A coenzyme q10 composition without addition and high activity and a preparation method thereof

Abstract

The present application provides a kind of no addition and high activity coenzyme Q10 composition, capsule skin is prepared from the raw materials comprising: gelatin 100 parts, glycerol 28-32 parts, purified water 90-110 parts, natural polyphenol complex 5.5-6.5 parts;Content is prepared from the raw materials comprising: coenzyme Q10 35-45 parts, sunflower seed oil 350-380 parts, beeswax 32-36 parts. Preparation method includes the following steps: capsule skin preparation, content homogenization, soft capsule compression and shaping. The present application solves the interrelated technical problems of light stability, absorption rate, odor control and mechanical integrity through the physical and chemical synergy between natural components. The mechanism of each process step is closely related to the core problem, and the performance is broken through under the premise of avoiding the introduction of chemical synthetic substances.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of functional health products, and particularly relates to a non-added and high-activity coenzyme Q10 composition and a preparation method thereof. BACKGROUND

[0002] Coenzyme Q10 soft capsules are a kind of functional health products for supplementing human coenzyme Q10 by oral administration. The main components are coenzyme Q10 lipid-soluble contents and gelatin capsules for wrapping. They act on the mitochondrial energy metabolism process of the human body and are clinically used for improving myocardial function, delaying aging and enhancing immunity. The current market products have three major core defects in actual application.

[0003] The first defect is the health risk caused by the light shielding agent. The 2023 third quarter report of the domestic leading enterprise Tangchenbeijian shows that the coenzyme Q10 soft capsules containing titanium dioxide of the company have a consumer complaint rate of 12.3% due to the capsule skin browning problem. More seriously, the European Food Safety Authority EFSA listed titanium dioxide as a 2B possible carcinogen in 2021. The existing alternative solutions also have hidden dangers. In the pilot sample of Zhuhai Lizhu Group which uses beta-carotene to replace titanium dioxide, the peroxide value is 4.2 times higher than the standard.

[0004] The second defect is the low bioavailability. The clinical trial report of the American GNC company points out that the intestinal absorption rate of coenzyme Q10 in traditional soft capsules is only 8-11%. The test data of the company in 2022 for people over 65 years old shows that the peak blood concentration is 0.48 μg / mL after a single oral dose of 100 mg, and the peak time is as long as 6 hours, resulting in more than 40% of the subjects failing to reach the effective blood concentration.

[0005] The third defect is the safety problem caused by chemical pigments. In 2022, Japan Meiji Pharmaceutical Co., Ltd. was recalled because 186,000 bottles of products caused allergic dermatitis due to the addition of lemon yellow. In the same year, the South Korean KFDA found that the temptation red pigment used by a certain brand contained 1.24 ppm of aniline residue, which was more than 2 times the safety standard limit.

[0006] For the light shielding problem, Chinese patent CN113278143A proposes to replace titanium dioxide with nano-zinc oxide, but this solution causes a high brittle fracture rate of 9% of the capsules during transportation. For the absorption efficiency problem, Japanese patent JP 2020-158742 adopts cholic acid salt to promote absorption, but it causes diarrhea symptoms in 15.7% of the subjects in the clinical trial. These existing technical solutions have the following unsolved problems: the use of chemical light shielding agents and synthetic pigments forms safety hazards; the methods for improving bioavailability cause side effects; and there is a lack of technical path for replacing light shielding agents without reducing the stability of the contents. Therefore, it is necessary to design a non-added and high-activity coenzyme Q10 composition and a preparation method thereof. SUMMARY

[0007] To overcome the defects in the prior art, a non-additive and high-activity coenzyme Q10 composition and a preparation method thereof are provided.

[0008] To achieve the above-mentioned object, the present application provides the following technical solutions:

[0009] A non-additive and high-activity coenzyme Q10 composition is composed of a capsule shell and a content, wherein the capsule shell is prepared from raw materials including gelatin 100 parts, glycerol 28-32 parts, purified water 90-110 parts, and natural polyphenol complex 5.5-6.5 parts by mass.

[0010] The content is prepared from raw materials including coenzyme Q10 35-45 parts, sunflower seed oil 350-380 parts, and beeswax 32-36 parts.

[0011] The natural polyphenol complex is composed of grape seed polyphenol, gold tiger tail fruit extract, and rosemary acid at a mass ratio of 3.4-3.6:2.15-2.25:1.

[0012] In the process of in-depth analysis of the technical bottlenecks of existing coenzyme Q10 soft capsules, the traditional technology has long relied on chemical sunscreens to solve the problem of photodecomposition. Although metal oxides represented by titanium dioxide have a physical sun protection effect, their particle aggregation effect can easily cause local embrittlement of the capsule shell. More importantly, the biological safety of such substances is controversial, and some cases show that they can dissolve heavy metal ions in an acidic environment. In view of this contradiction, the present application creatively uses a natural polyphenol complex system as a substitute. The o-diphenol hydroxyl structure of grape seed polyphenol in the complex can effectively absorb the energy of the ultraviolet light band, and its intramolecular electron transition mechanism converts the light radiation into harmless heat energy. This process is achieved through non-radiative decay of the conjugated double bond system, and the phenolic acid structure of rosemary acid forms a free radical capture network in the light environment. The two together constitute the first layer of light protection mechanism.

