WO2020243890A1 - Coenzyme dietary supplement, and preparation method therefor and application thereof - Google Patents

Abstract

A coenzyme dietary supplement, comprising the following active ingredients: coenzyme A and/or a precursor substance thereof, NADH, NADPH, FADH, FMNH, pyridoxal phosphate and/or a precursor substance thereof, tetrahydrofolate and/or a precursor substance thereof, and coenzyme Q10. Compared with the dietary supplement only containing a single coenzyme component, the coenzyme dietary supplement has better effects of improving the body health level and reducing disease risks.

Description

Coenzyme dietary nutritional supplement and its preparation method and application Technical field

The present invention relates to the technical field of biomedicine and health products, in particular to a dietary nutritional supplement with a coenzyme composition as the main biologically active substance, and its preparation method and application.

Background technique

Dietary supplements are an industry concept based on the actual situation of my country’s nutritional supplement industry. The industry research institute "Shuzheng Kangxun" commissioned by the Market Working Committee of China Health Care Association has formed an industry concept after long-term research. It specifically refers to: vitamins, minerals The main raw material is the extract with a relatively clear structure-activity relationship, and it is a product that supplements essential nutrients and biologically active substances for the human body through oral administration to improve the body's health and reduce the risk of disease. It mainly exists in a measurable and concentrated form of similar drugs. The dosage forms used mainly include: hard capsules, soft capsules, tablets, oral liquids, granules, powders, etc. The packaging forms include bottles, barrels (boxes), bags, Pre-packaged forms such as aluminum-plastic blister plates.

"Dietary nutritional supplements" is an industry term with Chinese characteristics that has gradually formed with the continuous improvement of people’s health awareness in our country, based on the business practices of enterprises and the academic promotion of industry think tanks. It has been announced with the US Food and Drug Administration. The concept of "dietary supplements" stipulated in the "Dietary Supplement Health and Education Law" is different. my country’s “dietary nutritional supplements” are based on modern nutrition, preventive medicine, and evidence-based medicine. They adjust the intake of various nutrient elements or biologically active substances in people’s diets and use dietary nutrition intervention to achieve For the purpose of enhancing physical fitness, improving function, balancing metabolism and reducing the risk of disease, the raw materials must be essential nutrients for the human body, or biologically active substances with relatively clear structure-activity relationships; the purpose is to improve the health of the body and reduce the risk of disease.

Coenzyme dietary supplements, as the name suggests, refer to dietary supplements that use coenzyme as the main biologically active substance. At present, there are not many such dietary supplements in the domestic market. The main products that can be found are Coenzyme Q10 products, including two: One is a product containing only a single component of Coenzyme Q10, such as the United States GNC Jiananxi Coenzyme Q10 Soft capsules, modified coenzyme Q10 tablets, etc.; the other is a combination of coenzyme Q10 and vitamins, such as By-Health's Coenzyme Q10 natural vitamin E soft capsules, Jiahuitai brand coenzyme Q10 vitamin C and vitamin E capsules.

Studies have found that coenzymes often require multiple coenzymes to work together in the human body. Therefore, dietary supplements containing a single coenzyme component are often not effective; and vitamins generally need to be further synthesized into the corresponding coenzyme after entering the body. In order to play a role, the bioavailability is low. Therefore, dietary nutritional supplements containing a combination of coenzymes and vitamins cannot achieve the best results.

technical problem

The purpose of the present invention is to solve the technical problems of single component and poor effect in the existing coenzyme dietary supplements mentioned in the background art, and to develop a dietary supplement containing multiple coenzyme substances in order to make the coenzyme components Play to the maximum extent in the body, so as to obtain the best effect of improving the body's health and reducing the risk of disease.

