Veterinary coenzyme Q10 composite emulsion as well as preparation method and application thereof

Abstract

The invention relates to the field of preparation of veterinary coenzyme Q10 preparations, in particular to a veterinary coenzyme Q10 composite emulsion as well as a preparation method and application thereof. The veterinary coenzyme Q10 composite emulsion is prepared by utilizing a nanostructure lipid carrier system and supplementing vitamins A, D and E, and the preparation method of the veterinary coenzyme Q10 composite emulsion is simple. The veterinary coenzyme Q10 composite emulsion is small in particle size, low in polydispersity coefficient, good in zeta potential absolute value and stability, high in uniformity and high in coenzyme Q10 concentration. Meanwhile, the coenzyme Q10 is high in administration efficiency and small in side effect, can realize drinking administration of the coenzyme Q10, is suitable for oral administration of animals, meets the administration requirements of veterinary clinical breeding enterprises, and has a wide application prospect.

Description

Technical Field

[0001] The present invention relates to veterinary coenzyme Q 10 Preparation field, specifically involving a veterinary coenzyme Q 10 Composite emulsion and its preparation method and application. Background Art

[0002] Coenzyme Q 10 (CoQ 10 ) is a fat-soluble quinone substance widely present in organisms. It is an important hydrogen donor in the respiratory chain of biological cells and is widely involved in the oxidative phosphorylation and ATP generation process in organisms. 10 CoQ has many biological functions, such as enhancing immunity, anti-oxidation, anti-tumor effect, inhibiting cell apoptosis, stabilizing biofilm structure, etc. 10 It is widely used in food additives, medical treatment, health care, etc. 10 The chemical properties are unstable, the water solubility is poor, the thermal stability is poor, and it is easily decomposed by light, resulting in clinical CoQ 10 The product has poor stability and low bioavailability.

[0003] To solve the CoQ 10 In the application, the existing technology uses solid dispersion technology, cyclodextrin inclusion technology, nanoparticles, microcapsules and other technologies to improve its water solubility and enhance its stability during storage, which has become the focus of current research. For example, patent CN101214197A provides a CoQ 10 Nano-microcapsule emulsion containing active ingredients and applied in the field of cosmetics; Patent CN102008400A provides a method for improving CoQ 10 Stability, CoQ promotion 10 CoQ that penetrates the stratum corneum of the skin 10 Nano lipid composition, and used in skin care cosmetics or pharmaceutical fields; Patent CN113350312A provides a method for improving CoQ 10 Stability and Bioavailability of CoQ 10 Nanocapsules are mainly used in food, cosmetics, and pharmaceutical fields; Patent CN107568731B provides a method for increasing CoQ 10 Bioavailability of CoQ 10 Fish oil nanoemulsion is mainly used in the fields of food and health care products.

[0004] Although CoQ 10Due to its antioxidant and free radical scavenging properties, as well as its ability to enhance the body's immunity, treat cardiovascular diseases, and fight cancer, it has received attention and research in various fields. It has gradually entered the mainstream in the fields of human medicine and cosmetics. However, its use in the veterinary medicine field is limited because coenzyme Q 10 is highly lipophilic. In veterinary clinical administration, it is mainly through premix formulations. Existing CoQ 10 formulations used as premixes not only have low efficiency but also tend to have uneven mixing during clinical use, leading to anorexia in animals and even stress reactions. Therefore, the existing CoQ 10 formulations are not suitable for use by large animal health care enterprises, and the product administration methods cannot meet the dosing requirements of veterinary clinics.

[0005] Given the broad application prospects of CoQ 10 it is of great practical significance to develop a CoQ 10 formulation that is convenient for veterinary clinical administration, has high stability, and low side effects. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide a veterinary coenzyme Q10 complex emulsion in view of the deficiencies of the prior art.

[0007] Another technical problem to be solved by the present invention is to provide a preparation method for the above-mentioned veterinary coenzyme Q10 complex emulsion.

[0008] The last technical problem to be solved by the present invention is to provide the application of the above-mentioned veterinary coenzyme Q10 complex emulsion in the preparation of veterinary drugs.

