation: The flaxseed enzymatic hydrolysate is centrifuged at a speed of 8000 rpm for 25 min to separate the upper layer of clear oil I, the middle layer of emulsion I and the lower layer of precipitate I, the lower layer of precipitate I is discarded, the obtained emulsion I is centrifuged again to separate the upper layer of clear oil II, the middle layer of emulsion II and the lower layer of precipitate II, the lower layer of precipitate II is discarded, the obtained emulsion II is frozen at a temperature of -18°C for 24 h, and the upper layer of free clear oil III is separated;

[0051] (4) Combining and drying: combining the upper layer clear oil I, the upper layer clear oil II and the upper layer free clear oil III, and drying them until the mass is constant at a drying temperature of 55° C. to obtain linseed oil.

[0052] The preparation process of the coenzyme Q10 self-emulsifying solution comprises the following steps:

[0053] The other auxiliary materials except coenzyme Q10 powder were mixed uniformly according to weight parts, heated to 65°C, and after the other auxiliary materials were dissolved, the coenzyme Q10 powder was slowly added, and a three-roll grinder was used to grind the mixture to obtain a mixed liquid. The mixed liquid was put into an emulsification vacuum tank, filled with nitrogen, stirred until the coenzyme Q10 was completely dissolved, and emulsified at 32°C for 11 hours to obtain a coenzyme Q10 self-emulsifying solution.

[0054] Embodiment 2:

[0055] The coenzyme Q10 self-emulsifying solution of this embodiment contains the following components by weight: 15g coenzyme Q10, 8g medium-chain fatty acid glyceride, 3g linseed oil, 3g oleic acid, 3g olive oil, 5g sweet orange oil essence, 1.5g Tween 80, 10g polyglycerol laurate, 10g phospholipids, 10g citric acid fatty acid glyceride, 5g polyglycerol myristate, 2g polyethylene glycol 400, 1g ethanol, 1g glycerol, 1g propylene glycol, 3g polyglycerol monopalmitate, 0.01g ascorbic acid and 0.01g natural vitamin E.

[0056] The preparation of linseed oil comprises the following steps:

[0057] (1) Pretreatment: After flax seeds are shelled and peeled, they are placed in a forced air drying oven to dry at a temperature of 72° C. for 5 h to obtain dry and clean flax seeds. The dry and clean flax seeds are crushed through a 150-mesh sieve to obtain flax seed powder. 100 g of the flax seed powder is weighed and added to 550 mL of distilled water. After mixing evenly, a flax seed mixed solution is obtained. The flax seed mixed solution is placed in an ultrasonic cleaning apparatus for ultrasonic treatment at an intensity of 420 W, an ultrasonic time of 50 min, and an ultrasonic temperature of 53° C. to obtain a flax seed pretreatment solution.

[0058] (2) Enzymatic hydrolysis: The flax seed pretreatment solution was adjusted to pH = 10 with sodium hydroxide solution, the temperature was set to 44°C, alkaline protease was added for enzymatic hydrolysis, the enzymatic hydrolysis time was 2.5 h, the constant temperature water bath was heated to 98°C, the enzyme was inactivated for 9 min, and the flax seed enzymatic hydrolyzate was obtained;

[0059] (3) Centrifugal separation: The flaxseed hydrolysate was centrifuged at a speed of 9000 rpm for 28 min to separate the upper layer of clear oil I, the middle layer of emulsion I and the lower layer of precipitate I. The lower layer of precipitate I was discarded, and the obtained emulsion I was centrifuged again to separate the upper layer of clear oil II, the middle layer of emulsion II and the lower layer of precipitate II. The lower layer of precipitate II was discarded, and the obtained emulsion II was frozen at a temperature of -18°C for 25 h, and centrifuged to separate the upper layer of free clear oil III;

[0060] (4) Combining and drying: combining the upper layer clear oil I, the upper layer clear oil II and the upper layer free clear oil III, and drying them until the mass is constant at a drying temperature of 58° C. to obtain linseed oil.

