CN111579672A - Coenzyme Q10 direct-pressure controlled release agent and analysis method - Google Patents
Coenzyme Q10 direct-pressure controlled release agent and analysis method Download PDFInfo
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Abstract
The invention relates to the field of pharmaceutical analysis, in particular to a coenzyme Q10 direct-pressure controlled release agent and an analysis method, wherein the detection wavelength is 275nm, the mobile phase is 100% ethanol, and the column temperature is as follows: the flow rate of the mobile phase was 1.0ml/min at room temperature, the column was C18, the column parameters 0.45 μm, 250mm, 5 μm, and the injection volume was 20 μ l.
Description
Technical Field
The invention belongs to the field of pharmaceutical analysis, and particularly relates to a coenzyme Q10 direct-pressure sustained-release controlled-release agent and an analysis method.
Background
Coenzyme Q10, known under the English name coenzyme Q10, is ubiquinone and is a yellow or pale yellow crystalline powder. The product is unstable in acid, alkaline, high temperature and oxidative environments under light, and has high solubility in weak polar solvent and lipid substances. Coenzyme Q10 is mainly used for adjuvant treatment of mild and moderate heart failure, and also for adjuvant treatment of hepatitis and cancer. Coenzyme Q10 is unstable under acidic and alkaline liquid conditions, so that the coenzyme Q10 solid preparation is relatively stable. Coenzyme Q10 is usually administered to patients in solid dosage forms such as tablets and capsules, and is disintegrated and dispersed in the stomach. Normal coenzyme Q10 levels and concentrations in the stomach can help the body to quickly repair injured tissue. Coenzyme Q10 is not uniformly diffused and dissolved in the stomach, and coenzyme Q10 is excessively concentrated in the local part of the stomach, which can cause stomach discomfort, including inappetence, nausea, stomach discomfort or diarrhea and other adverse reactions. The dispersed coenzyme Q10 has too low local concentration in stomach, and is difficult to enter blood for absorption and utilization. The coenzyme Q10 controlled release preparation is mainly used for treating diabetes, hypertension and cardiovascular and cerebrovascular diseases.
China has more than 2.7 hundred million patients with cardiovascular and cerebrovascular diseases. Cerebrovascular disease refers to cerebrovascular dysfunction caused by the blockage or rupture of the blood vessels due to various reasons, and causes related symptoms. It is a common disease and frequently encountered disease which endanger the health of people, threaten life and influence labor force.
Cardiovascular and cerebrovascular diseases mainly refer to diseases of the circulatory system, have a large range, and are commonly seen as coronary atherosclerotic heart disease, cerebral hemorrhage, cerebral infarction, atherosclerosis and the like.
Coenzyme Q10 can enhance metabolism of cardiac muscle and brain cell, protect integrity of biological membrane structure of cardiovascular and cerebrovascular cell, and improve heart rate and rhythm stability. The coenzyme Q10 can be used as an auxiliary medicine for coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, heart failure and cerebrovascular diseases, thereby relieving angina pectoris, reducing myocardial infarction area, relieving arrhythmia, and normalizing cardiac function. In order to prevent the onset of cardiovascular diseases, particularly the onset within a long period of time during sleep at night for 10 hours, there is a definite trend to develop sustained-release preparations of various cardiovascular drugs which release over a long period of time and take effect. The sustained-release controlled-release preparation can achieve the stable treatment effect for 24 hours aiming at cardiovascular and cerebrovascular diseases, gradually release and stabilize the drug effect, play the role in 24 hours, keep the release amount of coenzyme Q10 consistent in the stage time, and have stable release speed, thereby overcoming the defects of quick drug metabolism, incapability of continuously playing the drug effect, poor patient tolerance, large systemic adverse reaction and the like of the traditional preparation.
A large number of researches show that the sustained-release preparation type is increasingly emphasized as a cardiovascular and cerebrovascular drug carrier, and a new way is opened up for the targeted sustained-release treatment of cardiovascular diseases.
Currently, coenzyme Q10 controlled release agents are less studied. The controlled release agent is prepared by the process steps of mixing, granulating, sieving, embedding, coating and the like, the process is complex, more required equipment is needed, the process is simplified, the controlled release product is directly prepared by the modes of mixing, sieving and direct pressing, the energy is saved, the operation steps are simplified, and the process of the controlled release agent is optimized.