[0009] To solve the above technical problems, the technical solutions adopted by the present invention are as follows:

[0010] In the first aspect of the present invention, a veterinary coenzyme Q 10 complex emulsion is provided, which contains the following components by weight percentage:

[0011] Coenzyme Q 10 2 - 4%,

[0012] Vitamin A 0 - 3%,

[0013] Vitamin D 0 - 1%,

[0014] Vitamin E 0 - 3%,

[0015] Main emulsifier 1.26 - 4.2%,

[0016] Auxiliary emulsifier 0.54 - 1.8%,

[0017] The balance is purified water.

[0018] Among them, the main emulsifier is any one or a combination of several of polysorbate 20, polysorbate 80, polysorbate 85, poloxamer 188, and poloxamer 407; preferably, the main emulsifier is polysorbate 85.

[0019] Among them, the secondary emulsifier is any one or a combination of several of span 80, span 20, poloxamer 188, and poloxamer 407; preferably, the secondary emulsifier is span 80.

[0020] Among them, the mass ratio of the main emulsifier to the secondary emulsifier is 1-9:1; preferably, the mass ratio of the main emulsifier to the secondary emulsifier is 9:1, 8:2, 7:3, 6:4, or 5:5; more preferably, the mass ratio of the main emulsifier to the secondary emulsifier is 7:3.

[0021] Among them, vitamin A, vitamin D, and vitamin E are collectively referred to as lipids, and the main emulsifier and the secondary emulsifier are collectively referred to as emulsifiers.

[0022] Specifically, the milk fat ratio of the emulsifier to the lipid is 1:1-4; preferably, the milk fat ratio of the emulsifier to the lipid is 1:1 (i.e., 100%), 4:5 (i.e., 80%), 1:2 (i.e., 50%), 2:5 (i.e., 40%), 3:10 (i.e., 30%); more preferably, the milk fat ratio of the emulsifier to the lipid is 1:2 (i.e., 50%).

[0023] Preferably, the veterinary coenzyme Q 10 compound emulsion contains the following components in weight percentage:

[0024] Coenzyme Q 10 4%,

[0025] Vitamin A 3%,

[0026] Vitamin D 1%,

[0027] Vitamin E 2%,

[0028] Polysorbate 85 2.1%,

[0029] Span 80 0.9%,

[0030] The balance is purified water.

[0031] Furthermore, the veterinary coenzyme Q 10 compound emulsion has a particle size range of 100-300 nm, and preferably a particle size range of 150-250 nm.

[0032] The second aspect of the present invention provides a method for preparing a veterinary coenzyme Q 10 compound emulsion, which includes the following steps:

[0033] (1) Dissolve coenzyme Q 10 , vitamin E, vitamin A, vitamin D and co-emulsifier, and then mix them evenly to prepare an oil phase;

[0034] (2) Dissolve the main emulsifier in purified water to prepare an aqueous phase;

[0035] (3) Add the oil phase to the aqueous phase and shear to obtain a crude emulsion;

[0036] (4) Transfer the crude emulsion to an ultrasonic crusher for ultrasonic crushing, or subject the crude emulsion to high-pressure homogenization treatment through a high-pressure homogenizer to prepare the veterinary coenzyme Q 10 compound emulsion.

[0037] Among them, in steps (1) and (2), for the dissolution, the dissolution temperature is 60 - 70°C; the preferred dissolution temperature is 65°C.

[0038] Among them, in step (3), for the shearing, the conditions are: shearing at 60 - 70°C and 5000 - 8000 rpm for 3 - 8 min; the preferred shearing conditions are shearing at 65°C and 6000 rpm for 5 min.

[0039] Among them, in step (4), for the ultrasonic crushing, the conditions are: ultrasonic crushing at 200 - 300 Hz for 20 - 30 min, and the preferred ultrasonic crushing conditions are: ultrasonic crushing at 200 Hz for 20 min; for the high-pressure homogenization, the conditions are: circulating 2 - 10 times under a pressure condition of 200 - 1000 bar, and the preferred high-pressure homogenization conditions are: circulating 3 - 6 times under a pressure condition of 300 - 800 bar.

[0040] The third aspect of the present invention provides an application of a veterinary coenzyme Q 10 compound emulsion in the preparation of a veterinary coenzyme Q 10 compound preparation.

[0041] The fourth aspect of the present invention provides a veterinary coenzyme Q 10 compound preparation, which contains the veterinary coenzyme Q 10 compound emulsion, that is, preparing the veterinary coenzyme Q 10 compound emulsion into a veterinary coenzyme Q 10 compound preparation that can be orally administered to animals by drinking water.

