Cationic self-emulsifying coenzyme Q10 drug delivery system formula and preparation method thereof

Abstract

The invention relates to the technical field of biology and new medicine, in particular to a cationic self-emulsifying coenzyme Q10 drug delivery system formula and a preparation method thereof.The preparation method comprises the following steps that phospholipid, sorbitol and a cationic surface active agent are added into sunflower seed oil, full heating and stirring are conducted, ultrasonic treatment is conducted, and a mixture is obtained; the preparation method comprises the following steps: taking coenzyme Q10 as a raw material, forming cationic amphiphilic compound molecules through hydrogen bond combination, and dissolving the coenzyme Q10 in a mixed solution to form a stable and uniform solution, so as to obtain a cationic self-emulsifying coenzyme Q10 drug delivery system formula with positive charges on the surface; according to the formula of the cationic self-emulsifying coenzyme Q10 drug delivery system provided by the invention, the obtained product can be directly taken orally and can also be filled into a capsule or a soft capsule to be swallowed or extruded to be taken orally or chewed, the preparation process is simple and easy to implement, and the obtained self-emulsifying coenzyme Q10 drug delivery system realizes multiple biological effects and has a wide application prospect. The product has the advantages of good quality stability, easiness in absorption, high biological safety, convenience in taking and the like.

Description

Technical Field

[0001] The invention relates to the technical field of functional food produced by microbial fermentation, and specifically relates to a cationic self-emulsifying coenzyme Q10 drug delivery system formula and a preparation method thereof. Background Art

[0002] Coenzyme Q10 (Coenzyme Q10), also known as ubiquinone, is a coenzyme present in all eukaryotic organisms that perform aerobic respiration. It is a benzoquinone fat-soluble compound with a structure similar to vitamin K. Q represents the quinone group, and 10 represents the number of isoprene attached to its tail. It is mainly formed in the inner membrane of mitochondria, and a small part can also be obtained through food, such as beef, eggs, oily fish, nuts, oranges, broccoli and other fruits and vegetables. A large number of clinical studies have confirmed that Coenzyme Q10 has the functions of improving human immunity, enhancing antioxidant capacity and delaying aging. It is widely used in medicine for the auxiliary treatment of cardiovascular diseases, and is also widely used as a nutritional supplement and food additive. However, due to its large relative molecular mass and weak polarity, it is almost insoluble in water, so the oral absorption process is slow and the absorption is very small, and the bioavailability is very low, which seriously limits its clinical application effect.

[0003] At present, the main types of clinical preparations of coenzyme Q10 are soft capsules, tablets and water-soluble injections. However, oral soft capsules and tablets have poor solubility, resulting in low absorption efficiency; and water-soluble injections mainly rely on surfactants for solubilization. When diluted with a large amount of body fluids, there is a risk of drug precipitation, and surfactants also have certain toxicity, so it is necessary to develop new preparations to overcome the above disadvantages.

[0004] Studies in recent years have shown that the use of cationic emulsifiers or the addition of some cationic materials in self-emulsifying drug delivery systems can form microemulsion droplets with positively charged surfaces in the gastrointestinal tract after oral administration, which can produce adsorption effects on negatively charged gastrointestinal epithelial cells through electrostatic attraction, further increasing drug absorption. Many documents and patents report the use of self-emulsifying systems to increase the bioavailability of coenzyme Q10, but most of the patents on coenzyme Q10 (such as CN200810012923 a coenzyme Q10 self-emulsifying microcapsule, CN20091009001 a coenzyme Q10 self-emulsifying composition and its preparation method and application, CN201410033991 a self-emulsifying drug release system of coenzyme Q10 with high absorption rate and its preparation method and application, CN201610487702 a coenzyme Q10 pharmaceutical composition and its preparation process, CN202111208573 a coenzyme Q10 self-emulsifying composition with high absorption and utilization and its preparation method, CN202311615387 a high-content, water-soluble coenzyme Q10 composition and its preparation method) do not consider the effect of the surface charge of the droplets on the gastrointestinal absorption characteristics. Summary of the invention

[0005] The object of the present invention is to provide a cationic self-emulsifying coenzyme Q10 drug delivery system formulation and a preparation method thereof to solve the problems raised in the above background technology.