Disclosure of Invention
In order to solve the above problems, the present invention provides the following technical solutions.
An analytical method of a coenzyme Q10 controlled release product, which is characterized in that: coenzyme Q10 in the controlled release ball fat according to the weight ratio of 1:10, dissolving in 100% ethanol, extracting for 30 minutes at room temperature, oscillating for 3 minutes, standing for 2 minutes, repeating for 6 times to obtain a solution to be detected, detecting the coenzyme Q10 controlled release product by a high performance liquid detection method, wherein the detection wavelength is 275nm, the mobile phase is 100% ethanol, and the column temperature is as follows: the flow rate of the mobile phase was 1.0ml/min at room temperature, the column was C18, the column parameters 0.45. mu. mX250mm, 5 μm, and the injection volume was 20. mu.l.
A composition of a controlled release product of coenzyme Q10, comprising: the preparation method comprises the following steps:
a coenzyme Q10 controlled release product comprises controlled release globule lipid and controlled release carrier, wherein the controlled release globule lipid comprises coenzyme Q10, plastic fat and surfactant. The weight ratio of the controlled release ball fat to the controlled release carrier is 6-8:1-3, and the weight ratio of the coenzyme Q10, the plastic fat and the surfactant in the controlled release ball fat is 1-3:1-3: 1-2.
The plastic fat includes beeswax, butter, cacao butter, lard, etc.; the surfactant includes ionic surfactants, amphoteric surfactants, and the like. The surfactant includes Tween 80, polyoxyethylene castor oil, and poloxamer 188. Preferably, the diameter of the controlled release balloon is about 0.4 to 1.3mm, more preferably 0.5 to 1mm, and most preferably 0.8 mm.
The controlled release carrier comprises gums, cellulose and high molecular weight polymers. The weight ratio of the glue, the cellulose and the high molecular polymer in the controlled release carrier is 1-2:3-6: 1-3. The glue includes gelatin, pectin, etc. The cellulose includes hydroxypropyl methylcellulose and methylcellulose. The high molecular polymer includes polyethylene glycol and polyvinylpyrrolidone. Preferably, the diameter of the controlled release carrier is about 0.4 to 1.3mm, more preferably 0.5 to 1mm, and most preferably 0.8 mm.
The weight ratio of the controlled release ball fat to the controlled release carrier is 6-8: 1-3. Respectively mixing the controlled release spherical lipid and the controlled release carrier, sieving, totally mixing, and sieving to obtain the direct-pressure controlled release agent. Preferably, the controlled release diameter is about 0.4 to 1.3mm, more preferably 0.5 to 1mm, and most preferably 0.8 mm.
The coenzyme Q10 of the invention is orally administered in the following dosage: the dose administered to humans is 6 mg/kg/day,
obviously, the composition of the invention has less dosage than the preparation using coenzyme Q10 or coenzyme Q10 alone, and the absorption and utilization effect of the composition by human bodies is better than that of other similar products.
The invention provides a scheme of a solid preparation of releasing coenzyme Q10, which can be kept stable all the time in the effective period. The coenzyme Q10 is released in stomach uniformly at a controlled speed, and the side effect of the coenzyme Q10 is reduced.
A coenzyme Q10 controlled release agent is created for detection, the release speed and the concentration of the coenzyme Q10 controlled release agent are analyzed, and the quality of the coenzyme Q10 controlled release agent is controlled.
The coenzyme Q10 controlled release product coenzyme Q10 is uniformly dispersed and dissolved in gastric juice and absorbed by human body, so that the stimulation of the drug to the gastrointestinal tract can be effectively reduced while the drug is uniformly released.
The coenzyme Q10 controlled release product has the advantages of reducing the side reaction of coenzyme Q10, having long effective blood concentration duration, small blood concentration fluctuation, small side effect, small individual difference and good patient compliance, and is beneficial to the purposes of disease prevention and treatment.
Experimental example 1: preferred procedure for controlled release of the greases
Dissolving coenzyme Q10, Tween 80 and beeswax in proportion to obtain mixture 1, heating beeswax, adding mixture 1, stirring, and sieving to obtain controlled release spherical lipid.
