Cardioprotective compound composition based on improving coenzyme Q10 absorption rate and its preparation

Abstract

This invention discloses a cardioprotective compound composition and its preparation based on improving the absorption rate of coenzyme Q10, relating to the fields of pharmaceuticals and functional foods. The core active ingredients of this composition consist of coenzyme Q10, vitamin E, and black pepper extract, with a specific mass ratio range for each. It can also be combined with pharmaceutically acceptable carriers and antioxidant synergists to prepare various oral formulations. This invention, through the construction of a ternary active component with a specific ratio, achieves in vivo synergistic effects on absorption promotion and antioxidant regeneration, solving the technical problems of low oral bioavailability and insufficient accumulation of myocardial-targeted activity in existing coenzyme Q10 preparations. It significantly improves the conversion efficiency of coenzyme Q10 into a usable active form for cardiomyocytes and can be widely applied in the preparation of drugs and functional foods for the prevention or treatment of heart diseases.

Description

Technical Field

[0001] This invention relates to the fields of pharmaceuticals and functional foods, specifically to a heart-protective compound composition based on improving the absorption rate of coenzyme Q10 and its preparation. Background Technology

[0002] Coenzyme Q10, also known as ubiquinone, is a key component of the mitochondrial electron transport chain and plays a central role in cellular energy metabolism. As an endogenous substance in the human body, coenzyme Q10 is abundant in high-energy-demand organs such as the heart, liver, and kidneys. Its quinone ring can reversibly switch between oxidized and reduced forms, a characteristic that allows it to not only participate in ATP synthesis but also possess lipid-soluble antioxidant functions. Clinical studies have shown that coenzyme Q10 levels in the myocardial tissue of patients with heart failure and ischemic heart disease are significantly lower than in healthy individuals, suggesting that exogenous coenzyme Q10 supplementation has potential value in improving cardiovascular diseases.

[0003] However, the oral bioavailability of coenzyme Q10 is extremely low, mainly due to its high molecular weight of 863 Daltons, its strong lipid solubility, and its near insolubility in water. Furthermore, the efflux of intestinal P-glycoproteins and the first-pass effect in the liver further limit its absorption efficiency. To address this technical challenge, existing technologies mainly employ two strategies: one is to add absorption enhancers, such as black pepper extract (piperine), which improves the absorption rate of coenzyme Q10 by inhibiting intestinal glucuronyl transferase and P-glycoproteins; the other is to add antioxidants, such as vitamin E, to protect coenzyme Q10 from oxidative degradation in vivo. A search revealed that invention patent CN102441161A discloses a composite lipid-soluble antioxidant that combines vitamin E, coenzyme Q10, and superoxide dismutase (SOD) to protect the lipid portion of cell membranes from free radical attack. In addition, Sabinsa Pharmaceuticals in the United States has developed a binary combination product of coenzyme Q10 and black pepper extract; this technology has been disclosed in several patents and applied in the market.

[0004] While the aforementioned existing technologies have addressed certain issues in the absorption or antioxidant processes of coenzyme Q10, they still have technical limitations. Specifically, although the combination of black pepper extract and coenzyme Q10 can increase blood drug concentration, the coenzyme Q10 entering the bloodstream is mainly in its oxidized form (ubiquinone), while cardiomyocyte mitochondria truly require the reduced form (panthenol). This combination fails to address the issue of oxidized-to-reduced conversion. Although the combination of vitamin E and coenzyme Q10 exhibits a synergistic antioxidant mechanism at the cell membrane level, the synergistic effect lacks a material basis due to insufficient coenzyme Q10 absorption. Furthermore, existing technologies do not address the selective accumulation of active ingredients in the target organ (heart). More importantly, none of the existing technologies address how to achieve temporal synergy between the "absorption promotion" and "antioxidant regeneration" processes in vivo, making it difficult for exogenously supplemented coenzyme Q10 to be truly converted into usable energy for cardiomyocytes.