[0061] The preparation process of the coenzyme Q10 self-emulsifying solution comprises the following steps:

[0062] The other auxiliary materials except coenzyme Q10 powder were mixed uniformly according to weight parts, heated to 68°C, and after the other auxiliary materials were dissolved, the coenzyme Q10 powder was slowly added, and the mixture was fully ground using a three-roll grinder to obtain a mixed liquid. The mixed liquid was put into an emulsification vacuum tank, filled with nitrogen, stirred until the coenzyme Q10 was completely dissolved, and emulsified at 35°C for 10 hours to obtain a coenzyme Q10 self-emulsifying solution.

[0063] Embodiment 3:

[0064] The coenzyme Q10 self-emulsifying solution of this embodiment contains the following components in weight percentage: 30g coenzyme Q10, 10g medium-chain fatty acid glyceride, 5g linseed oil, 5g oleic acid, 5g olive oil, 10g sweet orange oil essence, 10g peppermint oil, 2g Tween 80, 10g polyglycerol laurate, 10g phospholipids, 10g citric acid fatty acid glyceride, 10g polyglycerol myristate, 19g polyglycerol oleate, 2g polyethylene glycol 400, 2g ethanol, glycerol, 2g propylene glycol, 5g polyglycerol monopalmitate, 0.005g ascorbic acid, 0.002g calcium ascorbate, 0.001g sodium ascorbate and 0.002g natural vitamin E.

[0065] The preparation of linseed oil comprises the following steps:

[0066] (1) Pretreatment: After flax seeds are shelled and peeled, they are placed in a forced air drying oven to dry at a temperature of 75° C. for 6 h to obtain dry and clean flax seeds. The dry and clean flax seeds are crushed through an 80-mesh sieve to obtain flax seed powder. 100 g of flax seed powder is weighed and added to 600 mL of distilled water. After mixing evenly, a flax seed mixed solution is obtained. The flax seed mixed solution is placed in an ultrasonic cleaning apparatus for ultrasonic treatment at an intensity of 450 W, an ultrasonic time of 60 min, and an ultrasonic temperature of 55° C. to obtain a flax seed pretreatment solution.

[0067] (2) Enzymatic hydrolysis: The flax seed pretreatment solution was adjusted to pH = 11 with sodium hydroxide solution, the temperature was set to 45°C, alkaline protease was added for enzymatic hydrolysis, the enzymatic hydrolysis time was 3 hours, the constant temperature water bath was heated to 100°C, the enzyme was inactivated for 10 minutes, and the flax seed enzymatic hydrolyzate was obtained;

[0068] (3) Centrifugal separation: The flaxseed hydrolysate is centrifuged at a speed of 10,000 rpm for 30 min to separate the upper layer of clear oil I, the middle layer of emulsion I and the lower layer of precipitate I. The lower layer of precipitate I is discarded, and the obtained emulsion I is centrifuged again to separate the upper layer of clear oil II, the middle layer of emulsion II and the lower layer of precipitate II. The lower layer of precipitate II is discarded, and the obtained emulsion II is frozen at a temperature of -18°C for 26 h, and centrifuged to separate the upper layer of free clear oil III;

[0069] (4) Combining and drying: combining the upper layer of clear oil I, the upper layer of clear oil II and the upper layer of free clear oil III, and drying them until the mass is constant at a drying temperature of 60° C. to obtain linseed oil.

[0070] The preparation process of the coenzyme Q10 self-emulsifying solution comprises the following steps:

[0071] The other auxiliary materials except coenzyme Q10 powder were mixed uniformly according to weight parts, heated to 70°C, and after the other auxiliary materials were dissolved, the coenzyme Q10 powder was slowly added, and a three-roll grinder was used to grind the mixture to obtain a mixed liquid. The mixed liquid was put into an emulsification vacuum tank, filled with nitrogen, stirred until the coenzyme Q10 was completely dissolved, and emulsified at 30°C for 11 hours to obtain a coenzyme Q10 self-emulsifying solution.

