A sustained-release tablet containing coenzyme Q10 and preparation method thereof

By developing Coenzyme Q10 sustained release tablets, using the combination of Coenzyme Q10 coating and plant extracts, the problem of poor results of existing Coenzyme Q10 products has been solved, and efficient and safe antioxidant, immune enhancement and fatigue improvement effects have been achieved.

CN118975997BActive Publication Date: 2025-03-11GUANGDONG RUNHE BIOTECHNOLOGY CO LTD
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Patent Information

Application Number
CN202411085949.6
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2024-08-08
Publication Date
2025-03-11
Estimated Expiration
2044-08-08

AI Technical Summary

Technical Problem

The existing Coenzyme Q10 products have mixed results and cannot meet consumers' demand for efficient and safe biological products, especially in anti-oxidation, improving immunity and improving fatigue.

Method used

A sustained-release tablet containing Coenzyme Q10 was developed. The active substances were composed of Coenzyme Q10 coating, herb kernel extract, perilla seed extract and gorgon chestnut rice extract. It was prepared by enzymatic decomposition of various enzymes, combined with auxiliary materials such as ethyl cellulose, starch, microcrystalline cellulose, and designed as sustained-release tablets to ensure the stability and sustained-release effect of Coenzyme Q10.

Benefits of technology

It has achieved safe and efficient release of Coenzyme Q10, significantly improved the effects of antioxidant, increased immunity and improved fatigue, and met consumers' demand for efficient biological products.

✦ Generated by Eureka AI based on patent content.

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Patent Text Reader

Abstract

The invention relates to a sustained-release tablet containing coenzyme Q10 and a preparation method thereof, belonging to the field of biotechnology. The active ingredients of the sustained-release tablet include a coenzyme Q10 coating, a grass fruit kernel extract, a perilla seed extract and a gorgon rice extract; the coenzyme Q10 coating is a coating agent coated on the surface of coenzyme Q10 powder particles; the grass fruit kernel extract is obtained by sequentially hydrolyzing the grass fruit kernel with ficin, subtilisin and trypsin; the perilla seed extract is obtained by sequentially hydrolyzing the perilla seeds with pepsin, acid protease and bromelain; the gorgon rice extract is obtained by sequentially hydrolyzing the gorgon rice with papain, trypsin and bromelain. The grass fruit kernel extract, the perilla seed extract and the gorgon rice extract are used in combination with the coenzyme Q10 coating at the same time, and can play a good anti-oxidation, improve immunity, and improve fatigue effects, and are safe and efficient; the coenzyme Q10 coating has sustained release and good absorption regulation.
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Description

Technical Field

[0001] The invention belongs to the field of biotechnology, and specifically relates to a sustained-release tablet containing coenzyme Q10 and a preparation method thereof. Background Art

[0002] Coenzyme Q10 is a quinone compound that exists in various organs and tissues of the human body, especially in organs with high energy demands such as the heart, liver, and kidneys. Coenzyme Q10 plays a key role in the energy metabolism of cells. It is an important component of the mitochondrial respiratory chain and participates in the process of electron transfer and energy generation. By accepting and transferring electrons, coenzyme Q10 promotes the synthesis of adenosine triphosphate (ATP) and provides the energy required for various physiological activities of cells. Therefore, the content and functional status of coenzyme Q10 are directly related to the energy supply of cells and the maintenance of normal physiological functions.

[0003] As research deepens, it is found that coenzyme Q10 has many important uses:

[0004] (1) It helps to provide energy for myocardial cells, enhance myocardial function, and is helpful in preventing and improving cardiovascular diseases such as cardiomyopathy, arrhythmia, and heart failure.

[0005] (2) It can scavenge free radicals, reduce the damage of oxidative stress to cells, delay the aging process, and protect cells from oxidative damage.

[0006] (3) Participate in the energy metabolism of immune cells, enhance the body's immune function, and improve the body's resistance.

[0007] (4) Helps relieve physical and mental fatigue and improve physical endurance and vitality.

[0008] However, the synthesis of Coenzyme Q10 in the human body is affected by many factors. Aging, certain disease states, unhealthy lifestyles (such as long-term smoking, alcoholism, overwork, etc.) and the use of certain drugs may lead to reduced synthesis or increased consumption of Coenzyme Q10. When the level of Coenzyme Q10 in the body is insufficient, it may cause a series of health problems.

[0009] In order to meet the human body's demand for coenzyme Q10, in addition to consuming foods rich in coenzyme Q10 (such as animal offal, fish, nuts, etc.) through diet, you can also increase the intake of coenzyme Q10 through supplements. Currently, there are many types of coenzyme Q10 supplements on the market, including capsules, tablets, oral liquids and other dosage forms. Coenzyme Q10 is a fat-soluble substance that forms micelles under the action of bile salts and is mainly absorbed in the intestines, while the stomach has a relatively small effect on the absorption of coenzyme Q10.

[0010] There are many existing coenzyme Q10 products, most of which are complex ingredients. The specific compatibility of coenzyme Q10 with other functional ingredients, as well as the body's absorption rate of coenzyme Q10 and other active ingredients, also affect the specific therapeutic effect. Therefore, the various products on the market have varying effects and cannot meet consumers' increasing demand for use. It is necessary to continuously develop safer and more efficient biological products to better supplement coenzyme Q10 and give full play to the product's good antioxidant, immunity-enhancing, fatigue-alleviating and other effects. Summary of the invention

[0011] In view of the variety of existing coenzyme Q10 products, the specific compatibility of coenzyme Q10 with other functional ingredients, and the absorption rate of coenzyme Q10 and other active ingredients by the human body, all affect the specific therapeutic effect. Various products on the market have mixed effects and cannot meet the increasing demand of consumers for use. It is necessary to continuously develop safer and more efficient biological products to better supplement coenzyme Q10, and give full play to the good antioxidant, immunity and fatigue improvement of the product. The present invention provides a sustained-release tablet containing coenzyme Q10 and a preparation method thereof. The active substance of the sustained-release tablet contains coenzyme Q10 coating, grass fruit kernel extract, perilla seed extract and gorgon rice extract; grass fruit kernel extract, perilla seed extract and gorgon rice extract are used as raw materials and prepared by multiple enzyme graded enzymolysis. Grass fruit kernel extract, perilla seed extract and gorgon rice extract are used in combination with coenzyme Q10 coating at the same time, which can play a good antioxidant, immunity and fatigue improvement effect, and is safe and efficient. Its specific technical scheme is as follows:

[0012] A sustained-release tablet containing coenzyme Q10, wherein the sustained-release tablet is made of the following raw materials in parts by weight: 2 to 5 parts of coenzyme Q10 coating, 5 to 8 parts of grass fruit kernel extract, 8 to 12 parts of perilla seed extract, 15 to 20 parts of Euryale ferox extract, 8 to 12 parts of ethyl cellulose, 20 to 30 parts of starch, 10 to 15 parts of microcrystalline cellulose, 2 to 5 parts of hydroxypropyl cellulose, 0.5 to 1.5 parts of magnesium stearate, and 0.5 to 2 parts of sodium carboxymethyl starch;

[0013] The coenzyme Q10 coating material is a layer of coating agent coated on the surface of coenzyme Q10 powder particles, and the coating agent contains chitosan, konjac gum, nano calcium carbonate and polysorbate;

[0014] The cardamom kernel extract is an extract below 5kDa obtained by sequentially hydrolyzing the cardamom kernel with ficin, subtilisin and trypsin; the perilla seed extract is an extract below 5kDa obtained by sequentially hydrolyzing the perilla seeds with pepsin, acid protease and bromelain; the gorgon rice extract is an extract below 5kDa obtained by sequentially hydrolyzing the gorgon rice with papain, trypsin and bromelain.

