Nutritional composition containing coenzyme Q10 and preparation method and application thereof

Abstract

The present invention provides a nutritional composition with coenzyme CoQ10 as a main component, a preparation method of the composition, and an application of the composition.

Description

Technical Field

[0001] The present invention relates to the field of nutritional compositions, and more specifically, to a nutritional composition containing coenzyme Q10 and a preparation method and application thereof. Background Art

[0002] Coenzyme Q10 has a core function as coenzyme Q10 (CoQ10) in cellular metabolism and performs a variety of essential functions in mitochondria and elsewhere in the cell. As an electron carrier from complex I and II to complex III in the mitochondrial electron transport chain, CoQ10 is essential for the production of ATP via oxidative phosphorylation within mitochondria. CoQ10 is the primary endogenously produced lipid-soluble antioxidant that protects all types of cell membranes from free radical-induced oxidative damage and plays a role in the metabolism of pyrimidines, sulfides, and amino acids, in addition to its role in lysosomal pH maintenance. CoQ10 can also regulate the expression of a variety of genes, including those involved in inflammation. The purpose of this patent is to optimize the bioavailability of CoQ10 supplements from initial ingestion to uptake and cellular utilization. CoQ10 produced by yeast fermentation is a transformation of CoQ10, and its chemical structure is identical to the form of CoQ10 biosynthesized in the human body. However, CoQ10 exists in the structural form of polymorphic crystals and cannot be absorbed in the gastrointestinal tract (Lee et al., 2017).

[0003] Coenzyme Q10 in polymorphic crystalline form is not absorbed by the gastrointestinal tract (Moesgaard and Paulin, 2016). The thermal crystal dispersion process breaks down the Coenzyme Q10 crystals into individual molecules, increasing absorption and bioavailability by 75% (López-Lluch et al., 2019). Evidence suggests that increasing blood levels of Coenzyme Q10 may help reduce the oxidation of ubiquinol to ubiquinone, thereby providing protection against oxidative damage and various health problems.

[0004] Because it is thought that the initial absorption of CoQ10 into the absorptive cells of the intestine is facilitated by the reduction of ubiquinone to ubiquinol, some continue to believe that ingesting CoQ10 in the ubiquinol form will aid the absorption process. Because ubiquinol is inherently unstable and oxidizes to ubiquinone, CoQ10 exists in the body in both oxidized (ubiquinone) and reduced (ubiquinol) forms; these two oxidized and reduced forms are constantly converted to each other within cells as part of CoQ10's normal function. CoQ10 is a fat-soluble compound that is typically encapsulated in bovine gelatin capsules. The journey from the stomach through the small intestine and lymph to the bloodstream typically takes 5 to 8 hours. CoQ10 enters the duodenum as part of a mixture. As CoQ10 travels from the stomach to the duodenum, any CoQ10 that is still in the reduced form, the ubiquinol form, is oxidized to the ubiquinone form; this process typically takes 90 minutes in CoQ10 absorption studies conducted under simulated gastric acid conditions (Judy, 2021). Therefore, the highest quality CoQ10 preparations should dissolve CoQ10 in a suitable carrier lipid.

[0005] Twenty-four hours after intravenous injection, the redox level of [14C]CoQ10 dissolved with HCO-60 in guinea pig liver was approximately one-fourth that of [14C]CoQ10 dissolved with ethanol-water (1:5 volume ratio) (18.2% vs. 63.4%). Furthermore, after 30 minutes of incubation in liver cytoplasmic solution, the redox levels of CoQ10 dissolved with HCO-60 or ethanol-water were 20.2% or 82.3%, respectively. Thus, Q10 dissolved with HCO-60 was only slightly reduced in vivo and in vitro. The critical micelle concentrations of HCO-60 in the presence and absence of Q10 were 0.02% and 0.002% (w / v), respectively. The concentration of HCO-60 micelles containing Q10 in the cytoplasmic incubation mixture was estimated to be 0.0048% (w / v), while the concentration in the blood circulation was 0.0041% (w / v). These results indicate that HCO-60 micelles containing Q10 are more stable than ethanol-water emulsions not only in the blood circulation but also in tissues (Takada & Watanabe, 1987).

[0006] There is limited research on the more specific effects of capric acid on the bioavailability of CoQ10, but some studies suggest that medium-chain triglycerides including capric acid may enhance the absorption and bioavailability of CoQ10. A study published in the Journal of Functional Foods found that a combination of MCTs and CoQ10 increased the absorption of CoQ10 by three times compared to CoQ10 alone. The study suggests that MCTs may enhance the solubility and absorption of CoQ10, potentially increasing its bioavailability. Another study published in the Journal of Nutritional Science and Vitaminology found that a combination of MCTs and CoQ10 increased the bioavailability and antioxidant activity of CoQ10 in healthy adults.