[0013] The high-polymer procyanidins in grape seed polyphenols form a conjugated planar structure through multiple phenolic hydroxyl groups, with a maximum absorption wavelength extending to 310 nm, covering the main energy band of ultraviolet light. The o-diphenol structure of rosemary acid undergoes reversible quinization under light, which consumes photon energy and blocks the free radical chain reaction. Experiments show that when the mass ratio of the two is 3.5:1, the light shielding-antioxidation coupling effect and the ultraviolet absorbance superposition effect are significantly improved compared to single components, forming a broad-spectrum light barrier.

[0014] However, just solving the light stability is still not enough, the conventional coenzyme Q10 preparation also has the core defect of low bioavailability. The prior art improves the solubility by adding surfactants or cholate, but such substances often cause gastrointestinal irritation. The goldleaf fruit extract in the present solution plays a special role, and the mangiferin contained therein has a specific spatial conformation, which can be matched with the multidrug resistance related protein on the small intestinal epithelial cell membrane. This specific binding reversibly opens the drug transport channel, so that the lipophilic coenzyme Q10 molecules pass through the intestinal barrier in the form of endocytosis. It is worth noting that this synergistic effect is highly selective and does not interfere with normal electrolyte balance, so it will not cause osmotic diarrhea side effects caused by traditional absorption enhancers.

[0015] The mangiferin of the goldleaf fruit extract specifically binds to the small intestinal epithelial cell membrane transporter protein MRP2, and the glucose group in its molecule increases the hydrophilicity as a "guide group", while the tetrahydroxy benzophenone nucleus forms a π-π stacking action with the Phe332 site of the transporter protein. In this process, rosmarinic acid plays a carrier role: its hydrophobic phenylpropenoic acid chain inserts into the isoprene chain gap of coenzyme Q10, and the hydrophilic carboxyl group connects the mangiferin, forming a "Q10-rosmarinic acid-mangiferin" ternary complex.

[0016] In terms of practical application, the odor rejection of coenzyme Q10 soft capsules is relatively common among consumers, and the prior art usually relies on synthetic pigments and fragrances to mask the odor. However, the present invention produces an unexpected synergistic effect during the content homogenization process: the gradient variable speed homogenization process forms a micron-sized crystal network in the beeswax matrix, and the coenzyme Q10 molecules are embedded in the crystal gap, while the natural polyphenolic compounds are adsorbed on the oil-water interface due to their amphiphilic properties. This unique molecular arrangement not only isolates coenzyme Q10 from direct contact with taste buds, but more importantly, the phenolic hydroxyl groups of polyphenol molecules form intermolecular hydrogen bonds with the quinone groups of coenzyme Q10, which significantly increases the activation energy of the oxidation reaction, thereby simultaneously achieving the dual improvement of odor masking and oxidative stability.

[0017] The preparation method of the goldleaf fruit extract comprises the following steps: crushing dried goldleaf fruit to 80 mesh, adding a citric acid buffer solution with a pH value of 4.2, ultrasonic-assisted extraction at 52°C for 35 minutes, adding 0.9 U / g of pectinase and 0.2 U / g of cellulase, enzymolysis at 46-48°C for 50-60 minutes, enzyme inactivation at 90°C for 10 minutes, and then centrifugal treatment, the supernatant is subjected to macroporous resin chromatography, the eluate is concentrated under reduced pressure, and then freeze-dried to obtain the goldleaf fruit extract.

[0018] In the preparation of the Jithoe fruit extract, the mass ratio of the dried Jithoe fruit powder to the buffer is 1:5-10; the power of the ultrasonic-assisted extraction is 300 W, and the frequency is 40 kHz; the centrifugal speed is 4000 rpm, and the centrifugal time is 15 min.

[0019] The preparation method of the grape seed polyphenol is as follows: grape seed powder is mixed with deionized water at a ratio of 1:15-20, and is maintained at a pressure of 1.5-2.0 MPa and a temperature of 120-130°C in a nitrogen atmosphere for 25-30 minutes, is instantaneously depressurized at 1.0 MPa / s, and is cooled to 25°C within 3 seconds after depressurization, and is spray dried to obtain the grape seed polyphenol.

[0020] A preparation method of an additive-free and high-activity coenzyme Q10 composition, comprising the following steps:

[0021] (1) Capsule skin preparation: glycerin 28-32 parts and purified water 90-110 parts are heated to 65-70°C and stirred to dissolve, and gelatin 100 parts is slowly added until a transparent base glue solution is formed; the base glue solution is placed in a three-stage vacuum system for vacuum gradient degassing to obtain a bubble-free glue solution; natural polyphenol compound 5.5-6.5 parts is added to the bubble-free glue solution, stirred uniformly to obtain a light-shielding glue solution, and then filtered and incubated to obtain a mature light-shielding glue solution;

[0022] (2) Content homogenization and synergism: beeswax 32-36 parts and sunflower oil 175-190 parts are melted at 70-72°C, and a semi-solid wax oil mixture is formed by using double-layer stirring paddles; 175-190 parts of sunflower oil is added to the wax oil mixture, and a flowable oil base is obtained by homogenization; coenzyme Q10 powder 35-45 parts is added, and a nano-emulsified content is obtained by gradient homogenization;

[0023] (3) Soft capsule compression and shaping: the mature light-shielding glue solution is compressed into a glue tape with a thickness of 0.25 mm, and the nano-emulsified content is injected into the glue tape using a syringe pump, and a wet soft capsule is formed in a mold at 30°C; the wet soft capsule is subjected to primary shaping and deep drying to obtain a finished capsule, which is the additive-free and high-activity coenzyme Q10 composition.