[0015] In the above technical solution, the preparation method of the coenzyme Q10 coating is: a layer of coating agent is coated on the surface of the coenzyme Q10 powder particles by a fluidized spray method, and freeze-dried to obtain the coenzyme Q10 coating.

[0016] The mass ratio of coenzyme Q10 and coating agent is coenzyme Q10: coating agent = 100: (10-20); the mass ratio of the components of the coating agent is water: chitosan: konjac gum: nano-calcium carbonate: polysorbate = (80-90): (2-5): (1-3): (5-8): (0.5-1.5).

[0017] In the above technical scheme, the preparation method of the grass kernel extract is: crush the grass kernel, add 6 to 8 times the mass of water of the grass kernel, add 0.5% to 1.5% by mass of fig protease of the grass kernel, enzymolysis at 60°C to 70°C for 2h to 3h, inactivate the enzyme at high temperature, cool to room temperature, adjust the pH to 7.8 to 8.5, add 0.5% to 1.5% by mass of subtilisin of the grass kernel, enzymolysis at 40°C to 50°C for 1h to 1.5h, inactivate the enzyme at high temperature, cool to room temperature, add 0.5% to 1% by mass of trypsin of the grass kernel, enzymolysis at 35°C to 38°C for 2h to 3h, inactivate the enzyme at high temperature, cool to room temperature, filter with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, spray dry, and obtain the grass kernel extract.

[0018] The enzymatic activity of fig protease is 50,000 to 100,000 U / g; the enzymatic activity of subtilisin is 20,000 to 30,000 U / g; the enzymatic activity of trypsin is 50,000 to 100,000 U / g; the temperature of high-temperature enzyme inactivation is 80°C to 90°C, and the time is 15min to 25min.

[0019] In the above technical scheme, the preparation method of the perilla seed extract is as follows: crush the perilla seeds, add 6 to 8 times the mass of water of the perilla seeds, adjust the pH to 1.5 to 2.0 with hydrochloric acid, add 0.3% to 0.8% of pepsin by mass of the perilla seeds, enzymolysis at 35°C to 38°C for 2h to 3h, inactivate the enzyme at high temperature, cool to room temperature, adjust the pH to 2.5 to 3.0, add 0.5% to 1.5% of acid protease by mass of the perilla seeds, enzymolysis at 40°C to 60°C for 1h to 1.5h, inactivate the enzyme at high temperature, cool to room temperature, adjust the pH to 6 to 8, add 0.5% to 1.5% of bromelain by mass of the perilla seeds, enzymolysis at 50°C to 60°C for 2h to 3h, inactivate the enzyme at high temperature, cool to room temperature, filter with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, spray dry, and obtain the perilla seed extract.

[0020] The enzymatic activity of pepsin is 5,000 to 10,000 U / g; the enzymatic activity of acidic protease is 50,000 to 100,000 U / g, which comes from Aspergillus niger; the enzymatic activity of bromelain is 50,000 to 100,000 U / g; the temperature of high-temperature enzyme inactivation is 90°C to 100°C, and the time is 15min to 20min.

[0021] In the above technical scheme, the preparation method of the gorgon rice extract is: crushing the gorgon rice, adding water 6 to 8 times the mass of the gorgon rice, adding 1.5% to 3% papain of the gorgon rice, enzymolysis at 55°C to 65°C for 2h to 3h, high temperature inactivating the enzyme, cooling to room temperature, adjusting the pH to 7.8 to 8.5, adding 0.5% to 1.5% trypsin of the gorgon rice, enzymolysis at 35°C to 38°C for 2h to 3h, high temperature inactivating the enzyme, cooling to room temperature, filtering with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, spray drying, and obtaining the gorgon rice extract.

[0022] The enzymatic activity of papain is 200,000 to 400,000 U / g, and the enzymatic activity of trypsin is 50,000 to 100,000 U / g; the temperature for high-temperature enzyme inactivation is 80°C to 90°C, and the time is 15 min to 25 min.

[0023] The method for preparing the above-mentioned sustained-release tablet containing coenzyme Q10 comprises the following steps:

[0024] S1: premix the grass kernel extract, the perilla seed extract and the gorgon rice extract in parts by mass to obtain a mixture A;

[0025] S2: uniformly mixing ethyl cellulose, starch, microcrystalline cellulose, hydroxypropyl cellulose and sodium carboxymethyl starch according to parts by mass to obtain a mixture B;

[0026] S3: uniformly mixing magnesium stearate and coenzyme Q10 coating according to weight proportions to obtain a mixture C;

[0027] S4: Mix mixture A and mixture B evenly, and finally add mixture C. After mixing evenly, put into a tablet press, dry-press into tablets, and coat with sugar to obtain sustained-release tablets.

[0028] The invention provides a sustained-release tablet containing coenzyme Q10 and a preparation method thereof, which has the following beneficial effects compared with the prior art:

[0029] 1. The active substance of the sustained-release tablet of the present invention contains coenzyme Q10 coating, grass fruit kernel extract, perilla seed extract and euryale ferox extract; among the excipients, ethyl cellulose is used as a sustained-release agent, starch and microcrystalline cellulose are used as fillers, hydroxypropyl cellulose is used as a binder, magnesium stearate is used as a lubricant, and an appropriate amount of sodium carboxymethyl starch is added as a disintegrant; the prepared sustained-release tablet has a safe and efficient effect, and can exert good antioxidant, immunity-enhancing and fatigue-improving effects.

[0030] 2. The present invention is designed to coat the surface of coenzyme Q10 powder particles with a coating agent, wherein the coating agent contains chitosan, konjac gum, nano-calcium carbonate and polysorbate; the coating agent can isolate coenzyme Q10, and the diaphragm can effectively prevent coenzyme Q10 from contacting other drug ingredients and auxiliary ingredients, reduce the influence of other ingredients on coenzyme Q10, and prolong the storage stability of coenzyme Q10. At the same time, the coating film has a sustained release effect on the release of coenzyme Q10, which can delay the release of coenzyme Q10 in the intestine to the greatest extent, and can be absorbed in time periods with other ingredients, reducing the burden of simultaneous absorption, improving the absorption rate of plant ingredients, and promoting synergistic effects.