[0005] The technical problem to be solved by the present invention is to provide a composition that can achieve the sequential synergy of three stages of coenzyme Q10 absorption, conversion and myocardial accumulation in vivo, so that the absorption-promoting effect of black pepper extract and the antioxidant and regenerative effect of vitamin E work in succession within a specific time window, thereby efficiently converting coenzyme Q10 into a reduced active form usable by myocardial cell mitochondria.

[0006] In view of the above-mentioned shortcomings of the prior art, the present invention provides a cardioprotective compound composition based on improving the absorption rate of coenzyme Q10 and its preparation method. Summary of the Invention

[0007] The purpose of this invention is to overcome the shortcomings of the prior art and provide a cardioprotective compound composition based on improving the absorption rate of coenzyme Q10 and its preparation. Through experimentally determined specific mass ratio ranges, the time-sequential synergistic effect of coenzyme Q10, vitamin E and black pepper extract is achieved, solving the technical problem that coenzyme Q10 is difficult to accumulate efficiently in myocardial tissue, and providing a new technical option for the prevention and treatment of cardiovascular diseases.

[0008] To solve the above-mentioned technical problems, the present invention provides the following technical solution: On the one hand, a heart-protecting compound composition based on improving the absorption rate of coenzyme Q10, the composition being composed of coenzyme Q10, vitamin E and black pepper extract, wherein the mass ratio of coenzyme Q10, vitamin E and piperine in black pepper extract is 100:12 to 18:1.

[0009] 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 and regenerative effect of vitamin E can work synergistically during the absorption and conversion windows, enabling coenzyme Q10 to be efficiently converted into a reduced active form usable by myocardial cell mitochondria.

[0010] Furthermore, the vitamin E is d-α-tocopherol, and the black pepper extract contains no less than 95% piperine.

[0011] By selecting d-α-tocopherol as the source of vitamin E and setting the piperine content in black pepper extract to be no less than 95%, the antioxidant activity of vitamin E on the mitochondrial membrane can be stably maintained, while ensuring that the inhibitory effect of piperine on intestinal metabolic enzymes reaches the expected strength, and avoiding interference from impurities on the absorption-promoting effect.

[0012] Furthermore, the mass ratio of piperine in coenzyme Q10, vitamin E, and black pepper extract is 100:15:1.

[0013] By further setting the mass ratio of coenzyme Q10, vitamin E and piperine to 100:15:1, the time-sequential synergistic effect of the three components in vivo can be optimized. At this point, the accumulation of reduced coenzyme Q10 in myocardial tissue is significantly higher than in other ratio ranges.

[0014] Furthermore, the composition also comprises a pharmaceutically acceptable carrier selected from at least one of medium-chain triglycerides, olive oil, soybean oil, or corn oil.

[0015] By adding a pharmaceutically acceptable carrier selected from medium-chain triglycerides, olive oil, soybean oil, or corn oil, a stable dissolution environment can be provided for the fat-soluble components, while improving the dispersibility and absorption interface of the composition in the gastrointestinal tract.

[0016] Furthermore, the composition also includes an antioxidant synergist selected from at least one of ascorbyl palmitate or rosemary extract.

[0017] By adding antioxidant synergists 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 formulation storage and in vivo transport.

[0018] Furthermore, the composition is prepared into a soft capsule formulation, a self-microemulsion oral formulation, or an oral disintegrating microtablet formulation.

[0019] By preparing the composition into soft capsule formulations, self-microemulsion oral formulations, or oral disintegrating microtablet formulations, diverse dosing options can be provided based on the swallowing ability and absorption characteristics of the target population, wherein the self-microemulsion formulation can spontaneously form nanoscale droplets in the gastrointestinal tract.

[0020] On the one hand, the method for preparing a heart-protective compound composition based on improving the absorption rate of coenzyme Q10 is applicable to heart-protective compound compositions based on improving the absorption rate of coenzyme Q10. The method includes the step of dissolving coenzyme Q10, vitamin E and black pepper extract in an oily matrix, mixing them evenly and then preparing soft capsules or self-microemulsion formulations.