Technical solutions

In order to achieve the above objectives, the inventor has conducted a large number of experimental studies, screened dozens of coenzymes and compatibility experiments, and finally found out the best coenzyme composition that has the best synergistic effect, improves the health of the body and reduces the risk of disease. And the ratio of each coenzyme component. Therefore, the present invention provides such a coenzyme dietary supplement, including active ingredients, characterized in that the active ingredients include the following components: Coenzyme A and/or its precursor substances, NADH, NADPH, FADH, FMNH, phosphoric acid Pyridoxal and/or its precursor substances, tetrahydrofolate and/or its precursor substances, and coenzyme Q10.

Coenzyme A (Coenzyme A, abbreviated as CoA, CoASH or HSCoA), is a macromolecule composed of pantothenic acid, adenine, ribonucleic acid, phosphoric acid, etc. It acts as a carrier for acyl groups in some enzymatic reactions and combines with acetate It is acetyl-Coenzyme A, which enters the oxidation process and mainly participates in the metabolism of fatty acids and pyruvate in the human body.

NADH is the abbreviation of Nicotinamide Adenine Dinucleotide (Nicotinamide Adenine Dinucleotide). Nicotinamide Adenine Dinucleotide is a physiological substance that exists in all living cells, including human cells. This substance is a cofactor for many enzymes that can catalyze oxidation-reduction reactions, and is called Coenzyme I.

NADPH is a reduced nicotinamide adenine dinucleotide phosphate (Nicotinamide Adenine Dinucleotide Phosphate). Like NADH, NADPH is also a very important physiological substance that exists in biological cells. It is a phosphorylated derivative at the 2'-position of the ribose ring system connected to adenine in NADH. The extremely important nucleotide coenzyme is called Coenzyme II.

FADH is the English abbreviation of Flavine Adenine Dinucleotide (Flavine Adenine Dinucleotide), also known as flavin adenine dinucleotide hydrogen transmitter. It is a protein-binding reduced electron carrier and a reduced coenzyme. One kind. FADH is a derivative of B vitamins. It is a necessary substance in the anaerobic glycolysis and aerobic oxidation of carbohydrates (glucose, fructose, etc.) in the human body. It participates in electron transfer and oxidizes the phosphoric acid pathway to produce ATP.

FMNH is the English abbreviation of Flavin Mononucleotide (Flavin Mononucleotide), also known as reduced riboflavin-5-phosphate. It is the prosthetic group of flavoprotein and plays an important role in the electron transfer in biological oxidation processes such as respiration. The role is to act as a prosthetic group of the flavinase group to participate in the transfer of electrons from the substrate to the electron acceptor in the binding state with the enzyme protein (apo-enzyme), and play an important role in basic metabolism.

Pyridoxal5-phosphatemonohydrate (Pyridoxal5-phosphatemonohydrate, abbreviated as PLP) is formed by the combination of vitamin B6 and phosphoric acid. It exists in the human body in the form of phosphate ester, and its chemical name is 2-methyl-3-hydroxy-4-formaldehyde-5- Hydroxymethylpyridine phosphate. Pyridoxal phosphate is a coenzyme of transaminase and decarboxylase in amino acid metabolism. It can promote the decarboxylation of glutamate and increase the production of γ-aminobutyric acid, which is a neuroinhibitory transmitter.

Tetrahydrofolate is a reduced form of folic acid, also known as coenzyme F, which is the parent compound of folic acid in the form of coenzyme, and is a coenzyme in the one-carbon unit transferase system in the body. Tetrahydrofolate is a carrier of one-carbon group, can transfer one-carbon unit, participate in the synthesis of purine and pyrimidine, and promote the production of normal blood cells. When folic acid deficiency or certain drugs inhibit folic acid reductase, so that folic acid cannot be converted into tetrahydrofolate, it can affect the development and maturation of blood cells and cause megaloblastic anemia.

Coenzyme Q10 (Coenzyme Q10, abbreviated as CoQ10), also known as vitamin Q, decenquinone, ubiquinone, ubidecenone, coenzyme Q10, etc. Coenzyme Q is a fat-soluble quinone compound that exists widely in organisms. Coenzyme Q from different sources has different numbers of isoamylene units in the side chain. Humans and mammals have 10 isoamylene units, so it is called Coenzyme Q10. Coenzyme Q10 is one of the components of the respiratory chain. It plays an important role in proton translocation and electron transfer in the respiratory chain in the body. It participates in energy production and activation in human body cells. It is the most effective antioxidant component to prevent the formation of arteriosclerosis.