[0031] 3. The cardamom kernel extract is an extract below 5kDa obtained by sequentially enzymatic hydrolysis of cardamom kernels with ficin, subtilisin and trypsin; the obtained extract contains rich small molecule active nutrients and various small molecule peptide components, and has certain antioxidant, immunity-enhancing and fatigue-improving effects.

[0032] 4. Perilla seed extract is an extract below 5kDa obtained by graded enzymatic hydrolysis of perilla seeds with pepsin, acid protease and bromelain in sequence; the obtained extract contains rich small molecule active nutrients and various small molecule peptide components, and has certain antioxidant, immunity-enhancing and fatigue-improving effects.

[0033] 5. Gorgon rice extract is an extract below 5kDa obtained by graded enzymatic hydrolysis of Gorgon rice with papain, trypsin and bromelain in sequence; the obtained extract contains rich small molecule active nutrients and various small molecule peptide components, and has certain antioxidant, immunity-enhancing and fatigue-improving effects.

[0034] 6. When the extracts of Amomum villosum, Perilla frutescens and Euryale ferox are used together with Coenzyme Q10, they have a synergistic effect, which can greatly enhance the effects of Coenzyme Q10 and each extract, and significantly improve the effects of anti-oxidation, immunity and fatigue. However, the plant extracts prepared by omitting the enzymatic hydrolysis step have obviously different ingredients, and the synergistic effect of each extract when used together with Coenzyme Q10 is not ideal.

[0035] 7. In the preparation method, magnesium stearate and the coenzyme Q10 coating are designed to be uniformly mixed, which can improve the dispersibility and lubricity of the coenzyme Q10 coating; the coenzyme Q10 coating is designed to be added last and mixed to prepare mixture C; improving the dispersibility and lubricity of the coenzyme Q10 coating and adding it last can protect the coenzyme Q10 coating layer to the maximum extent, prevent it from being damaged by mixing friction, quickly mix it, reduce the mixing time, and maintain the integrity of the coating film. DETAILED DESCRIPTION

[0036] The present invention is further described below in conjunction with specific implementation cases, but the present invention is not limited to these embodiments.

[0037] Example 1

[0038] A sustained-release tablet containing coenzyme Q10 is made of the following raw materials in parts by mass: 3 parts of coenzyme Q10 coating, 7 parts of grass fruit kernel extract, 10 parts of perilla seed extract, 18 parts of Euryale ferox extract, 10 parts of ethyl cellulose, 25 parts of starch, 12 parts of microcrystalline cellulose, 3 parts of hydroxypropyl cellulose, 1 part of magnesium stearate, and 1.5 parts of sodium carboxymethyl starch.

[0039] The preparation method of the coenzyme Q10 coating is as follows: according to the mass ratio of coenzyme Q10: coating agent = 100:15, a layer of coating agent is coated on the surface of coenzyme Q10 powder particles by fluidized spray method, and freeze-dried to obtain the coenzyme Q10 coating. The mass ratio of the coating agent is water: chitosan: konjac gum: nano calcium carbonate: polysorbate = 85:3:2:6:1.

[0040] The preparation method of the grass kernel extract is as follows: crush the grass kernel, add water 7 times the weight of the grass kernel, add 1% of the weight of fig protease in the grass kernel, enzymolyze at 65°C for 2.5 hours, inactivate the enzyme at 85°C for 20 minutes, cool to room temperature, adjust the pH to 8.2, add 1% of the weight of subtilisin in the grass kernel, enzymolyze at 45°C for 1 hour, inactivate the enzyme at 85°C for 20 minutes, cool to room temperature, add 0.8% of the weight of trypsin in the grass kernel, enzymolyze at 37°C for 2.5 hours, inactivate the enzyme at 85°C for 20 minutes, cool to room temperature, filter with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, spray dry, and obtain the grass kernel extract.

[0041] The preparation method of the perilla seed extract is as follows: crushing the perilla seeds, adding water 7 times the mass of the perilla seeds, adjusting the pH to 1.8 with hydrochloric acid, adding pepsin 0.5% by mass of the perilla seeds, enzymolysis at 37°C for 2.5 hours, inactivating the enzyme at 95°C for 15 minutes, cooling to room temperature, adjusting the pH to 2.8, adding acid protease 1% by mass of the perilla seeds, enzymolysis at 50°C for 1 hour, inactivating the enzyme at 95°C for 15 minutes, cooling to room temperature, adjusting the pH to 7, adding bromelain 1% by mass of the perilla seeds, enzymolysis at 55°C for 2.5 hours, inactivating the enzyme at 95°C for 15 minutes, cooling to room temperature, filtering with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, spray drying, and obtaining the perilla seed extract.

[0042] The preparation method of the gorgon rice extract is as follows: crushing the gorgon rice, adding water 7 times the mass of the gorgon rice, adding 2% papain of the gorgon rice, performing enzymolysis at 60°C for 2.5 hours, inactivating the enzyme at 85°C for 20 minutes, cooling to room temperature, adjusting the pH to 8.2, adding 1% trypsin of the gorgon rice, performing enzymolysis at 37°C for 2.5 hours, inactivating the enzyme at 85°C for 20 minutes, cooling to room temperature, filtering with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, spray drying, and obtaining the gorgon rice extract.

[0043] The enzymatic activity of the ficin used in this embodiment is 100,000 U / g. The enzymatic activity of subtilisin is 30,000 U / g. The enzymatic activity of trypsin is 100,000 U / g. The enzymatic activity of pepsin is 10,000 U / g. The enzymatic activity of acid protease is 100,000 U / g, which is derived from Aspergillus niger. The enzymatic activity of bromelain is 100,000 U / g. The enzymatic activity of papain is 200,000 U / g.

[0044] The method for preparing the above-mentioned sustained-release tablet containing coenzyme Q10 comprises the following steps:

[0045] S1: premix the grass kernel extract, the perilla seed extract and the gorgon rice extract in parts by mass to obtain a mixture A;

[0046] S2: uniformly mixing ethyl cellulose, starch, microcrystalline cellulose, hydroxypropyl cellulose and sodium carboxymethyl starch according to parts by mass to obtain a mixture B;

[0047] S3: uniformly mixing magnesium stearate and coenzyme Q10 coating according to weight proportions to obtain a mixture C;

[0048] S4: Mix mixture A and mixture B evenly, and finally add mixture C. After mixing evenly, put into a tablet press, dry-press into tablets, and coat with sugar to obtain sustained-release tablets.