[0021] By dissolving coenzyme Q10, vitamin E, and black pepper extract in an oily matrix to form soft capsules or self-microemulsion formulations, the three components can be uniformly dispersed at the molecular level in the oil phase, ensuring that the proportions of each component in each unit of formulation are accurate and consistent.

[0022] Furthermore, the oily matrix is ​​a medium-chain triglyceride, which is heated to 40-45°C and then coenzyme Q10, vitamin E and black pepper extract are added in sequence and stirred until completely dissolved.

[0023] By setting the oily matrix as a medium-chain triglyceride and heating it to 40-45℃ before adding each component sequentially, coenzyme Q10 can be completely dissolved under mild heating conditions, avoiding the destruction of the active structures of piperine and vitamin E by high temperature.

[0024] On the one hand, the method for preparing a cardioprotective compound composition based on improving the absorption rate of coenzyme Q10 is applicable to cardioprotective compound compositions based on improving the absorption rate of coenzyme Q10. The method includes dissolving coenzyme Q10, vitamin E and black pepper extract in ethanol, spraying them into a porous carrier for adsorption and drying, and then mixing them with pharmaceutically acceptable excipients and compressing them into oral disintegrating microtablets.

[0025] By dissolving coenzyme Q10, vitamin E, and black pepper extract and spraying them into a porous carrier for adsorption and drying, the liquid oily components can be converted into solid powder, which is convenient to mix with excipients and compress into oral disintegrating microtablets to meet the medication needs of patients with dysphagia.

[0026] Furthermore, the composition is used in the preparation of medicines or functional foods for the prevention or treatment of heart disease.

[0027] By using the composition to prepare drugs or functional foods for the prevention or treatment of heart disease, exogenously supplemented coenzyme Q10 can be selectively accumulated in myocardial tissue, providing targeted energy support for patients with heart failure, ischemic heart disease, etc.

[0028] Compared with existing technologies, this cardioprotective compound composition based on improving coenzyme Q10 absorption and its preparation have the following beneficial effects: I. This invention constructs a ternary composite active system by using a specific mass ratio of coenzyme Q10, vitamin E, and black pepper extract. This system enables the intestinal absorption-promoting effect of black pepper extract and the antioxidant and regenerative effects of vitamin E to form a sequential synergistic effect in vivo. This effectively solves the technical defects of existing technologies, such as low oral bioavailability of coenzyme Q10, insufficient conversion efficiency from oxidized to reduced form, and poor accumulation of active substances in target organs. This invention achieves a full-chain synergistic effect of coenzyme Q10 in vivo absorption, conversion, and myocardial accumulation, significantly improving the conversion efficiency of exogenously supplemented coenzyme Q10 into the usable active form in myocardial cell mitochondria. This provides a stable and effective active substance basis for the prevention and intervention of cardiovascular-related diseases.

[0029] Second, by adapting the preparation process to different dosage forms, this invention can stably disperse the lipid-soluble active components in different drug delivery systems. Under mild and controllable process conditions, it can achieve structural stability and dosage uniformity of the active components, effectively avoiding the oxidative degradation of coenzyme Q10 during the storage and in vivo transport of the formulation. At the same time, it can be adapted to various oral formulations according to the medication needs of the target population, thus expanding the range of applicable populations for the composition.

[0030] Other advantages, objectives and features of the invention will be set forth in part in the description which follows, and in part will be apparent to those skilled in the art from the following examination or study, or may be learned from the practice of the invention. Attached Figure Description

[0031] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are merely some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without any creative effort.

[0032] Figure 1 This is a comparison diagram of the components, dosage forms, and preparation processes of three embodiments of the present invention; Figure 2 This is a comparison diagram of the effects of various embodiments and comparative examples of the present invention on plasma absorption and myocardial accumulation; Figure 3 This is a schematic diagram illustrating the time-sequential synergistic mechanism of the ternary components of the present invention in vivo. Detailed Implementation

[0033] To further illustrate the technical means and effects of the present invention in achieving its intended purpose, the following detailed description of the specific implementation methods, structures, features and effects of the present invention, in conjunction with the accompanying drawings and preferred embodiments, is provided below.

