A liquid-phase stable high-content coenzyme Q 10 Composite microcapsules, their preparation methods and applications

Abstract

This invention discloses a liquid-phase stable high-content coenzyme Q. 10 Composite microcapsules, their preparation methods and applications, and liquid-phase stable high-content coenzyme Q. 10 The composite microcapsules include the following ingredients: Coenzyme Q 10 The active ingredients, emulsifiers, co-emulsifiers, fillers, and anti-caking agents; the coenzyme Q... 10 The components are: 10-60 parts by weight of the active ingredient, 5-15 parts by weight of the active ingredient, 2-10 parts by weight of the emulsifier, 1-5 parts by weight of the co-emulsifier, 10-50 parts by weight of the filler, and 0.1-1 parts by weight of the anti-caking agent. This invention provides a liquid-phase stable high-content coenzyme Q10. 10 The composite microcapsules have both high encapsulation efficiency and long-term stability in the liquid phase, and have significant anti-fatigue and physical strength enhancement effects.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical formulation technology, specifically relating to a liquid-phase stable high-content coenzyme Q. 10 Composite microcapsules, their preparation methods, and applications. Background Technology

[0002] Coenzyme Q 10 (Coenzyme Q 10 CoQ (abbreviated as CoQ) 10 Coenzyme Q10 is a naturally occurring, fat-soluble antioxidant found in human cells. It possesses significant antioxidant and cellular energy metabolism-boosting effects and is widely used in the food, health supplement, and cosmetic industries. With age or increased stress, the amount of coenzyme Q10 in the human body decreases. 10 As its content gradually decreases, coenzyme Q10 is prone to oxidative damage and energy metabolism disorders. In recent years, due to its potential in cardiovascular health, anti-aging, and anti-fatigue applications, coenzyme Q10 has gained attention. 10 The market demand for antioxidant health supplements is growing rapidly. However, Coenzyme Q10... 10 Its poor solubility, easy oxidation, and low bioavailability limit its development and application in food.

[0003] To overcome these problems, microencapsulation technology has become a key technology for improving coenzyme Q10. 10 A key means of ensuring stability and bioavailability. This is achieved through coenzyme Q... 10 Encapsulation in microcapsules made of polysaccharides, proteins, or other food-grade materials effectively protects Coenzyme Q from oxidative degradation and improves its dispersibility and solubility in water-based systems. Furthermore, microencapsulation technology can also enable the production of Coenzyme Q. 10 The sustained-release effect improves absorption efficiency. In the process of realizing this invention, the inventors discovered at least the following problems in the prior art: Current Coenzyme Q10... 10 Microencapsulation technology generally suffers from problems such as low encapsulation efficiency, material safety, and high process costs. This paper discusses the integration of multiple active ingredients with coenzyme Q. 10 When using multiple nutrients to form microcapsules, it is often difficult to obtain microcapsules that simultaneously achieve high encapsulation efficiency, physical stability, and high performance. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to provide a liquid-phase stable high-content coenzyme Q solution that addresses the shortcomings of the prior art. 10 Composite microcapsules, their preparation method, and applications. These liquid-phase stable high-content coenzyme Q capsules... 10 The composite microcapsules have both high encapsulation efficiency and long-term stability in the liquid phase, and have significant anti-fatigue and physical strength enhancement effects.

[0005] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is as follows:

[0006] On the one hand, it provides a liquid-phase stable high-content coenzyme Q. 10 The composite microcapsules include the following ingredients: Coenzyme Q 10 The active ingredients, emulsifiers, co-emulsifiers, fillers, and anti-caking agents; the coenzyme Q... 10 The ingredients are present in the following proportions: 10-60 parts by weight, 5-15 parts by weight of active ingredient, 2-10 parts by weight of emulsifier, 1-5 parts by weight of co-emulsifier, 10-50 parts by weight of filler, and 0.1-1 parts by weight of anti-caking agent.

[0007] On the other hand, a method for preparing the above-mentioned liquid-phase stable high-content coenzyme Q is provided. 10 Methods involving composite microcapsules include:

[0008] Step 1: Disperse the emulsifier and filler in pure water, add the water-soluble active ingredient, and stir until dissolved to obtain phase a;

[0009] Step 2: Under heating conditions, add coenzyme Q... 10 The mixture is melted into a co-emulsifier, and an oil-soluble active ingredient is added and stirred until homogeneous to obtain phase b.

[0010] Step 3: Heat phase a to the same temperature as phase b in step 2, then add it to phase b, shear, homogenize, and cool to obtain an emulsion;

[0011] Step 4: Spray dry to obtain powder;

[0012] Step 5: Mix the powder with an anti-caking agent, granulate by boiling, and sieve to obtain Coenzyme Q. 10 Microcapsules.

[0013] On the other hand, a high-content coenzyme Q that is stable in the liquid phase is provided. 10 Application of composite microcapsules in the preparation of pharmaceuticals, health products or cosmetics with antioxidant and anti-fatigue effects.

[0014] Compared with the prior art, the present invention has the following advantages:

[0015] 1. The liquid-phase stable high-content coenzyme Q10 composite microcapsules of the present invention have both high encapsulation efficiency and long-term liquid-phase stability, and have significant anti-fatigue and physical strength enhancement effects.