[0072] Embodiment 4:

[0073] The components of the coenzyme Q10 self-emulsifying solution of this embodiment are shown in the following table:

[0074]

[0075] Preparation method: Preparation of coenzyme Q10 self-emulsifying solution: Mix the prescribed amount of excipients evenly, heat to 70°C, slowly add coenzyme Q10 powder and vitamin C after other excipients are dissolved, stir until coenzyme Q10 powder and vitamin C are completely dissolved, keep warm at 37°C for 12 hours to obtain coenzyme Q10 self-emulsifying solution. The whole system is orange-red and uniform transparent liquid.

[0076] Embodiment 5:

[0077] The components of the coenzyme Q10 self-emulsifying solution of this embodiment are shown in the following table:

[0078]

[0079] Preparation method: Preparation of coenzyme Q10 self-microemulsion solution: Mix the prescribed amount of excipients evenly, heat to 70°C, slowly add coenzyme Q10 powder after other excipients are dissolved, stir until coenzyme Q10 is completely dissolved, keep warm at 37°C for 12 hours, and obtain coenzyme Q10 self-microemulsion solution. The whole system is orange-red and uniform transparent liquid.

[0080] Embodiment 6:

[0081] The components of the coenzyme Q10 self-emulsifying solution of this embodiment are shown in the following table:

[0082]

[0083] Preparation method: Preparation of coenzyme Q10 self-microemulsion solution: Mix the prescribed amount of excipients evenly, heat to 70°C, slowly add coenzyme Q10 powder and vitamin C after other excipients are dissolved, stir until coenzyme Q10 powder and vitamin C are completely dissolved, keep warm at 37°C for 12 hours, and obtain coenzyme Q10 self-microemulsion solution. The whole system is orange-red and uniform transparent liquid.

[0084] Embodiment 7:

[0085] The components of the coenzyme Q10 self-emulsifying solution of this embodiment are shown in the following table:

[0086]

[0087]

[0088] Preparation method: Preparation of coenzyme Q10 self-microemulsion solution: Mix the prescribed amount of excipients evenly, heat to 70°C, slowly add coenzyme Q10 powder and vitamin C after other excipients are dissolved, stir until coenzyme Q10 powder and vitamin C are completely dissolved, keep warm at 37°C for 12 hours, and obtain coenzyme Q10 self-microemulsion solution. The whole system is orange-red and uniform transparent liquid.

[0089] Comparative Example 1:

[0090] Comparative Example 1 Compared with Example 3, in the process of preparing the coenzyme Q10 self-emulsifying solution in Comparative Example 3, linseed oil was not added, and other conditions remained unchanged.

[0091] Comparative Example 2:

[0092] Comparative Example 2 Compared with Example 3, in the process of preparing the coenzyme Q10 self-emulsifying solution in Comparative Example 2, no polyglycerol monopalmitate was added, and other conditions remained unchanged.

[0093] Experimental example

[0094] The samples prepared in Examples 1-3 and Comparative Example 1 were subjected to the following performance tests:

[0095] 1. Particle size determination

[0096] The particle sizes of the coenzyme Q10 self-emulsifying solutions prepared in Examples 1-3 and Comparative Example 1 were measured using a particle size potential measuring instrument. The results are shown in Table 1:

[0097] Table 1

[0098]

[0099]

[0100] It can be seen from the measurement results in Table 1 that the average particle size of the coenzyme Q10 self-emulsifying solution prepared in Examples 1-3 of the present invention is relatively small, wherein the average particle size of Example 3 is 41.92. The particle size measurement diagram of the coenzyme Q10 self-emulsifying solution in Example 3 is shown in Figure 1 As shown, by comparing Comparative Examples 1-2 with Examples 1-3, it can be seen that adding linseed oil and polyglycerol monopalmitate can reduce the particle size of the coenzyme Q10 self-emulsifying solution, which helps to improve its solubility and bioavailability.

