Heart-protective complex composition for improving the absorption rate of coenzyme q10 and preparation method thereof

Abstract

The present invention discloses a heart-protective complex composition for improving the absorption rate of Coenzyme Q10 and a preparation method thereof, relating to the technical field of medicine and functional foods. The core active ingredients comprise Coenzyme Q10, Vitamin E, and black pepper extract within a specific mass ratio range. Pharmaceutically acceptable carriers and antioxidant synergists may also be combined to prepare various oral dosage forms. By constructing a ternary active component system with a specific ratio, the present invention achieves temporal synergy between absorption promotion and antioxidant regeneration in vivo, thereby solving the technical problems of low oral bioavailability and insufficient myocardial targeted accumulation of existing Coenzyme Q10 preparations. It significantly enhances the conversion efficiency of Coenzyme Q10 into the active form available to myocardial cells, and can be widely used in the preparation of drugs or functional foods for preventing or treating heart diseases.

Description

[0001] DESCRIPTION

[0002] Heart-protective complex composition for improving the absorption rate of Coenzyme Q10 and preparation method thereof

[0003] TECHNICAL FIELD

[0004] The present invention relates to the technical field of medicine and functional foods, specifically to a heart-protective complex composition for improving the absorption rate of Coenzyme Q10 and a preparation method thereof.

[0005] BACKGROUND

[0006] Coenzyme Q10 (CoQlO), also known as ubiquinone, is a key component of the mitochondrial electron transport chain in cells and plays a central role in cellular energy metabolism. As an endogenous substance in the human body, CoQlO is abundant in high-energy-demand organs such as the heart, liver, and kidneys. The quinone ring in its molecular structure can reversibly convert between oxidized and reduced forms; this characteristic enables it not only to participate in ATP synthesis but also to possess lipophilic antioxidant functions. Clinical studies have shown that the level of CoQlO in myocardial tissue of patients with heart failure and ischemic heart disease is significantly lower than that in healthy individuals, and exogenous supplementation of CoQlO has potential value for improving cardiovascular diseases.

[0007] However, the oral bioavailability of CoQlO is extremely low, mainly due to its high molecular weight of 863 Daltons, strong lipophilicity, and near insolubility in water. Simultaneously, intestinal P-glycoprotein efflux and hepatic first-pass effect further limit its absorption efficiency. To solve this technical problem, existing technologies mainly adopt two strategies: one is adding absorption enhancers, such as black pepper extract (piperine), which increases the absorption rate of CoQlO by inhibiting intestinal UDP-glucuronosyltransferase and P-glycoprotein; the other is adding i antioxidants, such as Vitamin E, to protect CoQlO from oxidative degradation in vivo. A search revealed that invention patent publication No. CN1 02441161 A discloses a composite lipophilic antioxidant combining Vitamin E, Coenzyme Q10, and Superoxide Dismutase (SOD) into one entity, aiming to protect the lipid portion of cell membranes from free radical attack. Additionally, the US company Sabinsa has developed a binary combination product of Coenzyme Q10 and black pepper extract; this technology has been disclosed in multiple patents and applied in the market.

[0008] Although the above-mentioned prior art respectively solves certain problems in the absorption or antioxidant aspects of CoQlO, technical defects still exist. Specifically, although the binary combination of black pepper extract and CoQlO can increase blood concentration, the CoQlO entering the bloodstream mainly exists in the oxidized form (ubiquinone), whereas the mitochondria of myocardial cells truly require the reduced form (ubiquinol); this combination fails to solve the problem of conversion from the oxidized to the reduced form. Although the binary combination of Vitamin E and CoQlO has an antioxidant synergistic mechanism at the cell membrane level, the synergistic effect lacks a material basis due to the inherently insufficient absorption of CoQlO, and the prior art does not address the issue of selective accumulation of active ingredients in the target organ (heart). More importantly, the prior art does not involve how to achieve temporal synergy between the "absorption promotion" and "antioxidant regeneration" stages in vivo, making it difficult for exogenously supplemented CoQlO to be truly converted into energy usable by myocardial cells.

[0009] The technical problem to be solved by the present invention is to provide a composition capable of achieving temporal synergy across the three stages of in-vivo absorption, conversion, and myocardial accumulation of Coenzyme Q10, allowing the absorption-promoting effect of black pepper extract and the antioxidant regeneration effect of Vitamin E to synergize in a relay manner within a specific time window, thereby efficiently converting Coenzyme Q10 into the reduced active form usable by myocardial cell mitochondria.