[0016] 2. The method for preparing the liquid-phase stable high-content coenzyme Q10 complex microcapsules of the present invention is based on the preparation of liquid-phase stable high-content coenzyme Q10 by phase separation blending of water-soluble and oil-soluble active ingredients, followed by spray drying and fluidized bed granulation. 10 Composite microcapsules, compared to microencapsulation of water-soluble active ingredients followed by blending, provide a liquid-phase stable high-content coenzyme Q content. 10 Composite microcapsules combine high encapsulation efficiency with stable long-term liquid-phase storage performance.

[0017] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0018] Figure 1 Example 1: Liquid-phase stable high-content coenzyme Q 10 Morphological images of the composite microcapsules;

[0019] Figure 2 This invention contains a high-content, liquid-phase stable coenzyme Q. 10 Morphological images of liquid beverages containing composite microcapsules;

[0020] Figure 3 This is a schematic diagram showing the results of mouse survival time determination;

[0021] Figure 4 This is a schematic diagram showing the test results of various indicator factors in the mouse anti-fatigue test.

[0022] Figure 5 This is a schematic diagram showing the test results of various indicator factors in the weighted swimming test of mice. Detailed Implementation

[0023] The technical solution will now be clearly and completely described with reference to the embodiments of this application. Obviously, the described embodiments are only a part of the embodiments of this application, not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this application without creative effort are within the scope of protection of this application.

[0024] In the following description, the term "and / or" is used to describe the relationship between related objects, indicating that there can be three relationships. For example, A and / or B can mean: A exists alone, B exists alone, and A and B exist simultaneously. A and B can be singular or plural.

[0025] In the following description, the terms “including,” “containing,” “having,” and “containing” are open-ended terms, meaning that they include but are not limited to.

[0026] Those skilled in the art should understand that, in the following description of the embodiments of this application, the sequence of numbers does not imply the order of execution. Some or all steps may be executed in parallel or sequentially. The execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of this application.

[0027] Those skilled in the art will understand that the numerical ranges in the embodiments of this application should be understood to specifically disclose each intermediate value between the upper and lower limits of the range. Each smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included in this application. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0028] Unless otherwise stated, the technical / scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains. While this application describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this application. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0029] The technical principle employed in this invention is based on the phase-separated blending of oil-soluble and water-soluble active ingredients to obtain a high-content coenzyme Q with high encapsulation capacity and long-term stability in liquid phase storage. 10 Composite microcapsules, various active ingredients and Q 10 Synergistic effects give microcapsules high antioxidant and anti-fatigue properties.

[0030] Epigallocatechin gallate (EGCG) is a polyphenolic compound extracted from green tea. It has strong antioxidant capabilities, can effectively scavenge free radicals, protect cells from oxidative damage, and also has anti-inflammatory, immune-boosting, and metabolic-regulating effects. It helps prevent cardiovascular disease and certain cancers. In addition, EGCG can promote fat metabolism and help control weight. It is often used in health foods.

[0031] Grape seed extract is rich in proanthocyanidins (OPCs), which have antioxidant properties. They can effectively scavenge free radicals, protect cells from oxidative damage, support cardiovascular health, and delay aging.

[0032] Vitamin B5, a key factor in energy metabolism, can indirectly exert antioxidant effects. By participating in the synthesis of coenzyme A, it enhances cell vitality and supports the healthy function of the skin and mucous membranes.

[0033] Vitamin E, a fat-soluble vitamin, can neutralize free radicals, protect cell membranes from oxidative damage, help delay aging, and can be used as a dietary supplement to support the immune system, promote skin health and cardiovascular protection. It can also help improve blood circulation, reduce the risk of atherosclerosis, prevent certain chronic diseases, and promote hair and nail growth.

[0034] This invention co-encapsulates the above-mentioned active ingredients, enabling them to work with Coenzyme Q. 10The compound formulation achieves a synergistic effect, providing multi-dimensional antioxidant and highly effective anti-fatigue benefits.

[0035] On the one hand, it provides a liquid-phase stable high-content coenzyme Q. 10 The composite microcapsules include the following ingredients: Coenzyme Q 10 The active ingredients, emulsifiers, co-emulsifiers, fillers, and anti-caking agents; the coenzyme Q... 10 The ingredients are present in a mixture of 10-60 parts by weight, 5-15 parts by weight of the active ingredient, 2-10 parts by weight of the emulsifier, 1-5 parts by weight of the co-emulsifier, 10-50 parts by weight of the filler, and 0.1-1 parts by weight of the anti-caking agent. This invention provides a liquid-phase stable high-content coenzyme Q10. 10 The composite microcapsules contain coenzyme Q10, active ingredients, emulsifiers, co-emulsifiers, fillers, and anti-caking agents. They can be stably dispersed in the liquid phase and can significantly improve the body's antioxidant capacity, reduce oxidative damage, and relieve physical fatigue.

[0036] In some embodiments, the coenzyme Q 10 It is oxidized coenzyme Q. 10 .