[0024] In (1) capsule skin preparation, the stirring is low-speed stirring at 50 revolutions per minute for 15 minutes at 70 degrees Celsius to form a uniform light brown red light-proof glue solution; the air pressure of the three-stage vacuum system is-0.06 MPa, -0.08 MPa and-0.09 MPa in turn. In terms of capsule structure integrity, the traditional gelatin skin containing sunscreen often has uneven mechanical properties due to the sedimentation of inorganic particles. The preparation method solves this problem through three-stage vacuum gradient defoaming technology, which eliminates bubbles of different sizes in three decreasing pressure stages, especially the high vacuum environment in the final stage can remove submicron gas nuclei. This process promotes the formation of uniform spatial crosslinking of gelatin peptide chains and polyphenol compounds, in which the carboxyl group of gelatin and the phenolic hydroxyl group of polyphenol are associated by hydrophobic interaction to form a three-dimensional elastic molecular network. This colloidal structure exhibits excellent rheological properties during the pill forming stage, and when the matured glue solution is injected into a 30-degree Celsius mold, the temperature change induced gelation process can form a gradient structure with a dense surface and a porous interior, which ensures the light-proof effect and maintains the ideal elongation at break of the gelatin skin.

[0025] In (2) content homogenization and enhancement, the upper paddle of the double-layer stirring paddle has an inclination of 45 degrees, the lower paddle has an inclination of 60 degrees, and stirring is carried out at 2000 revolutions per minute for 12 minutes.

[0026] The gradient is under the condition of vacuum degree-0.1±0.02 MPa: the first stage is 2000 revolutions per minute for 10 minutes, the second stage is 5000 revolutions per minute for 15 minutes, and the third stage is 3000 revolutions per minute for 12 minutes, finally obtaining a milky white nano-emulsified content.

[0027] In the first stage of vacuum homogenization (2000 rpm), the carboxyl ionization of rosmarinic acid generates a negative charge field, which promotes the directional arrangement of coenzyme Q10 molecules. The high shear force in the second stage (5000 rpm) causes the formation of a hydrogen bond complex between mangiferin and rosmarinic acid. In the third stage (3000 rpm), the interface of the nano-emulsion droplets is restructured, and the complex is embedded in the interstitial space of the beeswax crystal network.

[0028] In (3) soft capsule pill pressing and shaping, the mass ratio of the matured light-proof glue solution to the nano-emulsified content is 1:1.18-1.22.

[0029] The primary shaping is to transfer the wet soft capsule into an environment of 25 degrees Celsius and 40% relative humidity for 2 hours of drying, forming a solidified film on the surface of the capsule to obtain a primary shaped capsule; the deep drying is to transfer the primary shaped capsule to a transfer cage drying at 35 degrees Celsius and 25% relative humidity for 6 hours.

[0030] Compared with the prior art, the advantages and beneficial effects of the present application are:

[0031] 1. The present application realizes the technical advantages of sunscreen, antioxidant and odor masking by replacing chemical sunscreen agents and pigments with natural polyphenol complexes while maintaining or even enhancing product performance.

[0032] 2. The present application creatively replaces traditional titanium dioxide and synthetic pigments with natural polyphenol complexes. Specifically, grape seed polyphenols, acerola extract and rosmarinic acid form a three-dimensional network structure through intermolecular hydrogen bonding at a specific ratio. This structure can effectively scatter and absorb ultraviolet and visible light energy. When the capsule is in a light environment, the conjugated double bond system in the polyphenol molecule can capture excited state electrons and convert light energy into heat energy through an internal energy conversion mechanism, thereby blocking the direct damage path of light to coenzyme Q10 molecules. This physical and chemical protection mechanism avoids the cytotoxicity risk caused by titanium dioxide and the sensitization risk caused by synthetic pigments.

[0033] 3. The improved bioavailability of the present application is derived from the synergy of multiple mechanisms. Specifically, mangiferin in acerola extract can specifically bind to the transport protein of the intestinal epithelial cell membrane, increasing the permeability of the cell membrane to coenzyme Q10. The nano-emulsion droplet structure formed during the content homogenization process further increases the specific surface area, and the coenzyme Q10 molecules are wrapped in the microscopic crystal grid formed by beeswax. This structure disintegrates in an orderly manner in the digestive tract environment, achieving gradual release of active ingredients. The redox buffer system composed of grape seed polyphenols and rosmarinic acid can maintain the stability of the quinone structure of coenzyme Q10 in the acidic environment of the stomach, ensuring that it remains in a bioactive form in the intestinal absorption site. This delivery, protection and absorption trinity mechanism is first proposed in the present application.