[0049] Example 2

[0050] A sustained-release tablet containing coenzyme Q10 is made of the following raw materials in parts by mass: 2 parts of coenzyme Q10 coating, 5 parts of cardamom kernel extract, 8 parts of perilla seed extract, 15 parts of Euryale ferox extract, 8 parts of ethyl cellulose, 20 parts of starch, 10 parts of microcrystalline cellulose, 2 parts of hydroxypropyl cellulose, 0.5 parts of magnesium stearate, and 0.5 parts of sodium carboxymethyl starch.

[0051] The preparation method of the coenzyme Q10 coating is as follows: according to the mass ratio of coenzyme Q10: coating agent = 100:10, a layer of coating agent is coated on the surface of coenzyme Q10 powder particles by fluidized spray method, and freeze-dried to obtain the coenzyme Q10 coating. The mass ratio of the coating agent components is water: chitosan: konjac gum: nano calcium carbonate: polysorbate = 80:2:1:5:0.5.

[0052] The preparation method of the grass kernel extract is as follows: crush the grass kernel, add water 6 times the weight of the grass kernel, add 0.5% of the weight of fig protease in the grass kernel, enzymolyze at 60°C for 2 hours, inactivate the enzyme at 80°C for 15 minutes, cool to room temperature, adjust the pH to 7.8, add 0.5% of the weight of subtilisin in the grass kernel, enzymolyze at 40°C for 1 hour, inactivate the enzyme at 80°C for 15 minutes, cool to room temperature, add 0.5% of the weight of trypsin in the grass kernel, enzymolyze at 37°C for 2 hours, inactivate the enzyme at 80°C for 15 minutes, cool to room temperature, filter with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, spray dry, and obtain the grass kernel extract.

[0053] The preparation method of the perilla seed extract comprises the following steps: crushing the perilla seeds, adding water 6 times the mass of the perilla seeds, adjusting the pH to 1.5 with hydrochloric acid, adding pepsin 0.3% by mass of the perilla seeds, performing enzymolysis at 35°C for 2h, inactivating the enzyme at 90°C for 15min, cooling to room temperature, adjusting the pH to 2.5, adding acid protease 0.5% by mass of the perilla seeds, performing enzymolysis at 40°C for 1h, inactivating the enzyme at 90°C for 15min, cooling to room temperature, adjusting the pH to 6, adding bromelain 0.5% by mass of the perilla seeds, performing enzymolysis at 50°C for 2h, inactivating the enzyme at 90°C for 15min, cooling to room temperature, filtering with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, and spray drying to obtain the perilla seed extract.

[0054] The preparation method of the gorgon rice extract is as follows: crushing the gorgon rice, adding water 6 times the mass of the gorgon rice, adding 1.5% papain of the gorgon rice, performing enzymolysis at 55°C for 2h, inactivating the enzyme at 80°C for 15min, cooling to room temperature, adjusting the pH to 7.8, adding 0.5% trypsin of the gorgon rice, performing enzymolysis at 37°C for 2h, inactivating the enzyme at 80°C for 15min, cooling to room temperature, filtering with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, spray drying, and obtaining the gorgon rice extract.

[0055] The enzymatic activity of the ficin used in this embodiment is 50,000 U / g. The enzymatic activity of subtilisin is 20,000 U / g. The enzymatic activity of trypsin is 50,000 U / g. The enzymatic activity of pepsin is 5,000 U / g. The enzymatic activity of acid protease is 50,000 U / g, which is derived from Aspergillus niger. The enzymatic activity of bromelain is 50,000 U / g. The enzymatic activity of papain is 300,000 U / g.

[0056] The method for preparing the above-mentioned sustained-release tablet containing coenzyme Q10 comprises the following steps:

[0057] S1: premix the grass kernel extract, the perilla seed extract and the gorgon rice extract in parts by mass to obtain a mixture A;

[0058] S2: uniformly mixing ethyl cellulose, starch, microcrystalline cellulose, hydroxypropyl cellulose and sodium carboxymethyl starch according to parts by mass to obtain a mixture B;

[0059] S3: uniformly mixing magnesium stearate and coenzyme Q10 coating according to weight proportions to obtain a mixture C;

[0060] S4: Mix mixture A and mixture B evenly, and finally add mixture C. After mixing evenly, put into a tablet press, dry-press into tablets, and coat with sugar to obtain sustained-release tablets.

[0061] Example 3

[0062] A sustained-release tablet containing coenzyme Q10 is made of the following raw materials in parts by mass: 2 parts of coenzyme Q10 coating, 8 parts of cardamom kernel extract, 8 parts of perilla seed extract, 20 parts of Euryale ferox extract, 8 parts of ethyl cellulose, 30 parts of starch, 10 parts of microcrystalline cellulose, 5 parts of hydroxypropyl cellulose, 0.5 parts of magnesium stearate, and 2 parts of sodium carboxymethyl starch.

[0063] The preparation method of the coenzyme Q10 coating is as follows: according to the mass ratio of coenzyme Q10: coating agent = 100:10, a layer of coating agent is coated on the surface of coenzyme Q10 powder particles by fluidized spray method, and freeze-dried to obtain the coenzyme Q10 coating. The mass ratio of the coating agent components is water: chitosan: konjac gum: nano calcium carbonate: polysorbate = 90:2:3:5:1.5.

[0064] The preparation method of the grass kernel extract is as follows: crush the grass kernel, add water 6 times the weight of the grass kernel, add 1.5% of the weight of fig protease in the grass kernel, enzymolyze at 60°C for 3 hours, inactivate the enzyme at 80°C for 25 minutes, cool to room temperature, adjust the pH to 7.8, add 1.5% of the weight of subtilisin in the grass kernel, enzymolyze at 40°C for 1.5 hours, inactivate the enzyme at 80°C for 25 minutes, cool to room temperature, add 0.5% of the weight of trypsin in the grass kernel, enzymolyze at 38°C for 2 hours, inactivate the enzyme at 90°C for 15 minutes, cool to room temperature, filter with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, spray dry, and obtain the grass kernel extract.

[0065] The preparation method of the perilla seed extract comprises the following steps: crushing the perilla seeds, adding water 8 times the mass of the perilla seeds, adjusting the pH to 1.5 with hydrochloric acid, adding pepsin 0.8% by mass of the perilla seeds, performing enzymolysis at 35°C for 3h, inactivating the enzyme at 90°C for 20min, cooling to room temperature, adjusting the pH to 2.5, adding acid protease 1.5% by mass of the perilla seeds, performing enzymolysis at 40°C for 1.5h, inactivating the enzyme at 90°C for 20min, cooling to room temperature, adjusting the pH to 6, adding bromelain 1.5% by mass of the perilla seeds, performing enzymolysis at 50°C for 3h, inactivating the enzyme at 90°C for 20min, cooling to room temperature, filtering with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, and spray drying to obtain the perilla seed extract.