[0037] In some embodiments, the active ingredient includes water-soluble and oil-soluble active ingredients, wherein the water-soluble active ingredients include one or more of epigallocatechin gallate, grape seed extract, vitamin B5, and vitamin C, and the oil-soluble active ingredients include vitamin E.

[0038] In some embodiments, the active ingredients are epigallocatechin gallate, grape seed extract, vitamin B5, and vitamin E. Preferably, the active ingredients in this invention are an active composition that includes both oil-soluble and water-soluble active ingredients. The combination of multiple active ingredients can act synergistically on the body, exhibiting high efficacy and high safety.

[0039] In some embodiments, the emulsifier includes one or more of whey protein isolate, sodium caseinate, sucrose fatty acid esters, and mono- and diglycerides of fatty acids. In some preferred embodiments, the emulsifier is a sucrose fatty acid ester.

[0040] In some embodiments, the co-emulsifier includes one or more of soybean lecithin, mono- and diglyceride fatty acid esters, polyoxyethylene (20) sorbitan monooleate, and polyoxyethylene (20) sorbitan monolaurate; the soybean lecithin has a phosphatidylcholine content of 15% to 90%. In some preferred embodiments, the co-emulsifier is soybean lecithin, and the phosphatidylcholine content is 50%. During their research, the inventors discovered that when the co-emulsifier is soybean lecithin PC50, the emulsifier is sucrose fatty acid ester, and the active ingredient is the aforementioned product containing both oil-soluble and water-soluble active ingredients, the resulting liquid phase is stable with a high content of coenzyme Q. 10 The composite microcapsules have both high encapsulation efficiency and long-term stability in the liquid phase, and have higher antioxidant and anti-fatigue effects.

[0041] In some embodiments, the filler includes one or more of maltodextrin, resistant dextrin, resistant starch, sodium octenyl succinate starch, lactose, isomaltooligosaccharide, and trehalose; and / or, the anticaking agent is tricalcium phosphate and / or silicon dioxide.

[0042] On the other hand, a method for preparing the above-mentioned liquid-phase stable high-content coenzyme Q is provided. 10 Methods involving composite microcapsules include:

[0043] Step 1: Disperse the emulsifier and filler in pure water, add the water-soluble active ingredient, and stir until dissolved to obtain phase a;

[0044] Step 2: Under heating conditions, add coenzyme Q... 10 The mixture is melted into a co-emulsifier, and an oil-soluble active ingredient is added and stirred until homogeneous to obtain phase b.

[0045] Step 3: Heat phase a to the same temperature as phase b in step 2, then add it to phase b, shear, homogenize, and cool to obtain an emulsion;

[0046] Step 4: Spray dry to obtain powder;

[0047] Step 5: Mix the powder with an anti-caking agent, granulate by boiling, and sieve to obtain Coenzyme Q. 10 Composite microcapsules.

[0048] In some embodiments, the emulsifier is a sucrose fatty acid ester, the co-emulsifier is soybean lecithin, and the phosphatidylcholine content is 50%.

[0049] This invention provides a liquid-phase stable high-content coenzyme Q solution. 10 The preparation method of the composite microcapsules involves first blending an emulsifier with a water-soluble active ingredient to obtain phase a, and then mixing a co-emulsifier with coenzyme Q. 10Phase b was obtained by blending with oil-soluble active ingredients, and then the two were mixed under heating conditions, followed by spray drying and fluidized bed granulation to obtain a liquid-phase stable high-content coenzyme Q. 10 Composite microcapsules, prepared using this method, yield liquid-phase stable high-content coenzyme Q. 10 The composite microcapsules combine high encapsulation efficiency with long-term stability in the liquid phase, and have low free degree of each active ingredient, resulting in significant efficacy.

[0050] During their research, the inventors discovered that coenzyme Q obtained by using PC50 as a co-emulsifier and sucrose fatty acid esters as emulsifiers... 10 The composite microcapsules exhibit higher encapsulation efficiency and long-term liquid-phase stability under various operating conditions. They fully utilize the water-soluble active ingredients emulsified by soybean lecithin and the oil-soluble active ingredients emulsified by sucrose fatty acid esters. Based on the amphiphilic groups of soybean lecithin, the oil-water interfacial tension is reduced, stabilizing the emulsion and absorbing water. This promotes the full dispersion of the aqueous and oil phases during phase separation and blending, forming a homogeneous emulsion containing active ingredients, thus achieving the desired effect for Coenzyme Q10. 10 It effectively encapsulates various functional components and exhibits high physical stability.

[0051] On the other hand, a high-content coenzyme Q that is stable in the liquid phase is provided. 10 Application of composite microcapsules in the preparation of pharmaceuticals, health products or cosmetics with antioxidant and anti-fatigue effects.

[0052] Prior to this application, a series of experiments were conducted. Some of the experimental results are listed below to provide a more detailed description of the invention. The following is a detailed description in conjunction with the embodiments.