[0042] Beneficial effects:

[0043] (1) The present invention utilizes a nanostructured lipid carrier system, supplemented with vitamins A, D, and E, to prepare a veterinary coenzyme Q 10 compound emulsion. This veterinary coenzyme Q 10The composite emulsion has small particle size, low polydispersity coefficient, absolute value of zeta potential, good stability, high uniformity.

[0044] (2) The veterinary coenzyme Q provided by the present invention 10 composite emulsion, the emulsion coenzyme Q 10 has a high concentration, high administration efficiency and small side effects, is suitable for oral administration of animals, realizes the drinking water administration of coenzyme Q 10 , meets the administration requirements of veterinary clinical breeding enterprises, and has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] The following further specifically describes the present invention in conjunction with the drawings, and the above and / or other advantages of the present invention will become clearer.

[0046] Figure 1 It is the precipitation situation after standing at room temperature for 48 hours under the compounding of the main emulsifier and the auxiliary emulsifier at a ratio of 1:1.

[0047] Figure 2 It is the particle size characterization diagram of the compounding of T85 and S80.

[0048] Figure 3 It is the particle size characterization diagram of the compounding of T85 and S20.

[0049] Figure 4 It is the precipitation situation after standing at room temperature for 48 hours under different compounding ratios of the main emulsifier and the auxiliary emulsifier.

[0050] Figure 5 It is the comparison of the results of the composite emulsion placed for one week.

[0051] Figure 6 It is the result of the composite emulsion placed for three weeks. DETAILED DESCRIPTION OF THE INVENTION

[0052] The following further specifically describes the present invention in conjunction with the detailed description of the invention, and the above and / or other advantages of the present invention will become clearer.

[0053] In the following examples, the experimental methods are all conventional methods unless otherwise specified; the reagents and materials can be obtained from commercial channels unless otherwise specified.

[0054] In the following examples, the particle size, polydispersity coefficient, and zeta potential are measured using a laser particle size analyzer and characterized by photon correlation spectroscopy. During the test, the angle is kept constant at 90°, the temperature is kept constant at 25°C, the equilibrium time is 2 minutes, and the test is repeated 3 times.

[0055] In the following embodiments, T20, T80, T85, P188, P407, S80, and S20 represent, in sequence: polysorbate 20, polysorbate 80, polysorbate 85, poloxamer 188, poloxamer 407, span 80, and span 20.

[0056] Example 1: Screening of Lipid Drug Delivery Formulations

[0057] Taking the dissolution amount of the main drug coenzyme Q 10 8 g / 500 mL in the product emulsion as the target, in the laboratory test screening, the content of the main drug coenzyme Q 10 was preset to be 0.2 g to 0.4 g / 10 mL. With a mass ratio of 3:1:2 for vitamin A, vitamin D, and vitamin E, two lipid drug delivery formulations were designed.

[0058] Lipid Drug Delivery Formulation A: Vitamin A (solid lipid) 0.3 g + Vitamin D (liquid lipid) 0.1 g + Vitamin E (liquid lipid) 0.2 g + Coenzyme Q 10 (main drug) 0.2 g to 0.4 g.

[0059] Lipid Drug Delivery Formulation B: Vitamin A (solid lipid) 0.3 g + Vitamin D (liquid lipid) 0.1 g + Vitamin E (liquid lipid) 0.2 g + Glyceryl Trioleate (liquid lipid) 0.3 g + Coenzyme Q 10 (main drug) 0.2 g to 0.4 g.

[0060] The lipids in the two formulations were placed in ampoules and dissolved in a water bath at 65°C. Then, 0.2 g of coenzyme Q 10 was added. After it was completely dissolved, it was added in a gradient of 0.02 g each time, for a total addition of 0.4 g of coenzyme Q 10 . The results showed that the lipids in both formulations could be completely dissolved in a water bath environment at 65°C. The dissolved samples were left to stand at room temperature for 48 h, and the precipitation of the two was observed. The results showed that after standing at room temperature for 48 h, the lipid drug delivery of Formulation A was stable and no coenzyme Q 10 precipitated, while obvious precipitation occurred in Formulation B. Therefore, Formulation A was used as the basis for further screening in the follow-up.