[0006] To achieve the above object, the present invention provides the following technical solution: a cationic self-emulsifying coenzyme Q10 drug delivery system formulation, wherein the ingredients and their weight percentage contents in the drug delivery system formulation are as follows: Coenzyme Q10 6%-30% Sunflower oil 20%-50% Phospholipids 10%-50% Sorbitol 5%-30% Cationic surfactant 0%~15%.

[0007] Preferably, the preparation method comprises the following steps: adding phospholipids, sorbitol and cationic surfactants to sunflower oil, fully heating, stirring and ultrasonicating to form cationic amphiphilic composite molecules through hydrogen bonding, and then dissolving coenzyme Q10 in the mixed solution to form a stable and uniform solution, thereby obtaining a cationic self-emulsifying coenzyme Q10 drug delivery system formula with a positive charge on the surface.

[0008] Preferably, the hydrophile-lipophile balance value of the sorbitol is 1.6-8.5.

[0009] Preferably, the phospholipid is selected from one or more of soybean lecithin, DC-cholesterol, 4-(N,N-dimethylamino)butyric acid (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl lipid, (2,3-dioleoyl-propyl)-trimethylamine, 1,2-dioleyl-3-dimethylamino-propane, and 1,2-dioleoylphosphatidylethanolamine.

[0010] Preferably, the cationic surfactant is selected from one or more of tetrabutylammonium acetate, hexadecyltrimethylammonium bromide, didodecyldimethylammonium bromide, 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol 2000 and 3β-[N-(N',N'-dimethylaminoethyl)carbamoyl]cholesterol hydrochloride.

[0011] Preferably, the heating temperature is 25°C to 80°C, the stirring speed is 50rpm to 2000rpm, the stirring time is 5min to 50min, the ultrasonic power is 10W to 5kW, and the ultrasonic time is 1min to 30min.