Weighing coenzyme Q10 and tween at a ratio of 1:1, and mixing to obtain a mixture 1. Mixing beeswax: the coenzyme is weighed according to the proportion of 1:1, and the beeswax is heated in a water bath at the temperature of 60 ℃ for 0.5 hour to obtain clear and transparent beeswax liquid. Adding the mixture 1 into the beeswax liquid with the temperature of 60 ℃, stirring, standing at room temperature, and sieving to obtain the controlled release ball grease.
Experimental example 2: preferred procedure for controlled Release of the Carrier
Weighing pectin, hydroxypropyl methylcellulose and polyvinylpyrrolidone in proportion, mixing to obtain a mixture, stirring for 0.5 h, waiting for the mixture to have uniform color, sieving, and directly pressing to obtain the controlled release carrier.
Weighing pectin, hydroxypropyl methylcellulose and polyvinylpyrrolidone according to a ratio of 1:1:1, mixing to obtain a mixture, stirring for 0.5 hour, waiting until the mixture is uniform in color, sieving, drying, and directly pressing to obtain the controlled release carrier. The controlled release carrier particles are moderate and uniform in size.
Experimental example 3: preferred procedure for the method of pretreatment of samples in controlled release greases
Coenzyme Q10 is mostly detected by adopting a high performance liquid chromatography method, and the high performance liquid chromatography method cannot monitor the quality of products in the processing process in real time in the actual production and preparation process. By adopting a flat scanning method, the coenzyme Q10 direct-pressure sustained-release controlled-release preparation can be rapidly detected, the detection time is short, the product is qualitatively and quantitatively detected, and the quality of a semi-finished product (intermediate product) is controlled for the coenzyme controlled spherical fat product.
A small amount of coenzyme Q10 product is pretreated according to the following method to eliminate the interference of auxiliary materials and the like, and then is analyzed.
The coenzyme Q10 product is pretreated by adopting organic solvent extraction and filter paper filtration separation methods to eliminate the interference of auxiliary materials and the like. Coenzyme Q10 has good solubility in organic solvents, namely acetone and ethanol. The organic solvent adopts ethanol, acetone and the like as extracting agents, and the weight ratio of materials to the solvent is 1: 5; 1: 10; 15, performing pretreatment extraction on a coenzyme Q10 product, extracting for 30 minutes, oscillating for 3 minutes at room temperature, standing for 2 minutes, repeating for 6 times, and filtering the extract liquor by using filter paper after extraction is finished to obtain a clear and transparent pretreatment product of the coenzyme Q10 product.
| Extraction solvent | Weight ratio of material to solvent | Measured/actual value | Characteristics of the pretreated | |
| Pretreatment | ||||
| 1 | Ethanol | 1：5 | 90％ | Clear and transparent |
| Pretreatment 2 | Ethanol | 1：10 | 96％ | Clear and transparent |
| Pretreatment 3 | Ethanol | 1：15 | 97％ | Clear and transparent |
| Pretreatment 4 | Acetone (II) | 1：5 | 91％ | Turbid with particles |
| Pretreatment 5 | Acetone (II) | 1：10 | 93％ | Turbid with particles |
| Pretreatment 6 | Acetone (II) | 1：15 | 95％ | Turbid with particles |
Ethanol is used as an extraction solvent, the weight ratio of materials to the solvent is 1:10, the extraction is carried out for 30 minutes at room temperature, the oscillation is carried out for 3 minutes, the standing is carried out for 2 minutes, the extraction is repeated for 6 times, the extraction liquid is filtered by filter paper to obtain a coenzyme Q10 pretreatment product, the content of the coenzyme Q10 in the extraction liquid is detected, the measured value is close to the true value, the character of the pretreatment product is clear and transparent, the effect of removing auxiliary materials is good, and the analysis and the detection are facilitated.
Experimental example 4: preferred procedure for the analytical method of coenzyme Q10 in controlled-Release liposomes
Taking a small amount of coenzyme Q10 pretreatment product after auxiliary materials are removed, extracting by ethanol to obtain a clear and transparent coenzyme Q10 pretreatment product, dissolving the product in a developing agent, soaking one end of a silica gel plate in the developing agent, scanning the developing plate at an ultraviolet wavelength of 260nm, 285nm and 20mm/min at a scanning speed after 10 minutes, scanning in situ by using a thin-layer scanner to obtain an absorption spectrum curve, and performing rapid and accurate qualitative analysis and quantitative analysis.