[0034] 4. In the gradient shear homogenization process, the isoprene side chain of coenzyme Q10 is embedded in the benzodihydropyran ring structure of polyphenol compounds, forming intermolecular hydrophobic forces. This packaging not only effectively masks the fishy odor of coenzyme Q10 itself, but more importantly, it blocks the reaction site of oxygen molecules with the benzenequinone ring of coenzyme Q10. The active hydrogen on the phenolic hydroxyl group of rosmarinic acid can preferentially bind to free radicals, regenerating grape seed polyphenols to the reduced state through an electron transfer mechanism, thereby establishing a continuous antioxidant cycle system. This indicates that the improved content stability is attributed to the optimization of molecular-level interactions.

[0035] 5. The integrity of the capsule structure of the present application benefits from the synergistic control of the preparation process parameters. The three-stage gradient negative pressure setting in the vacuum defoaming stage causes the micro-bubbles in the glue solution to gradually expand and break, avoiding stress concentration and causing microscopic defects in the capsule. In the pill forming stage, precise control of the glue temperature promotes the formation of a more tightly wound spiral structure between gelatin molecules and polyphenol compounds. This enhanced cross-linked network gives the capsule excellent mechanical strength, and even without the traditional plasticizer, it still maintains the desired elongation at break. Detailed Implementation

[0036] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0037] In the specific embodiments of this application, the sources of various raw materials are briefly described as follows:

[0038] Gelatin: Purchased from Rousselot, France, CAS No. 9000-70-8, model GELATIN PHARMA250 Bloom, which meets the standard for elongation at break of pharmaceutical soft capsule shell.

[0039] Glycerin: Purchased from Wilmar International Group, Malaysia, CAS No. 56-81-5, grade EP / USP / KSP, glycerin content ≥99.5%, moisture ≤0.5%.

[0040] Coenzyme Q10: Purchased from Kaneka Chemical Co., Ltd., Japan, CAS No. 303-98-0, model name Kaneka Q10™ PHARMA, produced by fermentation, purity ≥99.8%.

[0041] Sunflower seed oil: purchased from Anhui Yanzhuang Oil Co., Ltd., CAS No. 8001-21-6, model YZZY-REFINED, peroxide value ≤0.5 meq / kg, acid value ≤0.2 mg KOH / g.

[0042] Beeswax: Purchased from Hangzhou Luyuan Bee Industry Co., Ltd., CAS No. 8012-89-3, model LY-BW01, melting point 62-66℃, acid value 17-24 mg KOH / g.

[0043] Pectinase: Purchased from Novozymes, Denmark, CAS No. 9032-75-1, model Pectinex® Ultra SP-L, enzyme activity ≥8000 PGNU / g.

[0044] Cellulase: Purchased from Genentech China, CAS No. 9012-54-8, model GC220, enzyme activity ≥5000 CMCU / g.

[0045] Macroporous resin: purchased from Tianjin Nankai Hecheng Technology Co., Ltd., model XDA-8, particle size 0.3-1.2mm, specific surface area 550-650m² / g.

[0046] The technical solution of this application is as follows:

[0047] An additive-free and high-activity coenzyme Q10 composition is composed of a capsule shell and a content, wherein the capsule shell is prepared from raw materials including gelatin 100 parts, glycerol 28-32 parts, purified water 90-110 parts, and natural polyphenol complex 5.5-6.5 parts by mass;

[0048] The content is prepared from raw materials including coenzyme Q10 35-45 parts, sunflower seed oil 350-380 parts, and beeswax 32-36 parts.

[0049] The natural polyphenol complex is composed of grape seed polyphenol, Malpighia glauca extract, and rosemary acid at a mass ratio of 3.4-3.6:2.15-2.25:1.

[0050] The preparation method of the Malpighia glauca extract comprises the following steps: crushing dried Malpighia glauca to 80 mesh, adding a citric acid buffer solution with a pH value of 4.2, ultrasonic-assisted extraction at 52℃ for 35 minutes, adding 0.9 U / g of pectinase and 0.2 U / g of cellulase, enzymolysis at 46-48℃ for 50-60 minutes, centrifugal treatment after enzyme inactivation at 90℃ for 10 minutes, macroporous resin chromatography of the supernatant, concentration of the eluate under reduced pressure, and freeze-drying to obtain the Malpighia glauca extract.

[0051] In the preparation of the Malpighia glauca extract, the mass ratio of the dried Malpighia glauca powder to the buffer solution is 1:5-10; the ultrasonic-assisted extraction is performed at a power of 300 W and a frequency of 40 kHz; and the centrifugal treatment is performed at a speed of 4000 rpm for 15 minutes.

[0052] The preparation method of the grape seed polyphenol is as follows: mixing grape seed powder with deionized water at a ratio of 1:15-20, maintaining at a pressure of 1.5-2.0 MPa and a temperature of 120-130℃ for 25-30 minutes in a nitrogen atmosphere, instantaneously releasing the pressure at 1.0 MPa / s, and cooling the water to 25℃ within 3 seconds after the pressure release, and then spray drying to obtain the grape seed polyphenol.

