Aqueous solution containing coenzyme Q10 particles and preparation method thereof

Abstract

The invention discloses an aqueous solution containing coenzyme Q10 particles and a preparation method thereof, and belongs to the technical field of health care products. The coenzyme Q10 is embedded by the liposome, so that the stability of the coenzyme Q10 can be improved, the utilization rate of the coenzyme Q10 is increased, and the medicinal effect is improved; chitosan is used as a carrier and is non-toxic and degradable, so that the stability and bioavailability of the coenzyme Q10 are further enhanced, and the water solubility of the coenzyme Q10 is also improved by performing hydrophilic modification on the chitosan; therefore, the coenzyme Q10 in the prepared aqueous solution is good in stability, high in availability and good in medicinal effect, the oral liquid prepared from the coenzyme Q10 can help people with difficulty in swallowing capsules to ingest the coenzyme Q10, and the coenzyme Q10 aqueous solution has important application value in the technical field of health care products.

Description

Technical Field

[0001] The present invention belongs to the technical field of health care products, and in particular, relates to an aqueous solution containing coenzyme Q10 particles and a preparation method thereof. Background Art

[0002] Coenzyme Q10, also known as ubiquinone, decenequinone, ubiquinone, etc., is a type of fat-soluble vitamin substance naturally present in the human body, with high content in the heart, liver, kidney and pancreas. It mainly participates in aerobic cell respiration, providing sufficient oxygen and energy to organs, and thus plays an important role in the energy metabolism process of the human body. It is a nutritional health product recognized worldwide.

[0003] As we all know, the brain and heart are high-energy demand organs in the human body and are extremely sensitive to the concentration of coenzyme Q10. Studies have shown that coenzyme Q10 is effective in improving myocardial function and improving cardiovascular diseases. For example, it can effectively alleviate the condition of patients with heart disease and increase the survival of heart failure, thereby greatly reducing the risk of sudden death. In addition, coenzyme Q10 can also maintain healthy brain nerve cells, significantly enhance brain vitality, and ensure sufficient energy. It is especially suitable for patients with chronic fatigue syndrome. Coenzyme Q10 has a wide range of clinical applications. It was initially approved by Japan as an auxiliary drug for the treatment of ischemic heart disease and heart failure. During clinical application, doctors have gradually discovered that coenzyme Q10 can also assist in the treatment of metabolic abnormalities, periodontitis, gingivitis, chronic fatigue syndrome, neuropathy (Parkinson's disease) and depression in patients with hypertension. Due to its excellent efficacy, coenzyme Q10 has been commonly used in health foods in recent years to improve the body's fatigue and improve people's energy and brain power.

[0004] Coenzyme Q10 has poor water solubility, so most of the health products containing coenzyme Q10 on the domestic market are soft capsules. However, it is difficult for people who have difficulty swallowing capsules to ingest coenzyme Q10. Therefore, in the face of this problem, it is urgent to improve the water solubility of coenzyme Q10 and make it into an oral liquid so that people who have difficulty swallowing capsules can supplement coenzyme Q10 more conveniently. Summary of the invention

[0005] The purpose of the present invention is to overcome the defects of the prior art and provide an aqueous solution containing coenzyme Q10 particles and a preparation method thereof.

[0006] The purpose of the present invention can be achieved through the following technical solutions:

[0007] A method for preparing an aqueous solution containing coenzyme Q10 particles comprises the following steps:

[0008] A1. Place coenzyme Q10 and caprylic / decanoic acid triglyceride in a water bath at 65°C and stir continuously until coenzyme Q10 is completely dissolved to form a uniform oil phase.

[0009] A2. Add egg yolk lecithin and Tween 80 to a glycerol aqueous solution (mass fraction 30%), and place in a constant temperature water bath at 65°C for 30 minutes to form an aqueous phase.

[0010] A3, the oil phase obtained in step A1 and the water phase obtained in step A2 were mixed, stirred at a high speed of 5000 rpm for 5 min to fully mix the water phase and the oil phase, and then high-pressure homogenization was circulated for 6 times, cooled at room temperature, and filtered with a sterile filter membrane to obtain a coenzyme Q10 solution;

[0011] A4, mixing the modified chitosan with glacial acetic acid solution (mass fraction 1%), stirring thoroughly and letting stand for 12 hours, and filtering under reduced pressure to obtain a chitosan solution;

[0012] A5. Slowly add the coenzyme Q10 solution prepared in step A3 to the chitosan solution prepared in step A4 at room temperature using a peristaltic pump while performing magnetic stirring. After the addition is completed, continue stirring for 40 minutes to obtain an aqueous solution containing coenzyme Q10 particles.

[0013] Furthermore, in step A1, the ratio of coenzyme Q10 to caprylic / decanoic acid triglyceride is 1 g:20 mL.