[0010] The present invention addresses the above-mentioned shortcomings of the prior art by providing a heart-protective complex composition for improving the absorption rate of Coenzyme Q10 and a preparation method thereof.

[0011] SUMMARY

[0012] An objective of the present invention is to compensate for the deficiencies of the prior art by providing a heart-protective complex composition for improving the absorption rate of Coenzyme Q10 and a preparation method thereof. Through a specific mass ratio range determined experimentally, the composition achieves a temporal synergistic effect among Coenzyme Q10, Vitamin E, and black pepper extract, solving the technical problem of the difficulty in efficiently accumulating Coenzyme Q10 in myocardial tissue, and providing a new technical option for the prevention and treatment of cardiovascular diseases.

[0013] To solve the above technical problems, the present invention provides the following technical solutions: In one aspect, a heart-protective complex composition for improving the absorption rate of Coenzyme Q10, the composition consisting of Coenzyme Q10, Vitamin E, and black pepper extract, wherein the mass ratio of Coenzyme Q10, Vitamin E, and piperine in the black pepper extract is 100: 12 to 18: 1.

[0014] By setting the mass ratio of Coenzyme Q10, Vitamin E, and piperine to 100: 12 to 18: 1, the absorption-promoting effect of black pepper extract and the antioxidant regeneration effect of Vitamin E form a relay synergy within the absorption window period and the conversion window period, enabling the efficient conversion of Coenzyme Q10 into the reduced active form usable by myocardial cell mitochondria.

[0015] Further, the Vitamin E is d-a-tocopherol, and the content of piperine in the black pepper extract is not less than 95%.

[0016] By selecting d-a-tocopherol as the Vitamin E source and setting the piperine content in the black pepper extract to not less than 95%, it ensures the stable exertion of the antioxidant activity of Vitamin E on the mitochondrial membrane, while guaranteeing that the inhibitory effect of piperine on intestinal metabolic enzymes reaches the expected intensity, avoiding interference from impurity components on the absorption-promoting effect.

[0017] Furthermore, the mass ratio of Coenzyme Q10, Vitamin E, and piperine in the black pepper extract is 100: 15: 1.

[0018] By further setting the mass ratio of Coenzyme Q10, Vitamin E, and piperine to 100: 15: 1, the temporal synergistic effect of the three components in vivo can reach an optimal state, where the accumulation of reduced Coenzyme Q10 in myocardial tissue is significantly higher than in other ratio ranges.

[0019] Furthermore, the composition further comprises a pharmaceutically acceptable carrier, and the carrier is selected from at least one of medium-chain triglycerides, olive oil, soybean oil, or corn oil.

[0020] By adding a pharmaceutically acceptable carrier selected from medium-chain triglycerides, olive oil, soybean oil, or corn oil, a stable dissolution environment is provided for the lipophilic components, while improving the dispersibility and absorption interface of the composition in the gastrointestinal tract.

[0021] Furthermore, the composition further comprises an antioxidant synergist, and the antioxidant synergist is selected from at least one of ascorbyl palmitate or rosemary extract.

[0022] By adding an antioxidant synergist selected from ascorbyl palmitate or rosemary extract, an antioxidant network can be formed with Vitamin E, further delaying the oxidative degradation of Coenzyme Q10 during preparation storage and in-vivo transport.

[0023] Furthermore, the composition is prepared into a soft capsule preparation, a self-microemulsifying oral preparation, or an orally disintegrating micro-tablet preparation.

[0024] By preparing the composition into a soft capsule preparation, a self-microemulsifying oral preparation, or an orally disintegrating micro-tablet preparation, diversified administration options can be provided based on the swallowing ability and absorption characteristics of the target population, wherein the self-microemulsifying preparation can spontaneously form nano-scale droplets in the gastrointestinal tract.

[0025] In one aspect, a method for preparing the heart-protective complex composition for improving the absorption rate of Coenzyme Q10, applicable to the heart-protective complex composition for improving the absorption rate of Coenzyme Q10, the method comprising the steps of dissolving Coenzyme Q10, Vitamin E, and black pepper extract in an oily base, mixing uniformly, and then preparing into soft capsules or a self-microemulsifying preparation.

[0026] By dissolving Coenzyme Q10, Vitamin E, and black pepper extract in an oily base and then preparing into soft capsules or a self-microemulsifying preparation, the three components can achieve molecular-level uniform dispersion in the oil phase, ensuring that the ratio of each component per unit dose is accurately consistent.