[0012] Compared with the prior art, the present invention has the following beneficial effects: The cationic self-emulsifying coenzyme Q10 drug delivery system provided by the present invention can be directly orally administered, or can be filled into capsules or soft capsules and swallowed, or the contents can be squeezed out and taken orally or chewed. The preparation process is simple and easy. The self-emulsifying coenzyme Q10 drug delivery system obtained achieves multiple biological effects and has the advantages of good product quality stability, easy absorption, high biological safety, and convenient administration. At the same time, the positively charged microemulsion droplets produce adsorption with the negatively charged gastrointestinal epithelial cells through electrostatic attraction, which can further increase the absorption of the drug. The present invention uses phospholipids and sorbitol to form amphiphilic composite molecules through hydrogen bonding, which play a role in reducing oil-water interfacial tension and protecting the stability of the emulsion in the self-emulsifying system, forming a stable and uniform self-emulsifying drug delivery system; The product preparation of the present invention can be self-emulsified in water into a stable and uniform nanoemulsion, and the particle size of the emulsion is less than 500nm, which ensures the self-emulsification effect and significantly improves the in vitro dissolution and bioavailability; The present invention can obtain a cationic self-emulsifying coenzyme Q10 drug delivery system with a positive charge on the surface by adding a cationic surfactant or a cationic phospholipid. Compared with the existing coenzyme Q10 self-emulsifying drug delivery system, the bioavailability of coenzyme Q10 can be further improved, the amount of surfactant used can be reduced, and the occurrence of side effects during oral administration can be prevented; The self-emulsifying formula involved in the present invention can realize multiple biological functions. The sunflower seed oil used contains rich active ingredients such as vitamins, linoleic acid, carotene, etc., and has biological activities such as improving blood circulation, promoting cholesterol decomposition and excretion from the body, lowering cholesterol, protecting cardiovascular system, protecting eyesight, etc. The soybean lecithin used has physiological activities such as delaying aging, preventing cardiovascular and cerebrovascular diseases, enhancing brain vitality, protecting the liver, etc. The sorbitol used can increase appetite, control body weight, moisturize the intestines and promote bowel movements, beautify the skin, and prevent hypoglycemia. At the same time, sorbitol has a cool sweet taste, can improve the taste of the drug delivery system, improve sensory properties, but will not cause fluctuations in blood sugar levels, and is suitable for use by diabetic patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 This is a graph showing the particle size and potential of the cationic self-emulsifying coenzyme Q10 drug delivery system nanoemulsion in Example 1; Figure 2 This is a graph showing the particle size and potential of the cationic self-emulsifying coenzyme Q10 drug delivery system nanoemulsion in Example 2; Figure 3 This is a graph showing the particle size and potential of the cationic self-emulsifying coenzyme Q10 drug delivery system nanoemulsion in Example 3; Figure 4 This is a graph showing the particle size and potential of the cationic self-emulsifying coenzyme Q10 drug delivery system nanoemulsion in Example 4; Figure 5 The following are the actual pictures of the cationic self-emulsifying coenzyme Q10 drug delivery system (a) and nanoemulsion (b); Figure 6 This is a transmission electron microscopy image of a cationic self-emulsifying coenzyme Q10 drug delivery system nanoemulsion; Figure 7 It is the dissolution curve of the cationic self-emulsifying coenzyme Q10 drug delivery system in artificial gastric juice; Figure 8 It is the dissolution curve of the cationic self-emulsifying coenzyme Q10 drug delivery system in artificial intestinal fluid; Fig. 9 This is the blood drug concentration-time curve of the cationic self-emulsifying coenzyme Q10 drug delivery system in SD rats. DETAILED DESCRIPTION

[0014] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0015] The present invention provides a technical solution: a cationic self-emulsifying coenzyme Q10 drug delivery system formulation and a preparation method thereof, and the specific preparation steps are as follows: The phospholipids, sorbitol and cationic surfactant are added to sunflower oil, and the mixture is heated, stirred and ultrasonicated to form cationic amphiphilic composite molecules through hydrogen bonding. Coenzyme Q10 is dissolved in the mixed solution to form a stable and uniform solution, thereby obtaining a cationic self-emulsifying coenzyme Q10 drug delivery system.

[0016] DC-cholesterol is a commonly used cationic lipid that plays a key role in the use of liposomes in gene transfection and other processes. DC-cholesterol can interact with negatively charged nucleic acid molecules such as DNA, forming complexes through electrostatic adsorption, and helping nucleic acids enter cells.

[0017] Soy lecithin is a natural ingredient extracted from soybeans, mainly composed of phosphatidylcholine (also known as lecithin), phosphatidylethanolamine, phosphatidylinositol, etc., and is a complex lipid mixture. Soy lecithin has many physiological functions in the human body, including lowering blood cholesterol levels, increasing the content of high-density lipoprotein cholesterol (good cholesterol), helping to remove cholesterol and triglycerides in blood vessels, preventing cardiovascular diseases such as atherosclerosis, preventing and treating fatty liver and cirrhosis, helping to repair liver poisoned by alcohol, enhancing brain function, improving immunity, improving digestive function, anti-oxidation and delaying aging.

[0018] Sorbitol is a natural compound and a common sugar alcohol (polyol) that can be found in fruits and plants. It has the effects of increasing appetite, controlling weight, moisturizing the intestines, beautifying the skin, and preventing hypoglycemia. The sweetness of sorbitol is about 60% of that of sucrose, with a refreshing taste and lower calories than sucrose, about 2.6 kcal / g. In addition, sorbitol is not fermented by bacteria in the mouth, so it does not cause tooth decay and has little effect on blood sugar and insulin levels.