[0007] Therefore, people have been looking for new ways to utilize Coenzyme Q10. Summary of the invention

[0008] In order to solve the above problems, the present invention provides a nutritional composition containing coenzyme Q10, which is prepared from the following raw materials according to the weight percentage: 35.9-48.6% of panthenol; 9.6-13.0% of metoclopramide mesylate; 2.4-3.2% of ubiquinone; 1.0-5.0% (w / v) of HCO-60 polyoxyethylene hydrogenated castor carrier lipid 60; 0.5-2.0% (w / v) of octanoic acid; 0.1-1.0% (w / w) of ethyl cellulose; 0.5-2% (w / v) of sorbic acid monoester; 4.8- 6.5% NADH; 9.6-13% bovine colostrum; 0.2-0.3% vitamin B1, 0.2-0.3% vitamin B2; 1.0-1.3% niacin; 1.2-1.6% pantothenic acid; 0.2-0.3% vitamin B6; 0.2-0.3% biotin; 0.2-0.3% folic acid; 0.2-0.3% vitamin B12; 0.010-0.013% selenium; 12.0-16.2% L-carnitine; and 7.2-9.7% vitamin D3.

[0009] Preferably, the nutritional composition is an emulsion-type capsule that is hydrophilic on the outside and hydrophobic on the inside, and the total liquid weight of each capsule is 154.6-221.9 mg.

[0010] More preferably, the coenzyme Q10 is reduced coenzyme Q10.

[0011] The present invention also provides a method for preparing a nutritional composition containing coenzyme Q10, the method comprising the following steps: (1) Place the formulated amount of diluent in a mixing tank, add the carrier lipid in the self-emulsifying preparation: HCO-60 (polyoxyethylene hydrogenated castor carrier lipid 60, 1.0-5.0% (w / v)) and caprylic acid 0.5-2.0% (w / v); coating agent: ethyl cellulose 0.1-1.0% (w / w), heat to dissolve and stir evenly; (2) adding a formulated amount of surfactant: 0.5-2% (w / v) of sorbic acid monoester at the dissolution temperature of step (1), stirring evenly and cooling to room temperature to obtain an emulsion; (3) adding the formulated amount of coenzyme Q10 and the coenzyme Q10 bioactivity enhancing agent to the self-emulsifying liquid prepared in step (2), stirring evenly, and obtaining the liquid medicine in the capsule; (4) The liquid medicine content and capsule shell rubber obtained in step (3) are compressed into pills by a soft capsule machine and dried to obtain the product.

[0012] Preferably, the heating and dissolving temperature in step (1) is 60-90°C.

[0013] According to the present invention, preferably, the capsule shell rubber described in step (4) is prepared from gelatin, carrier lipid, sunscreen, preservative, pigment and water according to the prior art; the sunscreen, preservative and pigment are selected from conventional reagents in the field of capsule shell preparation.

[0014] Coenzyme Q10 (coenzyme Q, ubiquinone) is also known as decanonequinone, ubiquinone and vitamin Q10. Its chemical name is 2,3-dimethyl-5-methyl-6-decyl isopentenyl benzoquinone, and it is a fat-soluble vitamin analog. In 1957, Dr. Klein of the United States isolated coenzyme Q10 from the myocardium of cattle. In the same year, Professor Morton of the United Kingdom also obtained this compound from the liver of mice with vitamin A deficiency and named it. In 1958, Professor Karl Folkers of the University of Texas in the United States identified its chemical structure. Since then, scholars from all over the world have joined the research on coenzyme Q10. In 1972, Professor Littarru of Italy proved that the lack of coenzyme Q10 is one of the causes of heart disease and other diseases. In 1977, Japan achieved the industrial production of coenzyme Q10 by microorganisms. In 1978, Professor Mitchell used the chemical osmotic theory to explain the important proton transfer role of coenzyme Q10 in biological energy transfer, including in the energy conversion system, and won the Nobel Prize in Chemistry. In 1990, Professor Karl Folkers' research showed that coenzyme Q10 has vitamin-like properties. In Japan and European countries, basic and clinical research on coenzyme Q10 has been carried out extensively and deeply. At present, there are more than 100 drugs involving independent or compound components of coenzyme Q10, and the annual sales in the United States exceeded 200 million in 2002. Coenzyme Q10 is an essential component of tissues with active energy metabolism. It is concentrated in the mitochondria in tissue cells, between complex I and complex II. Its main function is to transfer electrons between redox substances in the electron transport chain, thereby generating an electron gradient across the biological membrane. Coenzyme Q10 accepts hydrogen from complex I and complex II, releases protons into the mitochondrial matrix, and transfers electrons to cytochromes. Through this process, oxidative phosphorylation and active electron transfer are promoted, thereby forming ATP, the main substance for energy storage in the body, and increasing ATP levels by reducing myocardial AMP loss, reducing calcium ion loss, stabilizing cell membranes, and maintaining the integrity of calcium ion channels. In addition, coenzyme Q10 has a strong free radical scavenging effect. Its mechanism of action is to transfer hydrogen to free radicals, which react under the action of antioxidant enzymes to inhibit the damage of free radicals to biological membranes. Therefore, it is used as a natural antioxidant and free radical scavenger.