[0027] Furthermore, the oily base is medium-chain triglycerides, heated to 40-45°C, then Coenzyme Q10, Vitamin E, and black pepper extract are added sequentially, and stirred until completely dissolved.

[0028] By setting the oily base as medium-chain triglycerides, heating to 40-45°C, and then adding the components sequentially, complete dissolution of Coenzyme Q10 can be achieved under mild heating conditions, avoiding high-temperature damage to the active structures of piperine and Vitamin E.

[0029] In one aspect, a method for preparing the heart-protective complex composition for improving the absorption rate of Coenzyme Q10, applicable to the heart-protective complex composition for improving the absorption rate of Coenzyme Q10, the method comprising the steps of dissolving Coenzyme Q10, Vitamin E, and black pepper extract in ethanol, spraying the solution onto a porous carrier for adsorption and drying, then mixing with pharmaceutically acceptable excipients and compressing into orally disintegrating micro-tablets.

[0030] By dissolving Coenzyme Q10, Vitamin E, and black pepper extract and then spraying onto a porous carrier for adsorption and drying, the liquid oily components can be converted into a solid powder, facilitating mixing with excipients and compression into orally disintegrating micro-tablets, meeting the medication needs of patients with swallowing difficulties.

[0031] Furthermore, the composition is used in the preparation of a medicament or functional food for preventing or treating heart diseases.

[0032] By using the composition for preparing a medicament or functional food for preventing or treating heart diseases, exogenously supplemented Coenzyme Q10 can achieve selective accumulation in myocardial tissue, providing targeted energy support for patients with conditions such as heart failure and ischemic heart disease.

[0033] Compared with the prior art, this heart-protective complex composition for improving the absorption rate of Coenzyme Q10 and its preparation method have the following beneficial effects:

[0034] I. The present invention constructs a ternary composite active system through a specific mass ratio of Coenzyme Q10, Vitamin E, and black pepper extract, enabling the intestinal absorption-promoting effect of black pepper extract and the antioxidant regeneration effect of Vitamin E to form a temporal relay synergy in vivo. This effectively solves the technical deficiencies of the prior art, such as low oral bioavailability of Coenzyme Q10, insufficient conversion efficiency from the oxidized to the reduced form, and poor target organ active accumulation. It achieves full-chain synergy in the absorption, conversion, and myocardial accumulation of Coenzyme Q10, significantly enhancing the conversion efficiency of exogenously supplemented Coenzyme Q10 into the active form available to myocardial cell mitochondria, providing a stable and effective active substance basis for the prevention and intervention of cardiovascular-related conditions.

[0035] II. By adapting the preparation processes for different dosage forms, the present invention can stably disperse the lipophilic active components in different administration systems, achieving structural stability and dose uniformity of the active components under mild and controllable process conditions. This effectively avoids the oxidative degradation of Coenzyme Q10 during preparation storage and in-vivo transport, and simultaneously adapts to various oral dosage forms according to the medication needs of the target population, expanding the applicable population range of the composition.

[0036] Other advantages, objectives, and features of the present invention will be set forth in part in the following description, and in part will become apparent to those skilled in the art upon examination of the following or may be learned from practice of the invention.

[0037] BRIEF DESCRIPTION OF DRAWINGS

[0038] To explain the technical solutions in the embodiments of the present invention or the prior art more clearly, the following briefly introduces the drawings required for describing the embodiments or the prior art. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without inventive effort.

[0039] Figure 1 is a comparison chart of the components, dosage forms, and preparation processes of three embodiments of the present invention;

[0040] Figure 2 is a comparison chart of the plasma absorption and myocardial accumulation effects of each embodiment and comparative example of the present invention;

[0041] Figure 3 is a schematic diagram of the in-vivo temporal synergistic mechanism of the ternary components of the present invention.

[0042] DETAILED DESCRIPTION

[0043] To further elaborate on the technical means and effects adopted by the present invention to achieve the intended invention objectives, the following, in conjunction with the accompanying drawings and preferred embodiments, provides a detailed description of the specific implementation, structure, features, and effects of the present invention.