[0019] The phosphate groups of soybean lecithin can combine with the hydroxyl groups of sorbitol through hydrogen bonds to form an amphiphilic supramolecular complex, which significantly improves the emulsification ability of soybean lecithin. The soybean lecithin-sorbitol supramolecular complex can achieve the dispersion stability of the oil-water mixture by reducing the tension of the oil-water interface, reducing the area of ​​the relatively static oil-water interface, improving the dispersion, and forming a micellar structure.

[0020] The present invention is further described below in conjunction with embodiments; the following embodiments are illustrative rather than restrictive, and the protection scope of the present invention cannot be limited by the following embodiments.

[0021] The methods used in the present invention, unless otherwise specified, are all conventional methods in the art; the percentage contents of various raw materials in the present invention are all percentage contents by weight. Example 1

[0022] A cationic self-emulsifying coenzyme Q10 drug delivery system, the components and weight percentages of which are as follows: Coenzyme Q10 10% Sunflower oil 40% DC-cholesterol 35% Sorbitol 15% The preparation method of the above-mentioned cationic self-emulsifying coenzyme Q10 drug delivery system comprises the following steps: The components were weighed according to the above weight percentage content, DC-cholesterol, sorbitol and sunflower oil were mixed, stirred at 45°C for 3 minutes, and then ultrasonicated at 800W for 3 minutes, and coenzyme Q10 was added thereto. Since DC-cholesterol is a cationic lipid, in this embodiment, even without adding a cationic surfactant, a stable and uniform cationic self-emulsifying coenzyme Q10 drug delivery system can be formed after full dissolution. Example 2

[0023] A cationic self-emulsifying coenzyme Q10 drug delivery system, the components and weight percentages of which are as follows: Coenzyme Q10 10% Sunflower oil 40% Soybean lecithin 32% Sorbitol 13% Hexadecyltrimethylammonium bromide 5% The preparation method of the above-mentioned cationic self-emulsifying coenzyme Q10 drug delivery system comprises the following steps: The components were weighed according to the above weight percentages, and soybean lecithin, sorbitol, cetyltrimethylammonium bromide and sunflower oil were mixed, stirred at 40°C for 5 minutes, and then ultrasonicated at 500W for 5 minutes, and coenzyme Q10 was added thereto to fully dissolve to form a stable and uniform cationic self-emulsifying coenzyme Q10 delivery system. Example 3

[0024] A cationic self-emulsifying coenzyme Q10 drug delivery system, the components and weight percentages of which are as follows: Coenzyme Q10 10% Sunflower oil 40% Soybean lecithin 32% Sorbitol 13% Tetrabutylammonium acetate 5% The preparation method of the above-mentioned cationic self-emulsifying coenzyme Q10 drug delivery system comprises the following steps: The components were weighed according to the above weight percentage content, and soybean lecithin, sorbitol, tetrabutylammonium acetate and sunflower oil were mixed, stirred at 50°C for 13 minutes, and then ultrasonicated at 400W for 8 minutes, and coenzyme Q10 was added thereto and fully dissolved to form a stable and uniform cationic self-emulsifying coenzyme Q10 delivery system. Example 4

[0025] A cationic self-emulsifying coenzyme Q10 drug delivery system, the components and weight percentages of which are as follows: Coenzyme Q10 10% Sunflower oil 40% Soybean lecithin 32% Sorbitol 13% Didodecyl dimethyl ammonium bromide 5% The preparation method of the above-mentioned cationic self-emulsifying coenzyme Q10 drug delivery system comprises the following steps: The components were weighed according to the above weight percentages, and soybean lecithin, sorbitol, didodecyl dimethyl ammonium bromide and sunflower oil were mixed, stirred at 55° C. for 5 minutes, and then ultrasonicated at 700 W for 3 minutes, and coenzyme Q10 was added thereto and fully dissolved to form a stable and uniform cationic self-emulsifying coenzyme Q10 delivery system. Test Case