[0015] The clinical applications of coenzyme Q10 mainly include the following aspects: (1) Congestive heart failure. Through blood measurement studies of patients with clinical heart diseases, it was found that the myocardial coenzyme Q10 content of patients with congestive heart failure was lower than that of normal people, confirming that the myocardial endogenous coenzyme Q10 content of patients with congestive heart failure was lower than the normal level; and through myocardial biopsy, it was shown that the more severe the heart failure, the lower the myocardial coenzyme Q10 content. After daily oral coenzyme Q10 treatment of patients with congestive heart failure, it was found that more than half of the patients had significantly improved clinical symptoms such as dyspnea and fatigue, and the stroke volume and left ventricular ejection fraction of the patients in the oral coenzyme Q10 group increased significantly. (2) Hypertension. Coenzyme Q10 has a certain degree of antihypertensive effect on both humans and animals. Because supplementing with exogenous coenzyme Q10 can increase the synthesis of ATP, it can act as a free radical scavenger to reduce the peroxidation state of blood vessels, reduce superoxide in endothelial cells and vascular smooth muscle cells, protect and reduce damage to endothelial cells, reduce the level of cytoplasmic NADH, promote endothelial cells to release active substances NO and PGI2 that can maintain vascular tension, dilate peripheral blood vessels and reduce peripheral resistance, and play a role in lowering blood pressure. (3) Nervous system diseases: exogenous coenzyme Q10 can improve the coenzyme Q10 deficiency state of diseased tissues, pass through the blood-brain barrier, reduce cell apoptosis caused by lipid peroxidation damage of cell carriers, or stabilize cell membrane structure, maintain the integrity of calcium ion channels to reduce cell damage, and slow down the damage of dopamine to mitochondria, thereby protecting nerves. (4) Skin diseases: Light damage such as skin photosensitivity, photoaging and skin cancer caused by continuous light exposure is caused by the generation of a large number of reactive oxygen species by light exposure, which causes an imbalance in the skin's oxidation and antioxidant systems. Through research, it was found that the occurrence of photoaging is related to the reduction of the content of endogenous antioxidant coenzyme Q10. Coenzyme Q10 can significantly inhibit the expression of collagen kinase in human skin fibroblasts, thereby reducing the degradation of collagen in the skin and blocking the various damages caused by photoaging. (5) Cancer. The phenomenon of low blood coenzyme Q10 in some cancer patients has attracted the attention of researchers. A large number of experiments have shown that the onset of cancer is related to oxygen free radicals. Oxygen free radicals have a destructive effect on cell membranes, mitochondria, proteins, lipids, and DNA. Supplementing coenzyme Q10 can consume a large number of oxygen free radicals, so coenzyme Q10 has a certain therapeutic and preventive effect on cancer. (6) Anti-oxidation and anti-fatigue in sports medicine. Coenzyme Q10 is an activator of cell metabolism and cell respiration, and is also a natural antioxidant and free radical scavenger. It plays an important role in protecting and restoring the integrity of biological membrane structures. Taking coenzyme Ql0 can reduce serum CK levels after exercise, promote the improvement of aerobic capacity of middle- and long-distance runners, effectively remove free radicals produced during exercise, have a certain anti-fatigue effect, improve muscle malnutrition, improve sports endurance, leg pain, fatigue and other symptoms, and improve people's energy and brain power.

[0016] In the composition of the present invention, the coenzyme Q10 combination preparation is composed of CoQ10, mitoxantrone mesylate, and ubiquinol produced by a patented thermal crystal dispersion process.

[0017] CoQ10 produced by yeast fermentation is a transformation of CoQ10, and its chemical structure is the same as the form of CoQ10 biosynthesized in the human body (Lee et al., 2017). However, CoQ10 produced by yeast fermentation often exists in the form of polymorphic crystals, which are not absorbed by the gastrointestinal tract (Moesgaard and Paulin, 2016). The thermal crystal dispersion process can break down CoQ10 crystals into single molecules, increasing absorption and bioavailability by 75% (López-Lluch et al., 2019). Evidence suggests that increasing the concentration of CoQ10 in the blood may help reduce the oxidation of ubiquinol to ubiquinone, thereby providing protection against oxidative damage and various health problems.