[0053] The sources of all raw materials in this invention are not limited. In the following examples, the sources described herein shall prevail. For instance, Coenzyme Q10 was purchased from Changsha Huirui Biotechnology Co., Ltd., with a purity of 98%; Epigallocatechin gallate was purchased from Anhui Hongxing Pharmaceutical Co., Ltd., with a purity of 98%; Grape seed extract was purchased from Fufeng Sinote Biotechnology Co., Ltd., with a purity of 95%; Vitamin B5 was purchased from Xinfeng Pharmaceutical Co., Ltd., with a purity of 99%; Vitamin C was purchased from Zhejiang Xinhecheng Co., Ltd., with a purity of 99%; Vitamin E was purchased from Shandong Jurong Bioengineering Co., Ltd., with a purity of 98%; and whey protein isolate was purchased from Fujian Lixing Food Co., Ltd. The purity is 90%. Sodium caseinate was purchased from Linxia Huaan Biological Products Co., Ltd., model parameter N1-B. Sucrose fatty acid ester was purchased from Guangxi Gaotong Food Technology Co., Ltd., model parameter SE-15G. Mono- and diglyceride fatty acid ester was purchased from Jialishi Additives (Hai'an) Co., Ltd., model parameter SF-4. Soybean lecithin was purchased from Shandong Lanhe Biotechnology Co., Ltd., model parameter PC15-90. Polyoxyethylene (20) sorbitan monooleate was purchased from Guangdong Huana Chemical Co., Ltd., HLB value 15.0. Polyoxyethylene (20) sorbitan monolaurate was purchased from Guangdong Huana Chemical Co., Ltd., HLB value 16.7.

[0054] Example 1

[0055] This embodiment provides a liquid-phase stable high-content coenzyme Q. 10 Complex microcapsules, including coenzyme Q 10 The active ingredients include grape seed extract, vitamin B5, epigallocatechin gallate (EGCG), and vitamin E; the emulsifier is sucrose fatty acid ester; the co-emulsifier is soybean lecithin (phosphatidylcholine content of 50%, i.e., PC50); the fillers are resistant dextrin and maltodextrin; and the anti-caking agent is calcium triphosphate.

[0056] This embodiment also provides a liquid-phase stable high-content coenzyme Q as described above. 10 The preparation method of composite microcapsules includes:

[0057] Step 1: Add 5g of emulsifier sucrose fatty acid ester, 15.5g of filler resistant dextrin and 20g of maltodextrin to 300g of pure water, stir thoroughly until dissolved, let stand at 4℃ for 12h, add 2g of grape seed extract, 2g of vitamin B5 and 2g of epigallocatechin gallate, stir at 4℃ until dissolved to obtain phase a, and store at 4℃ in the dark.

[0058] Step 2: Under a temperature of 60℃, add 40g of Coenzyme Q. 10Melt it in 5g of co-emulsifier PC50, add 5g of vitamin E, stir and mix well to obtain phase b, and keep it warm at 60℃ for later use;

[0059] Step 3: Rapidly heat phase a to 60°C and add it to phase b. Shear at 10,000 rpm for 5 minutes, homogenize three times at 60°C and 100 MPa pressure, and then rapidly cool to 4°C to obtain an emulsion.

[0060] Step 4: Spray dry the emulsion to obtain powder; during spray drying, the inlet air temperature is 140℃ and the outlet air temperature is 70℃.

[0061] Step 5: Mix the powder with 0.5g of anti-caking agent calcium triphosphate, granulate by boiling, and pass through a 40-60 mesh sieve to obtain a liquid-phase stable high-content coenzyme Q. 10 Composite microcapsules; in fluidized bed granulation, the inlet air temperature was 70℃, the outlet air temperature was 50℃, and the fluidization time was 60 min; liquid-phase stable high-content coenzyme Q. 10 The morphology of the composite microcapsules is shown in the figure below. Figure 1 As shown.

[0062] Example 2

[0063] This embodiment examines the effect of co-emulsifiers on performance. It is the same as in Example 1, except that in step two, the co-emulsifier is PC15.

[0064] Example 3

[0065] This embodiment examines the effect of co-emulsifiers on performance. It is the same as in Example 1, except that in step two, the co-emulsifier is PC30.

[0066] Example 4

[0067] This embodiment examines the effect of co-emulsifiers on performance. It is the same as in Example 1, except that in step two, the co-emulsifier is PC70.

[0068] Example 5

[0069] This embodiment examines the effect of co-emulsifiers on performance. It is the same as in Example 1, except that in step two, the co-emulsifier is PC80.

[0070] Example 6

[0071] This embodiment examines the effect of co-emulsifiers on performance. It is the same as in Example 1, except that in step two, the co-emulsifier is PC90.

[0072] Example 7

[0073] This embodiment examines the effect of co-emulsifiers on performance. It is the same as in Example 1, except that in step two, the co-emulsifiers are PC50 and PC30 in a mass ratio of 1:1.

[0074] Example 8

[0075] This embodiment examines the effect of co-emulsifiers on performance. It is the same as in Example 1, except that in step two, the co-emulsifiers are PC50 and PC15 in a mass ratio of 1:2.

[0076] Example 9

[0077] This embodiment examines the effect of co-emulsifiers on performance. It is the same as in Example 1, except that in step two, the co-emulsifiers are PC50 and PC90 in a mass ratio of 1:1.