[0044] Embodiment 1

[0045] The purpose of this embodiment is to provide an implementation plan for a soft capsule preparation of the heart-protective complex composition for improving the absorption rate of Coenzyme Q10, adopting the optimal mass ratio ternary active components of the present invention, combined with pharmaceutical oily carriers and antioxidant synergists, fully presenting the preparation method and formulation process of the composition of the present invention, and verifying the implementability of the technical solution of the present invention in conventional soft capsule production. The following is a detailed description in conjunction with Figures 1 to 3 and the specific implementation content. The raw materials used in this embodiment all comply with corresponding pharmaceutical standards or health food raw material standards. Among them, Coenzyme Q10 complies with the 2025 edition of the Pharmacopoeia standard, with a content not less than 98.0%. Vitamin E is d-a-tocopherol, complying with food additive standards, with a content not less than 96.0%. The measured content of piperine in the black pepper extract is 95.2%, complying with health food raw material related standards. The oily carrier is medium-chain triglycerides, complying with the 2025 edition of the Pharmacopoeia pharmaceutical excipient standards. The antioxidant synergist is ascorbyl palmitate, complying with the 2025 edition of the Pharmacopoeia pharmaceutical excipient standards. The capsule shell materials, including gelatin, glycerin, and purified water, are all special pharmaceutical excipients for soft capsules, complying with corresponding standards.

[0046] The mass ratio of the active components in the composition of this embodiment is Coenzyme Q10, Vitamin E, and piperine in the black pepper extract at 100:15:1. The specific prescription dosage is as follows: Coenzyme Q10 100g, d-a-tocopherol 15g, black pepper extract 1.05g, medium-chain triglycerides 1000g, ascorbyl palmitate 2g. The capsule shell prescription is gelatin 300g, glycerin 120g, purified water 300g.

[0047] The preparation process of this embodiment is divided into four core stages: content preparation, capsule shell preparation, encapsulation, and post-treatment. The specific operation steps are as follows.

[0048] The first stage is content preparation. Place medium-chain triglycerides in a mixing tank with a constant temperature jacket, turn on the heating device, and raise the material temperature to 40°C to 45 °C. In this embodiment, the temperature is controlled at 42 °C. Turn on the stirring device, set the stirring speed to 60 rpm. Under stirring, first add Coenzyme Q10, continue stirring for 25 minutes until Coenzyme Q10 is completely dissolved with no visible solid particles. Then add d-a-tocopherol, continue stirring for 10 minutes until the material is uniformly mixed. Then add black pepper extract, continue stirring for 15 minutes until the black pepper extract is completely dissolved and the system is uniform and transparent. Finally, add ascorbyl palmitate, continue stirring for 5 minutes until completely dissolved, stop heating and stirring, obtain the soft capsule content, let stand for defoaming for 30 minutes, and set aside.

[0049] The second stage is capsule shell preparation. Place gelatin, glycerin, and purified water in a gelatinizing tank, turn on the heating device, control the temperature at 65°C to 70°C, continue stirring until the gelatin is completely dissolved, turn on the vacuum device for defoaming until there are no visible bubbles in the capsule shell glue, test the glue viscosity and control it at 3000 mPa s to 4000 mPa s, keep warm at 60°C for later use.

[0050] The third stage is encapsulation. Use a rotary soft capsule encapsulation machine for encapsulation, with a mold specification of 0.5g per capsule, a content fill amount of 0.5g per capsule, and a capsule shell thickness controlled at 0.7mm. The encapsulation environment temperature is controlled at 18°C to 22°C, and the relative humidity is controlled at 35% to 45%. During the encapsulation process, monitor the fill weight variation in real-time to ensure it complies with the requirements of the Pharmacopoeia for soft capsule preparations.

[0051] The fourth stage is post-treatment. First, place the encapsulated soft capsules in a tumbling dryer for setting, with a tumbling speed of 15 rpm, a setting time of 4 hours, and environmental parameters consistent with the encapsulation environment. After setting, place the soft capsules in a hot air circulation drying oven, with a drying temperature controlled at 24°C to 26°C, a relative humidity controlled at 30% to 40%, and a drying time of 24 hours. Turn the material every 4 hours during this period. The drying endpoint is controlled to achieve a capsule shell moisture content of 8% to 10%. After drying, spray the soft capsules with 95% medicinal ethanol to wash and io remove surface oil stains. After washing, place them in a ventilated environment to volatilize ethanol for 1 hour. Finally, perform capsule selection, removing deformed capsules, flat capsules, and capsules with unqualified fill weight, to obtain the finished soft capsule preparation.

[0052] This embodiment fully implements the core technical solution of the present invention. Through clear raw material specifications, precise component ratios, and controllable preparation processes, a soft capsule preparation of the heart-protective complex composition with stable quality and good uniformity is obtained. The process parameters set in this embodiment are all within a mild and controllable range, require no special production equipment, and can be directly adapted to existing medicinal soft capsule production lines. Through step-by-step feeding and precise temperature control, this embodiment ensures the structural stability and uniform dispersion of each active component, providing qualified test samples for subsequent verification of the composition's absorption efficiency and myocardial targeted accumulation effect.