[0066] The preparation method of the gorgon rice extract is as follows: crushing the gorgon rice, adding water 6 times the mass of the gorgon rice, adding 3% papain of the gorgon rice, performing enzymolysis at 55°C for 3h, inactivating the enzyme at 80°C for 25min, cooling to room temperature, adjusting the pH to 7.8, adding 1.5% trypsin of the gorgon rice, performing enzymolysis at 35°C for 3h, inactivating the enzyme at 80°C for 25min, cooling to room temperature, filtering with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, spray drying, and obtaining the gorgon rice extract.

[0067] The enzymatic activity of the ficin used in this embodiment is 50,000 U / g. The enzymatic activity of subtilisin is 30,000 U / g. The enzymatic activity of trypsin is 50,000 U / g. The enzymatic activity of pepsin is 10,000 U / g. The enzymatic activity of acid protease is 50,000 U / g, which is derived from Aspergillus niger. The enzymatic activity of bromelain is 100,000 U / g. The enzymatic activity of papain is 200,000 U / g.

[0068] The method for preparing the above-mentioned sustained-release tablet containing coenzyme Q10 comprises the following steps:

[0069] S1: premix the grass kernel extract, the perilla seed extract and the gorgon rice extract in parts by mass to obtain a mixture A;

[0070] S2: uniformly mixing ethyl cellulose, starch, microcrystalline cellulose, hydroxypropyl cellulose and sodium carboxymethyl starch according to parts by mass to obtain a mixture B;

[0071] S3: uniformly mixing magnesium stearate and coenzyme Q10 coating according to weight proportions to obtain a mixture C;

[0072] S4: Mix mixture A and mixture B evenly, and finally add mixture C. After mixing evenly, put into a tablet press, dry-press into tablets, and coat with sugar to obtain sustained-release tablets.

[0073] Example 4

[0074] A sustained-release tablet containing coenzyme Q10 is made of the following raw materials in parts by mass: 5 parts of coenzyme Q10 coating, 8 parts of grass fruit kernel extract, 12 parts of perilla seed extract, 20 parts of Euryale ferox extract, 12 parts of ethyl cellulose, 30 parts of starch, 15 parts of microcrystalline cellulose, 5 parts of hydroxypropyl cellulose, 1.5 parts of magnesium stearate, and 2 parts of sodium carboxymethyl starch.

[0075] The preparation method of the coenzyme Q10 coating is as follows: according to the mass ratio of coenzyme Q10: coating agent = 100:20, a layer of coating agent is coated on the surface of coenzyme Q10 powder particles by fluidized spray method, and freeze-dried to obtain the coenzyme Q10 coating. The mass ratio of the coating agent components is water: chitosan: konjac gum: nano calcium carbonate: polysorbate = 90:5:3:8:1.5.

[0076] The preparation method of the grass kernel extract is as follows: crush the grass kernel, add water 8 times the weight of the grass kernel, add 1.5% of the weight of fig protease in the grass kernel, enzymolyze at 70°C for 3 hours, inactivate the enzyme at 90°C for 25 minutes, cool to room temperature, adjust the pH to 8.5, add 1.5% of the weight of subtilisin in the grass kernel, enzymolyze at 50°C for 1.5 hours, inactivate the enzyme at 90°C for 25 minutes, cool to room temperature, add 1% of the weight of trypsin in the grass kernel, enzymolyze at 38°C for 3 hours, inactivate the enzyme at 90°C for 25 minutes, cool to room temperature, filter with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, spray dry, and obtain the grass kernel extract.

[0077] The preparation method of the perilla seed extract comprises the following steps: crushing the perilla seeds, adding water 8 times the mass of the perilla seeds, adjusting the pH to 2.0 with hydrochloric acid, adding pepsin 0.8% by mass of the perilla seeds, performing enzymolysis at 37°C for 3h, inactivating the enzyme at 100°C for 20min, cooling to room temperature, adjusting the pH to 3.0, adding acid protease 1.5% by mass of the perilla seeds, performing enzymolysis at 60°C for 1.5h, inactivating the enzyme at 100°C for 20min, cooling to room temperature, adjusting the pH to 8, adding bromelain 1.5% by mass of the perilla seeds, performing enzymolysis at 60°C for 3h, inactivating the enzyme at 100°C for 20min, cooling to room temperature, filtering with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, and spray drying to obtain the perilla seed extract.

[0078] The preparation method of the gorgon rice extract is as follows: crushing the gorgon rice, adding water of 8 times the mass of the gorgon rice, adding 3% papain of the gorgon rice, performing enzymolysis at 65°C for 3h, inactivating the enzyme at 90°C for 25min, cooling to room temperature, adjusting the pH to 8.5, adding 1.5% trypsin of the gorgon rice, performing enzymolysis at 37°C for 3h, inactivating the enzyme at 90°C for 25min, cooling to room temperature, filtering with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, spray drying, and obtaining the gorgon rice extract.

[0079] The enzymatic activity of the ficin used in this embodiment is 100,000 U / g. The enzymatic activity of subtilisin is 30,000 U / g. The enzymatic activity of trypsin is 100,000 U / g. The enzymatic activity of pepsin is 10,000 U / g. The enzymatic activity of acid protease is 100,000 U / g, which is derived from Aspergillus niger. The enzymatic activity of bromelain is 100,000 U / g. The enzymatic activity of papain is 400,000 U / g.

[0080] The method for preparing the above-mentioned sustained-release tablet containing coenzyme Q10 comprises the following steps:

[0081] S1: premix the grass kernel extract, the perilla seed extract and the gorgon rice extract in parts by mass to obtain a mixture A;

[0082] S2: uniformly mixing ethyl cellulose, starch, microcrystalline cellulose, hydroxypropyl cellulose and sodium carboxymethyl starch according to parts by mass to obtain a mixture B;

[0083] S3: uniformly mixing magnesium stearate and coenzyme Q10 coating according to weight proportions to obtain a mixture C;

[0084] S4: Mix mixture A and mixture B evenly, and finally add mixture C. After mixing evenly, put into a tablet press, dry-press into tablets, and coat with sugar to obtain sustained-release tablets.

[0085] Example 5

[0086] A sustained-release tablet containing coenzyme Q10 is made of the following raw materials in parts by mass: 5 parts of coenzyme Q10 coating, 5 parts of grass fruit kernel extract, 12 parts of perilla seed extract, 15 parts of Euryale ferox extract, 12 parts of ethyl cellulose, 20 parts of starch, 15 parts of microcrystalline cellulose, 2 parts of hydroxypropyl cellulose, 1.5 parts of magnesium stearate, and 0.5 parts of sodium carboxymethyl starch.

[0087] The preparation method of the coenzyme Q10 coating is as follows: according to the mass ratio of coenzyme Q10: coating agent = 100:20, a layer of coating agent is coated on the surface of coenzyme Q10 powder particles by fluidized spray method, and freeze-dried to obtain the coenzyme Q10 coating. The mass ratio of the coating agent components is water: chitosan: konjac gum: nano calcium carbonate: polysorbate = 80:5:1:8:0.5.