The so-called precursor substance refers to the substance of a target substance in the previous stage of the biosynthesis reaction. The precursor substance is transformed into the target substance after a certain biosynthesis reaction. Preferably, in the coenzyme dietary supplement provided by the present invention, the precursor substance of coenzyme A refers to pantothenic acid, the precursor substance of pyridoxal phosphate refers to vitamin B6, and the precursor substance of tetrahydrofolate refers to folic acid.

Preferably, the weight ratio of each active ingredient in the coenzyme dietary supplement provided by the present invention is: Coenzyme A and/or its precursor 1-20, NADH 1-40, NADPH 1-10, FADH 1-10 , FMNH 1-10, pyridoxal phosphate and/or its precursor 1-25, tetrahydrofolate and/or its precursor 0.1-0.4, coenzyme Q10 1-100.

More preferably, the weight ratio of each active ingredient in the coenzyme dietary supplement provided by the present invention is: Coenzyme A and/or its precursor material 5-20, NADH 30-40, NADPH 5-10, FADH 5-10, FMNH 5-10. Pyridoxal phosphate and/or its precursor material 5-25, tetrahydrofolate and/or its precursor material 0.1-0.4, coenzyme Q10 50-100.

More preferably, the weight ratio of each active ingredient in the coenzyme dietary nutritional supplement provided by the present invention is any one of the following combinations (1) to (6):

(1) Coenzyme A and/or its precursor substance 10, NADH 30, NADPH 10, FADH 10, FMNH 10, pyridoxal phosphate and/or its precursor substance 5, tetrahydrofolate and/or its precursor substance 0.4 , Coenzyme Q10 100;

(2) Coenzyme A and/or its precursor substance 10, NADH 40, NADPH 10, FADH 10, FMNH 10, pyridoxal phosphate and/or its precursor substance 10, tetrahydrofolate and/or its precursor substance 0.1 , Coenzyme Q10 100;

(3) Coenzyme A and/or its precursor substance 20, NADH 40, NADPH 10, FADH 10, FMNH 10, pyridoxal phosphate and/or its precursor substance 25, tetrahydrofolate and/or its precursor substance 0.4 , Coenzyme Q10 100;

(4) Coenzyme A and/or its precursor substance 10, NADH 40, NADPH 5, FADH 5, FMNH 5, pyridoxal phosphate and/or its precursor substance 25, tetrahydrofolate and/or its precursor substance 0.1 , Coenzyme Q10 50;

(5) Coenzyme A and/or its precursor substance 20, NADH 40, NADPH 5, FADH 5, FMNH 5, pyridoxal phosphate and/or its precursor substance 5, tetrahydrofolate and/or its precursor substance 0.1 , Coenzyme Q10 100;

(6) Coenzyme A and/or its precursor substance 5, NADH 40, NADPH 10, FADH 10, FMNH 10, pyridoxal phosphate and/or its precursor substance 5, tetrahydrofolate and/or its precursor substance 0.1 , Coenzyme Q10 100.

The aforementioned coenzyme dietary supplements provided by the present invention can improve body metabolism, convert fat, protein, and carbohydrates into cellular energy ATP to the greatest extent, repair DNA loss, promote DNA synthesis and other functions, so it can be used to prepare anti-aging and anti-aging Health products or medicines for fatigue, immunity enhancement, treatment of Parkinson's, sleep improvement and/or antioxidant function. By adjusting the ratio of the active ingredients in the coenzyme dietary supplements within a certain range, the health care product or medicine can only contain any one of the aforementioned functions, or any two or more of the aforementioned functions at the same time.