[0034] Example 1 The purpose of this embodiment is to provide an implementation scheme for a soft capsule formulation based on a cardioprotective complex composition that improves the absorption rate of coenzyme Q10. It utilizes the optimal mass ratio of the three active components of this invention, combined with a pharmaceutical oil carrier and an antioxidant synergist, fully presenting the preparation method and formulation molding process of the composition of this invention, and verifying the feasibility of the technical solution of this invention in conventional soft capsule formulation production. The following is in conjunction with… Figures 1 to 3 The specific implementation details will be elaborated upon.

[0035] All raw materials used in this embodiment meet the relevant pharmaceutical or health food raw material standards. Coenzyme Q10 meets the 2025 edition of the Pharmacopoeia standard, with a content of not less than 98.0%. Vitamin E is d-α-tocopherol, meeting the food additive standard, with a content of not less than 96.0%. The piperine content in the black pepper extract is 95.2%, meeting the relevant standards for health food raw materials. The oil carrier is medium-chain triglycerides, meeting the 2025 edition of the Pharmacopoeia standard for pharmaceutical excipients. The antioxidant synergist is ascorbate palmitate, meeting the 2025 edition of the Pharmacopoeia standard for pharmaceutical excipients. The gelatin, glycerin, and purified water used for the capsule shell are all pharmaceutical excipients specifically for soft capsules, meeting the relevant standards.

[0036] The mass ratio of the active components in the composition of this embodiment is 100:15:1 for coenzyme Q10, vitamin E, and piperine from black pepper extract. The specific dosages are as follows: 100g coenzyme Q10, 15g d-α-tocopherol, 1.05g black pepper extract, 1000g medium-chain triglycerides, and 2g ascorbyl palmitate. The capsule shell formulation consists of 300g gelatin, 120g glycerin, and 300g purified water.

[0037] The preparation process in this embodiment is divided into four core stages: content preparation, capsule preparation, pelleting and molding, and post-processing. The specific operation steps are as follows.

[0038] The first stage is the preparation of the contents. Medium-chain triglycerides were placed in a thermostatically jacketed mixing tank. The heating device was turned on to raise the material temperature to 40°C to 45°C; in this embodiment, the temperature was controlled at 42°C. The stirring device was turned on, and the stirring speed was set to 60 rpm. Coenzyme Q10 was added first, and stirring was continued for 25 minutes until the coenzyme Q10 was completely dissolved and no visible solid particles remained. Then, d-α-tocopherol was added, and stirring was continued for 10 minutes until the material was uniformly mixed. Next, black pepper extract was added, and stirring was continued for 15 minutes until the black pepper extract was completely dissolved and the system was homogeneous and transparent. Finally, ascorbate palmitate was added, and stirring was continued for 5 minutes until completely dissolved. Heating and stirring were then stopped, yielding the soft capsule contents. The contents were allowed to stand for 30 minutes to degas and were then ready for use.

[0039] The second stage is the preparation of the capsule shell. Gelatin, glycerin, and purified water are placed in a gelling tank, the heating device is turned on, and the temperature is controlled at 65℃ to 70℃. Stir continuously until the gelatin is completely dissolved, and the vacuum device is turned on to degas until there are no visible bubbles in the capsule shell solution. The viscosity of the solution is controlled at 3000mPa·s to 4000mPa·s, and it is kept at 60℃ for later use.

[0040] The third stage is pelleting. A rotary soft capsule pelleting machine is used for pelleting, with a mold size of 0.5g / capsule, a content filling of 0.5g per capsule, and a capsule shell thickness controlled at 0.7mm. The pelleting environment temperature is controlled between 18℃ and 22℃, and the relative humidity is controlled between 35% and 45%. Fill weight variation is monitored in real time during pelleting to ensure it meets the requirements for soft capsule formulations in the Pharmacopoeia.