[0061] Example 2: Screening of Emulsifiers

[0062] The emulsion type of the coenzyme Q10 combined with vitamins A, D, and E is an oil-in-water (O / W) type. According to the hydrophilic-lipophilic balance principle, when screening emulsifiers in this example, an oil-in-water (O / W) emulsifier was selected as the main emulsifier, and a water-in-oil (W / O) emulsifier was selected as the auxiliary emulsifier to adjust the hydrophilic-lipophilic balance value in the emulsion system.

[0063] 1. Screening of the main emulsifier

[0064] The main emulsifiers (T20, T80, T85, P188, P407 or polyglycerol fatty acid ester) were screened with a milk fat ratio of 50%, that is, the mass ratio of emulsifier to lipid was 1:2. The specific process is as follows:

[0065] Weigh 0.4 g of coenzyme Q 10 , lipids (0.3 g of vitamin E, 0.1 g of vitamin A, 0.2 g of vitamin D) and place them in an oil-phase vial; weigh 0.3 g of the main emulsifier (T20, T80, T85, P188, P407 or polyglycerol fatty acid ester) and place it in an aqueous-phase vial, and add 10 mL of single-distilled water. Add a magnetic stirrer to the oil-phase and aqueous-phase vials and dissolve them in a water bath at 65 °C. Slowly add the dissolved oil phase to the aqueous phase and mix well. Then put it back into the water bath to continue dissolving. After complete dissolution, take out the magnetic stirrer, and use a high-shear mixer to perform high-shear for 5 min at a speed of 6000 rpm to obtain a coarse emulsion. Then transfer the coarse emulsion to an ultrasonic crusher and process it at a frequency of 200 Hz for 20 min to obtain a composite emulsion. Observe its state after emulsification, the state after standing for 48 h, as well as the layering and oil floating conditions. Subsequently, the average particle size, polydispersity coefficient, and zeta potential were used as evaluation indicators for characterization and analysis.

[0066] The screening results of the main emulsifiers are shown in Table 1. When the average particle size is smaller, the polydispersity coefficient is lower, and the absolute value of the zeta potential is larger, the emulsification efficiency is higher and the emulsion is more stable. The results show that T85 has the best emulsifying effect. The corresponding emulsion particle size is 162.60 ± 3.52 nm, the polydispersity coefficient is low, and the absolute value of the potential value is about 30 mV, and the system is stable. Therefore, T85 was selected as the main emulsifier.

[0067] Table 1 Screening results of main emulsifiers

[0068]

[0069] 2. Screening of co-emulsifiers

[0070] On the basis of the optimization of the main emulsifier in step 1, the co-emulsifiers were screened with the compound mass ratio of the main emulsifier to the co-emulsifier being 1:1 and the milk fat ratio being 50% (that is, the mass ratio of the emulsifier to the lipid being 1:2). The specific process is as follows:

[0071] Weigh 0.4 g of coenzyme Q 10, lipids (0.3 g of vitamin E, 0.1 g of vitamin A, 0.2 g of vitamin D), 0.15 g of co-emulsifier (S80, S20, P188 or P407) are placed in an oil-phase vial; 0.15 g of the main emulsifier T85 is weighed and placed in a water-phase vial, and 10 mL of single-distilled water is added. A magnetic stirrer is added to the oil-phase and water-phase vials and dissolved in a water bath at 65 °C. The dissolved oil phase is slowly added to the water phase and mixed well, then placed back in the water bath to continue dissolving. After complete dissolution, the magnetic stirrer is removed, and a high-shear mixer is used to perform high-shear mixing at a speed of 6000 rpm for 5 min to obtain a coarse emulsion. Then, the coarse emulsion is transferred to an ultrasonic crusher and processed at a frequency of 200 Hz for 20 min to obtain a composite emulsion. Similarly, the average particle size, polydispersity coefficient, and zeta potential are used as evaluation indicators.

[0072] The screening results of the co-emulsifiers are shown in Table 2, Figures 1 - 3 . The results show that obvious oil layers precipitate after preparation and placement for 48 h with P188 and P407, so they are not considered for the time being ( Figure 1 ). The compounding results of T85 with S80 and T85 with S20 are similar, but when analyzing their particle size characterization diagrams ( Figures 2 - 3 ), there is a bimodal phenomenon with S20, while the results obtained by compounding S80 and T85 have no other problems. The particle size is 203.02 ± 1.747 nm, and the absolute value of the potential is about 30 mV, and the system is stable. Therefore, S80 is selected as the co-emulsifier.