[0026] The specific results of the particle size and potential measurements of the cationic self-emulsifying coenzyme Q10 drug delivery systems in Examples 1, 2, 3 and 4 are as follows: Figure 1 , Figure 2 , Figure 3 and Figure 4 The particle size and potential measurement results of the cationic self-emulsifying coenzyme Q10 drug delivery system in Example 1, Example 2, Example 3 and Example 4 are shown respectively. Figure 1 It can be seen that when the formula of the self-emulsifying coenzyme Q10 drug delivery system is coenzyme Q10 (10%), sunflower oil (40%), soybean lecithin (35%), and sorbitol (15%), the corresponding microemulsion droplet size is 340.0nm and the potential is +4.9mV. Figure 2 It can be seen that when the formula of the self-emulsifying coenzyme Q10 drug delivery system is coenzyme Q10 (10%), sunflower oil (40%), soybean lecithin (32%), sorbitol (13%), and cetyltrimethylammonium bromide (5%), the corresponding microemulsion droplet size is 514.6nm and the potential is +6.0mV. Figure 3It can be seen that when the formula of the self-emulsifying coenzyme Q10 drug delivery system is coenzyme Q10 (10%), sunflower oil (40%), soybean lecithin (32%), sorbitol (13%), and tetrabutylammonium acetate (5%), the corresponding microemulsion droplet size is 1051.0nm and the potential is +26.2mV. Figure 4 It can be seen that when the formula of the self-emulsifying coenzyme Q10 drug delivery system is coenzyme Q10 (10%), sunflower oil (40%), soybean lecithin (32%), sorbitol (13%), and didodecyldimethylammonium bromide (5%), the corresponding microemulsion droplet size is 694.6nm and the potential is +12.5mV.

[0027] The cationic self-emulsifying coenzyme Q10 drug delivery system in Example 1 was observed in real form and at a microscopic level. The specific results are as follows: Figure 5 Figure 2 shows the cationic self-emulsifying coenzyme Q10 drug delivery system (a) and nanoemulsion (b). Figure 5 It can be seen that the formed cationic self-emulsifying coenzyme Q10 drug delivery system is stable and uniform.

[0028] Figure 6 This is a transmission electron microscopy image of a cationic self-emulsifying coenzyme Q10 drug delivery system nanoemulsion. It can be seen that the particle size of the coenzyme Q10 self-emulsifying nanoemulsion is uniform and less than 500nm.

[0029] The cationic self-emulsifying coenzyme Q10 drug delivery system in Example 1 was subjected to an in vitro dissolution test. The specific steps and results are as follows: Step (1): Determine the sample dosage (per 100 mL in vitro release system) Coenzyme Q10 raw material: 0.0045g Commercially available coenzyme Q10 capsule: 1 capsule (containing 0.0045g coenzyme Q10) Commercially available coenzyme Q10 tablets: Grind and remove the sugar coating to weigh 4.5 mg (containing 0.0045 g coenzyme Q10) Cationic self-emulsifying coenzyme Q10 delivery system: 0.067g (containing 0.0045g coenzyme Q10) Step (2): Preparation of artificial gastric juice and artificial intestinal juice Preparation of artificial gastric juice: Take 16.4 mL of dilute hydrochloric acid (equivalent to 3.84 mL of hydrochloric acid), add 800 mL of water and 10 g of pepsin, shake well, add water to dilute to 1000 mL, and set aside.

[0030] Preparation of artificial intestinal fluid: Take 6.8g of potassium dihydrogen phosphate, add 500mL of water to dissolve it, add 0.1mol / L of sodium hydroxide to adjust the pH to 6.8, take another 10g of pancreatic enzyme, add appropriate amount of water to dissolve it, mix the two liquids, and dilute with water to 1000mL. Set aside.