[0101] 2. Bioavailability Assessment

[0102] Oral bioavailability experiments were conducted on rats. The specific experimental steps are as follows:

[0103] Establishment of in vivo analysis method of coenzyme Q10: The content of coenzyme Q10 in plasma was determined by high performance liquid chromatography, and the chromatographic conditions were as follows: chromatographic column: ZORBAX Eclipse XDB-C18 (250 mm × 4.6 mm, 5 μm); mobile phase: methanol-anhydrous ethanol = 50-50; column temperature: 35 °C; detection wavelength: 275 nm; flow rate: 1 mL / min;

[0104] Plasma sample processing method: Take 200 μL of plasma sample, add 800 μL of methanol, vortex for 1 min, add 1 mL of n-hexane, vortex for 3 min, centrifuge at 2000 rpm for 10 min, transfer the organic layer to a new centrifuge tube, add 1 mL of n-hexane to the water layer, vortex for 3 min, centrifuge at 4000 rpm for 10 min, and combine the organic layers. Dry the organic layer with high-purity nitrogen in a 50°C water bath. Add 100 μL of ethanol to the centrifuge tube for re-dissolution, vortex for 5 min, centrifuge at 14000 rpm for 15 min at 4°C, and take 50 μL for injection analysis.

[0105] Drawing of the standard curve of plasma samples: accurately weigh 10 mg of coenzyme Q10, place it in a 50 mL volumetric flask, dissolve it in ethanol and make up the volume. Dilute a series of coenzyme Q10 standard solutions with ethanol to a final drug concentration of 2, 4, 6, 8, 12.8, 16, and 20 μg / mL.

[0106] Take 10 μL of the above coenzyme Q10 standard solution of different concentrations, add 200 μL of blank plasma, vortex mix for 1 min, and use them as plasma standard curve samples of different concentrations. Record the drug peak area at different concentrations and draw a standard curve of peak area and plasma drug concentration.

[0107] Animal dosing regimen: The dosage for rats was 10 mg / kg. Eighteen male SD rats were randomly divided into three groups, with 6 rats in each group. The rats were fasted for 12 hours before administration (water was not allowed). After 4 hours of administration, the rats were allowed to eat freely. The drug was administered by gavage. 0.5 mL of blood was collected from the tail vein at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours after administration. The blood was anticoagulated with sodium heparin and centrifuged at 4000 rpm for 10 minutes to obtain plasma. The plasma was determined by high performance liquid chromatography and the time-dependent change curve of blood drug concentration was plotted. The results are shown in the following table. Figure 1 shown.

[0108] Depend on Figure 1 The results show that compared with the commercially available oxidized coenzyme, The relative bioavailability of the coenzyme Q10 self-emulsifying solution was 446%, that is, The bioavailability of the coenzyme Q10 self-emulsifying solution is 4.5 times that of the reference substance. Compared with the commercially available reduced coenzyme, the The relative bioavailability of the coenzyme Q10 self-emulsifying solution was 255%, that is, The bioavailability of the coenzyme Q10 self-emulsifying solution is 2.6 times that of the reference substance, indicating that the coenzyme Q10 self-emulsifying solution provided by the present invention can significantly improve oral bioavailability.

[0109] like Figure 3 As shown in the figure, the excipients with good compatibility are selected by the five-star evaluation method of self-microemulsification, and a pseudo-ternary phase diagram is established. The pseudo-ternary phase diagram is made into mixed surfactants according to the mass ratio of surfactant to co-surfactant of 1:1, 2:1, 3:1, and 4:1, and then the mixed surfactant is mixed with the oil phase to make the mass fraction of the oil phase 10%. Take an appropriate amount of the above microemulsion matrix, add it to deionized water, and shake it slightly. Observe the appearance of the liquid, increase the mass ratio of the oil phase, and repeat the above operation. Draw a ternary phase diagram with the oil phase, surfactant, and co-surfactant as the three vertices of the triangular phase diagram, and select the prescription ratio with an average particle size of less than 100nm to draw the self-microemulsification area. In the ternary phase diagram with the largest self-microemulsification area, select the appropriate ratio as the alternative prescription.

[0110] like Figure 4 and Fig. 9 As shown, the present invention also provides a preparation device for the above-mentioned coenzyme Q10 self-emulsifying solution, which includes a multi-roll grinder 100 and an emulsifying vacuum tank 200.