[0053] A preparation method of an additive-free and high-activity coenzyme Q10 composition, comprising the following steps:

[0054] (1) Capsule shell preparation: heating glycerol 28-32 parts and purified water 90-110 parts to 65-70℃ and stirring to dissolve, slowly adding gelatin 100 parts until a transparent base glue solution is formed; placing the base glue solution in a three-stage vacuum system for vacuum gradient degassing to obtain a bubble-free glue solution; adding natural polyphenol complex 5.5-6.5 parts to the bubble-free glue solution, stirring uniformly to obtain a light-blocking glue solution, and then filtering and standing to obtain a mature light-blocking glue solution;

[0055] (2) Content homogenization: Take 32-36 parts of beeswax and 175-190 parts of sunflower oil at 70-72℃ to melt, and use double-layer stirring paddle to homogenize to form a semi-solid wax-oil mixture; add 175-190 parts of sunflower oil to the wax-oil mixture, and homogenize to obtain a flowable oil base; add 35-45 parts of coenzyme Q10 powder, and gradient homogenize to obtain a nano-emulsified content;

[0056] (3) Soft capsule compression and shaping: the matured light-blocking glue solution is compressed into a glue tape with a thickness of 0.25 mm, and the nano-emulsified content is injected into the glue tape at the same time, and a wet soft capsule is formed in a mold at 30℃, and the wet soft capsule is subjected to primary shaping and deep drying to obtain a finished capsule, which is a coenzyme Q10 composition without additives and with high activity.

[0057] In (1) capsule skin preparation, the stirring is carried out at 70℃ with a low speed of 50 rpm for 15 minutes to form a uniform light-blocking glue solution with a light brown red color; the air pressure of the three-stage vacuum system is-0.06 MPa, -0.08 MPa, and-0.09 MPa in turn.

[0058] In (2) content homogenization, the upper paddle of the double-layer stirring paddle has an inclination angle of 45 degrees, and the lower paddle has an inclination angle of 60 degrees, and the stirring is carried out at 2000 rpm for 12 minutes.

[0059] The gradient homogenization is carried out under a vacuum degree of-0.1±0.02 MPa: the first stage is 2000 rpm for 10 minutes, the second stage is 5000 rpm for 15 minutes, and the third stage is 3000 rpm for 12 minutes, and finally a milky white nano-emulsified content is obtained.

[0060] In (3) soft capsule compression and shaping, the mass ratio of the matured light-blocking glue solution to the nano-emulsified content is 1:1.18-1.22.

[0061] The primary shaping is to transfer the wet soft capsule to an environment with a temperature of 25℃ and a relative humidity of 40% for drying for 2 hours, so that a solidification film is formed on the surface of the capsule to obtain a primary shaped capsule; and the deep drying is to transfer the primary shaped capsule to a transfer cage with a temperature of 35℃ and a relative humidity of 25% for drying for 6 hours.

[0062] In summary, the technical scheme solves the problems of light stability, absorption rate, odor control, and mechanical integrity in a layer-by-layer progressive manner through the physical and chemical synergy between natural components. The mechanism of each process step is closely related to the core problem, and the comprehensive performance is broken through without introducing chemical synthetic substances.

[0063] The technical scheme of the present application is further illustrated by the following examples and comparative examples, but the protection scope of the present application is not limited thereto.

[0064] Example 1

[0065] A preparation method of a non-additive and high-activity coenzyme Q10 composition comprises the following steps:

[0066] (1) Preparation of Malpighia emarginata extract: Dry Malpighia emarginata is crushed to 80 mesh, and a citric acid buffer solution with a pH value of 4.2 is added, with a mass ratio of dry Malpighia emarginata powder to buffer solution of 1:10. Ultrasonic-assisted extraction is performed at 52°C for 35 minutes at a power of 300W and a frequency of 40kHz. 0.9U / g pectinase and 0.2U / g cellulase are added, and enzymolysis is performed at 46°C for 60 minutes. The enzyme is inactivated at 90°C for 10 minutes, and centrifugation is performed at 4000rpm for 15 minutes. The supernatant is subjected to macroporous resin chromatography, vacuum concentration, and freeze-drying to obtain the Malpighia emarginata extract.

[0067] Preparation of grape seed polyphenol: Grape seed powder is mixed with deionized water at a ratio of 1:20, and is subjected to steam explosion treatment at 120°C and 1.5MPa for 30 minutes in a nitrogen atmosphere. The pressure is instantaneously released at 1.0MPa / s, and the water is cooled to 25°C within 3 seconds. Spray drying is performed to obtain the grape seed polyphenol.

[0068] (2) Preparation of natural polyphenol compound: Grape seed polyphenol, Malpighia emarginata extract, and rosemary acid are mixed at a mass ratio of 3.6:2.20:1.

[0069] (3) Preparation of capsule shell: Glycerol 32 parts and purified water 100 parts are dissolved at 65°C, and stirred at 50rpm for 15 minutes. Gelatin 100 parts is slowly added to form a basic gel solution. The gel solution is subjected to three-stage vacuum system gradient degassing, with negative pressures of-0.06MPa, -0.08MPa, and-0.09MPa, respectively. Natural polyphenol compound 5.5 parts is added, and the filtered solution is incubated at 65°C to obtain a mature gel solution.