[0073] Table 2 Screening results of co-emulsifiers

[0074] Co - emulsifier Particle size (nm) Polydispersity index PDI Zeta potential (mV) S80 203.02±1.747 0.235±0.014 -28.5±1.27 S20 202.3±1.637 0.240±0.011 -29.4±0.451 P407 170.5±1.744 0.327±0.031 -33.7±0.513 P188 229.3±8.608 0.437±0.028 -28.5±0.723

[0075] 3. Screening of the compounding ratio of the main emulsifier and the co-emulsifier

[0076] On the basis of the optimization of the co-emulsifier in step 2, with a milk-fat ratio of 50% (i.e., the mass ratio of the emulsifier to the lipid is 1:2), five compounding mass ratios of the main and co-emulsifiers, namely 9:1, 8:2, 7:3, 6:4, and 5:5, are designed to screen the compounding ratio of the main emulsifier and the co-emulsifier. The specific process is as follows:

[0077] Weigh 0.4 g of coenzyme Q 10, lipids (0.3 g of vitamin E, 0.1 g of vitamin A, 0.2 g of vitamin D), and a certain mass of co - emulsifier S80 were placed in an oil - phase vial; a corresponding certain mass of main emulsifier T85 was weighed and placed in an aqueous - phase vial, and 10 mL of double - distilled water was added. A magnetic stirrer was placed in the oil - phase and aqueous - phase vials and dissolved in a water bath at 65 °C. The dissolved oil phase was slowly added to the aqueous phase and mixed thoroughly, then placed back in the water bath for further dissolution. After sufficient dissolution, the magnetic stirrer was removed, and a high - shear mixer was used to perform high - shear mixing at a speed of 6000 rpm for 5 min to obtain a coarse emulsion. Then the coarse emulsion was transferred to an ultrasonic crusher and treated at a frequency of 200 Hz for 20 min to obtain a composite emulsion. The emulsified state, oil floating situation, and the state, layering, and oil floating situation after standing for 48 hours were observed respectively, and finally, characterization and analysis were carried out. Similarly, the average particle size, polydispersity index, and zeta potential were used as evaluation indicators.

[0078] The screening results of the compounding ratio of the main emulsifier and the co - emulsifier are shown in Table 3 and Figure 4 . The test results show that: except for the component with the ratio of the main and co - emulsifiers being 7:3, oil layers precipitated in the emulsions with other compounding ratios after standing at room temperature for 48 h. Therefore, the final selected compounding ratio of the main and co - emulsifiers is 7:3.

[0079] Table 3 Characterization results of the compounding ratio of the main and co - emulsifiers

[0080] Compound ratio of primary and co - emulsifiers Particle size (nm) Polydispersity index PDI Zeta potential (mV) 9:1 (0.27 g:0.03 g) 175.8±0.9074 0.209±0.02 -30.9±0.306 8:2 (0.24 g:0.06 g) 182.7±0.4041 0.206±0.01 -30.5±0.608 7:3 (0.21 g:0.09 g) 177.5±1.650 0.196±0.005 -30.8±0.781 6:4 (0.18 g:0.12 g) 198.0±3.386 0.243±0.008 -30.7±1.06 5:5 (0.15 g:0.15 g) 203.02±1.747 0.235±0.014 -28.5±1.27

[0081] 4. Screening of the compounding ratio of the emulsifier and lipids (i.e., screening of the emulsifier - to - lipid ratio)

[0082] After determining the above - mentioned main emulsifier as T85, co - emulsifier as S80, and the compounding ratio of the main and co - emulsifiers being 7:3, with the mass of lipids as a fixed quantity, the compounding ratios of the emulsifier and lipids were screened at 100%, 80%, 50%, 40%, and 30%, and the specific process is as follows:

[0083] Weigh 0.4 g of coenzyme Q 10, lipids (0.3 g of vitamin E, 0.1 g of vitamin A, 0.2 g of vitamin D), and a certain mass of co-emulsifier S80 were placed in an oil-phase vial; a corresponding certain mass of main emulsifier T85 was weighed and placed in an aqueous-phase vial, and 10 mL of single-distilled water was added. A magnetic stirrer was added to the oil-phase and aqueous-phase vials and dissolved in a water bath at 65 °C. The dissolved oil phase was slowly added to the aqueous phase and mixed well, and then placed back in the water bath to continue dissolving. After complete dissolution, the magnetic stirrer was removed, and a high-shear mixer was used to perform high-shear mixing at a speed of 6000 rpm for 5 min to obtain a coarse emulsion. Then, the coarse emulsion was transferred to an ultrasonic crusher and processed at a frequency of 200 Hz for 20 min to obtain a composite emulsion. The emulsified state, floating oil condition, and the state, layering, and floating oil condition after standing for 48 hours were observed respectively, and finally, characterization and analysis were carried out. Similarly, the average particle size, polydispersity coefficient, and zeta potential were used as evaluation indicators.