Investigating the interference of the auxiliary material on the thin layer scanning:
dissolving a small amount of coenzyme Q10 controlled release spherical lipid in a developing solvent (methanol 100%), soaking one end of a silica gel plate in the developing solvent, after 10 minutes, carrying out ultraviolet wavelength scanning on the developing plate at an excitation wavelength of 260nm, a scanning wavelength of 285nm and a scanning speed of 20mm/min, carrying out in-situ scanning by using a thin-layer scanner to obtain a reading, and carrying out quantitative analysis. When developing agent (methanol 100%), spots were blurred and irregular in shape. The auxiliary material adopts a thin-layer scanning method to detect coenzyme Q10 controlled release grease, which causes interference. After auxiliary materials of the coenzyme Q10 product are removed, thin-layer scanning analysis is carried out, spots are clear, the shape is regular, and the analysis result is accurate and quick.
Example 5 gastric fluid Dispersion test
In the coenzyme Q10 controlled release product, the coenzyme Q10 is uniformly dispersed and dissolved in gastric juice and absorbed by the body, so that the stimulation of the drug to the gastrointestinal tract can be effectively reduced while the drug is uniformly released. The coenzyme Q10 controlled release product has the advantages of reducing the side reaction of coenzyme Q10, having long effective blood concentration duration, small blood concentration fluctuation, small side effect, small individual difference and good patient compliance, and is beneficial to the purposes of disease prevention and treatment.
Preparing artificial gastric juice according to the standard on pharmacopeia, namely' artificial gastric juice: taking 16.4ml of dilute hydrochloric acid, adding about 800ml of water and 10g of pepsin, shaking up, adding water, weighing and releasing to 1000ml to obtain the finished product. The device comprises a lower magnetic glass stirring tank and a peristaltic pump, wherein the lower magnetic glass stirring tank is made of glass, observation is facilitated, and the growth of microorganisms in each link of the gastrointestinal tract digestion process is realized by adjusting various parameters such as temperature, humidity, PH and the like in the lower magnetic glass stirring tank.
The coenzyme Q10 controlled release product is put into artificial gastric juice, the digestion solution is cancelled after 2 hours by a device simulating the gastrointestinal tract digestive system, the detection wavelength is 275nm according to a high performance liquid detection method, and the concentration of coenzyme Q10 in the digestive juice is detected. Continuously adding the coenzyme Q10 controlled-release product after 2 hours of digestion into 1000ml of the newly prepared artificial gastric juice, continuously digesting for 4 hours in the simulated gastrointestinal tract digestive system, and taking the 4-hour digestive juice. Detecting the concentration of coenzyme Q10 in the digestive juice with high performance liquid chromatography at 275 nm. This was repeated, and the digestion solution was taken after digestion was completed for 2 hours, 6 hours, 12 hours, and 24 hours, respectively. The high performance liquid phase detection result of digestive juice shows that the release concentration of coenzyme Q10 should be 20% -30%, 20% -30% and 20% -30% respectively, which indicates that the coenzyme Q10 controlled release product can be released uniformly, and the coenzyme Q10 is released uniformly within 24 hours in the artificial gastric juice according to time.
Experimental example 6 controlled Release degradation experiment
Taking the product, and performing dissolution and release determination method (second method of 0931 in general) with 900ml of hydrochloric acid solution (9 → 1000) as dissolution medium at 50 rpm. After 2 hours, 6 hours, 12 hours and 16 hours, respectively taking 10ml of solution, filtering, instantly supplementing dissolution media with the same temperature and the same volume, respectively precisely taking 3.0ml, 1.0ml and 1.0ml of subsequent filtrate, placing the subsequent filtrate in a 25ml measuring flask, adding hydrochloric acid solution (9 → 1000) to dilute to scale, shaking uniformly, detecting the wavelength of 275nm by a high performance liquid detection method, and respectively calculating the dissolution amount at different times. The dissolution amount of the product at 2 hours, 6 hours, 12 hours and 16 hours is 10-30%, 30-55%, 50-85% and more than 75% of the marked amount respectively, which meets the regulation.
Experimental example 7 safety test
And (3) testing the sample: taking the product of example 1 as a test sample for testing, taking SD healthy rats with weight of 180-; the cumulative administration volume is 50ml/kg, the administration is performed by intragastric administration for 3 times in one day for a rat, no obvious toxic reaction and gastrointestinal reaction are observed after 7 days, and no obvious abnormality exists in main organs after the observation by naked eyes after dissection. The observation of acute toxicity test shows that the medicine has no obvious toxicity.