[0014] Furthermore, in step A2, the ratio of egg yolk lecithin, Tween 80 and glycerol aqueous solution is 0.1 g:0.03 g:10 mL.

[0015] Furthermore, in step A3, the pressure of high-pressure homogenization is 750 bar; and the pore size of the sterile filter membrane is 0.22 μm.

[0016] Furthermore, in step A4, the ratio of the amount of modified chitosan to the amount of glacial acetic acid solution is 0.1-0.3 g:100 mL.

[0017] Furthermore, in step A5, the speed of magnetic stirring is 600-700 r / min, and the speed of continued stirring is 1000-1200 r / min.

[0018] Coenzyme Q10 is encapsulated in liposomes. Liposomes are lipid bilayers spontaneously formed by lipids and fatty acids containing phospholipids dispersed in water. The unique bilayer structure can be used to deliver both hydrophilic and hydrophobic substances. The biological membrane-like structure of liposomes gives them the advantages of good biocompatibility, biodegradability, and low toxicity. It can improve the stability of coenzyme Q10 in the body and increase its utilization rate.

[0019] Furthermore, the modified chitosan is prepared by the following steps:

[0020] Chitosan, acrylic acid and ethanol solution were added to a round-bottom flask equipped with a thermometer and a stirring device. After stirring and mixing evenly, the reaction temperature was controlled to 75°C and the reaction was stirred for 12 hours. After the reaction was completed, the ethanol was removed by vacuum distillation and washed with a sodium hydroxide / ethanol aqueous solution to a pH of 9. Then, the mixture was shaken and washed with an ethanol aqueous solution until it was neutral and finally dried to obtain modified chitosan.

[0021] Furthermore, the ratio of chitosan, acrylic acid and ethanol solution is 1 g:3.1 g:100 mL.

[0022] The double bonds in the acrylic acid molecules react with the amino groups on chitosan to form modified chitosan.

[0023] Chitosan (CS), as a natural cationic polysaccharide, is non-toxic, biocompatible and biodegradable. It can be adsorbed on the surface of liposomes through electrostatic interactions and hydrogen bonds. Chitosan modification can enhance the electrostatic repulsion between liposomes, prevent liposome aggregation, enhance the sustained release of drugs, improve the stability of liposomes, and thus improve the stability of coenzyme Q10. In addition, by modifying chitosan, the hydrophilicity of chitosan is improved, and using it as a carrier also improves the water solubility of coenzyme Q10.

[0024] Beneficial effects of the present invention:

[0025] 1. The present invention utilizes liposomes to embed coenzyme Q10, which can improve the stability of coenzyme Q10, increase the utilization rate of coenzyme Q10, and improve the medicinal effect;

[0026] 2. Using chitosan as a carrier is non-toxic and degradable, which further enhances the stability and bioavailability of coenzyme Q10. By modifying chitosan to be hydrophilic, the water solubility of coenzyme Q10 is also improved.

[0027] Therefore, the coenzyme Q10 in the aqueous solution prepared by the present invention has good stability, high utilization, and good medicinal effect. Making it into an oral liquid can help people who have difficulty swallowing capsules to ingest coenzyme Q10, and has important application value in the field of health care product technology. DETAILED DESCRIPTION

[0028] The following will be combined with 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.

[0029] Embodiment 1

[0030] Preparation of modified chitosan:

[0031] In a round-bottom flask equipped with a thermometer and a stirring device, add 1g of chitosan, 3.1g of acrylic acid and 100mL of ethanol solution, stir and mix evenly, control the reaction temperature to 75°C, stir and react for 12h, and after the reaction is completed, remove ethanol by vacuum distillation, wash with sodium hydroxide / ethanol aqueous solution to pH 9, then shake and wash with ethanol aqueous solution until neutral, and finally dry to obtain modified chitosan.

[0032] Embodiment 2

[0033] Preparation of modified chitosan:

[0034] In a round-bottom flask equipped with a thermometer and a stirring device, add 2g of chitosan, 6.2g of acrylic acid and 200mL of ethanol solution, stir and mix evenly, control the reaction temperature to 75°C, stir and react for 12h, after the reaction is completed, remove ethanol by vacuum distillation, wash with sodium hydroxide / ethanol aqueous solution to pH 9, then shake and wash with ethanol aqueous solution to neutrality, and finally dry to obtain modified chitosan.

[0035] Embodiment 3

[0036] A1. Place 1 g of coenzyme Q10 and 20 mL of caprylic / decanoic acid triglyceride in a 65°C water bath and stir continuously until the coenzyme Q10 is completely dissolved to form a uniform oil phase.