[0018] Mitoxantrone mesylate is composed of a ubiquinone (oxidized coenzyme Q10) group and triphenylphosphine (TPP + ) cations to accumulate in mitochondria (Ross et al., 2005). The lipophilic cation triphenylphosphine (TPP) mitocinol mesylate has been reported to accumulate in mitochondria at 100-1000 times higher levels than in the cytoplasm (Ross et al., 2005). Ubiquinol is very sensitive to oxygen free radicals and produces ubiquinone upon oxidation. Therefore, based on its definition, the ratio of ubiquinol to ubiquinone should be a good indicator of oxidative stress. In the plasma of healthy human donors, the ratio of ubiquinol-10 to ubiquinone-10 is approximately 95:5. The content of the oxidized form (ubiquinone-10) is significantly increased in the plasma of patients with hepatitis, cirrhosis, and hepatocellular carcinoma relative to normal subjects, indicating that these patients experience higher levels of oxidative stress. Therefore, the addition of 5 mg of ubiquinone is very sensitive to oxygen free radicals and produces ubiquinone upon oxidation. Therefore, based on its definition, the ratio of ubiquinol to ubiquinone should be a good indicator of oxidative stress. In the plasma of healthy human donors, the ratio of ubiquinone-10 to ubiquinone-10 is approximately 95:5. The oxidized form (ubiquinone-10) is significantly increased in the plasma of patients with hepatitis, cirrhosis, and hepatocellular carcinoma relative to normal subjects, indicating that these patients experience higher levels of oxidative stress. Therefore, 5 mg of ubiquinone (Yamamoto and Yamashita, 1997) was added to create a combination of ubiquinol and ubiquinone in a ratio of 95:5.

[0019] The inventors also proposed to use a self-emulsifying preparation to improve the bioabsorption rate. The self-emulsifying preparation comprises: a carrier lipid, a coating agent, and a surfactant.

[0020] Since it is thought that CoQ10 is initially absorbed into the intestinal absorptive cells by reducing ubiquinone to ubiquinol, some believe that ingesting CoQ10 in the ubiquinol form will aid the absorption process. Since ubiquinol is inherently unstable and oxidizes to ubiquinone, CoQ10 exists in both oxidized (ubiquinone) and reduced (ubiquinol) forms in the body. These two oxidized and reduced forms are constantly converted within cells as part of CoQ10's normal function. CoQ10 is a fat-soluble compound and is typically encapsulated in bovine gelatin capsules. The passage of CoQ10 from the stomach through the small intestine and lymph to the bloodstream typically takes 5 to 8 hours. CoQ10 enters the duodenum as part of a mixture. As CoQ10 travels from the stomach to the duodenum, any CoQ10 that is in the reduced form, ubiquinol, is oxidized to the ubiquinone form. In CoQ10 absorption studies conducted under simulated gastric acid conditions, this process typically takes 90 minutes (Judy, 2021). Therefore, the highest quality CoQ10 preparations dissolve the CoQ10 in a suitable carrier lipid.

[0021] Twenty-four hours after intravenous injection, the redox level of [14C]CoQ10 dissolved with HCO-60 in guinea pig liver was approximately one-fourth that of [14C]CoQ10 dissolved with ethanol-water (1:5 volume ratio) (18.2% vs. 63.4%). Furthermore, after 30 minutes of incubation in liver cytoplasmic solution, the redox levels of CoQ10 dissolved with HCO-60 or ethanol-water were 20.2% or 82.3%, respectively. Thus, Q10 dissolved with HCO-60 was only slightly reduced in vivo and in vitro. The critical micelle concentrations of HCO-60 in the presence and absence of Q10 were 0.02% and 0.002% (w / v), respectively. The concentration of HCO-60 micelles containing Q10 in the cytoplasmic incubation mixture was estimated to be 0.0048% (w / v), while the concentration in the blood circulation was 0.0041% (w / v). These results indicate that HCO-60 micelles containing Q10 are more stable than ethanol-water emulsions not only in the blood circulation but also in tissues (Takada & Watanabe, 1987).

[0022] While maintaining high doses of CoQ10 dissolved in medium-chain triglyceride (MCT) carrier lipids, ethylcellulose (EC) was used for gelation and a surfactant (sorbic acid monostearate-SMS) was used to form a gel in the presence of the surfactant (Masotta et al., 2019). A thermoreversible carrier lipid gel was successfully developed, containing 1 gram of dissolved CoQ10 per 5-gram disk, demonstrating stability and solubility, and can be stored at 25.0°C for 12 months. SMS as a surfactant has lower water runoff and higher CoQ10 retention over 12 months relative to lecithin, and the oxidative stability of the MCT carrier lipid is higher, preferably fixed by its true gel network. The SMS-carrier lipid gel enables maximum loading of dissolved CoQ10 doses and maximum stability, and may be easier to chew for patients with secondary dysphagia due to CoQ10 deficiency.