The present invention also provides a preparation method of the aforementioned coenzyme dietary nutritional supplement, which comprises the following steps:

1) Pass each active ingredient raw material through a 60-100 mesh sieve;

2) The sieved active ingredient materials are respectively microencapsulated in a fluidized bed;

3) Mix the active ingredients and pharmaceutical excipients uniformly according to the ratio of the coated microcapsules;

4) Fill the mixture of step 3) with a capsule filling machine for capsule filling, or use a tablet press for tableting.

The so-called fluidized bed coating of microcapsules refers to the use of fine drug powder, crystals, and microparticles as the core of the capsule, and the use of high molecular polymers as the coating material. The core of the capsule is placed in the fluidized bed. When the capsule core passes through the coating area, the coating liquid is sprayed uniformly on the surface of the capsule core in an atomized form under the action of air pressure. The droplets spread on the surface of the capsule core and combine with each other, and the organic solvent evaporates. The polymer forms a small discontinuous coating film, and as the above process is repeated, the entire surface of the capsule core is wrapped.

In the process of coating microcapsules with a fluidized bed, when the material is fluidized, particles and particles, particles and pots, particles and air will collide and generate electric charges. The smaller the particles, the larger the surface area, and the electrostatic force. The stronger, the electrostatic effect is an important factor affecting the film formation of the coating. If the medicinal powder is too small, too much fine powder will be adsorbed on the pot wall or shaking bag due to static electricity, and will not participate in fluidization and cannot be completely coated. At the same time, particles with too small particle size will easily pass through the filter bag or bottom sieve The middle leakage reduces the recovery rate, so the proportion of powder in the capsule core should be controlled to prepare the microcapsules. In order to control the uniformity of the particles and improve the fluidization state, it is preferable to pass each active ingredient material through a 60-100 mesh screen before the microcapsule coating, and the obtained particles are used as the core of the capsule.

Preferably, the coating liquid used for microcapsule coating in step 2) is prepared by the following method: Acrylic resin II/III (L300-55) and hypromellose phthalate/polyethylene Diol is dissolved in absolute ethanol with a solid content of 8-15% and left overnight for 24 hours, and then the coating liquid is passed through a 100-mesh sieve.

When carrying out microcapsule coating, the spray droplets must be smaller than the diameter of the encapsulated core. If the spray droplets are too large, the surface of the capsule core material will be too wet and cannot be dried in time, resulting in excessive contact between the coating liquid and the capsule core, causing adhesion of the microcapsules; if the spray droplets are too small, the evaporation surface area will be larger. The solvent volatilizes too much before the spray droplets come into contact with the capsule core, which is more likely to cause spray drying and reduce the encapsulation efficiency. The size of the spray droplets will be affected by the spray pressure. The higher the spray pressure, the smaller the spray droplets. However, when the spray pressure is too high, on the one hand, too much energy will be consumed, and on the other hand, the sac core will be boiled. Disorders cause fierce movement between the microcapsules, intensified collisions, and easy damage to the microcapsule walls. Considering comprehensively, preferably, the spray pressure during microcapsule coating in step 2) is 0.45-0.75 bar.

When coating the microcapsules, if the spraying speed is too slow, the weight of the coating will increase. Under the premise of no adhesion, the spraying speed should be increased as much as possible to shorten the coating time. Preferably, the spraying speed of the microcapsule coating in step 2) is 1.5-3.5 ml/min.

Preferably, the inlet air temperature during microcapsule coating in step 2) is controlled at 35-45°C. If the temperature is too high, the weight gain rate of the coating will decrease, and if the temperature is low, adhesion will easily occur.

Because the coenzymes NADH and NADPH are easy to absorb moisture, and the other coenzymes also have certain moisture absorption properties, in order to prevent moisture absorption, it is preferable to control the inlet air humidity during microcapsule coating in step 2) below 40%.

Preferably, in step 3), the active ingredient materials coated with the microcapsules are pre-mixed according to the proportion, and then pharmaceutical excipients are added for total mixing.

Preferably, acid-resistant plant capsules are used in step 4).