[0037] A2, add 0.1g egg yolk lecithin and 0.03g Tween 80 into 10mL glycerol aqueous solution (mass fraction 30%), and keep in a constant temperature water bath at 65℃ for 30min to form an aqueous phase;

[0038] A3, the oil phase obtained in step A1 and the water phase obtained in step A2 were mixed, stirred at a high speed of 5000 rpm for 5 min to fully mix the water phase and the oil phase, and then high-pressure homogenization was circulated for 6 times at 750 bar, cooled at room temperature, and filtered with a 0.22 μm sterile filter membrane to obtain a coenzyme Q10 solution;

[0039] A4, 0.1 g of the modified chitosan prepared in Example 1 was mixed with 100 mL of glacial acetic acid solution (mass fraction 1%), stirred thoroughly and allowed to stand for 12 h, and filtered under reduced pressure to obtain a chitosan solution;

[0040] A5. Slowly add the coenzyme Q10 solution prepared in step A3 to the chitosan solution prepared in step A4 at room temperature using a peristaltic pump, while performing magnetic stirring at a speed of 600 r / min. After the addition is completed, continue stirring for 40 minutes at a stirring speed of 1000 r / min to obtain an aqueous solution containing coenzyme Q10 particles.

[0041] Embodiment 4

[0042] A1. Place 1 g of coenzyme Q10 and 20 mL of caprylic / decanoic acid triglyceride in a 65°C water bath and stir continuously until the coenzyme Q10 is completely dissolved to form a uniform oil phase.

[0043] A2, add 0.1g egg yolk lecithin and 0.03g Tween 80 into 10mL glycerol aqueous solution (mass fraction 30%), and keep in a constant temperature water bath at 65℃ for 30min to form an aqueous phase;

[0044] A3, the oil phase obtained in step A1 and the water phase obtained in step A2 were mixed, stirred at a high speed of 5000 rpm for 5 min to fully mix the water phase and the oil phase, and then high-pressure homogenization was circulated for 6 times at 750 bar, cooled at room temperature, and filtered with a 0.22 μm sterile filter membrane to obtain a coenzyme Q10 solution;

[0045] A4, 0.2 g of the modified chitosan prepared in Example 1 was mixed with 100 mL of glacial acetic acid solution (mass fraction 1%), stirred thoroughly and allowed to stand for 12 h, and filtered under reduced pressure to obtain a chitosan solution;

[0046] A5. Slowly add the coenzyme Q10 solution prepared in step A3 to the chitosan solution prepared in step A4 at room temperature using a peristaltic pump, while performing magnetic stirring at a speed of 700 r / min. After the addition is completed, continue stirring for 40 minutes at a stirring speed of 1100 r / min to obtain an aqueous solution containing coenzyme Q10 particles.

[0047] Embodiment 5

[0048] A1. Place 1 g of coenzyme Q10 and 20 mL of caprylic / decanoic acid triglyceride in a 65°C water bath and stir continuously until the coenzyme Q10 is completely dissolved to form a uniform oil phase.

[0049] A2, add 0.1g egg yolk lecithin and 0.03g Tween 80 into 10mL glycerol aqueous solution (mass fraction 30%), and keep in a constant temperature water bath at 65℃ for 30min to form an aqueous phase;

[0050] A3, the oil phase obtained in step A1 and the water phase obtained in step A2 were mixed, stirred at a high speed of 5000 rpm for 5 min to fully mix the water phase and the oil phase, and then high-pressure homogenization was circulated for 6 times at 750 bar, cooled at room temperature, and filtered with a 0.22 μm sterile filter membrane to obtain a coenzyme Q10 solution;

[0051] A4, 0.3 g of the modified chitosan prepared in Example 1 was mixed with 100 mL of glacial acetic acid solution (mass fraction 1%), stirred thoroughly and allowed to stand for 12 h, and filtered under reduced pressure to obtain a chitosan solution;

[0052] A5. Slowly add the coenzyme Q10 solution prepared in step A3 to the chitosan solution prepared in step A4 at room temperature using a peristaltic pump, while performing magnetic stirring at a speed of 700 r / min. After the addition is completed, continue stirring for 40 minutes at a stirring speed of 1200 r / min to obtain an aqueous solution containing coenzyme Q10 particles.

[0053] Comparative Example 1

[0054] Unmodified chitosan of the same mass was used to replace the modified chitosan in Example 5, and the remaining steps were the same as in Example 5 to prepare an aqueous solution.

[0055] Comparative Example 2

[0056] Use commercially available coenzyme Q10 oral solution.

[0057] Comparative Example 3

[0058] Use commercially available coenzyme Q10 capsules.

[0059] The stability tests of Examples 3, 4, 5 and Comparative Examples 1 and 2 were carried out according to the following standards:

[0060] The samples were placed in sealed colorless and transparent vials and placed under 4200Lx light intensity and anaerobic filling (25°C constant temperature) conditions for 10 days, and then the coenzyme Q10 content was determined by HPLC.