[0023] NADH (nicotinamide adenine dinucleotide) is an important coenzyme that participates in the production of cellular energy in the electron transport chain. The electron transport chain is a series of proteins and enzymes that transfer electrons to generate ATP, the body's main energy source. NADH plays a role in assisting in the regeneration of CoQ10, which is also involved in the electron transport chain. CoQ10 receives electrons from other molecules and transfers them to other proteins in the electron transport chain to generate ATP. As CoQ10 receives electrons, it is oxidized to ubiquinone, which must then be reduced back to its active form, ubiquinol, to continue to work. NADH can transfer electrons to CoQ10 to help regenerate its active form, ubiquinol. This regenerated CoQ10 can enhance cellular energy production and increase the body's overall energy levels, so NADH can increase the absorption and bioavailability of CoQ10 (Ross & Siegel, 2017).

[0024] All cells contain CoQ10. The relative levels of CoQ10 in tissues reflect the extent of metabolic activity and energy requirements of different tissues and organs; thus, the highest levels of CoQ10 are found in myocardial tissue. Given its carrier lipid nature, CoQ10 is thought to enter cell membranes by diffusion from lipoprotein carriers in the blood; however, no known transporters for CoQ10 entry from the blood into cells have been identified to date. Diffusion relies on the movement of CoQ10 molecules from areas of high CoQ10 concentration to areas of lower CoQ10 concentration; this requires higher CoQ10 concentrations in the blood than in tissue cells, which is the rationale for using CoQ10 doses of 300 mg per day (and plasma CoQ10 levels of at least 3 g / mL) in clinical studies of patients with heart failure. Thus, transport of CoQ10 from the circulation into tissues such as the myocardium would be facilitated. In addition, there is evidence that the enzyme NAD(P)H dehydrogenase quinone 1 (NQO1) acts as a component of the plasma membrane redox system. The NQO1 enzyme acts as a direct superoxide reductase, producing the antioxidant forms of ubiquinone and vitamin E (Ross & Siegel, 2017).

[0025] CoQ10 is transferred from the blood into the cell by a diffusion-controlled process that requires a higher concentration of CoQ10 in the blood than in the cell to achieve net access. The concentration of CoQ10 in the blood needs to be raised to at least 2.5 μg / mL to benefit from it. However, CoQ10 is primarily found in the plasma membrane and in the membranes of the endoplasmic reticulum, Golgi apparatus, peroxisomes, and lysosomes. Exogenous CoQ10 needs to enter the cell and be transported to the inner mitochondrial membrane to function.

[0026] A transporter associated with human CoQ10 metabolism was identified as the carrier lipid binding protein salipoprotein B, which is required for sphingolipid hydrolysis in lysosomes. Aqueous salipoprotein B can extract CoQ10 from hexane to form a complex of salipoprotein B and CoQ10. CoQ10 has a greater carrier lipid binding affinity to salipoprotein B than to CoQ9, CoQ7, α-tocopherol, and cholesterol (unbound). The maximum affinity of CoQ10 to salipoprotein B was found to occur at pH 7.4. In contrast, when the pH decreased, the CoQ10 donor activity of the salipoprotein B-CoQ10 complex to the erythrocyte phantom membrane increased. Based on these results, salipoprotein B binds and transports CoQ10 in human cells (Jin et al., 2008). Sarpoprotein B is a protein derived from the larger precursor protein prosaposin and is naturally present in bovine colostrum.

[0027] B vitamins include thiamine (B1, 1.1 mg), riboflavin (B2, 1.1 mg), niacin (B3, 10 mg), pantothenic acid (B5, 5 mg), pyridoxine (B6, 1.1 mg), biotin (B7, 1.1 mg), folic acid (B9, 1.1 mg) and cobalamin (B12, 2.4 mg).