[0053] Embodiment 2

[0054] The purpose of this embodiment is to provide an implementation plan for a self-microemulsifying oral preparation of the heart-protective complex composition for improving the absorption rate of Coenzyme Q10, adopting the lower limit mass ratio ternary active components of the present invention, combined with composite oily carriers and natural antioxidant synergists, fully presenting the formulation design and preparation process of the self-microemulsifying preparation, verifying the implementability of the technical solution of the present invention in a nano-scale self-emulsifying drug delivery system, clarifying the self-emulsifying performance and particle size control points of the self-microemulsifying preparation, and expanding the applicable dosage form range of the composition of the present invention. The following is a detailed description in conjunction with Figures 1 to 3 and ii the specific implementation content.

[0055] The raw materials used in this embodiment all comply with corresponding pharmaceutical standards or health food raw material standards. The specifications of Coenzyme Q10, d-a-tocopherol, and black pepper extract are consistent with Embodiment 1. The oily carriers are olive oil and soybean oil, both complying with the 2025 edition of the Pharmacopoeia pharmaceutical excipient standards. The emulsifier is Polyoxyl 40 Hydrogenated Castor Oil (RH40), and the co-emulsifier is propylene glycol, both complying with the 2025 edition of the Pharmacopoeia pharmaceutical excipient standards. The antioxidant synergist is rosemary extract, with a carnosic acid content not less than 60%, complying with health food raw material related standards.

[0056] The mass ratio of the active components in the composition of this embodiment is Coenzyme Q10, Vitamin E, and piperine in the black pepper extract at 100:12:1. The specific prescription dosage is as follows: Coenzyme Q10 100g, d-a-tocopherol 12g, black pepper extract 1.05g, olive oil 300g, soybean oil 200g, Polyoxyl 40 Hydrogenated Castor Oil (RH40) 400g, propylene glycol 100g, rosemary extract 5g.

[0057] The preparation process of this embodiment is divided into three core stages: oil phase preparation, system mixing, sterile filtration and filling. The specific operation steps are as follows.

[0058] The first stage is oil phase preparation. Place olive oil and soybean oil in a mixing tank with a constant temperature jacket, mix evenly, turn on the heating device, and raise the material temperature to 40°C to 45°C. In this embodiment, the temperature is controlled at 43 °C. Turn on the stirring device, set the stirring speed to 80 rpm. Under stirring, first add Coenzyme Q10, continue stirring for 30 minutes until Coenzyme Q10 is completely dissolved with no visible solid particles. Then add d-a-tocopherol, continue stirring for 10 minutes until the material is uniformly mixed. Then add black pepper extract, continue stirring for 15 minutes until the black pepper extract is completely dissolved and the system is uniform and transparent. Then add rosemary extract, continue stirring for 10 minutes until completely dissolved, obtaining the basic oil phase mixture.

[0059] The second stage is system mixing. While maintaining the temperature and stirring state, sequentially add Polyoxyl 40 Hydrogenated Castor Oil (RH40) and propylene glycol to the basic oil phase mixture, continue stirring for 20 minutes until the system forms a uniform and transparent oil phase mixture, stop heating and stirring, let stand for defoaming for 20 minutes, obtaining the self-microemulsifying oral preparation stock solution.

[0060] This embodiment simultaneously conducts self-emulsifying performance verification. Take 0.5 mL of the prepared self-microemulsifying preparation stock solution, add it to 100 mL of purified water at 37 °C, gently invert 10 times, and the system spontaneously forms a slightly bluish opalescent nanoemulsion. Using a laser particle size analyzer for detection, the average droplet size is 25.6 nm, and the polydispersity index is 0.128, meeting the particle size requirements for self-microemulsifying preparations, ensuring that the preparation can rapidly and spontaneously form nano-scale droplets in the gastrointestinal tract, enhancing the dissolution and absorption efficiency of the active components.

[0061] The third stage is sterile filtration and filling. Filter the self-microemulsifying preparation stock solution through a 0.22pm organic membrane for sterile filtration. Fill the filtrate into brown oral liquid bottles, with a fill volume of 10 mL per bottle, seal, and store to obtain the finished self-microemulsifying oral preparation.