[0070] (4) Homogenization and synergistic effect of content: Beeswax 32 parts and sunflower oil 190 parts are melted at 70°C, and homogenized at 2000rpm for 12 minutes using double-layer stirring paddles. Sunflower oil 190 parts is added, and gradient homogenization is performed at 2000rpm for 10 minutes, 5000rpm for 15 minutes, and 3000rpm for 12 minutes, with a vacuum degree of-0.1MPa, to obtain nanometer emulsified content.

[0071] (5) Soft capsule compression, pill formation, and shaping: The mature gel solution is compressed into a 0.25mm gel strip, and the content is injected at a mass ratio of gel solution to content of 1:1.22, and molded at 30°C. Primary shaping is performed at 25°C and 40% humidity for 2 hours, and the product is obtained after drying in a drying oven at 35°C and 25% humidity for 6 hours.

[0072] Example 2

[0073] In this example, the same as in Example 1 is not described again, and the differences are as follows:

[0074] (1) Extract of Malpighia glauca (DC.) Benth. fruit: dry fruit powder to buffer solution at a mass ratio of 1:5, ultrasonic extraction at 52°C for 35 minutes; enzyme hydrolysis at 48°C for 50 minutes, and the rest is the same as in Example 1.

[0075] Grape seed polyphenol: grape seed powder to deionized water at a mass ratio of 1:15, 130°C, 2.0 MPa for 25 minutes, and water cooling drying after pressure relief.

[0076] (2) Natural polyphenol compound: grape seed polyphenol, extract of Malpighia glauca (DC.) Benth., and rosemary acid at a mass ratio of 3.4:2.25:1.

[0077] (3) Capsule shell: glycerol 28 parts, purified water 110 parts dissolved at 70°C, add gelatin 100 parts, three-stage vacuum degassing, add natural polyphenol compound 6.0 parts, and keep at 70°C.

[0078] (4) Homogenization of content: melt homogenization of beeswax 36 parts and sunflower oil 175 parts at 72°C; add sunflower oil 175 parts, gradient homogenization vacuum degree-0.12 MPa.

[0079] (5) Pill pressing and shaping: the mass ratio of glue solution to content is 1:1.18.

[0080] Example 3

[0081] In this example, the same as in Example 1 will not be repeated, and the differences are as follows:

[0082] (1) Extract of Malpighia glauca (DC.) Benth. fruit: dry fruit powder to buffer solution at a mass ratio of 1:7.5, enzyme hydrolysis at 47°C for 55 minutes. Grape seed polyphenol: grape seed powder to water at a mass ratio of 1:17.5, 125°C, 1.75 MPa for 27.5 minutes.

[0083] (2) Natural polyphenol compound: component mass ratio 3.5:2.15:1.

[0084] (3) Capsule shell: glycerol 30 parts, purified water 90 parts dissolved at 67.5°C, add natural polyphenol compound 6.5 parts.

[0085] (4) Homogenization of content: melt of beeswax 34 parts and sunflower oil 182.5 parts at 71°C, gradient homogenization vacuum degree-0.08 MPa.

[0086] (5) Pill pressing and shaping: the mass ratio of glue solution to content is 1:1.20.

[0087] Comparative Example 1

[0088] In this comparative example, the same as in Example 1 will not be repeated, and the differences are as follows:

[0089] The capsule shell is replaced with 1.0 part of titanium dioxide instead of the natural polyphenol complex.

[0090] Comparative Example 2

[0091] In the present comparative example, the same as in Example 2 is not repeated, and the differences are described as follows:

[0092] The capsule shell is replaced with 5.5 parts of β-carotene instead of the natural polyphenol complex.

[0093] Comparative Example 3

[0094] In the present comparative example, the same as in Example 3 is not repeated, and the differences are described as follows:

[0095] The content is added with 0.5 parts of sodium cholate.

[0096] Comparative Example 4

[0097] In the present comparative example, the same as in Example 1 is not repeated, and the differences are described as follows:

[0098] The content homogenization is changed to 2000 revolutions / minute single-speed homogenization for 37 minutes.

[0099] Comparative Example 5

[0100] In the present comparative example, the same as in Example 1 is not repeated, and the differences are described as follows:

[0101] The capsule shell is added with 0.1 parts of lemon yellow.

[0102] Performance test results and analysis

[0103] The compositions are prepared according to the parameters of the examples and comparative examples, respectively, and the obtained compositions are tested, and the test results are shown in Table 1. Among them, the ultraviolet absorbance (310 nm) is measured by ISO 13468, the in vitro intestinal absorption model is measured by USP <711>, the blood drug concentration (single oral administration of 100 mg to subjects over 65 years old) is measured by HPLC method, the accelerated oxidation method (40℃ / 14 days for peroxide value) is measured by AOAC 965.33, the brittle fracture rate is measured by vibration test, and the sensitization is measured by patch test.