The same test solution suspension with concentration of 0.1g/ml, 0.5g/ml, 0.75g/ml and 1g/ml is used as large and small dose group test drug, and is continuously administrated to 20 rats of SD healthy hermaphrodite for 3 months, and long-term toxicity test is carried out, and distilled water with equal solvent is used as control.
The long-term toxicity test result shows that the general behavior and activity and weight increase of the test animal are normal, the hematology index, the liver and kidney function and the organ coefficient of the main organ are not obviously influenced, the main organ has no obvious pathological injury, and the drug has no obvious toxicity.
EXAMPLE 8 cardiovascular and cerebrovascular Studies with compositions of the invention
60 patients with viral myocarditis were selected. Inclusion criteria were: 1) all patients met the viral myocarditis diagnostic criteria; 2) has not received related drug treatment. Exclusion criteria: 1) the patient is not the first onset; 2) the related antiviral myocarditis is treated by the related antiviral myocarditis medicine; 3) patients allergic to the medicine. The patients take coenzyme Q10 capsules. The selected patients are treated by performing electrocardiogram, heart ultrasound, myocardial zymogram, thrombin zymogram and liver and kidney function examination according to the requirements. During the treatment period, other thrombolytic, anticoagulant and fiber reducing medicines are stopped in the coenzyme Q10 group, and cerebral edema, hypertension, diabetes and various infections accompanied by the disease are correspondingly treated.
The number of ischemic cerebral apoplexy and death cases of each patient during the administration period, and adverse reactions comprise gastrointestinal tract reaction, gum, epistaxis, skin rash and cerebral hemorrhage. Under normal dietary conditions, fasting venous blood lipid levels were measured before and 6 months after treatment. Total Cholesterol (TC) was measured by an enzyme reagent method, Triacylglycerol (TG) was measured by a GPO-PAP method, high density lipoprotein (HDL-C) and low density lipoprotein (LDL-C) were measured by a direct method, and kits were provided by doctor Deg. The follow-up visit is 2 years.
All parameters are expressed as mean ± standard deviation (x ± s), two groups of comparisons are performed by t-test, data analysis is performed by SPSS13.0 statistical analysis software, and P <0.05 is statistically significant for differences.
All the selected subjects have follow-up visit for 2 years, and the follow-up visit rate is 100%. The relapse rate and mortality rate of stroke in the dosed group were significantly lower than in the blank group (P < 0.05).
Drawings
FIG. 1: coenzyme Q10 high performance liquid chromatography
FIG. 2: coenzyme Q10 thin-layer scanning map
Detailed Description
The invention will be further described with reference to specific examples:
experimental example 1: preparation experiment of controlled release ball fat
Mixing coenzyme Q10, Tween 80 and beeswax according to the weight ratio of 1:1, weighing and uniformly mixing, performing ultrasonic mixing at 50 ℃ for 10 minutes to obtain a mixture, observing that the color of the mixture is uniform and consistent without obvious color difference, stopping stirring, standing at room temperature, and sieving to prepare the controlled release ball fat with the diameter of about 0.8 mm. The controlled release spherical lipid particles have moderate and uniform size.
Experimental example 2: preparation experiment of controlled Release vehicle
Weighing pectin, hydroxypropyl methylcellulose and polyvinylpyrrolidone according to the weight ratio of 1:1:1, mixing to obtain a mixture, stirring for 0.5 h, sieving after the mixture is uniform in color, drying to obtain a controlled release carrier, and preparing the controlled release carrier with the diameter of about 0.8 mm. The controlled release carrier particles are moderate and uniform in size.
EXAMPLE 3 preparation of controlled Release agent by direct compression
The weight ratio of the controlled release ball fat to the controlled release carrier is 6: 1. Respectively mixing the controlled release spherical lipid and the controlled release carrier, sieving, totally mixing, and sieving to obtain the direct-pressure controlled release agent. Preferably, the controlled release diameter is about 0.4 to 1.3mm, more preferably 0.5 to 1mm, and most preferably 0.8 mm.