[0078] Comparative Example 1

[0079] This comparative example examines the effect of emulsifier on performance, and is the same as in Example 1, except that the emulsifier is whey protein isolate.

[0080] Comparative Example 2

[0081] This comparative example examines the effect of emulsifier on performance, and is the same as in Example 1, except that the emulsifier is sodium caseinate.

[0082] Comparative Example 3

[0083] This comparative example examines the effect of emulsifiers on performance, and is the same as in Example 1, except that the emulsifier is a mono- or diglyceride fatty acid ester.

[0084] Comparative Example 4

[0085] This comparative study examines the effect of the active ingredient on performance in the same way as in Example 1, except that the active ingredient also includes vitamin C. The vitamin C is added simultaneously with vitamin B5 in step one, and the mass of vitamin C and vitamin B5 in step one is 1g each.

[0086] Comparative Example 5

[0087] This comparative example examines the effect of active ingredients on performance in the same manner as Example 1, except that the active ingredient only includes vitamin E, with the remainder supplemented by maltodextrin. The preparation method includes:

[0088] Step 1: Add 5g of emulsifier sucrose fatty acid ester, 15.5g of filler resistant dextrin and 20g of maltodextrin to 300g of pure water, stir thoroughly until dissolved, let stand at 4℃ for 12h, add 6g of maltodextrin, stir at 4℃ until dissolved, and obtain phase a, which is stored at 4℃ in the dark.

[0089] Step 2: Under a temperature of 60℃, add 40g of Coenzyme Q. 10 Melt the mixture in 5g of co-emulsifier PC50, add 5g of vitamin E, shear at 10000rpm for 5min, homogenize three times at 60℃ and 100MPa pressure, and then rapidly cool to 4℃ to obtain an emulsion.

[0090] Step 3: Rapidly heat phase a to 60°C and add it to phase b. Shear at 10,000 rpm for 5 minutes, homogenize three times at 60°C and 100 MPa pressure, and then rapidly cool to 4°C to obtain an emulsion.

[0091] Step 4: Spray dry the emulsion to obtain powder; during spray drying, the inlet air temperature is 140℃ and the outlet air temperature is 70℃.

[0092] Step 5: Mix the powder with 0.5g of anti-caking agent calcium triphosphate, granulate by boiling, and pass through a 40-60 mesh sieve to obtain a high coenzyme Q content. 10 Composite microcapsules; in fluidized bed granulation, the inlet air temperature is 70℃, the outlet air temperature is 50℃, and the fluidization time is 60min.

[0093] Comparative Example 6

[0094] This comparative example examines the effect of water-soluble active ingredient treatment on performance, similar to Example 1, except that it does not contain coenzyme Q. 10 Furthermore, the active ingredients include only grape seed extract, vitamin B5, and epigallocatechin gallate, and the preparation method is as follows:

[0095] Add 5g of emulsifier sucrose fatty acid ester, 15.5g of filler resistant dextrin, and 25g of filler maltodextrin to 300g of pure water, stir thoroughly until dissolved, and let stand at 4℃. Add 2g of grape seed extract, 2g of vitamin B5, and 2g of epigallocatechin gallate, stir at 4℃ until dissolved, and spray dry to obtain powder. During spray drying, the inlet air temperature is 140℃ and the outlet air temperature is 70℃. Mix the powder with 0.5g of anti-caking agent calcium triphosphate, granulate by fluidized bed granulation, and pass through a 40-60 mesh sieve to obtain composite microcapsules. During fluidized bed granulation, the inlet air temperature is 70℃, the outlet air temperature is 50℃, and the fluidization time is 60min.

[0096] Comparative Example 7

[0097] This comparative example examines the effect of co-emulsifiers on performance, and is the same as in Example 1, except that the co-emulsifier is a mono- or diglyceride fatty acid ester.

[0098] Comparative Example 8

[0099] This comparative example examines the effect of the co-emulsifier on performance, and is the same as in Example 1, except that the co-emulsifier is polyoxyethylene (20) sorbitan monooleate.

[0100] Comparative Example 9

[0101] This comparative example examines the effect of the co-emulsifier on performance, and is the same as in Example 1, except that the co-emulsifier is polyoxyethylene (20) sorbitan monolaurate.

[0102] Example 10

[0103] This embodiment provides a product containing coenzyme Q. 10 Complex microcapsules, including coenzyme Q 10 The active ingredients, emulsifiers, co-emulsifiers, fillers, and anti-caking agents are the same as in Example 1, except that the emulsifier is whey protein isolate and the filler is maltodextrin.

[0104] The above-mentioned embodiment contains coenzyme Q. 10 The preparation method of the composite microcapsules is the same as in Example 1, except that:

[0105] Step one involves adding 10g of emulsifier whey protein isolate and 30.5g of filler maltodextrin to 300g of pure water, stirring thoroughly until dissolved, and letting it stand at 4℃ for 12 hours. Then, add 2g of grape seed extract, 2g of vitamin B5 and 2g of epigallocatechin gallate, and stir at 4℃ until dissolved to obtain phase a, which is then stored at 4℃ in the dark.