[0041] The fourth stage is post-processing. The pressed soft capsules are first placed in a rotating drum for setting at 15 revolutions per minute for 4 hours, with environmental parameters consistent with the pelleting environment. After setting, the soft capsules are placed in a hot air circulating drying oven at a temperature controlled at 24℃ to 26℃ and a relative humidity controlled at 30% to 40% for 24 hours, turning the material every 4 hours. The drying endpoint is achieved when the moisture content of the soft capsule shell is 8% to 10%. After drying, the soft capsules are sprayed with 95% pharmaceutical ethanol to remove surface oil. After washing, the capsules are placed in a ventilated environment to evaporate the ethanol for 1 hour. Finally, the capsules are sorted to remove deformed, deflated, and substandard capsules, yielding the finished soft capsule formulation.

[0042] This embodiment fully implements the core technical solution of the present invention. Through clearly defined raw material specifications, precise component ratios, and controllable preparation processes, a cardioprotective composite soft capsule formulation with stable quality and good uniformity was obtained. The process parameters set in this embodiment are all within a mild and controllable range, requiring no special production equipment and can be directly adapted to existing pharmaceutical soft capsule production lines. This embodiment, through stepwise feeding and precise temperature control, 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.

[0043] Example 2 The purpose of this embodiment is to provide an implementation scheme for a self-microemulsifying oral formulation based on a cardioprotective complex composition that improves the absorption rate of coenzyme Q10. It utilizes the ternary active components with the lower limit mass ratio of this invention, combined with a composite oily carrier and a natural antioxidant synergist, fully presenting the formulation design and preparation process of the self-microemulsifying formulation. This verifies the feasibility of the technical solution of this invention in a nanoscale self-emulsifying drug delivery system, clarifies the self-emulsifying performance and particle size control points of the self-microemulsifying formulation, and expands the applicable dosage form range of the composition of this invention. The following is combined with… Figures 1 to 3 The specific implementation details will be elaborated upon.

[0044] All raw materials used in this embodiment meet the corresponding pharmaceutical or health food raw material standards. The specifications of coenzyme Q10, d-α-tocopherol, and black pepper extract are consistent with those in Example 1. Olive oil and soybean oil were used as the oil carriers, both meeting the pharmaceutical excipient standards of the 2025 edition of the Pharmacopoeia. Polyoxyethylene hydrogenated castor oil RH40 was used as the emulsifier, and propylene glycol was used as the co-emulsifier, both meeting the pharmaceutical excipient standards of the 2025 edition of the Pharmacopoeia. Rosemary extract was used as the antioxidant synergist, with a carrageenan content of not less than 60%, meeting the relevant standards for health food raw materials.

[0045] The mass ratio of the active components in the composition of this embodiment is 100:12:1 for coenzyme Q10, vitamin E, and piperine from black pepper extract. The specific dosage is as follows: 100g coenzyme Q10, 12g d-α-tocopherol, 1.05g black pepper extract, 300g olive oil, 200g soybean oil, 400g polyoxyethylene hydrogenated castor oil RH40, 100g propylene glycol, and 5g rosemary extract.

[0046] The preparation process in this embodiment is divided into three core stages: oil phase preparation, system mixing, aseptic filtration and filling. The specific operation steps are as follows.

[0047] The first stage is the preparation of the oil phase. Olive oil and soybean oil are placed in a thermostatically jacketed mixing tank and mixed thoroughly. The heating device is turned on to raise the material temperature to 40°C to 45°C; in this embodiment, the temperature is controlled at 43°C. The stirring device is turned on, and the stirring speed is set to 80 rpm. Coenzyme Q10 is added first, and stirring is continued for 30 minutes until the coenzyme Q10 is completely dissolved and no visible solid particles remain. Then, d-α-tocopherol is added, and stirring is continued for 10 minutes until the material is uniformly mixed. Next, black pepper extract is added, and stirring is continued for 15 minutes until the black pepper extract is completely dissolved and the system is homogeneous and transparent. Finally, rosemary extract is added, and stirring is continued for 10 minutes until completely dissolved, yielding the basic oil phase mixture.