[0062] This embodiment fully implements the lower limit ratio technical solution. Through the design of composite oily carriers and a self-microemulsifying preparation system, a self-microemulsifying oral preparation of the heart-protective complex composition with excellent self-emulsifying performance and uniform particle size distribution is obtained. The components and processes adopted in this embodiment expand the applicable dosage form range of the present invention. The set process parameters can be directly adapted to existing oral liquid pharmaceutical production lines without the need for special equipment investment. Through the construction of a nano-scale self-emulsifying system, this embodiment further enhances the gastrointestinal dissolution efficiency of the active components, while verifying the implementability of the lower limit technical solution of the ratio range of the present invention.

[0063] Embodiment 3

[0064] The purpose of this embodiment is to provide an implementation plan for an orally disintegrating micro-tablet preparation of the heart-protective complex composition for improving the absorption rate of Coenzyme Q10, adopting the upper limit mass ratio ternary active components of the present invention, achieving solidification of oily active components through porous carrier adsorption drying technology, fully presenting the preparation process and quality control points of the orally disintegrating micro-tablets, verifying the implementability of the technical solution of the present invention in solid rapid-release dosage forms, and meeting the medication needs of populations with swallowing difficulties. The following is a detailed description in conjunction with Figures 1 to 3 and the specific implementation content.

[0065] The raw materials used in this embodiment all comply with corresponding pharmaceutical standards or health food raw material standards. The specifications of Coenzyme Q10, d-a-tocopherol, and black pepper extract are consistent with Embodiment 1. Anhydrous ethanol complies with the 2025 edition of the Pharmacopoeia pharmaceutical excipient standards. The porous carrier is silicon dioxide, complying with the 2025 edition of the Pharmacopoeia pharmaceutical excipient standards, with an average pore size of 15nm to 25nm and a specific surface area not less than 300m2 / g. Other pharmaceutical excipients include mannitol, crospovidone, aspartame, and magnesium stearate, all complying with the 2025 edition of the Pharmacopoeia pharmaceutical excipient standards.

[0066] The mass ratio of the active components in the composition of this embodiment is Coenzyme Q10, Vitamin E, and piperine in the black pepper extract at 100:18:1. The specific prescription dosage is as follows: Coenzyme Q10 100g, d-a-tocopherol 18g, black pepper extract 1.05g, anhydrous ethanol 500g, silicon dioxide 200g, mannitol 300g, crospovidone 50g, aspartame 5g, magnesium stearate 3g.

[0067] The preparation process of this embodiment is divided into four core stages: active component solution preparation, fluid bed adsorption drying, total mixing, and tableting. The specific operation steps are as follows.

[0068] The first stage is active component solution preparation. Place anhydrous ethanol in a batching tank with a stirring device, turn on stirring at room temperature, set the stirring speed to 100 rpm. Under stirring, sequentially add Coenzyme Q10, d-a-tocopherol, and black pepper extract, continue stirring for 40 minutes until all active components are completely dissolved, forming a uniform and transparent ethanol solution, and set aside.

[0069] The second stage is fluid bed adsorption drying. Place silicon dioxide into a fluid bed granulator, turn on the inlet air heating, control the inlet air temperature at 45°C to 50°C. In this embodiment, the inlet air temperature is controlled at 48°C. Turn on the fluidizing fan, adjust the fan frequency to make the silicon dioxide completely fluidized. Then, use the top spray method to uniformly spray the prepared active component ethanol solution onto the silicon dioxide at a spray rate controlled at 15 g / min. During spraying, maintain the material temperature at 40°C to 45°C. After spraying is complete, continue fluid bed drying for 30 minutes. Test the material to ensure the ethanol residue is not higher than 0.5%, stop heating and fan, obtain the solid powder with adsorbed active components, pass through an 80-mesh sieve, and set aside.

[0070] The third stage is total mixing. Place the sieved active powder into a three-dimensional motion mixer, sequentially add mannitol, crospovidone, and aspartame, turn on the mixer, set the mixing speed to 15 rpm, mix for 20 minutes until the materials are uniformly mixed. Then add magnesium stearate, continue mixing for 3 minutes, stop mixing, obtaining the total mixed powder. Test the powder to ensure the angle of repose does not exceed 35 degrees, confirming that the powder flowability meets tableting requirements.

[0071] The fourth stage is tableting. Use a rotary tablet press for tableting, with a mold specification of a 5mm diameter round flat punch, and a tablet weight controlled at 100 mg per tablet. During tableting, control the pressure at 5kN to 8kN to ensure tablet hardness is controlled at 2kg to 4kg, friability does not exceed 1%, and disintegration time is controlled within 30 seconds, meeting the quality requirements for orally disintegrating preparations. After tableting is complete, remove deformed tablets, cracked tablets, and tablets with unqualified weight variation to obtain the finished orally disintegrating micro-tablet preparation, sealed and stored in a dry environment.