[0031] Step (3): According to the dosage of each 100 mL of coenzyme Q10 original drug, commercially available capsules, commercially available tablets, and cationic self-emulsifying coenzyme Q10 drug delivery system as described in (1), 100 mL of artificial gastric juice (or artificial intestinal juice) is measured in two 250 mL beakers respectively, and injected into each beaker, mixed evenly, and the temperature is adjusted to maintain at 37°C ± 0.5°C, and the speed is adjusted to 100 r / min. Samples are taken at 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 60 min, 90 min, 2 h, 4 h, 6 h, 8 h, 12 h, and 24 h, respectively, and filtered through a 0.22 μm filter membrane, diluted, and filtered through the membrane again to measure the content through the liquid phase.

[0032] Figure 7 This is the dissolution curve of the cationic self-emulsifying coenzyme Q10 drug delivery system in artificial gastric juice. Figure 8 The dissolution curve of the cationic self-emulsifying coenzyme Q10 drug delivery system in artificial intestinal fluid is shown in Figure 2. Figure 7 and Figure 8 It can be seen that the release effect of the cationic self-emulsifying coenzyme Q10 drug delivery system in gastrointestinal fluid is significantly improved compared with the coenzyme Q10 API and the commercially available coenzyme Q10 capsules and tablets. After the dissolution experiment began, the final cumulative release of the coenzyme Q10 API, the self-emulsifying coenzyme Q10 drug delivery system, the commercially available coenzyme Q10 capsules, and the commercially available coenzyme Q10 tablets in artificial gastric fluid and artificial intestinal fluid is as follows: Serial number Coenzyme Q10 Types Dissolution rate in artificial gastric juice Dissolution rate in artificial intestinal fluid 1 Cationic self-emulsifying coenzyme Q10 drug delivery system 8.9% 9.2% 2 Coenzyme Q10 API 6.6% 6.9% 3 Commercially available coenzyme Q10 capsules 8.2% 8.4% 4 Commercially available coenzyme Q10 tablets 7.3% 7.5% The cationic self-emulsifying coenzyme Q10 drug delivery system in Example 1 was tested for bioavailability. The specific steps and results are as follows: The experiment selected SD male rats as model animals. Coenzyme Q10 original drug, commercially available coenzyme Q10 soft capsules and commercially available coenzyme Q10 tablets were used as controls. The drug was administered by gavage to investigate the time-dependent changes in blood drug concentration and to study the pharmacokinetics of the cationic self-emulsifying coenzyme Q10 drug delivery system.

[0033] Step (1): Determination of the animal dosing regimen. According to the dosage of commercially available coenzyme Q10 soft capsules, the daily dose for adults (60 kg) is determined to be 150 mg. According to the dosage conversion method for human and rat reported in the literature, the dosage for rats is determined to be 15 mg / kg. Fifteen male SD rats were randomly divided into five experimental groups (cationic self-emulsifying coenzyme Q10 delivery system group, commercially available coenzyme Q10 soft capsule group, commercially available coenzyme Q10 tablet group, and coenzyme Q10 original drug group), with 3 rats in each group. They were fasted for 12 hours before dosing (water was not prohibited). 0.5 mL of blood was collected from the rat's suborbital venous plexus at 0.5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, and 48 h after dosing. The blood was placed in a centrifuge tube pre-soaked with sodium heparin. The sample was centrifuged at 4000 rpm and the supernatant was stored at -80°C. Before use, plasma samples were thawed on ice.

[0034] Step (2): Plasma sample processing. Take 0.2 mL of plasma sample, add 0.8 mL of methanol and vortex for 1 min, add 1 mL of n-hexane and vortex for 3 min, and centrifuge at 2000 rpm for 10 min. Transfer the organic layer to a new centrifuge tube, add 1 mL of n-hexane to the water layer and vortex for 3 min, centrifuge at 4000 rpm for 10 min, and combine the organic layers. Dry the organic layer with high-purity nitrogen in a 50°C water bath. Add 0.3 mL of ethanol to the centrifuge tube for reconstitution, vortex for 5 min, take 0.3 mL for injection analysis, and determine it by high-performance liquid chromatography, and draw a time-varying curve of blood drug concentration.