[0111] The multi-roller grinding machine 100 comprises a frame 101, on which three rollers 103 are rotatably mounted. The three rollers 103 are arranged parallel to each other and have a small gap between each other. An installation cavity 102 is arranged in the frame 101, and three motors 104 are installed in the installation cavity 102. The power output shafts of the three motors 104 are connected to the three rollers 103 respectively. When the three motors 104 are running, the corresponding rollers 103 will be driven to run asynchronously. The rollers 103 are centrifugally cast by chilled alloy cast iron, and the surface hardness reaches HS70° or more. It is obvious that the multi-roller grinding machine in the present embodiment has three rollers 103 and the same number of motors 104, and can also be set to two, four or other numbers of rollers and motors according to actual needs.

[0112] like Figure 4 , Figure 7 and Figure 8 As shown, a scraping device is provided on the side 110 of the frame 101, and the scraping device includes a scraping plate 105, a threaded barrel 106 provided on the scraping plate 105, and a threaded rod 107 threadedly connected to the threaded barrel 106. The scraping plate 105 has a vertical portion 111 and an inclined portion 113. The threaded barrel 106 and through holes 114 provided on both sides of the threaded barrel 106 are installed through the vertical portion 111 of the scraping plate 105. A turntable 108 is installed on one end of the threaded rod 107 away from the frame 101. A threaded hole 112 and a pair of guide rods 109 fixedly installed on both sides of the threaded hole 112 are provided on the side 110 of the frame 101. The pair of guide rods 109 pass through the through holes 114 on the vertical portion 111 of the scraping plate 105 and are slidably connected to the scraping plate 105. The inclined portion 113 of the shovel plate 105 is provided with an inclined surface 115 which can contact the rotating roller 103 to scrape off the material attached to the circumferential surface of the roller 103 , that is, to scrape off the material protruding from the surface of the roller 103 .

[0113] When the multi-roller grinder is used, the three motors 104 are first started to drive the three rollers 103 to rotate asynchronously; then the coenzyme Q10 material to be ground is placed on the rollers 103 for grinding. In this way, when the three rollers 103 rotate, the surfaces of the rollers 103 perform a controllable and sufficient grinding effect on the coenzyme Q10 material through extrusion friction at different relative speeds.

[0114] When the material is ground and needs to be cleaned, the motor 104 is started to drive the roller 103 to rotate, and then the turntable 108 is rotated to drive the threaded rod 107 to rotate while moving the threaded cylinder 106 (that is, the shovel plate 105) toward the frame 101 until the inclined surface 115 of the shovel plate 105 contacts the roller 103, so that the residual material protruding from the surface of the roller 103 can be cleaned.

[0115] like Figure 9-10 As shown, the emulsifying vacuum tank 200 includes a fixed frame 201, a sealing cover 202 is installed on the top surface of the fixed frame 201, a driving motor 203 is installed on the top surface of the sealing cover 202, and a shaft 204 is installed on the power output shaft of the driving motor 203. The shaft 204 penetrates the sealing cover 202 and extends to the bottom of the sealing cover 202. A pair of stirring rods 205 are fixedly installed at the end of the shaft 204. A transparent tank 206 is slidably installed inside the fixed frame 201, and the transparent tank 206 is used to contain the ground coenzyme Q10 and corresponding ingredients. The top of the transparent tank 206 is open, and the transparent tank 206 can be plugged and matched with the sealing cover 202 to be sealed. The side wall of the transparent tank 206 is made of transparent material. A heating ring 215 is installed on the bottom surface of the transparent tank 206, and the bottom of the transparent tank 206 can be heated by starting the heating ring 215, thereby heating the material in the transparent tank 206.

[0116] like Fig.10 As shown, a multi-stage hydraulic cylinder 210 is installed on the inner bottom surface of the fixing frame 201, and a push plate 211 is installed at the extended end of the multi-stage hydraulic cylinder 210, and the push plate 211 is fixedly connected to the bottom surface of the transparent tank 206. When the multi-stage hydraulic cylinder 210 is running, the height of the transparent tank 206 can be adjusted by the push plate 211.