[0061] The samples were placed in sealed brown vials, placed in a 55°C thermostat for 10 days, and then the coenzyme Q10 content was determined by HPLC.

[0062] The samples were placed in brown vials, filled with oxygen (constant temperature at 25°C), and placed away from light for 10 days, and then the coenzyme Q10 content was determined by HPLC;

[0063] The measured results are shown in Table 1:

[0064] Table 1

[0065]

[0066] After the samples of Examples 3, 4, 5 and Comparative Example 1 were dehydrated and dried, they were subjected to dissolution tests together with Comparative Example 3; Dissolution test: The dissolution of the drug was measured after 5 min, 15 min and 30 min respectively using a dissolution apparatus, the medium was 500 ml of distilled water, the temperature was (37°C ± 0.5), and the high performance liquid chromatography method was used for the determination;

[0067] The measured results are shown in Table 2:

[0068] Table 2

[0069]

[0070] It can be seen from the above two tables that the stability and water solubility of coenzyme Q10 in the aqueous solution prepared in the embodiment of the present invention are higher than those in the comparative example. Therefore, the present invention has important application value in the field of health care product technology.

[0071] In the description of the specification, the description with reference to the terms "one embodiment", "example", "specific example", etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0072] The above contents are merely examples and explanations of the present invention. Those skilled in the art may make various modifications or additions to the specific embodiments described or replace them in a similar manner. As long as they do not deviate from the invention or exceed the scope defined by the claims, they shall all fall within the protection scope of the present invention.

Claims

1. A method for preparing an aqueous solution containing coenzyme Q10 particles, characterized in that: The following steps are involved: A1. Place coenzyme Q10 and caprylic / decanoic acid triglyceride in a water bath at 65°C and stir continuously until coenzyme Q10 is completely dissolved to form a uniform oil phase. A2, adding egg yolk lecithin and Tween 80 to the glycerol aqueous solution, and keeping it in a constant temperature water bath at 65°C for 30 minutes to form an aqueous phase; A3, the oil phase obtained in step A1 and the water phase obtained in step A2 are mixed, stirred at a high speed of 5000 rpm for 5 min to fully mix the water phase and the oil phase, and then high-pressure homogenization circulation is performed, cooled at room temperature, and filtered to obtain a coenzyme Q10 solution; A4, mixing the modified chitosan with the glacial acetic acid solution, stirring thoroughly and letting it stand for 12 hours, and filtering under reduced pressure to obtain a chitosan solution; A5. Slowly add the coenzyme Q10 solution prepared in step A3 to the chitosan solution prepared in step A4 while performing magnetic stirring. After the addition is completed, continue stirring for 40 minutes to obtain an aqueous solution containing coenzyme Q10 particles.

2. The method for preparing an aqueous solution containing coenzyme Q10 particles according to claim 1, characterized in that: In step A1, the ratio of coenzyme Q10 to caprylic / capric triglyceride is 1 g:20 mL.

3. The method for preparing an aqueous solution containing coenzyme Q10 particles according to claim 1, characterized in that: In step A2, the ratio of egg yolk lecithin, Tween 80 and glycerol aqueous solution is 0.1g:0.03g:10mL.

4. The method for preparing an aqueous solution containing coenzyme Q10 particles according to claim 1, characterized in that: The pressure of high-pressure homogenization in step A3 is 750 bar; the pore size of the sterile filter membrane is 0.22 μm.

5. The method for preparing an aqueous solution containing coenzyme Q10 particles according to claim 1, characterized in that: In step A4, the ratio of modified chitosan to glacial acetic acid solution is 0.1-0.3 g:100 mL.

6. The method for preparing an aqueous solution containing coenzyme Q10 particles according to claim 1, characterized in that: In step A5, the speed of magnetic stirring is 600-700 r / min, and the speed of continued stirring is 1000-1200 r / min.

7. The method for preparing an aqueous solution containing coenzyme Q10 particles according to claim 1, characterized in that: The modified chitosan is prepared by the following steps: Chitosan, acrylic acid and ethanol solution were added to a round-bottom flask equipped with a thermometer and a stirring device. After stirring and mixing evenly, the reaction temperature was controlled to 75°C and the reaction was stirred for 12 hours. After the reaction was completed, the ethanol was removed by vacuum distillation and washed with a sodium hydroxide / ethanol aqueous solution to a pH of 9. Then, the mixture was shaken and washed with an ethanol aqueous solution until it was neutral and finally dried to obtain modified chitosan.

8. The method for preparing an aqueous solution containing coenzyme Q10 particles according to claim 7, characterized in that: The ratio of chitosan, acrylic acid and ethanol solution is 1g:3.1g:100mL.

9. An aqueous solution containing coenzyme Q10 particles, characterized in that: Prepared according to the method according to any one of claims 1 to 8.

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