[0028] B vitamins are involved in various aspects of the Krebs cycle, a series of reactions that occur within mitochondria to produce ATP energy. For example, thiamine is required for the activity of pyruvate dehydrogenase, an enzyme that converts pyruvate (a product of glucose metabolism) into acetyl-CoA, which enters the Krebs cycle. Riboflavin is a precursor of flavin adenine dinucleotide (FAD), a coenzyme required for several enzymes in the Krebs cycle and oxidative phosphorylation. Niacin is a precursor of nicotinamide adenine dinucleotide (NAD+), required for several reactions in the Krebs cycle and oxidative phosphorylation. Pantothenic acid is a component of coenzyme A and is required for the transfer of acetyl groups during the Krebs cycle. Pyridoxine is involved in the metabolic process of amino acids, some of which can be converted into intermediates of the Krebs cycle. Biotin is a coenzyme required for several carboxylases in the Krebs cycle and other metabolic pathways. Folate and cobalamin are involved in nucleic acid metabolism and the formation of red blood cells, which are essential for the transport of oxygen to the mitochondria for energy production. In addition to their role in energy metabolism, some B vitamins such as thiamine, niacin, and riboflavin have antioxidant properties that help protect mitochondria from oxidative damage.

[0029] B vitamins can also help improve the function of CoQ10 in a variety of ways. CoQ10 is a coenzyme involved in mitochondrial energy production, and B vitamins are closely related to the function of CoQ10 as important cofactors of energy metabolism enzymes. B vitamins can improve the body's ability to produce CoQ10, one of which is to enhance the body's ability to synthesize CoQ10. For example, riboflavin (B2) is required for the synthesis of CoQ10, and riboflavin deficiency can lead to low levels of CoQ10 in the body. In addition, B vitamins can help the body absorb and use CoQ10. For example, pantothenic acid (B5) is required for the synthesis of CoQ10, and pantothenic acid deficiency can lead to low levels of CoQ10 in the body. In addition, some B vitamins, such as niacin (B3), can help improve blood flow and circulation, thereby enhancing the ability of CoQ10 to be delivered to tissues that need it. Some B vitamins, such as thiamine (B1) and pyridoxine (B6), can help improve the function of enzymes that use CoQ10 for energy metabolism. For example, thiamine is required for the activity of pyruvate dehydrogenase, which converts pyruvate into acetyl-CoA, which enters the tricarboxylic acid cycle and ultimately produces ATP. Coenzyme Q10 participates in the electron transport chain, which is the final stage of mitochondrial ATP production. Pyridoxine participates in amino acid metabolism, some of which can be converted into intermediates of the tricarboxylic acid cycle and ultimately used for ATP production.

[0030] Selenium is a trace element that is essential for many biological processes, including the function of CoQ10. Selenium is necessary for the activity of certain enzymes involved in the production of CoQ10, specifically proteins that contain selenium, known as selenoproteins. One of these selenoproteins is glutathione peroxidase, an enzyme that protects the body from oxidative damage by neutralizing harmful free radicals. Glutathione peroxidase requires selenium to function properly, and studies have shown that supplementing with selenium can increase the activity of this enzyme and improve the function of CoQ10. In addition, selenium can help the body absorb and utilize CoQ10. Studies have shown that selenium supplementation can increase the levels of CoQ10 in the blood and tissues, and can enhance the activity of enzymes involved in energy metabolism that use CoQ10. In addition, selenium and CoQ10 have a synergistic antioxidant effect, meaning that together they protect the body from oxidative damage. Coenzyme Q10 is a powerful antioxidant that neutralizes harmful free radicals and protects mitochondria from oxidative stress, while selenium is required for the production of glutathione peroxidase, another important antioxidant enzyme (Alehagen & Aaseth, 2015).

[0031] L-Carnitine is an important nutrient involved in transporting fatty acids into the mitochondria, where they can be oxidized to produce energy. Coenzyme Q10 is also involved in the energy production process within the mitochondria. Some studies have shown that supplementing with L-Carnitine and Coenzyme Q10 together may have a synergistic effect on mitochondrial function and energy production. For example, a study in older adults found that supplementing with L-Carnitine and Coenzyme Q10 together improved mitochondrial function and reduced levels of oxidative stress markers. (DiNicolantonio, 2012).

[0032] Adequate vitamin D (Vitamin D) levels have been shown to reduce vascular smooth muscle contraction and increase arterial compliance, which may be beneficial in hypertension. In addition, coenzyme Q10 (CoQ10) has been reported to have benefits in hypertension and heart failure through its effects on reducing oxidative stress. This study investigated the possible cardioprotective and renal effects of vitamin D and CoQ10, alone and in combination with the angiotensin II receptor antagonist valsartan (Vals), in l-NAME hypertensive rats (Shamardl et al., 2017).