[0072] This embodiment fully implements the upper limit ratio technical solution. Through fluid bed spray adsorption drying technology, the solidification of lipophilic active components is achieved, obtaining an orally disintegrating micro-tablet preparation with rapid disintegration, good mouthfeel, and excellent flowability. The process parameters set in this embodiment can be directly adapted to existing solid preparation production lines without the need for special equipment investment. This embodiment verifies the implementability of the upper limit ratio technical solution of the present invention, while expanding the applicable population range of the composition of the present invention.

[0073] Comparative Example The purpose of this comparative example is to provide an implementation plan for a soft capsule preparation of the binary combination of Coenzyme Q10 and black pepper extract disclosed in the prior art, adopting a preparation process, carrier dosage, and active component input amount completely consistent with Embodiment 1 of the present invention, only removing the Vitamin E component. Through parallel comparison with the embodiments of the present invention, it verifies the technical advantages of the ternary combination of the present invention compared to the binary combination of the prior art, clarifying the inventiveness and beneficial effects of the technical solution of the present invention.

[0074] The specifications and sources of the raw materials used in this comparative example are completely consistent with Embodiment 1. The prescription composition is as follows: Coenzyme Q10 100g, black pepper extract 1.05g, medium-chain triglycerides 1000g, ascorbyl palmitate 2g. The capsule shell prescription is completely consistent with Embodiment 1: gelatin 300g, glycerin 120g, purified water 300g.

[0075] The preparation process of this comparative example completely replicates the soft capsule preparation process of Embodiment 1, including the four core stages of content preparation, capsule shell preparation, encapsulation, and post-treatment. All process parameters, operating steps, and quality control standards are completely consistent with Embodiment 1, finally obtaining the binary combination soft capsule preparation, with a content fill amount of 0.5g per capsule, and fill weight variation complying with the requirements of the pharmacopoeia for soft capsule preparations.

[0076] This comparative example completely replicates the technical solution of the binary combination of Coenzyme Q10 and black pepper extract in the prior art. All preparation processes and parameters are consistent with Embodiment 1 of the present invention, only removing the Vitamin E component, ensuring the principle of a single variable for the comparative test. The binary combination soft capsule preparation prepared in this comparative example has stable quality and complies with relevant preparation standards. It can be used as a parallel control sample to verify the technical advantages of the ternary combination of the present invention in terms of in-vivo conversion of Coenzyme Q10, myocardial accumulation, and heart-protective activity, clarifying the inventive improvements of the present invention compared to the prior art.

[0077] The efficacy verification test is as follows.

[0078] This test uses SPF-grade male SD rats, weighing 200g to 220g, randomly divided into 4 groups, 10 rats per group, namely the Embodiment 1 group, Embodiment 2 group, Embodiment 3 group, and Comparative Example group. Rats in each group were administered by gavage at a dosage calculated based on Coenzyme Q10 of 10 mg per 100g body weight, once daily for 7 consecutive days. Four hours after the last administration, rats were anesthetized by intraperitoneal injection of pentobarbital sodium, blood was collected from the abdominal aorta, and then the heart tissue was rapidly removed. The total Coenzyme Q10 concentration in plasma and the accumulated amount of reduced Coenzyme Q10 in myocardial tissue were detected.

[0079] The detection method used high-performance liquid chromatography, with chromatographic conditions complying with relevant pharmacopoeia standards. The test results are expressed as mean ± standard deviation. Differences between groups were statistically analyzed using the t-test, with P < 0.05 considered statistically significant.

[0080] The test results showed that four hours after administration, the total Coenzyme Q10 concentration in plasma of rats in the Embodiment 1 group was 1.26 times that of the Comparative Example group, the Embodiment 2 group was 1.38 times that of the Comparative Example group, and the Embodiment 3 group was 1.19 times that of the Comparative Example group. Regarding the accumulated amount of reduced Coenzyme Q10 in myocardial tissue, the Embodiment 1 group was 2.13 times that of the Comparative Example group, the Embodiment 2 group was 1.87 times that of the Comparative Example group, and the Embodiment 3 group was 1.79 times that of the Comparative Example group.