Experimental example 4: preferred procedure for the method of pretreatment of samples in controlled release greases
A small amount of coenzyme Q10 products are pretreated according to the following method to eliminate the interference of auxiliary materials and the like, and then are analyzed:
taking a small amount of coenzyme Q10 product, and mixing the product according to the weight ratio of sample solvent of 1:10, placing the mixture into a container, extracting the mixture by using ethanol as an organic solvent for 30 minutes, oscillating the mixture for 3 minutes, standing the mixture for 2 minutes, repeating the extraction for 6 times, and filtering the extract by using filter paper after extraction at room temperature to obtain a pretreatment product of the coenzyme Q10 product.
Experimental example 5: preferred procedure for analytical method of coenzyme Q10 of pretreatment product of controlled-release glycolipid
Taking a small amount of coenzyme Q10 pretreatment product, dissolving the coenzyme Q10 pretreatment product in a developing agent (methanol 100%), soaking one end of a silica gel plate in the developing agent, after 10 minutes, carrying out ultraviolet wavelength scanning on the developing plate, wherein the excitation wavelength is 260nm, the scanning wavelength is 285nm, the scanning speed is 20mm/min, carrying out in-situ scanning by using a thin-layer scanner to obtain a reading, and carrying out quantitative analysis, and when the developing agent (methanol 100%) is used, spots are clear, the shape is regular, and no tailing is caused.
Example 6: analysis method of coenzyme Q10 in controlled release ball fat
Taking the controlled release ball grease according to the weight ratio of 1:10, dissolving in 100% ethanol, extracting for 30 minutes at room temperature, oscillating for 3 minutes, standing for 2 minutes, and repeating for 6 times to obtain a solution to be detected. The coenzyme Q10 controlled release product is detected by a high performance liquid detection method, the detection wavelength is 275nm, the mobile phase is 100% ethanol, and the column temperature is as follows: the flow rate of the mobile phase was 1.0ml/min at room temperature, the column was C18, the column parameters 0.45. mu. mX250mm, 5 μm, and the injection volume was 20. mu.l.
Experimental example 7: preferred procedure for analytical method of coenzyme Q10 of direct-pressure controlled Release agent
Dissolving a small amount of direct-pressure controlled release agent in a developing agent (methanol 100%), soaking one end of a silica gel plate in the developing agent, scanning the developing plate at an ultraviolet wavelength of 260nm, 285nm and 20mm/min after 10 minutes, performing in-situ scanning by using a thin-layer scanner to obtain a reading, and performing quantitative analysis, wherein when the developing agent (methanol 100%), spots are clear, the shape is regular and no tailing occurs.
Example 8: analysis method of coenzyme Q10 in direct-pressure controlled release agent
Taking a direct-pressure controlled release agent, and mixing the materials in a weight ratio of 1:10, dissolving in 100% ethanol, extracting for 30 minutes at room temperature, oscillating for 3 minutes, standing for 2 minutes, and repeating for 6 times to obtain a solution to be detected. The coenzyme Q10 controlled release product is detected by a high performance liquid detection method, the detection wavelength is 275nm, the mobile phase is 100% ethanol, and the column temperature is as follows: the flow rate of the mobile phase was 1.0ml/min at room temperature, the column was C18, the column parameters 0.45. mu. mX250mm, 5 μm, and the injection volume was 20. mu.l.
Claims (2)
1. An analytical method of a coenzyme Q10 controlled release product, which is characterized in that: coenzyme Q10 in the controlled release ball fat according to the weight ratio of 1:10, dissolving in 100% ethanol, extracting for 30 minutes at room temperature, oscillating for 3 minutes, standing for 2 minutes, and repeating for 6 times to obtain a solution to be detected. The coenzyme Q10 controlled release product is detected by a high performance liquid detection method, the detection wavelength is 275nm, the mobile phase is 100% ethanol, and the column temperature is as follows: the flow rate of the mobile phase was 1.0ml/min at room temperature, the column was C18, the column parameters 0.45. mu. mX250mm, 5 μm, and the injection volume was 20. mu.l.
2. The controlled release product of coenzyme Q10 according to claim 1, comprising controlled release spheroids, controlled release carrier. The controlled release ball lipid comprises coenzyme Q10, plastic fat and surfactant. The weight ratio of the controlled release ball fat to the controlled release carrier is 6-8:1-3, and the weight ratio of the coenzyme Q10, the plastic fat and the surfactant in the controlled release ball fat is 1-3:1-3: 1-2.
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