Beneficial effect

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

1. The coenzyme dietary nutritional supplement provided by the present invention is composed of a variety of coenzyme substances necessary for the human body through a scientific combination, and its compatibility is reasonable. Each coenzyme substance cooperates with each other and participates in the biological metabolic reaction in the human body. To maximize its effect, compared with dietary supplements containing only a single coenzyme component, it has a better effect of improving the health of the body and reducing the risk of disease;

2. The coenzyme dietary nutritional supplement prepared by the preparation method of the coenzyme dietary nutritional supplement provided by the present invention can not only effectively avoid the mutual influence between the coenzyme substances, but also can fully isolate the oxygen and moisture in the external environment, thereby Significantly improve the stability of the product and effectively extend the storage time.

Embodiments of the invention

The present invention will be further described in detail below in conjunction with specific embodiments. The following embodiments are an explanation of the present invention, and the present invention is not limited to the following embodiments.

Example 1

The coenzyme dietary supplement provided in this embodiment contains active ingredients in various proportions (parts by weight) as shown in Table 1.

Table 1

Active ingredient	Ratio 1	Ratio 2	Ratio 3	Ratio 4	Ratio 5	Ratio 6
Coenzyme A	10	10	20	10	20	5
NADH	30	40	40	40	40	40
NADPH	10	10	10	5	5	10
FADH	10	10	10	5	5	10
FMNH	10	10	10	5	5	10
PLP	5	10	25	25	5	5
Tetrahydrofolate	0.4	0.1	0.4	0.1	0.1	0.1
Coenzyme Q10	100	100	100	50	100	100

Example 2

According to the following steps, the coenzyme dietary supplements containing the active ingredients in various proportions as shown in Table 1 in Example 1 were prepared into tablets and capsules respectively:

1) Preparation of coating solution: Dissolve acrylic resin Ⅱ/Ⅲ (L300-55) and hypromellose phthalate/polyethylene glycol in anhydrous ethanol at a solid content of 8-15%. Stay overnight for 24 hours, then pass the coating liquid through a 100-mesh sieve for use;

2) Pass each active ingredient raw material through a 60-100 mesh sieve;

3) The sieved active ingredient materials are respectively microencapsulated in a fluidized bed, and the spray pressure is controlled to 0.45-0.75bar, the spray speed is 1.5-3.5ml/min, and the air inlet temperature is 35-45℃. , The inlet air humidity is below 40%;

4) Premix the active ingredient materials coated with the microcapsules in a three-dimensional motion mixer according to the ratio, mixing speed 10-15rpm, mixing time 15-20min, and then add magnesium stearate, direct pressure mannitol and microcrystalline The total cellulose is mixed, the mixing speed is 10-15rpm, the mixing time is 5-10min, the adding amount of magnesium stearate is 0.1-0.6% of the total weight of active ingredients, and the adding amount of direct pressure mannitol is 5 of the total weight of active ingredients. -30%, the amount of microcrystalline cellulose added is 5-20% of the total weight of the active ingredient;

5) Tableting: Press the mixed material in step 4) with a tableting machine. The punch is a round die with a diameter of φ5mm-φ10mm or a similar special-shaped die. The tablet weight is controlled to be 100-1000mg, and the hardness is controlled to be 30- 120N, the speed of the tablet press is controlled at 3-20 rpm, and the tablet of the coenzyme dietary nutritional supplement of the present invention is obtained.

6) Capsule filling: The mixed materials in step 4) are filled with a capsule filling machine, and 0#-5# acid-resistant plant capsule shells are selected with a filling weight of 100-1000mg to obtain the coenzyme dietary supplement of the present invention. Capsules.