[0088] The preparation method of the grass kernel extract is as follows: crush the grass kernel, add water 8 times the weight of the grass kernel, add 0.5% of the weight of fig protease in the grass kernel, enzymolyze at 70°C for 2 hours, inactivate the enzyme at 90°C for 15 minutes, cool to room temperature, adjust the pH to 8.5, add 0.5% of the weight of subtilisin in the grass kernel, enzymolyze at 50°C for 1 hour, inactivate the enzyme at 90°C for 15 minutes, cool to room temperature, add 1% of the weight of trypsin in the grass kernel, enzymolyze at 35°C for 3 hours, inactivate the enzyme at 80°C for 25 minutes, cool to room temperature, filter with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, spray dry, and obtain the grass kernel extract.

[0089] The preparation method of the perilla seed extract is as follows: crushing the perilla seeds, adding water 6 times the mass of the perilla seeds, adjusting the pH to 2.0 with hydrochloric acid, adding 0.3% of the mass of pepsin of the perilla seeds, enzymolysis at 38°C for 2h, inactivating the enzyme at 100°C for 15min, cooling to room temperature, adjusting the pH to 3.0, adding 0.5% of the mass of acid protease of the perilla seeds, enzymolysis at 60°C for 1h, inactivating the enzyme at 100°C for 15min, cooling to room temperature, adjusting the pH to 8, adding 0.5% of the mass of bromelain of the perilla seeds, enzymolysis at 60°C for 2h, inactivating the enzyme at 100°C for 15min, cooling to room temperature, filtering with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, spray drying, and obtaining the perilla seed extract.

[0090] The preparation method of the gorgon rice extract is as follows: crushing the gorgon rice, adding water of 8 times the mass of the gorgon rice, adding 1.5% papain of the gorgon rice, performing enzymolysis at 65°C for 2h, inactivating the enzyme at 90°C for 15min, cooling to room temperature, adjusting the pH to 8.5, adding 0.5% trypsin of the gorgon rice, performing enzymolysis at 38°C for 2h, inactivating the enzyme at 90°C for 15min, cooling to room temperature, filtering with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, spray drying, and obtaining the gorgon rice extract.

[0091] The enzymatic activity of the ficin used in this embodiment is 100,000 U / g. The enzymatic activity of subtilisin is 20,000 U / g. The enzymatic activity of trypsin is 100,000 U / g. The enzymatic activity of pepsin is 5,000 U / g. The enzymatic activity of acid protease is 100,000 U / g, which is derived from Aspergillus niger. The enzymatic activity of bromelain is 50,000 U / g. The enzymatic activity of papain is 400,000 U / g.

[0092] The method for preparing the above-mentioned sustained-release tablet containing coenzyme Q10 comprises the following steps:

[0093] S1: premix the grass kernel extract, the perilla seed extract and the gorgon rice extract in parts by mass to obtain a mixture A;

[0094] S2: uniformly mixing ethyl cellulose, starch, microcrystalline cellulose, hydroxypropyl cellulose and sodium carboxymethyl starch according to parts by mass to obtain a mixture B;

[0095] S3: uniformly mixing magnesium stearate and coenzyme Q10 coating according to weight proportions to obtain a mixture C;

[0096] S4: Mix mixture A and mixture B evenly, and finally add mixture C. After mixing evenly, put into a tablet press, dry-press into tablets, and coat with sugar to obtain sustained-release tablets.

[0097] Comparative Example 1

[0098] No tsaoko kernel extract was added. Other parameters and methods were the same as in Example 1.

[0099] Comparative Example 2

[0100] No perilla seed extract was added. Other parameters and methods were the same as in Example 1.

[0101] Comparative Example 3

[0102] No Euryale ferox extract was added. Other parameters and methods were the same as in Example 1.

[0103] Comparative Example 4

[0104] No grass kernel extract, perilla seed extract and Euryale ferox extract were added. Other parameters and methods were the same as in Example 1.

[0105] Comparative Example 5

[0106] The preparation method of the grass kernel extract is as follows: crushing the grass kernel, adding water 7 times the weight of the grass kernel, adjusting the pH to 8.2, adding 1% of the weight of subtilisin of the grass kernel, enzymolysis at 45°C for 1 hour, inactivating the enzyme at 85°C for 20 minutes, cooling to room temperature, adding 0.8% of the weight of trypsin of the grass kernel, enzymolysis at 37°C for 2.5 hours, inactivating the enzyme at 85°C for 20 minutes, cooling to room temperature, filtering with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, spray drying, and obtaining the grass kernel extract.

[0107] The preparation method of the perilla seed extract is as follows: crushing the perilla seeds, adding water 7 times the mass of the perilla seeds, adjusting the pH to 1.8 with hydrochloric acid, adding pepsin 0.5% by mass of the perilla seeds, performing enzymolysis at 37°C for 2.5 hours, inactivating the enzyme at 95°C for 15 minutes, cooling to room temperature, adjusting the pH to 2.8, adding acid protease 1% by mass of the perilla seeds, performing enzymolysis at 50°C for 1 hour, inactivating the enzyme at 95°C for 15 minutes, cooling to room temperature, filtering with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, spray drying, and obtaining the perilla seed extract.

[0108] The preparation method of the gorgon rice extract comprises the following steps: crushing the gorgon rice, adding water of 7 times the mass of the gorgon rice, adding 2% papain of the gorgon rice, performing enzymolysis at 60°C for 2.5 hours, inactivating the enzyme at 85°C for 20 minutes, cooling to room temperature, filtering with a 5kDa ultrafiltration membrane to obtain a filtrate below 5kDa, spray drying, and obtaining the gorgon rice extract.

[0109] Other parameters and methods are the same as in Example 1.

[0110] Comparative Example 6

[0111] Coenzyme Q10 is not coated, that is, the coenzyme Q10 coating is directly replaced by coenzyme Q10. Other parameters and methods are the same as in Example 1.

[0112] 1. Toxicity test:

[0113] 1.1 Acute oral toxicity test was performed on 6 mice (half male and half female) in each group: Mixture C of each embodiment and each comparative example was prepared with purified water to 0.5 g / mL, and the mixture was gavaged at a dose of 20 mL / kg·bw twice a day, and the physical signs were observed. Results: The maximum tolerated dose (MTD) was greater than 20.0 g / kg·bw, which was non-toxic.