[0106] Example 11

[0107] This embodiment provides a product containing coenzyme Q. 10 Complex microcapsules, including coenzyme Q 10 The active ingredients, emulsifiers, co-emulsifiers, fillers, and anti-caking agents are the same as in Example 1, except that the emulsifier is sodium caseinate and the filler is maltodextrin.

[0108] The above-mentioned embodiment contains coenzyme Q. 10 The preparation method of the composite microcapsules is the same as in Example 1, except that:

[0109] Step 1: Add 10g of emulsifier sodium caseinate and 30.5g of filler maltodextrin to 300g of pure water, stir thoroughly until dissolved, let stand at 4℃ for 12h, add 2g of grape seed extract, 2g of vitamin B5 and 2g of epigallocatechin gallate, stir at 4℃ until dissolved to obtain phase a, and store at 4℃ in the dark.

[0110] Example 12

[0111] This embodiment provides a product containing coenzyme Q. 10Complex microcapsules, including coenzyme Q 10 The active ingredients, emulsifiers, co-emulsifiers, fillers, and anti-caking agents are the same as in Example 1, except that the emulsifier is whey protein isolate and sodium caseinate in a mass ratio of 1:1, and the filler is sodium octenyl succinate starch and maltodextrin.

[0112] The above-mentioned embodiment contains coenzyme Q. 10 The preparation method of the composite microcapsules is the same as in Example 1, except that:

[0113] Step 1: Add 5g of emulsifier whey protein isolate, 5g of sodium caseinate, 20g of filler sodium octenyl succinate starch, and 10.5g of maltodextrin to 300g of pure water, stir thoroughly until dissolved, and let stand at 4℃ for 12h. Add 2g of grape seed extract, 2g of vitamin B5, and 2g of epigallocatechin gallate, and stir at 4℃ until dissolved to obtain phase a, which is stored at 4℃ in the dark.

[0114] Performance Evaluation

[0115] 1. Loading rate determination

[0116] Each embodiment and comparative example of Coenzyme Q 10 The encapsulation loading rates of the composite microcapsules are shown in Table 1. The encapsulation loading rate is calculated using the formula: Encapsulation loading rate (%) = (Q0 - Q1) / Q0, where Q0 is coenzyme Q. 10 Coenzyme Q in composite microcapsules 10 Total mass, Q1 is free coenzyme Q. 10 The total mass, Q0, is determined by taking 1g of coenzyme Q from each embodiment. 10 The composite microcapsule powder was dissolved in 100 mL of pure water. 1 mL of the solution was added to 10 mL of extraction solvent, and the mixture was sonicated for 20 min to break the emulsion. After standing and separating the layers, coenzyme Q was detected using liquid chromatography. 10 Concentration Q0. The method for determining Q1 is as follows: [The text abruptly ends here, likely due to an incomplete sentence or missing information.] 10 The composite microcapsules were dissolved in 100 mL of pure water. 1 mL of the solution was added to 10 mL of extraction solvent, vortexed for 10 seconds, and allowed to stand to allow for layering. The organic phase was then transferred and analyzed by liquid chromatography to determine the coenzyme Q. 10 The concentration is denoted as Q1; the extractant is a mixture of n-hexane and anhydrous ethanol in a volume ratio of 1:1.

[0117] Table 1. Coenzyme Q in each example and comparative example. 10 Packing rate

[0118] Packing rate Packing rate Packing rate Example 1 99.35％ Comparative Example 1 99.28％ Comparative Example 2 99.32％ Comparative Example 3 99.33％ Comparative Example 4 99.29％ Comparative Example 5 99.34％ Comparative Example 6 99.31％ Comparative Example 7 87.56％ Comparative Example 8 82.61％ Comparative Example 9 84.59％ Example 2 92.12％ Example 3 94.37％ Example 4 93.51％ Example 5 93.14％ Example 6 94.35％ Example 7 94.27％ Example 8 93.75％ Example 9 97.43％ Example 10 93.57％ Example 11 94.13％ Example 12 96.17％

[0119] As shown in Table 1, Example 1 exhibited the highest encapsulation loading rate of 99.35%, while Example 9 also showed a high encapsulation loading rate. This demonstrates that the present invention achieves phase a by blending sucrose fatty acid esters as emulsifiers with water-soluble active ingredients, and by using a co-emulsifier containing PC50 and coenzyme Q. 10 Coenzyme Q was prepared by blending it with oil-soluble active ingredients to obtain phase b. 10 The composite microcapsule process can effectively improve coenzyme Q. 10 Effective encapsulation.

[0120] 2. Stability Test

[0121] Take 1g of coenzyme Q from each example and comparative example. 10 The composite microcapsules were mixed with the liquid beverage formula in Table 2 below, stirred evenly, and then filled and sterilized under high pressure to obtain the liquid beverage. The liquid beverage was placed under a preset temperature and left to stand for a preset time to observe its state. The state of the liquid beverage after standing for the preset time is shown in Table 3.