[0033] The nutritional composition containing coenzyme Q10 of the present invention can play the following roles: Mechanism of action of coenzyme Q10: (1) Congestive heart failure. Through blood measurement studies of patients with clinical heart diseases, it was found that the myocardial coenzyme Q10 content of patients with congestive heart failure was lower than that of normal people, confirming that the myocardial endogenous coenzyme Q10 content of patients with congestive heart failure was lower than normal levels. Myocardial biopsy also showed that the more severe the heart failure, the lower the myocardial coenzyme Q10 content. After daily oral coenzyme Q10 treatment of patients with congestive heart failure, it was found that more than half of the patients had significantly improved clinical symptoms such as dyspnea and fatigue, and the stroke volume and left ventricular ejection fraction of the patients in the oral coenzyme Q10 group increased significantly. (2) Hypertension. Coenzyme Q10 has a certain degree of antihypertensive effect on both humans and animals. Because supplementing with exogenous coenzyme Q10 can increase the synthesis of ATP, it can act as a free radical scavenger to reduce the peroxidation state of blood vessels, reduce superoxide in endothelial cells and vascular smooth muscle cells, protect and reduce damage to endothelial cells, reduce the level of cytoplasmic NADH, promote endothelial cells to release active substances NO and PGI2 that can maintain vascular tension, dilate peripheral blood vessels and reduce peripheral resistance, and play a role in lowering blood pressure. (3) Nervous system diseases: exogenous coenzyme Q10 can improve the coenzyme Q10 deficiency state of diseased tissues, pass through the blood-brain barrier, reduce cell apoptosis caused by cell lipid peroxidation damage, or stabilize cell membrane structure, maintain the integrity of calcium ion channels to reduce cell damage, and slow down dopamine damage to mitochondria, thereby protecting nerves. (4) Skin diseases: Light damage such as skin photosensitivity, photoaging and skin cancer caused by continuous light exposure is caused by the generation of a large number of reactive oxygen species by light, which causes an imbalance in the skin's oxidation and antioxidant systems. Through research, it was found that the occurrence of photoaging is related to the reduction of the content of endogenous antioxidant coenzyme Q10. Coenzyme Q10 can significantly inhibit the expression of collagen kinase in human skin fibroblasts, thereby reducing the degradation of collagen in the skin and blocking the various damages caused by photoaging. (5) Cancer. The phenomenon of low blood coenzyme Q10 in some cancer patients has attracted the attention of researchers. A large number of experiments have shown that the onset of cancer is related to oxygen free radicals. Oxygen free radicals have a destructive effect on cell membranes, mitochondria, proteins, lipids, and DNA. Supplementing coenzyme Q10 can consume a large number of oxygen free radicals, so coenzyme Q10 has a certain therapeutic and preventive effect on cancer. (6) Anti-oxidation and anti-fatigue in sports medicine. Coenzyme Q10 is an activator of cell metabolism and cell respiration, and is also a natural antioxidant and free radical scavenger. It plays an important role in protecting and restoring the integrity of biological membrane structures. Taking coenzyme Ql0 can reduce serum CK levels after exercise, promote the improvement of aerobic capacity of middle- and long-distance runners, effectively remove free radicals produced during exercise, have a certain anti-fatigue effect, improve muscle malnutrition, improve sports endurance, leg pain, fatigue and other symptoms, and improve people's energy and brain power.

[0034] The beneficial effects of the present invention also lie in that: the self-emulsifying preparation is a homogeneous transparent solution composed of oil, surfactant and co-surfactant or a small amount of water, which can be used as a carrier of hydrophobic, difficult to absorb or easily hydrolyzed drugs. By encapsulating the drug in oil droplets, the drug is spontaneously dispersed under gastrointestinal peristalsis when it encounters body fluids after oral administration to form an O / W type microemulsion. The system can significantly improve the drug bioavailability by improving the solubility of the drug, reducing surface tension, forming a hydration layer that is easy to pass through the stomach and intestinal walls, and increasing the permeability to intestinal epithelial cells. The present invention adopts self-microemulsification nanotechnology to significantly improve the solubility and oral bioavailability of coenzyme Q10, and the preparation method is simple and low in cost. At the same time, the use of organic solvents such as DMSO is avoided, which is convenient for further promoting the transformation of coenzyme Q10 to clinical application and increasing the safety of its long-term application.

[0035] The beneficial effects of the present invention also lie in that: the absorption and bioavailability of CoQ10 can be increased by adding NADH, the CoQ10 transporter helps exogenous coenzyme Q10 to enter cells and be transported to the inner mitochondrial membrane to function, the VB group can also help improve the function of coenzyme Q10 in various ways, selenium can increase the activity of the enzyme and improve the function of coenzyme Q10, L-carnitine and CoQ10 can improve mitochondrial function and reduce the level of oxidative stress markers, and vitamin D reduces the effect of oxidative stress. DETAILED DESCRIPTION

[0036] The present invention is further described in detail below in conjunction with the embodiments. The following embodiments are only several specific embodiments of the present invention, but the design concept of the present invention is not limited thereto, and any non-substantial changes made to the present invention using this concept shall be deemed as acts that infringe the protection scope of the present invention.