[0114] 1.2 Six mice (half male and half female) were selected for feeding for 30 days in each group: Mixture C of each embodiment and each comparative example was taken respectively, and the recommended dosage for human body was 1 g / person / day. Three dosage groups were set at 0.5g / kg·bw / d, 1.09g / kg·bw / d, and 1.67g / kg·bw / d, which were 30, 65, and 100 times of the recommended dosage for human body. A blank control group of 0g / kg·bw was set. The test samples were mixed into the basic feed and fed to rats for 30 consecutive days. The body weight and food intake were weighed once and twice a week, and the weekly and total food utilization rate was calculated. The occurrence of poisoning and death was observed every day. At the end of the experiment, the hematology, blood biochemistry, and organ coefficient indicators were observed, and pathological examination was performed. The results showed that the indicators were all within the normal range and safe and non-toxic.

[0115] 2. Antioxidant Test:

[0116] The active substance compositions prepared in the above-mentioned embodiments and comparative examples 1 to 5 (coenzyme Q10 coating, grass fruit kernel extract, perilla seed extract and Euryale ferox extract, according to the mass ratio of the components in each embodiment and comparative example) were subjected to antioxidant testing.

[0117] Prepare samples: Take the active substance composition, dilute it to 6 times its mass with anhydrous ethanol, stir and mix for 50 min to obtain a diluted sample;

[0118] (1) DPPH free radical scavenging experiment:

[0119] Add 100 μL of sample to a 96-well plate and add 100 μL of 0.1M DPPH. For the negative control, replace the sample with water, and for the blank control, replace DPPH with ethanol. Mix the reaction solution thoroughly and incubate at room temperature in the dark for 30 min. Read the absorbance value at 517 nm with an ELISA reader. The lower the ΔOD value, the higher the free radical scavenging activity of the sample. Calculate the DPPH free radical scavenging rate:

[0120] DPPH free radical scavenging rate = (1-(A sample -A blank ) / A control )×100%;

[0121] in:

[0122] A sample is the absorbance after the sample solution reacts with the DPPH solution;

[0123] A blank It is the absorbance of the sample solution after the reaction with anhydrous ethanol;

[0124] A control It is the absorbance after the reaction of DPPH solution with water.

[0125] (2) ABTS free radical scavenging experiment:

[0126] Add 100 μL of sample to a 96-well plate and add 100 μL of 0.1M ABTS. Replace the sample with water for the blank control. Mix the reaction solution thoroughly and incubate at room temperature in the dark for 30 min. Read the absorbance value at 734 nm using an ELISA reader. The lower the ΔOD value, the higher the free radical scavenging activity of the sample. Calculate the ABTS free radical scavenging rate:

[0127] ABTS free radical scavenging rate = (A0-A) / A0×100%;

[0128] in:

[0129] A0 is the absorbance of the ABTS radical solution without the addition of sample;

[0130] A is the absorbance of the ABTS radical solution after adding the sample to react.

[0131] The test results are shown in Table 1 below:

[0132] Table 1 Free radical scavenging test results (average value)

[0133]

[0134]

[0135] From the above results, it can be seen that the extract of grass kernel, perilla seed and gorgon rice have a certain effect of clearing free radicals. From Comparative Example 4, it can be seen that the extract of grass kernel, perilla seed and gorgon rice are used in combination with coenzyme Q10 at the same time, which has a synergistic effect, can greatly improve the effect of coenzyme Q10 and each extract, and significantly improve the scavenging rate of free radicals. From Comparative Example 5, it can be seen that the plant extracts prepared by different methods, that is, the plant extracts prepared by omitting the enzymatic hydrolysis step, have significantly different ingredients, and the synergistic effect of each extract when used in combination with coenzyme Q10 is poor.

[0136] 3. Improving immunity testing:

[0137] The mixture C prepared in the above-mentioned embodiments and comparative examples 1 to 5 was tested for improving immunity.

[0138] Female I CR mice weighing 18 g to 22 g were randomly divided into groups of 6 mice each and adaptively raised for 3 days;

[0139] Spleen aminopeptide group: intragastrically administered spleen aminopeptide 1.3 g / kg;

[0140] Drug treatment group: Mixture C that has not been tableted (mixture C of each embodiment and each comparative example, 11 groups in total) was administered intragastrically at 0.15 g / kg;

[0141] Normal control group: gavage with equal volume of distilled water;

[0142] Model control group: gavage with an equal volume of distilled water;

[0143] Experiment: Except for the normal group, the other groups were given cyclophosphamide 40mg / kg, intraperitoneal injection, for two consecutive days for immunosuppression after continuous gavage for 3 weeks. After continuous gavage for 4 weeks, whole blood was collected by removing the mouse eyeballs and dripping the blood into a centrifuge tube filled with anticoagulant. The blood was mixed continuously during the blood collection process to prevent blood coagulation. 1ml of anticoagulated whole blood was collected from each mouse, and the total white blood cell count and lymphocyte count were detected by a complete blood cell analyzer within 24 hours.

[0144] The test results are shown in Table 2 below:

[0145] Table 2 Immunity improvement test results (average value)

[0146]

[0147] It can be seen from the above results that the extracts of grass kernel, perilla seed and gorgon rice have a certain effect of improving immunity. As shown in Comparative Example 4, the use of grass kernel extract, perilla seed extract and gorgon rice extract in combination with coenzyme Q10 has a synergistic effect, which can greatly improve the effects of coenzyme Q10 and each extract, and significantly improve immunity. As shown in Comparative Example 5, the plant extracts prepared by different methods, that is, the plant extracts prepared by omitting the enzymatic hydrolysis step, have significantly different ingredients, and the synergistic effect of each extract when used in combination with coenzyme Q10 is poor.

[0148] 4. Anti-fatigue detection:

[0149] The mixture C prepared in the above-mentioned embodiments and comparative examples 1 to 5 was subjected to anti-fatigue test.

[0150] Female I CR mice weighing 18 g to 22 g were randomly divided into groups of 6 mice each and adaptively raised for 3 days;

[0151] Drug treatment group: Mixture C that has not been tableted (mixture C of each embodiment and each comparative example, 11 groups in total) was administered intragastrically at 0.15 g / kg;

[0152] Blank control group: intragastric administration of equal volume of distilled water;

[0153] The mice were gavaged continuously for 30 days. 30 min after the last administration, a weight-bearing swimming test was conducted on the mice. Lead sheets of 3% of the corresponding body weight were added to the tails of the mice. The mice were placed in 25℃ water at a height of 25 cm. The timing was started and ended when the mice were exhausted. The first sinking time and exhaustion time of the mice were recorded. The longer the time, the better the endurance, that is, the better the fatigue resistance.

[0154] Testing standards: The first sinking standard is when the mouse nose tip is submerged below the water surface for the first time; the exhaustion standard is when the mouse sinks underwater for 10 seconds without floating up.