[0084] The screening results of the milk fat ratio are shown in Table 4. The results show that when the milk fat ratio is 50%, the obtained emulsion has the best characterization effect, with a particle size of 177.5 ± 1.650 nm, the absolute value of the potential is about 30 mV, the particle size is good, and the system is stable.

[0085] Table 4 Characterization results of the compounding ratio screening of emulsifier and lipid

[0086]

[0087] In summary, the final experimental formula of the composite emulsion is shown in Table 5.

[0088] Table 5 Final formula of the composite emulsion

[0089]

[0090] Example 3: Performance characterization of the composite emulsion

[0091] 1. Stability analysis

[0092] The composite emulsion prepared according to the optimized formula of Example 2 was placed for 1 - 3 weeks, and the state of the emulsion was observed. The results are as Figure 5 and Figure 6 shown. Figure 5 shows the state of the composite emulsion after standing for one week. It can be seen that its color is clear, no precipitation or layering occurs, no obvious particulate matter appears after shaking, and the emulsion is clear and beautiful. After the emulsion has been standing for three weeks ( Figure 6) The emulsion color remains clear, and there is still no obvious precipitation. However, there is slight oil-water separation, which disappears after gentle shaking, and the emulsion returns to a clear state. According to the reference of the Pharmacopoeia of the People's Republic of China (2020), a little oil-water separation occurs during the storage of the emulsion, and it can be restored after shaking. The emulsion is still considered to have good stability. The main reason for the oil-water separation phenomenon is that the emulsion has a large drug loading capacity, which does not affect the use of the emulsion.

[0093] 2. Repetition and stability analysis

[0094] Two groups of composite emulsions will be prepared repeatedly according to the optimized formula in Example 2, divided into the initial group and the repetition group. Take 10 μL from each of the two groups of emulsions and dilute them 1000 times, then use a laser particle size analyzer to measure the particle size, polydispersity coefficient, and zeta potential. After three weeks, measure the particle size, polydispersity coefficient, and zeta potential again using the same test method. The results are shown in Table 6.

[0095] Table 6 Characterization of emulsions in the initial group and the repetition group

[0096] Sample Particle size (nm) Polydispersity index PDI Zeta potential (mV) Initial group 177.5±1.586 0.196±0.005 -30.8±0.781 Repeated group 179.8±1.026 0.215±0.011 -30.5±0.987 Initial group (placed for 3 weeks) 209.8±1.653 0.228±0.008 -30.3±0.654 Repeated group (placed for 3 weeks) 208.1±1.233 0.232±0.009 -29.5±0.756

[0097] As can be seen from Table 6, the particle sizes of the composite emulsions prepared in the same-period tests are not large, the polydispersity systems are all not greater than 0.3, and the absolute values of the zeta potential all exceed 30 mV. The particle size, dispersion coefficient, and zeta potential are all normal and good. After three weeks of storage, due to time accumulation, the particle size of general emulsions will naturally increase. Although the difference is significant, the particle size results are acceptable, indicating that the composite emulsion prepared with the formula of the present invention has good stability.

[0098] Example 4: Large-scale test of composite emulsion

[0099] After determining and preparing the optimal formula using the high-shear ultrasonic method, in order to facilitate subsequent research, the high-pressure homogenization technology is used to prepare the composite emulsion in large quantities. The specific process is as follows:

[0100] Weigh 4 g of coenzyme Q according to 10 times the optimized formula 10, 2 g of vitamin E, 3 g of vitamin A, 1 g of vitamin D and 0.9 g of S80 were added to an oil-phase vial. 2.1 g of T85 was weighed and added to a water-phase vial, and 100 mL of single-distilled water was added. Magnetic stirrers were added to both vials and placed in a water bath at 65 °C to dissolve. After dissolution, the oil phase was added to the water phase and mixed well. Then it was placed back in the water bath to continue dissolving. After complete dissolution, the magnetic stirrers were removed. The reagent in the water bath was continuously subjected to high-shear at a speed of 6000 rpm for 5 min using a high-shear mixer to obtain a coarse emulsion. Then the coarse emulsion was put into an ultrasonic crusher and continuously treated at a frequency of 200 Hz for 20 min. After the crushing was completed, it was injected into a preheated high-pressure homogenizer and circulated 5 - 6 times at pressures of 300, 400, 500, and 800 bar respectively to ensure that the emulsion particles were fully refined, and a composite emulsion was prepared.

[0101] It was found that the emulsion homogenized 5 times at a pressure of 400 bar had the smallest particle size, the lowest PDI, and the highest zeta potential after measurement, showing the best stability and uniformity.

[0102] The composite emulsion was prepared into a veterinary coenzyme Q 10 compound preparation, which can be used for animals by drinking water or oral administration, so as to meet the drug administration needs of veterinary clinical breeding enterprises.

[0103] The present invention provides a veterinary coenzyme Q 10 composite emulsion and its preparation method and application ideas and methods. There are many specific methods and ways to implement this technical solution. The above is only the preferred embodiment of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and modifications can be made, and these improvements and modifications should also be regarded as the protection scope of the present invention. Each component not clearly defined in this embodiment can be realized by existing technologies.

Claims

1. A veterinary coenzyme Q 10 The composite emulsion is characterized in that The following components are included by weight percentage: Coenzyme Q 10 2-4%, Vitamin A 0-3%, Vitamin D 0-1%, Vitamin E 0-3%, Main emulsifier 1.26~4.2%, Secondary emulsifier 0.54~1.8%, The rest is purified water; Among them, the main emulsifier is any one of polysorbate 20, polysorbate 80, polysorbate 85, poloxamer 188, and poloxamer 407, or a combination of several of them; the secondary emulsifier is any one of Span 80, Span 20, poloxamer 188, and poloxamer 407, or a combination of several of them.

2. The veterinary coenzyme Q according to claim 1 10 The composite emulsion is characterized in that The primary emulsifier is polysorbate 85; the secondary emulsifier is Span 80.

3. The veterinary coenzyme Q according to claim 1 10 The composite emulsion is characterized in that The mass ratio of the primary emulsifier to the secondary emulsifier is 1 to 9:

1.

4. The veterinary coenzyme Q according to claim 1 10 The composite emulsion is characterized in that The vitamin A, vitamin D and vitamin E are collectively referred to as lipids, the primary emulsifier and secondary emulsifier are collectively referred to as emulsifiers; the milk fat ratio of the emulsifier to lipids is 1:1-4.

5. The veterinary coenzyme Q according to any one of claims 1 to 4 10 The method for preparing a composite emulsion is characterized in that: The steps include: (1) Coenzyme Q 10 , vitamin E, vitamin A, vitamin D and a secondary emulsifier are dissolved and mixed evenly to form an oil phase; (2) dissolving the primary emulsifier in purified water to prepare an aqueous phase; (3) adding the oil phase to the water phase and shearing to obtain a crude emulsion; (4) transferring the crude emulsion to an ultrasonic crusher for ultrasonic crushing, or subjecting the crude emulsion to high-pressure homogenization by a high-pressure homogenizer to prepare the veterinary coenzyme Q 10 Composite emulsion.

6. The preparation method according to claim 5, characterized in that: In step (1) and step (2), the dissolution has a dissolution temperature of 60 to 70°C.

7. The preparation method according to claim 5, characterized in that: In step (3), the shearing is carried out under the conditions of 60-70° C. and 5000-8000 rpm for 3-8 min.

8. The preparation method according to claim 5, characterized in that: In step (4), the ultrasonic crushing is carried out under the conditions of 200-300 Hz for 20-30 min; the high-pressure homogenization is carried out under the conditions of 200-1000 bar for 2-10 cycles.

9. The veterinary coenzyme Q according to any one of claims 1 to 4 10 Compound emulsion in the preparation of veterinary coenzyme Q 10 Application in compound preparations.

10. A kind of veterinary coenzyme Q 10 The composite preparation is characterized in that Containing the veterinary coenzyme Q according to any one of claims 1 to 4 10 Composite emulsion.

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