[0104] As can be seen from Table 1, the ultraviolet absorbance of Examples 1-3 is 0.78-0.85, close to the titanium dioxide group (0.91) of Comparative Example 1, but the sensitization rate is as low as 0.2-0.5%. This confirms that the natural polyphenol realizes physical light shielding through triple action, the conjugated double bond of grape seed polyphenol absorbs ultraviolet photons; the light scattering crystal of Vitis amurensis polyphenol; and the free radical capture of rosmarinic acid blocks the photooxidation chain reaction. The use of β-carotene in Comparative Example 2 not only reduces the ultraviolet absorbance to 0.75, but also causes the peroxide value to exceed the standard by 4.2 times due to photocatalysis, verifying the light stability and safety synergistic mechanism of the present application.

[0105] Table 1 Analysis test results

[0106] Test Index Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 UV absorbance (310 nm) 0.82 0.78 0.85 0.91 0.75 0.80 0.73 0.77 Intestinal absorption rate (%) 42.3 38.7 40.5 9.5 10.2 32.1 20.6 10.8 Peak blood concentration (μg / mL) 1.85 1.72 1.93 0.48 0.52 1.25 0.95 0.53 Time to peak (h) 3.2 3.5 3.1 6.0 5.8 4.0 4.8 5.7 Peroxide value (meq / kg) 3.1 3.4 3.0 5.8 12.6* 3.5 6.2 4.5 Brittleness rate (%) 1.2 1.5 1.1 2.8 2.2 1.4 8.5 2.0 Sensitization rate (%) 0.3 0.5 0.2 0.4 0.6 0.3 0.4 5.1

[0107] Intestinal absorption data showed that the absorption rates of Examples 1-3 were 38.7-42.3%, and the peak blood concentration was more than 3 times higher than that of the traditional preparation, due to the specific binding of the goldpalm fruit mangiferin to the intestinal MRP2 transporter. The glucose group in its molecule forms a hydrogen bond network with the Phe332 site of the transporter, and rosmarinic acid acts as a molecular bridge to connect the isoprene chain of coenzyme Q10, forming a "beeswax crystal embedding-polyphenol molecular bridging-transporter activation" three-level delivery system. Although the addition of bile salt in Comparative Example 3 increased the absorption rate to 32.1%, it caused diarrhea in 15.7% of the subjects; Comparative Example 4, due to the absence of the gradient homogenization process, resulted in uneven particle size distribution of the contents, leading to an absorption rate of only 20.6%.

[0108] Peroxide value and brittle fracture rate data revealed the synergistic effect of the process: the three-stage vacuum degassing promoted the formation of ionic bonds between the Arg / Lys residues of the gelatin peptide chain and the polyphenol phenolic hydroxyl group, and the breaking elongation rate of the gelatin skin was increased by 22%. The beeswax crystal network encapsulates the coenzyme Q10 molecule in the gradient homogenization, blocking its contact channel with oxygen molecules. The peroxide values of Examples 1-3 were all below 3.4 meq / kg, which was much better than that of Comparative Example 1, which was 5.8 meq / kg; the brittle fracture rate of 1.1-1.5% was significantly lower than that of the single-speed homogenization group of Comparative Example 4, which was 8.5%. The odor masking test showed that the intermolecular hydrogen bonds formed between the polyphenol phenolic hydroxyl group and the Q10 quinone group reduced the escape rate of free molecules, while the addition of lemon yellow in the control of Comparative Example 5 triggered a 5.1% sensitization rate.

[0109] The test results show that the application realizes the three technical breakthroughs of improving the light stability of the coenzyme Q10 soft capsule, enhancing the bioavailability and realizing the chemical additive zero risk through the natural polyphenol compound synergistic gradient process innovation. In terms of light shielding performance, the average ultraviolet absorbance of 0.82 of examples 1 to 3 reaches more than 90% of the light shielding effect of traditional titanium dioxide, while the peroxide value of the comparative example 2 using beta-carotene instead reaches 4.2 times of the national standard limit; in terms of absorption efficiency, the average intestinal absorption rate 40.5% and the blood concentration peak 1.83 μg / mL of the example group are respectively 3.3 times and 2.8 times higher than those of the comparative example 1, and the key peak time is shortened to 3.2 hours, while the comparative example 3 adds sodium cholate to improve the absorption rate but causes 15.7% diarrhea side effects; in terms of safety and stability, the peroxide value 3.2 meq / kg, the brittle rate 1.3% and the sensitization rate 0.3% of the example form a comprehensive advantage matrix, while the sensitization rate of the comparative example 5 using lemon yellow pigment rises to 5.1% and the complaint rate reaches 18.6%. It is especially worth noting that the performance fluctuation of the example group is less than 5% under the combination of multiple parameters such as high and low glycerol content and different amounts of beeswax, which proves that the natural polyphenol three-dimensional network and the process synergy have universal reliability, and completely avoid the three industry pain points of health risks of chemical light shielding agents, side effects of absorption agents and safety hazards of pigments.

[0110] The natural components of the application realize efficient light shielding, the bioactive ingredients maintain the targeted delivery function, and the physicochemical stability is simultaneously improved. The precise control of process parameters makes the molecular level design realize the maximum efficiency in the macroscopic product.

[0111] The above is the preferred embodiment of the application, and it should be pointed out that for ordinary skilled persons in the technical field, some improvements and refinements can be made without departing from the principles of the application, and these improvements and refinements should also be regarded as the protection scope of the application.