[0155] The test results are shown in Table 3 below:

[0156] Table 3 Anti-fatigue test results (average value)

[0157]

[0158] From the above results, it can be seen that the extract of grass kernel, perilla seed and gorgon rice have certain effects of improving endurance and anti-fatigue. From Comparative Example 4, it can be seen that the extract of grass kernel, perilla seed and gorgon rice are used in combination with coenzyme Q10 at the same time, which has a synergistic effect, can greatly improve the effect of coenzyme Q10 and each extract, and significantly improve endurance. From Comparative Example 5, it can be seen that the plant extracts prepared by different methods, that is, the plant extracts prepared by omitting the enzymatic hydrolysis step, have significantly different ingredients, and the synergistic effect of each extract when used in combination with coenzyme Q10 is poor.

Claims

1. A sustained-release tablet containing coenzyme Q10, characterized in that: The sustained-release tablet is made of the following raw materials in parts by mass: 2 to 5 parts of coenzyme Q10 coating, 5 to 8 parts of grass kernel extract, 8 to 12 parts of perilla seed extract, 15 to 20 parts of Euryale ferox extract, 8 to 12 parts of ethyl cellulose, 20 to 30 parts of starch, 10 to 15 parts of microcrystalline cellulose, 2 to 5 parts of hydroxypropyl cellulose, 0.5 to 1.5 parts of magnesium stearate, and 0.5 to 2 parts of sodium carboxymethyl starch; The coenzyme Q10 coating is a layer of coating agent coated on the surface of coenzyme Q10 powder particles, the mass ratio of the coenzyme Q10 and the coating agent is coenzyme Q10: coating agent = 100: (10-20); the mass ratio of the coating agent components is water: chitosan: konjac gum: nano calcium carbonate: polysorbate = (80-90): (2-5): (1-3): (5-8): (0.5-1.5); the preparation method of the coenzyme Q10 coating is: a layer of coating agent is coated on the surface of the coenzyme Q10 powder particles by a fluidized spray method, and freeze-dried to obtain the coenzyme Q10 coating; The preparation method of the grass kernel extract comprises the following steps: crushing the grass kernel, adding water 6 to 8 times the mass of the grass kernel, adding 0.5% to 1.5% by mass of fig protease of the grass kernel, performing enzymolysis at 60 to 70° C. for 2 to 3 hours, inactivating the enzyme at high temperature, cooling to room temperature, adjusting the pH to 7.8 to 8.5, adding 0.5% to 1.5% by mass of subtilisin of the grass kernel, performing enzymolysis at 40 to 50° C. for 1 hour to 1.5 hours, inactivating the enzyme at high temperature, cooling to room temperature, adding 0.5% to 1% by mass of trypsin of the grass kernel, performing enzymolysis at 35 to 38° C. for 2 hours to 3 hours, inactivating the enzyme at high temperature, cooling to room temperature, filtering with a 5 kDa ultrafiltration membrane to obtain a filtrate below 5 kDa, and spray drying to obtain the grass kernel extract; The preparation method of the perilla seed extract comprises the following steps: crushing the perilla seeds, adding water 6 to 8 times the mass of the perilla seeds, adjusting the pH to 1.5 to 2.0 with hydrochloric acid, adding pepsin 0.3% to 0.8% by mass of the perilla seeds, performing enzymolysis at 35 to 38° C. for 2 h to 3 h, inactivating the enzyme at high temperature, cooling to room temperature, adjusting the pH to 2.5 to 3.0, adding acid protease 0.5% to 1.5% by mass of the perilla seeds, performing enzymolysis at 40 to 60° C. for 1 h to 1.5 h, inactivating the enzyme at high temperature, cooling to room temperature, adjusting the pH to 6 to 8, adding bromelain 0.5% to 1.5% by mass of the perilla seeds, performing enzymolysis at 50 to 60° C. for 2 h to 3 h, inactivating the enzyme at high temperature, cooling to room temperature, filtering with a 5 kDa ultrafiltration membrane to obtain a filtrate below 5 kDa, and spray drying to obtain the perilla seed extract; The preparation method of the gorgon rice extract comprises the following steps: crushing the gorgon rice, adding water of 6 to 8 times the mass of the gorgon rice, adding 1.5% to 3% papain of the gorgon rice, performing enzymolysis at 55 to 65° C. for 2 to 3 hours, inactivating the enzyme at high temperature, cooling to room temperature, adjusting the pH to 7.8 to 8.5, adding 0.5% to 1.5% trypsin of the gorgon rice, performing enzymolysis at 35 to 38° C. for 2 to 3 hours, inactivating the enzyme at high temperature, cooling to room temperature, filtering with a 5 kDa ultrafiltration membrane to obtain a filtrate below 5 kDa, and spray drying to obtain the gorgon rice extract.

2. A sustained-release tablet containing coenzyme Q10 according to claim 1, characterized in that: In the preparation method of the grass kernel extract, the enzymatic activity of the ficin is 50,000 to 100,000 U / g; the enzymatic activity of the subtilisin is 20,000 to 30,000 U / g; the enzymatic activity of the trypsin is 50,000 to 100,000 U / g; the temperature of the high-temperature enzyme inactivation is 80°C to 90°C, and the time is 15min to 25min.

3. A sustained-release tablet containing coenzyme Q10 according to claim 1, characterized in that: The preparation method of perilla seed extract comprises the following steps: the enzymatic activity of pepsin is 5,000 to 10,000 U / g; the enzymatic activity of acidic protease is 50,000 to 100,000 U / g, and the acidic protease is derived from Aspergillus niger; the enzymatic activity of bromelain is 50,000 to 100,000 U / g; and the temperature of high temperature enzyme inactivation is 90°C to 100°C, and the time is 15min to 20min.

4. A sustained-release tablet containing coenzyme Q10 according to claim 1, characterized in that: In the preparation method of Gorgon rice extract, the enzymatic activity of papain is 200,000-400,000 U / g, and the enzymatic activity of trypsin is 50,000-100,000 U / g; the temperature of high-temperature enzyme inactivation is 80°C-90°C, and the time is 15min-25min.

5. A method for preparing a sustained-release tablet containing coenzyme Q10, for preparing the sustained-release tablet containing coenzyme Q10 according to claim 1, characterized in that: The steps include: S1: premix the grass kernel extract, the perilla seed extract and the gorgon rice extract in parts by mass to obtain a mixture A; S2: uniformly mixing ethyl cellulose, starch, microcrystalline cellulose, hydroxypropyl cellulose and sodium carboxymethyl starch according to parts by mass to obtain a mixture B; S3: uniformly mixing magnesium stearate and coenzyme Q10 coating according to weight proportions to obtain a mixture C; S4: Mix mixture A and mixture B evenly, and finally add mixture C. After mixing evenly, put into a tablet press, dry-press into tablets, and coat with sugar to obtain sustained-release tablets.

Citation Information

Patent Citations

  • Application of composition of perilla seed oil and coenzyme Q10

    CN110585266A

  • Nicotinamide mononucleotide sustained-release enteric orally disintegrating tablet and preparation method thereof

    CN112137977A