[0117] like Fig. 9 As shown, a slide groove 208 is provided on both inner walls of the fixing frame 201. A pair of slide bars 207 are pivotally connected to both sides of the transparent tank 206, so that the transparent tank 206 can rotate relatively around the slide bars 207. When the material in the transparent tank 206 needs to be taken out, or when the inner wall of the transparent tank 206 needs to be cleaned, the transparent tank 206 is rotated to tilt to one side, so that the material in the transparent tank 206 can be poured out, and the inside of the transparent tank 206 can be cleaned with tools. In addition, the end of the slide bar 207 can be slidably received in the corresponding slide groove 208.

[0118] like Fig. 9 As shown, a vacuum pump 212 and a barometer 209 are installed on the top surface of the sealing cover 202. The vacuum end of the vacuum pump 212 extends to the bottom of the sealing cover 202, and the detection end of the barometer 209 also extends to the bottom of the sealing cover 202. A gas storage tank 213 is also installed on the top surface of the sealing cover 202. The gas storage tank 213 is used to store inert gas, such as nitrogen. A gas delivery pipe 214 is installed on the gas storage tank 213, and the gas delivery pipe 214 extends to the bottom of the sealing cover 202. A switch valve (not shown) is installed on the gas delivery pipe 214.

[0119] When the emulsifying vacuum tank 200 is used, the materials are first added and sealed: that is, according to the above preparation method, the coenzyme Q10 and the corresponding percentage of ingredients ground by the multi-roll grinder 100 are successively added into the transparent tank 206, and then the multi-stage hydraulic cylinder 210 is started, so that the extended end of the multi-stage hydraulic cylinder 210 pushes the transparent tank 206 through the push plate 211, and the transparent tank 206 moves upward along the direction of the slide groove 208 through the cooperation and limitation of the slide rod 207 and the slide groove 208, until the transparent tank 206 is plugged and sealed with the sealing cover 202;

[0120] Then, the material vacuum emulsification step is performed: first, the air inside the transparent tank 206 is extracted by starting the vacuum pump 212, so that the inside of the transparent tank 206 is in a negative pressure state; then, the inert gas in the gas storage tank 213 is transported to the transparent tank 206 by opening the switch valve on the gas pipe 214; then, the bottom surface of the transparent tank 206 is heated by starting the heating ring 215, and then the material in the transparent tank 206 is heated to a suitable temperature and kept warm; finally, by starting the driving motor 203, the power output shaft of the driving motor 203 drives the shaft 204 to rotate, and then drives the stirring rod 205 to rotate, so that the stirring rod 205 stirs the material in the transparent tank 206 until a uniform and transparent coenzyme Q10 liquid is obtained by stirring. Since the transparent tank 206 is filled with inert gas, the material will not be oxidized during the heating and stirring process of the material.

[0121] Finally, the liquid medicine removal step is performed: the driving motor 203 is turned off, and the vacuum pump 212 is started to extract the air in the transparent tank 206, so as to facilitate the removal of bubbles in the material; after the bubble removal is completed, the air pressure in the transparent tank 206 is restored to normal pressure, and then the multi-stage hydraulic cylinder 210 is started to move the extended end of the multi-stage hydraulic cylinder 210 downward to drive the transparent tank 206 to move downward, thereby separating the transparent tank 206 from the sealing cover 202. Then, by rotating the transparent tank 206, the transparent tank 206 is in a tilted state, so as to facilitate the removal of the liquid in the transparent tank 206.

[0122] The preferred embodiments of the present invention disclosed above are only used to help explain the present invention. The preferred embodiments do not describe all the details in detail, nor do they limit the invention to only specific implementation methods. Obviously, many modifications and changes can be made according to the content of this specification. This specification selects and specifically describes these embodiments in order to better explain the principles and practical applications of the present invention, so that those skilled in the art can understand and use the present invention well. The present invention is limited only by the claims and their full scope and equivalents.