Claims

1. A coenzyme Q10 composition without addition and high activity, consisting of a capsule shell and a content, characterized in that, The capsule shell is prepared from raw materials comprising: gelatin 100 parts, glycerol 28-32 parts, purified water 90-110 parts, natural polyphenol complex 5.5-6.5 parts by mass; The content is prepared from raw materials comprising: coenzyme Q10 35-45 parts, sunflower seed oil 350-380 parts, beeswax 32-36 parts; The natural polyphenol complex is composed of grape seed polyphenol, Malpighia emarginata extract, and rosemary acid at a mass ratio of 3.4-3.6:2.15-2.25:1; The preparation method of the Malpighia emarginata extract The method comprises the following steps: crushing dried Malpighia emarginata to 80 mesh, adding a citric acid buffer solution with a pH value of 4.2, ultrasonic-assisted extraction at 52°C for 35 minutes, adding 0.9 U / g of pectinase and 0.2 U / g of cellulase, enzymolysis at 46-48°C for 50-60 minutes, centrifugal treatment after enzyme inactivation at 90°C for 10 minutes, macroporous resin chromatography of the supernatant, concentration of the eluate under reduced pressure, and freeze-drying to obtain the Malpighia emarginata extract; The preparation method of the grape seed polyphenol is: mixing grape seed powder and deionized water at a ratio of 1:15-20, maintaining at a pressure of 1.5-2.0 MPa and a temperature of 120-130°C for 25-30 minutes in a nitrogen atmosphere, instantaneously releasing the pressure at 1.0 MPa / s, and cooling the water to 25°C within 3 seconds after pressure release, and then spray drying to obtain the grape seed polyphenol.

2. The no-addition and high-activity coenzyme Q10 composition according to claim 1, characterized by, In the preparation of the Malpighia emarginata extract, the mass ratio of the dried Malpighia emarginata powder to the buffer solution is 1:5-10; the ultrasonic-assisted extraction power is 300 W, and the frequency is 40 kHz; the centrifugal treatment speed is 4000 rpm, and the centrifugal treatment time is 15 min.

3. A process for preparing the coenzyme Q10 composition of any one of claims 1-2, which is characterized by, The method comprises the following steps: (1) Capsule shell preparation: heat glycerol 28-32 parts and purified water 90-110 parts to 65-70°C and stir to dissolve, slowly add gelatin 100 parts until a transparent base glue solution is formed; place the base glue solution in a three-stage vacuum system for vacuum gradient degassing to obtain a bubble-free glue solution; add natural polyphenol complex 5.5-6.5 parts to the bubble-free glue solution, stir evenly to obtain a light-blocking glue solution, then filter, and store and stand to obtain a mature light-blocking glue solution; (2) Content homogenization and synergism: melt beeswax 32-36 parts and sunflower seed oil 175-190 parts at 70-72°C, homogenize using double-layer stirring paddles to form a semi-solid wax oil mixture; add another 175-190 parts of sunflower seed oil to the wax oil mixture, homogenize to obtain a flowable oil base; add coenzyme Q10 powder 35-45 parts, and gradient homogenize to obtain a nano-emulsified content; (3) Soft capsule compression and shaping: compress the mature light-blocking glue solution into a glue tape with a thickness of 0.25 mm, simultaneously inject the nano-emulsified content into the glue tape using a syringe pump, form a wet soft capsule in a mold at 30°C, and obtain a finished capsule after primary shaping and deep drying of the wet soft capsule; the finished capsule is a coenzyme Q10 composition with no additives and high activity.

4. The method of claim 3, wherein the coenzyme Q10 composition is prepared without addition of a solvent and has high activity. In (1) capsule skin preparation, the stirring is low-speed stirring at 50 revolutions per minute for 15 minutes at 70 degrees Celsius to form a uniform light brown red light-blocking glue solution; the air pressure of the three-stage vacuum system is-0.06 MPa, -0.08 MPa, and -0.09 MPa in turn.

5. The method of claim 3, wherein the method is characterized by, In (2) content homogenization and enhancement, the upper layer paddle of the double-layer stirring paddle has an inclination angle of 45 degrees, the lower layer paddle has an inclination angle of 60 degrees, and stirring is carried out at 2000 revolutions per minute for 12 minutes. The gradient is under the condition of vacuum degree-0.1±0.02 MPa: the first stage is 2000 revolutions per minute for 10 minutes, the second stage is 5000 revolutions per minute for 15 minutes, and the third stage is 3000 revolutions per minute for 12 minutes, and finally a milky white nano-emulsified content is obtained.

6. The method of claim 3, wherein the method is characterized by, In (3) soft capsule pressing and shaping, the mass ratio of the matured light-blocking glue solution to the nano-emulsified content is 1:1.18-1.

22.

7. The method of claim 3, wherein the method is characterized by, The primary shaping is to transfer the wet soft capsule into an environment of 25℃ and relative humidity of 40% for drying for 2 hours, so that a solidification film is formed on the surface of the capsule to obtain a primary shaped capsule; the deep drying is to transfer the primary shaped capsule to a transfer cage drying at 35℃ and relative humidity of 25% for 6 hours.