[0122] Table 2 Liquid Beverage Formulations

[0123]

[0124] Table 3 High-content Coenzyme Q that is stable in the liquid phase 10 Stability testing of compound microcapsule liquid beverages

[0125]

[0126]

[0127]

[0128]

[0129] As shown in Table 3, the coenzyme Q in Example 1 10 The composite microcapsules can be uniformly dispersed in liquid beverages, resulting in a homogeneous liquid phase without precipitation. Furthermore, this liquid beverage can be stably stored at 4–45°C for 3 months. (Example 9: Coenzyme Q) 10 The composite microcapsules exhibited stability substantially equivalent to that of Example 1, and the coenzyme Q of Example 7... 10 Except for slight liquid stratification after storage at 4℃ for 3 months, the composite microcapsules remained stable under all other operating conditions. The composite microcapsules in each comparative example exhibited stratification upon dispersion in liquid beverages, indicating a lack of stability in the liquid phase. Combined with the encapsulation loading data, it can be seen that the coenzyme Q in comparative examples 1–6… 10 The encapsulation rates of the composite microcapsules were all above 99%, which may be due to the synergistic relationship between the emulsifier and the active ingredient. The b-phase obtained by the emulsifier and the oil-soluble active ingredient, along with the co-emulsifier and coenzyme Q, forms a complex structure. 10In synergy with the water-soluble active ingredient, soybean lecithin emulsifies the water-soluble active ingredient. Its amphiphilic head structure can effectively reduce the interfacial tension between oil and water, forming a stable emulsion with uniform particle size distribution. Sucrose fatty acid esters, due to their unique strong hydrophilic sucrose groups and lipophilic fatty acid chains, have ultra-high interfacial activity in emulsifying oil-soluble active ingredients. When the co-emulsifier is PC50, the emulsifier is sucrose fatty acid ester, and the active ingredients are epigallocatechin gallate, grape seed extract, vitamin B5, and vitamin E, the surface properties of the product microcapsules are uniform and physically stable.

[0130] Example 1 of the present invention: Coenzyme Q 10 The morphology of the composite microcapsules is as follows Figure 1 As shown, it is yellow, powdery, and finely milled. It contains the coenzyme Q of this invention. 10 The morphology of the liquid beverage composed of microcapsules is as follows: Figure 2 As shown in the stability test results, the liquid beverage exhibits good stability during a 3-month storage period, with no significant changes in its properties, indicating that the Coenzyme Q of this invention is effective. 10 Composite microcapsules have good compounding effects and can be applied to liquid beverages, exhibiting liquid phase stability.

[0131] 3. Sensory evaluation

[0132] Sixty volunteers were recruited according to the following criteria and evaluated the taste of the above liquid beverages. The evaluation criteria are shown in Table 4, and the evaluation results are shown in Table 5.

[0133] Table 4 Taste Evaluation Criteria

[0134]

[0135] Table 5. Taste Evaluation Results

[0136]

[0137]

[0138] The results showed that the liquid beverage of this invention received high overall ratings from volunteers, with comments generally describing it as having a distinct rose-like aroma, a balanced sweet and sour taste, a smooth mouthfeel, and no noticeable residue in the mouth after drinking.

[0139] 4. Fatigue resistance test

[0140] Healthy C57 mice weighing 18–20 g were randomly divided into groups of 10 mice each and subjected to acclimatization feeding for 7 days. The mice were then fed according to their body weight and the actual amount of coenzyme Q10 in the sample. 10Mice were fed a solution of 100 mg / kg / day for 7 days, and then divided into three groups: a packaged sample group, a free sample group, and a control group. The packaged sample group contained composite microcapsules corresponding to the respective examples or comparative examples, while the free sample group contained pure coenzyme Q. 10 The control group was given an equal amount of pure water by gavage every day. All groups were fed continuously for 15 days. 30 minutes after the last feeding, the mice were placed in a 250ml wide-mouth bottle containing 5g of soda lime and filter paper. The bottle cap was sealed with Vaseline and the timing was started immediately. The death sign was the last respiratory arrest of the mouse (the mouse struggled and convulsed and then suddenly became limp, and the chest stopped rising and falling). The body weight of each mouse, the survival time (ST) under normal pressure and closed hypoxia were observed and recorded, and the volume (V) of the wide-mouth bottle was accurately measured.

[0141] After mice died from closed-loop hypoxia, blood was immediately collected by enucleation. The serum was collected by centrifugation at 3500 rpm and 4°C for 10 minutes. The mouse brain was collected, washed with physiological saline, and then homogenized with physiological saline at a ratio of 1:9 (tissue weight: saline). The homogenate was thoroughly homogenized in a high-throughput tissue homogenizer and centrifuged at 10000 rpm and 4°C for 10 minutes. The supernatant was collected to prepare a 10% tissue homogenate. The following indicators were measured according to the kit requirements. The results are shown in Tables 6 and 7. Figure 3 and Figure 4 As shown, the SOD test kit is ELISA ml001998, and the MDA test kit is ELISA ml037681.

[0142] Table 6 shows the body weight and survival time of mice in each example and comparative example during the fatigue resistance performance test.