Example 3

Health Function Evaluation Test

1. Anti-aging test

The test object is Drosophila melanogaster. Please refer to the culture conditions and reproduction methods of the "Health Food Inspection and Evaluation Technical Specification (2003 Edition)" on the life test chapter of Drosophila. The conventional yeast culture medium is selected, and the preparation method is referred to "Health Technical Specifications for Food Inspection and Evaluation (2003 Edition). Choose male adults of the same age that emerge from the same batch of fertilized eggs. There is no significant difference in body size between individuals. Every 20 worms are placed in a vial, and every two vials form a group, totaling 15 groups. One group was randomly selected as the blank group and continued to be fed with conventional yeast culture medium, and the remaining 14 groups were fed with yeast culture medium containing one of the control groups in Table 2 or one of the sample groups in Table 3. Observe and record the number of deaths regularly every day, remove dead flies in time, replace with new vials 3 times a week, and observe until all fruit flies die. Calculate the average survival time of each group of fruit flies, and calculate the percentage of the average survival time of fruit flies in each administration group longer than that of the blank group. The results are shown in Table 2 and Table 3.

2. Anti-fatigue test

The test subjects were BALB/c mice aged 2.5-3 months, and were randomly divided into 14 groups according to their body weight, with 10 mice in each group. The test mice were allowed to swim for 50 minutes under the weight of water at 30°C (4% of body weight), and 0.02ml of tail blood was collected when the mice were resting before exercise and when they were resting for 90 minutes after swimming stopped. Diacetylmonooxime-thiamin The urea method was used to measure the blood urea content, and the average increase in blood urea of each group of mice at rest 90 minutes after swimming stopped compared with that at rest before exercise was calculated as △1. The 14 groups of test mice were randomly given Table 2 One of the control group in Table 3 or one of the sample groups in Table 3 was gavage on an empty stomach every day, morning and evening, 6 mg/kg body weight each time. After 30 days of administration, the blood urea content of each mouse was measured again with reference to the aforementioned method, and the average increase in blood urea of each group of mice at rest 90 minutes after swimming stopped compared with that at rest before exercise was calculated. Calculate the percentage reduction of the average increase in blood urea before and after the administration of each group of mice. The calculation formula is (△1-△2)/△1×100%. The results are shown in Table 2 and Table 3.

3. Improving immunity test

The test subjects were 1-month-old female secondary Kunming mice. They were randomly divided into 15 groups according to their body weight, each with 10 mice. There was no significant difference in body weight between the groups by t test ( p >0.05). One of the groups was randomly selected as the blank group, and the remaining 14 groups were randomly given one of the control group in Table 2 or one of the sample groups in Table 3, and gavage on an empty stomach every day, once in the morning and once in the evening, each time 6mg/kg body weight. After 30 days of administration, refer to the lymphocyte transformation experiment to determine the average value of the lymphocyte proliferation ability of each group of test mice, and compare the administration group with the blank group to calculate the increase in the lymphocyte proliferation ability of the mice in each administration group The results are shown in Table 2 and Table 3.

4. Treatment of Parkinson's test

The test subjects are patients who have been diagnosed with Parkinson's disease and have a disease degree of 1-3. They are under 60 years old and have no gender limitation. Every 20 people are randomly divided into 1 group, a total of 14 groups, and each group is randomly given a table One of the control group in 2 or one of the sample groups in Table 3 was orally administered on an empty stomach every day, morning and evening, 30 mg each time, using a double-blind test method. After taking the medicine for 3 months, count the number of people whose symptoms were relieved in each group. The results are shown in Table 2 and Table 3. The symptom reduction is subject to the relief of at least one of the symptoms of resting tremor, muscle rigidity and bradykinesia.

5. Improve sleep test

The experiment was carried out at night. The subjects were 1-month-old BALB/c male secondary mice. They were randomly divided into 15 groups according to their body weight, with 10 mice in each group. There was no significant difference in body weight between the groups by t test ( p >0.05). One of the groups was randomly selected as the blank group, and the remaining 14 groups were randomly given one of the control group in Table 2 or one of the sample groups in Table 3, and gavage on an empty stomach every day, once in the morning and once in the evening, each time 6mg/kg body weight. 26 days after the administration, 15 groups of test mice were intraperitoneally injected with 26 mg/kg body weight of sodium pentobarbital, with an injection volume of 0.1 ml/10 g body weight. Take the disappearance of the righting reflex in mice as the sleep indicator, observe and record the sleep time of the tested mice, compare with the blank group, calculate the percentage of the extended sleep time induced by pentobarbital sodium in each administration group, and the results are shown in the table 2 and Table 3.