[0037] The methods in the following embodiments are conventional methods unless otherwise specified.

[0038] Unless otherwise specified, the percentages (%) in the following examples are by mass.

[0039] Example 1

[0040] The main and auxiliary raw materials used in the coenzyme Q10 soft capsule of the present invention can all be purchased on the market.

[0041] (1) Place the formulated amount of diluent in a mixing tank, add the carrier lipid in the self-emulsifying preparation: HCO-60 (polyoxyethylene hydrogenated castor carrier lipid 60, 1.0-5.0% (w / v)) and caprylic acid 0.5-2.0% (w / v); coating agent: ethyl cellulose 0.1-1.0% (w / w), heat to 75°C to dissolve and stir evenly; (2) adding a formulated amount of surfactant: 0.5-2% (w / v) of sorbic acid monoester at the dissolution temperature of step (1), stirring evenly and cooling to room temperature to obtain an emulsion; (3) adding the formulated amount of coenzyme Q10 and the coenzyme Q10 bioactivity enhancing agent to the self-emulsifying liquid prepared in step (2), stirring evenly, and obtaining the liquid medicine in the capsule; (4) The liquid medicine content and capsule shell rubber obtained in step (3) are compressed into pills by a soft capsule machine and dried to obtain the product.

[0042] It has been found that the nutritional composition containing coenzyme Q10 of the present invention can be used as an antioxidant and a free radical scavenger, and can prevent or treat congestive heart failure, hypertension, nervous system diseases, skin diseases or cancer.

Claims

1. A nutritional composition containing coenzyme Q10, characterized in that: It is prepared from the following raw materials according to the weight percentage: 35.9-48.6% of panthenol; 9.6-13.0% of metoclopramide mesylate; 2.4-3.2% of ubiquinone; 1.0-5.0% (w / v) of HCO-60 polyoxyethylene hydrogenated castor carrier lipid 60; 0.5-2.0% (w / v) of octanoic acid; 0.1-1.0% (w / w) of ethyl cellulose; 0.5-2% (w / v) of sorbic acid monoester; 4.8-6.5% of adenosine dinucleotide (NADH); 9.6-13% bovine colostrum; 0.2-0.3% vitamin B1, 0.2-0.3% vitamin B2; 1.0-1.3% niacin; 1.2-1.6% pantothenic acid; 0.2-0.3% vitamin B6; 0.2-0.3% biotin; 0.2-0.3% folic acid; 0.2-0.3% vitamin B12; 0.010-0.013% selenium; 12.0-16.2% L-carnitine; and 7.2-9.7% vitamin D3.

2. The nutritional composition containing coenzyme Q10 according to claim 1, characterized in that: The nutritional composition is an emulsion-type capsule that is hydrophilic on the outside and hydrophobic on the inside, and the total liquid weight of each capsule is 154.6-221.9 mg.

3. The nutritional composition containing coenzyme Q10 according to claim 1 or 2, characterized in that: The coenzyme Q10 is reduced coenzyme Q10.

4. A method for preparing a nutritional composition containing coenzyme Q10, the method comprising the following steps: (1) Place the formulated amount of diluent in a mixing tank, add the carrier lipid in the self-emulsifying preparation: HCO-60 (polyoxyethylene hydrogenated castor carrier lipid 60, 1.0-5.0% (w / v)) and caprylic acid 0.5-2.0% (w / v); coating agent: ethyl cellulose 0.1-1.0% (w / w), heat to dissolve and stir evenly; (2) adding a formulated amount of surfactant: 0.5-2% (w / v) of sorbic acid monoester at the dissolution temperature of step (1), stirring evenly and cooling to room temperature to obtain an emulsion; (3) adding the formulated amount of coenzyme Q10 and the coenzyme Q10 bioactivity enhancing agent to the self-emulsifying liquid prepared in step (2), stirring evenly, and obtaining the liquid medicine in the capsule; (4) The liquid medicine content and capsule shell rubber obtained in step (3) are compressed into pills by a soft capsule machine and dried to obtain the product.

5. The method for preparing the coenzyme Q10 soft capsule according to claim 4, characterized in that: The heating and dissolving temperature in step (1) is 60-90°C.

6. The nutritional composition containing coenzyme Q10 is used as an antioxidant and free radical scavenger.

7. Use of a nutritional composition containing coenzyme Q10 in preventing or treating congestive heart failure or hypertension.

8. Use of a nutritional composition containing coenzyme Q10 in preventing or treating nervous system diseases.

9. Use of a nutritional composition containing coenzyme Q10 in preventing or treating skin diseases.

10. Use of a nutritional composition containing coenzyme Q10 in preventing or treating cancer.