[0143] Group Body weight (g) before the experiment Body weight (g) after the experiment Survival time (min) control group 19.8±1.04 26.1±1.57 20.6±1.17 Example 1 20.3±1.21 26.8±2.02 24.7±2.52 Example 7 20.6±0.97 27.1±1.64 23.2±2.14 Example 9 19.5±1.37 25.9±1.79 22.8±2.24 Example 12 19.7±1.13 26.3±1.46 22.4±1.98 Comparative Example 1 20.4±1.09 26.2±1.85 21.6±1.76 Comparative Example 7 20.7±1.18 26.6±1.77 21.1±1.37

[0144] Table 7. Changes in oxidative stress biomarkers after fatigue resistance testing.

[0145]

[0146] Data showed that the drug administration had no significant effect on mouse body weight. In the normobaric hypoxia closed-loop experiment, the survival time of each group in the examples and comparative examples increased compared to the control group, with the increase in survival time being more significant in the examples, indicating a higher anti-fatigue effect. Serum SOD and SOD in brain tissue were significantly higher than those in the control group, indicating a higher antioxidant capacity. Serum MDA and MDA in brain tissue were significantly lower than those in the control group, indicating lower oxidative damage. Among the examples and comparative examples, the example 1 group had the highest serum SOD and SOD in brain tissue, with increases of approximately 1.8 and 1.9 times compared to the control group, respectively, indicating significantly enhanced antioxidant performance. It also had the lowest serum MDA and MDA in brain tissue, with decreases of 0.5 and 0.6 times compared to the control group, respectively, indicating a significantly reduced degree of oxidative stress. The increase factor was calculated as ((serum SOD in example group - serum SOD in control group) / serum SOD in control group).

[0147] 5. Weighted Swimming Experiment

[0148] A swimming tank measuring 100cm×80cm×50cm was filled with water at 25-27℃ to a depth of 30cm. Forty minutes after the last gavage in the fatigue resistance test described above, the mice were placed in the swimming tank with a weight of 3% of their body weight at the base of their tails, and the timing was started. The swimming time was recorded when the mice were considered exhausted (significantly incoordination during swimming, sinking into the water and unable to surface after 10 seconds; deep, rapid, and large-amplitude breathing upon surfacing; dull eyes; slow escape from strong stimuli; prone or sitting position; limbs drooping when the tail was lifted, with no signs of struggle). The mice were immediately removed after exhaustion, and blood was collected from the eyes and centrifuged to obtain serum. The liver and quadriceps femoris muscles were collected to prepare tissue homogenates. The test indicators are shown in Table 8. The results are as follows: Figure 5 As shown, the BUN test kit is ELISA ml07647 and the LDH test kit is ELISA ml107163.

[0149] Table 8. Results of various indicators in the weighted swimming experiment.

[0150]

[0151] In the weighted swimming experiment, compared with the exercise control group, the swimming exhaustion time of each example group and the comparative group was significantly increased, serum BUN and serum LDH were significantly decreased, and tissue MDA was decreased, indicating improved metabolic-oxidative stress. Among them, the reduction of the above indicators was most significant in the Example 1 group, indicating that the liquid-phase stable high content of coenzyme Q of the present invention 10 Composite microcapsules can achieve multi-organ protection and relieve physical fatigue.

Claims

1. A method for preparing liquid-phase stable high-content coenzyme Q 10 The method of composite microcapsules is characterized by, The liquid-phase stable high-content coenzyme Q 10 The composite microcapsules include the following raw materials: Coenzyme Q 10 The active ingredients, emulsifiers, co-emulsifiers, fillers, and anti-caking agents; the coenzyme Q... 10 The active ingredient is present in a mixture of 10-60 parts by weight, the active ingredient in a mixture of 5-15 parts by weight, the emulsifier in a mixture of 2-10 parts by weight, the co-emulsifier in a mixture of 1-5 parts by weight, the filler in a mixture of 10-50 parts by weight, and the anti-caking agent in a mixture of 0.1-1 parts by weight; the active ingredient is a water-soluble active ingredient and an oil-soluble active ingredient, the water-soluble active ingredient being epigallocatechin gallate, grape seed extract, and vitamin B5, and the oil-soluble active ingredient being vitamin E; The method includes: Step 1: Disperse the emulsifier and filler in pure water, add water-soluble active ingredients, and stir until dissolved to obtain phase a; the emulsifier is sucrose fatty acid ester; the filler is maltodextrin and resistant dextrin; Step 2: Under heating conditions, add coenzyme Q... 10 The mixture is melted in a co-emulsifier, and an oil-soluble active ingredient is added and stirred until homogeneous to obtain phase b; the co-emulsifier is soybean lecithin with a phosphatidylcholine content of 50%. Step 3: Heat phase a to the same temperature as phase b in step 2, then add it to phase b, shear, homogenize, and cool to obtain an emulsion; Step 4: Spray dry to obtain powder; Step 5: Mix the powder with an anti-caking agent, granulate by boiling, and sieve to obtain Coenzyme Q. 10 Composite microcapsules; the anti-caking agent is tricalcium phosphate.

2. A method for preparing a liquid-phase stable high-content coenzyme Q as described in claim 1 10 High-content coenzyme Q prepared by the composite microcapsule method 10 Application of composite microcapsules in the preparation of drugs or health products that relieve physical fatigue.

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