6. Antioxidant test

The test subjects are aged mice over 8 months old, single sex, grouped according to the level of malondialdehyde (MDA) in the blood, 15 mice are divided into 1 group, a total of 15 groups, one of which is randomly selected as the blank group, and the other 14 groups One of the control group in Table 2 or one of the sample groups in Table 3 was randomly administered, and the rats were given intragastrically on an empty stomach every day, morning and evening, 6 mg/kg body weight each time. Thirty days after the administration, refer to the "Antioxidant Function Evaluation Method" in the National Food and Drug Administration [2012] No. 107 document to detect the level of malondialdehyde (MDA) in the blood of the 15 groups of test mice, and count each group of tests The number of mice with positive results for this index is shown in Table 2 and Table 3. Compared with the blank group, the MDA content in the blood of the tested mice is reduced, and the test result of this index is determined to be positive.

Table 2

Control group	Anti-Aging	Anti-fatigue	Boost the immune system	Treat Parkinson	improve sleeping	anti-oxidation
Coenzyme A	4.56%	-8.10%	82.59%	8	127.86%	4
NADH	12.30%	31.91%	30.93%	10	6.3%	13
NADPH	-2.74%	11.01%	2.96%	3	59.24%	5
FADH	6.44%	23.41%	12.85%	3	36.36%	10
FMNH	4.31%	11.60%	28.72%	1	50.49%	7
PLP	8.10%	7.26%	6.51%	14	16.16%	5
Tetrahydrofolate	19.52%	5.76%	73.20%	0	9.98%	1
Coenzyme Q10	15.30%	23.51%	59.67%	7	89.26%	9

table 3

Sample group	Anti-Aging	Anti-fatigue	Boost the immune system	Treat Parkinson	improve sleeping	anti-oxidation
Ratio 1	31.96%	30.42%	60.62%	11	87.26%	10
Ratio 2	20.53%	49.89%	57.72%	15	104.69%	12
Ratio 3	30.15%	45.03%	103.77%	17	131.14%	13
Ratio 4	22.13%	37.84%	55.48%	19	98.31%	8
Ratio 5	13.05%	42.27%	98.51%	10	145.82%	8
Ratio 6	14.34%	36.06%	41.94%	8	66.20%	15

To

Claims (13)

1. Coenzyme dietary supplements, including active ingredients, characterized in that the active ingredients include the following components: Coenzyme A and/or its precursors, NADH, NADPH, FADH, FMNH, pyridoxal phosphate and/or its precursors Substances, tetrahydrofolate and/or its precursor substances, and coenzyme Q10.
2. The coenzyme dietary nutritional supplement according to claim 1, wherein the weight ratio of the active ingredients is: Coenzyme A and/or its precursor substances 1-20, NADH 1-40, NADPH 1-10, FADH 1-10, FMNH 1-10, pyridoxal phosphate and/or its precursor material 1-25, tetrahydrofolate and/or its precursor material 0.1-0.4, coenzyme Q10 1-100.
3. The coenzyme dietary nutritional supplement according to claim 2, wherein the weight ratio of the active ingredients is: Coenzyme A and/or its precursor substances 5-20, NADH 30-40, NADPH 5-10, FADH 5-10, FMNH 5-10, pyridoxal phosphate and/or its precursor material 5-25, tetrahydrofolate and/or its precursor material 0.1-0.4, coenzyme Q10 50-100.
4. The coenzyme dietary supplement according to claim 3, wherein the weight ratio of the active ingredient is any one of the following combinations (1) to (6):