Claims

1. A coenzyme Q10 self-emulsifying solution, characterized in that: The invention comprises the following components in parts by weight: 5-30 parts of coenzyme Q10, 0-30 parts of oil phase, 0-50 parts of flavor, 1-2 parts of Tween 80, 29-59 parts of surfactant, 1-10 parts of auxiliary surfactant, 0-5 parts of polyglycerol monopalmitate and 0-0.02 parts of antioxidant.

2. The coenzyme Q10 self-emulsifying solution according to claim 1, characterized in that The oil phase is a mixture of linseed oil, medium-chain fatty acid glycerides, oleic acid and olive oil, and the mass ratio of medium-chain fatty acid glycerides, linseed oil, oleic acid and olive oil is 2:(0.5-1):(0.5-1):(0.5-1); the flavor is one or more of sweet orange oil flavor, peppermint oil, rosemary oil, lemon flavor, lemongrass oil and lemon terpenes; the surfactant is one or more of phospholipids, citric acid fatty acid glycerides, polyglycerol laurate, polyglycerol myristate and polyglycerol oleate; the co-surfactant is one or more of polyethylene glycol 400, ethanol and glycerol; the antioxidant is one or more of ascorbic acid, calcium ascorbate, sodium ascorbate and natural vitamin E.

3. The coenzyme Q10 self-emulsifying solution according to claim 2, characterized in that: The preparation method of linseed oil comprises the following steps: (1) Pretreatment: After flax seeds are shelled and peeled, they are placed in a forced air drying oven to dry to obtain dry and clean flax seeds, the dry and clean flax seeds are crushed and sieved to obtain flax seed powder, the flax seed powder is weighed and added to distilled water, and after being mixed evenly, a flax seed mixed liquid is obtained, which is placed in an ultrasonic cleaning instrument for ultrasonic treatment to obtain a flax seed pretreatment liquid; (2) Enzymatic hydrolysis: adjusting the pH value and temperature of the flax seed pretreatment solution, adding alkaline protease for enzymatic hydrolysis, and after the enzymatic hydrolysis is completed, raising the temperature of the constant temperature water bath to inactivate the enzyme, and after the end, obtaining a flax seed enzymatic hydrolyzate; (3) Centrifugal separation: centrifuging the flaxseed hydrolysate to obtain an upper layer of clear oil I, a middle layer of emulsion I and a lower layer of precipitate I, discarding the lower layer of precipitate I, centrifuging the obtained emulsion I again to obtain an upper layer of clear oil II, a middle layer of emulsion II and a lower layer of precipitate II, discarding the lower layer of precipitate II, freezing the obtained emulsion II, centrifuging it and separating it to obtain an upper layer of free clear oil III; (4) Combining and drying: The upper layer of clear oil I, the upper layer of clear oil II and the upper layer of free clear oil III are combined and dried until the mass is constant to obtain linseed oil.

4. The coenzyme Q10 self-emulsifying solution according to claim 3, characterized in that: In step (1), the temperature of the blast drying oven is 70-75° C., the drying time is 4-6 hours, the mesh size of the flax seed sieve is 80-200 meshes, the solid-liquid ratio of the flax seed mixed solution is 1:5-6 g / mL, the intensity of the ultrasonic treatment is 400-450 W, the ultrasonic time is 40-60 minutes, and the ultrasonic temperature is 50-55° C.; in step (2), the pH value is adjusted to 9-11 with a sodium hydroxide solution, the temperature is 42-45° C., the enzymatic hydrolysis time is 2.5-3 hours, the constant temperature water bath is heated to 95-100° C., and the enzyme is inactivated for 8-10 minutes; in step (3), the centrifugal speed is 8000-10000 rpm, the centrifugal time is 25-30 minutes, the freezing temperature is -18° C., and the freezing time is 24-26 hours; and in step (4), the drying temperature is 55-60° C.