[0035] Fig. 9 The blood drug concentration-time curve of cationic self-emulsifying coenzyme Q10 delivery system in SD rats is shown in Figure 2. Fig. 9 It can be seen that the blood concentration of the original coenzyme Q10 reaches a maximum of 0.75μg / mL at 4 hours, the blood concentrations of the commercially available coenzyme Q10 capsules and tablets reach a maximum of 1.7μg / mL and 0.95μg / mL at 4 hours, respectively, and the cationic self-emulsifying coenzyme Q10 delivery system reaches a maximum of 2μg / mL at 2 hours, the peak time is slightly advanced and its blood concentration is much higher than that of the original coenzyme Q10.

[0036] Therefore, the cationic self-emulsifying coenzyme Q10 drug delivery system can effectively improve the bioavailability of the drug and is more easily absorbed by the body, so it is an ideal oral delivery form. It will be apparent to those skilled in the art that the invention is not limited to the details of the exemplary embodiments described above and that the invention can be implemented in other specific forms without departing from the spirit or essential features of the invention. Therefore, the embodiments should be considered in all respects as exemplary and non-restrictive, and the scope of the invention is defined by the appended claims rather than the foregoing description, and it is intended that all changes within the meaning and range of equivalents of the claims be included in the invention. Any reference numeral in a claim should not be considered as limiting the claim to which it relates.

[0037] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A cationic self-emulsifying coenzyme Q10 drug delivery system formulation, characterized in that: The ingredients and their weight percentages in the drug delivery system formulation are as follows: Coenzyme Q10 6%-30% Sunflower oil 20%-50% Phospholipids 10%-50% Sorbitol 5%-30% Cationic surfactant 0%~15%.

2. The cationic self-emulsifying coenzyme Q10 drug delivery system according to claim 1, characterized in that: The preparation method comprises the following steps: adding phospholipids, sorbitol and cationic surfactant into sunflower seed oil, fully heating, stirring and ultrasonicating, forming cationic amphiphilic composite molecules through hydrogen bonding, and then dissolving coenzyme Q10 in the mixed solution to form a stable and uniform solution, thereby obtaining a cationic self-emulsifying coenzyme Q10 drug delivery system formula with a positive charge on the surface.

3. The cationic self-emulsifying coenzyme Q10 drug delivery system according to claim 2, characterized in that: The hydrophile-lipophile balance value of the sorbitol is 1.6-8.

5.

4. The cationic self-emulsifying coenzyme Q10 drug delivery system according to claim 3, characterized in that: The phospholipid is selected from one or more of soybean lecithin, DC-cholesterol, 4-(N,N-dimethylamino)butyric acid (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl lipid, (2,3-dioleoyl-propyl)-trimethylamine, 1,2-dioleyl-3-dimethylamino-propane, and 1,2-dioleoylphosphatidylethanolamine.

5. The cationic self-emulsifying coenzyme Q10 drug delivery system according to claim 4, characterized in that: The cationic surfactant is selected from one or more of tetrabutylammonium acetate, hexadecyltrimethylammonium bromide, didodecyldimethylammonium bromide, 1,2-dimyristoyl-rac-glycerol-3-methoxypolyethylene glycol 2000 and 3β-[N-(N',N'-dimethylaminoethyl)carbamoyl]cholesterol hydrochloride.

6. The cationic self-emulsifying coenzyme Q10 drug delivery system according to claim 5, characterized in that: The heating temperature is 25° C. to 80° C., the stirring speed is 50 rpm to 2000 rpm, the stirring time is 5 min to 50 min, the ultrasonic power is 10 W to 5 kW, and the ultrasonic time is 1 min to 30 min.

Images