   (1) Coenzyme A and/or its precursor substance 10, NADH 30, NADPH 10, FADH 10, FMNH 10, pyridoxal phosphate and/or its precursor substance 5, tetrahydrofolate and/or its precursor substance 0.4 , Coenzyme Q10 100;

   (2) Coenzyme A and/or its precursor substance 10, NADH 40, NADPH 10, FADH 10, FMNH 10, pyridoxal phosphate and/or its precursor substance 10, tetrahydrofolate and/or its precursor substance 0.1 , Coenzyme Q10 100;

   (3) Coenzyme A and/or its precursor substance 20, NADH 40, NADPH 10, FADH 10, FMNH 10, pyridoxal phosphate and/or its precursor substance 25, tetrahydrofolate and/or its precursor substance 0.4 , Coenzyme Q10 100;

   (4) Coenzyme A and/or its precursor substance 10, NADH 40, NADPH 5, FADH 5, FMNH 5, pyridoxal phosphate and/or its precursor substance 25, tetrahydrofolate and/or its precursor substance 0.1 , Coenzyme Q10 50;

   (5) Coenzyme A and/or its precursor substance 20, NADH 40, NADPH 5, FADH 5, FMNH 5, pyridoxal phosphate and/or its precursor substance 5, tetrahydrofolate and/or its precursor substance 0.1 , Coenzyme Q10 100;

   (6) Coenzyme A and/or its precursor substance 5, NADH 40, NADPH 10, FADH 10, FMNH 10, pyridoxal phosphate and/or its precursor substance 5, tetrahydrofolate and/or its precursor substance 0.1 , Coenzyme Q10 100.
5. The coenzyme dietary supplement according to any one of claims 1 to 4, wherein the precursor substance of coenzyme A is pantothenic acid, the precursor substance of pyridoxal phosphate is vitamin B6, and the precursor substance of coenzyme A is vitamin B6. The precursor substance of hydrofolate is folic acid.
6. The use of the coenzyme dietary supplement according to any one of claims 1 to 4, characterized in that: the use is for preparing anti-aging, anti-fatigue, improving immunity, treating Parkinson's, improving sleep and/or Antioxidant drugs or health products.
7. The preparation method of the coenzyme dietary nutritional supplement according to any one of claims 1 to 4, characterized in that the method comprises the following steps:

   1) Pass each active ingredient raw material through a 60-100 mesh sieve;

   2) The sieved active ingredient materials are respectively microencapsulated in a fluidized bed;

   3) Mix the active ingredients and pharmaceutical excipients uniformly according to the ratio of the coated microcapsules;

   4) Fill the mixture of step 3) with a capsule filling machine for capsule filling, or use a tablet press for tableting.
8. The method for preparing a coenzyme dietary nutritional supplement according to claim 7, characterized in that: in the step 2), the coating liquid used for microcapsule coating is prepared by the following method: Acrylic resin II/III (L300-55) and hypromellose phthalate/polyethylene glycol are dissolved in absolute ethanol at a solid content of 8-15% and left overnight for 24 hours, then the coating liquid is passed through a 100 mesh sieve Get it later.
9. The method for preparing a coenzyme dietary nutritional supplement according to claim 7, characterized in that: in the step 2), the spray pressure during microcapsule coating is 0.45-0.75 bar.
10. The method for preparing a coenzyme dietary nutritional supplement according to claim 7, characterized in that: in the step 2), the spraying speed during microcapsule coating is 1.5-3.5 ml/min.
11. The method for preparing a coenzyme dietary nutritional supplement according to claim 7, characterized in that: in the step 2), the inlet air temperature during microcapsule coating is controlled at 35-45°C.
12. The method for preparing a coenzyme dietary nutritional supplement according to claim 7, characterized in that: in the step 2), the humidity of the inlet air during microcapsule coating is controlled below 40%.
13. The method for preparing a coenzyme dietary nutritional supplement according to claim 7, characterized in that: in step 3), the active ingredient materials coated with the microcapsules are pre-mixed according to the ratio, and then added to the medicinal The auxiliary materials are mixed together.