[0081] It can be understood that the above test results indicate that compared to the binary combination of the prior art, the ternary complex composition of the present invention can not only increase the plasma absorption concentration of Coenzyme Q10 but also significantly increase the accumulation of reduced Coenzyme Q10 in myocardial tissue, achieving the expected temporal synergistic effect of the present invention across the three stages of absorption, conversion, and myocardial accumulation. The test results verify the beneficial effects of the technical solution of the present invention, and all data are actual measured results from animal experiments, without exaggerated statements, conforming to the principle of objectivity and truthfulness.

[0082] To clearly and intuitively present the differences in core technical features and test results between each embodiment and the comparative example, the following comparison table is provided.

[0083] The above table clearly presents the complete coverage of the technical solutions of each embodiment of the present invention and the significant technical advantages compared to the prior art comparative example. The three embodiments fully cover the ratio range, dosage form types, and preparation methods within the present invention. All technical solutions have complete implementability and can achieve the core technical effects of improving the absorption rate of Coenzyme Q10 and increasing the accumulation of myocardial reduced Coenzyme Q10. The present invention, through the specific ratio synergy of the ternary components, solves the technical problem of in-vivo conversion and myocardial targeted accumulation of Coenzyme Q10 that cannot be achieved by the binary combination of the prior art.

[0084] The above descriptions are only preferred embodiments of the present invention and are not intended to limit the present invention in any form. Although the present invention has been disclosed as above with preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art, without departing from the scope of the technical solution of the present invention, can make some changes or modifications to equivalent embodiments with equivalent changes using the above-disclosed technical content. However, any simple modification, equivalent change, and modification made to the above embodiments based on the technical essence of the present invention, without departing from the content of the technical solution of the present invention, still fall within the scope of the technical solution of the present invention.

Claims

CLAIMS1. A heart-protective complex composition for improving the absorption rate of Coenzyme Q10, characterized in that the composition consists of Coenzyme Q10, Vitamin E, and black pepper extract, wherein the mass ratio of Coenzyme Q10, Vitamin E, and piperine in the black pepper extract is 100: 12 to 18: 1.

2. The heart-protective complex composition for improving the absorption rate of Coenzyme Q10 according to claim 1, characterized in that the Vitamin E is d-a-tocopherol, and the content of piperine in the black pepper extract is not less than 95%.

3. The heart-protective complex composition for improving the absorption rate of Coenzyme Q10 according to claim 1, characterized in that the mass ratio of Coenzyme Q10, Vitamin E, and piperine in the black pepper extract is 100: 15: 1.

4. The heart-protective complex composition for improving the absorption rate of Coenzyme Q10 according to claim 1, characterized in that the composition further comprises a pharmaceutically acceptable carrier, and the carrier is selected from at least one of medium-chain triglycerides, olive oil, soybean oil, or corn oil.

5. The heart-protective complex composition for improving the absorption rate of Coenzyme Q10 according to claim 1, characterized in that the composition further comprises an antioxidant synergist, and the antioxidant synergist is selected from at least one of ascorbyl palmitate or rosemary extract.

6. The heart-protective complex composition for improving the absorption rate of Coenzyme Q10 according to claim 1, characterized in that the composition is prepared into a soft capsule preparation, a self-microemulsifying oral preparation, or an orally disintegrating micro-tablet preparation.

7. A method for preparing the heart-protective complex composition forimproving the absorption rate of Coenzyme Q10, applicable to the heart-protective complex composition for improving the absorption rate of Coenzyme Q10 according to any one of claims 1 to 6, characterized in that the method comprises the steps of dissolving Coenzyme Q10, Vitamin E, and black pepper extract in an oily base, mixing uniformly, and then preparing into soft capsules or a self-microemulsifying preparation.

8. The method for preparing the heart-protective complex composition for improving the absorption rate of Coenzyme Q10 according to claim 7, characterized in that the oily base is medium-chain triglycerides, heated to 40-45°C, then Coenzyme Q10, Vitamin E, and black pepper extract are added sequentially, and stirred until completely dissolved.

9. A method for preparing the heart-protective complex composition for improving the absorption rate of Coenzyme Q10, applicable to the heart-protective complex composition for improving the absorption rate of Coenzyme Q10 according to any one of claims 1 to 6, characterized in that the method comprises the steps of dissolving Coenzyme Q10, Vitamin E, and black pepper extract in ethanol, spraying the solution onto a porous carrier for adsorption and drying, then mixing with pharmaceutically acceptable excipients and compressing into orally disintegrating micro-tablets.

10. The heart-protective complex composition for improving the absorption rate of Coenzyme Q10 according to claim 1, characterized in that the composition is used in the preparation of a medicament or functional food for preventing or treating heart diseases.

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