5. The process for preparing the coenzyme Q10 self-emulsifying solution according to claims 1-4, characterized in that: The method comprises the following steps: uniformly mixing other auxiliary materials except coenzyme Q10 powder according to weight parts, heating to 60-70°C, slowly adding coenzyme Q10 powder after other auxiliary materials are dissolved, grinding with a three-roll grinder (100) to obtain a mixed liquid, putting the mixed liquid into an emulsification vacuum tank (200), filling with nitrogen, stirring until coenzyme Q10 is completely dissolved, and emulsifying at a temperature of 10-12 hours to obtain a coenzyme Q10 self-emulsifying solution.

6. A preparation device for a coenzyme Q10 self-emulsifying solution, suitable for the preparation process for a coenzyme Q10 self-emulsifying solution according to claim 5, characterized in that: The preparation equipment comprises a three-roll mill (100) and an emulsification vacuum tank (200); The multi-roller grinding machine (100) is used for grinding the material of the coenzyme Q10 self-emulsifying solution, and comprises a frame (101), on which a plurality of rollers (103) are rotatably mounted, and a plurality of motors (104) are mounted on the frame (101), the number of the plurality of motors (104) being the same as the number of the plurality of rollers (103), and when the plurality of motors (104) are in operation, they respectively drive the corresponding rollers (103) to rotate and make the plurality of rollers (103) operate asynchronously with respect to each other so as to grind the material of the coenzyme Q10 self-emulsifying solution; the multi-roller grinding machine (100) further comprises a scraping device (105) movably arranged on the frame (101), and the scraping device (105) can contact the rotating roller (103) to scrape off the material attached to the circumferential surface of the roller (103); The emulsification vacuum tank (200) is used to self-emulsify the ground coenzyme Q10 self-emulsifying solution material, and comprises a fixed frame (201), a sealing cover (202) is installed through the top surface of the fixed frame (201), a driving motor (203) is installed on the sealing cover (202), a shaft (204) is installed on the power output shaft of the driving motor (203), and a stirring rod (205) is installed on the shaft (204); a slidable and rotatable transparent tank (206) is arranged in the fixed frame (201), and the transparent tank (206) and the sealing cover (202) can be plugged and matched.

7. The preparation device of the coenzyme Q10 self-emulsifying solution according to claim 6, characterized in that: The scraping device comprises a scraping plate (105), wherein the scraping plate (105) is provided with a vertical portion (111) and an inclined portion (113); a threaded cylinder (106) and a threaded rod (107) threadedly connected to the threaded cylinder (106) are mounted on the vertical portion (111); a rotating disk (108) is mounted on one end of the threaded rod (107) away from the frame (101); and the inclined portion (113) can be in contact with a roller.

8. The preparation equipment of the coenzyme Q10 self-emulsifying solution according to claim 6, characterized in that: The scraping device (105) is further provided with two guide rods (109), and the two guide rods (109) are fixedly arranged on the side of the frame (101) and penetrate the vertical portion (111).

9. The preparation device of the coenzyme Q10 self-emulsifying solution according to claim 6, characterized in that: A multi-stage hydraulic cylinder (210) is installed on the inner bottom surface of the fixed frame (201), and a push plate (211) is installed on the extended end of the multi-stage hydraulic cylinder (210), and the push plate (211) is fixedly connected to the bottom surface of the transparent tank (206). Slide grooves (208) are provided on the inner walls of both sides of the fixed frame (201), and a pair of slide bars (207) are pivotally connected to the two sides of the transparent tank 206, and the ends of each slide bar (207) are movably accommodated in the slide grooves (208).

10. The preparation device of the coenzyme Q10 self-emulsifying solution according to claim 6, characterized in that: A vacuum pump (212) and a pressure gauge (209) are installed on the top surface of the sealing cover (202). The vacuum end of the vacuum pump (212) extends to the bottom of the sealing cover (202). The detection end of the pressure gauge (209) also extends to the bottom of the sealing cover (202). A gas storage tank (213) is also installed on the top surface of the sealing cover (202). The gas storage tank (213) is used to store inert gas. A gas delivery pipe (214) is installed on the gas storage tank (213). The gas delivery pipe (214) extends to the bottom of the sealing cover (202). A switch valve is installed on the gas delivery pipe (214).

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