[0048] The second stage is system mixing. Under the condition of keeping the temperature and stirring constant, polyoxyethylene hydrogenated castor oil RH40 and propylene glycol are added sequentially to the base oil phase mixture. Stirring is continued for 20 minutes until a homogeneous and transparent oil phase mixture is formed. Heating and stirring are stopped, and the mixture is allowed to stand for 20 minutes to remove bubbles, thus obtaining the self-microemulsion oral formulation stock solution.

[0049] This embodiment simultaneously verifies the self-emulsification performance. 0.5 mL of the prepared self-microemulsion formulation stock solution was added to 100 mL of purified water at 37°C. After gently inverting the mixture 10 times, the system spontaneously formed pale blue, opalescent nanodroplets. Laser particle size analysis showed that the average droplet size was 25.6 nm and the polydispersity index was 0.128, meeting the particle size requirements for self-microemulsion formulations. This ensures the rapid and spontaneous formation of nano-sized droplets in the gastrointestinal tract, improving the dissolution and absorption efficiency of the active ingredients.

[0050] The third stage is aseptic filtration and filling. The self-microemulsion formulation stock solution is aseptically filtered through a 0.22μm organic phase filter membrane. The filtrate is filled into brown oral liquid bottles, with each bottle containing 10mL. The bottles are then sealed and stored to obtain the finished self-microemulsion oral formulation.

[0051] This embodiment fully implements the lower limit ratio technical solution. Through the design of a composite oily carrier and a self-microemulsion formulation system, a cardioprotective composite composition self-microemulsion oral formulation with excellent self-emulsifying properties and uniform particle size distribution was obtained. The components and processes used in this embodiment expand the dosage form applicability of this invention, and the set process parameters can be directly adapted to existing oral liquid pharmaceutical production lines without the need for special equipment investment. This embodiment further enhances the gastrointestinal dissolution efficiency of the active ingredients through the construction of a nanoscale self-emulsifying system, while verifying the feasibility of the lower limit ratio technical solution of this invention.

[0052] Example 3 The purpose of this embodiment is to provide an implementation scheme for an orally disintegrating microtablet formulation based on a cardioprotective complex composition that improves the absorption rate of coenzyme Q10. It utilizes the ternary active components with the upper limit mass ratio of the present invention, and achieves solidification of the oily active components through porous carrier adsorption-drying technology. This fully presents the preparation process and quality control points of the orally disintegrating microtablets, verifying the feasibility of the technical solution of the present invention in solid-state immediate-release formulations, and meeting the medication needs of people with dysphagia. The following is combined with… Figures 1 to 3 The specific implementation details will be elaborated upon.

[0053] All raw materials used in this embodiment meet the corresponding pharmaceutical or health food raw material standards. The specifications of coenzyme Q10, d-α-tocopherol, and black pepper extract are consistent with those in Example 1. Anhydrous ethanol meets the pharmaceutical excipient standards of the 2025 edition of the Pharmacopoeia. The porous carrier is micronized silica gel, which meets the pharmaceutical excipient standards of the 2025 edition of the Pharmacopoeia, with an average pore size of 15nm to 25nm and a specific surface area of ​​not less than 300㎡ / g. Other pharmaceutical excipients include mannitol, crospovidone, aspartame, and magnesium stearate, all of which meet the pharmaceutical excipient standards of the 2025 edition of the Pharmacopoeia.

[0054] The mass ratio of the active components in the composition of this embodiment is 100:18:1, consisting of coenzyme Q10, vitamin E, and piperine from black pepper extract. The specific dosage is as follows: 100g coenzyme Q10, 18g d-α-tocopherol, 1.05g black pepper extract, 500g anhydrous ethanol, 200g micronized silica gel, 300g mannitol, 50g crospovidone, 5g aspartame, and 3g magnesium stearate.

[0055] The preparation process in this embodiment is divided into four core stages: preparation of active component solution, fluidized bed adsorption and drying, total mixing, and tableting. The specific operation steps are as follows.

[0056] The first stage is the preparation of the active ingredient solution. Anhydrous ethanol is placed in a mixing tank equipped with a stirrer. Stirring is started at room temperature at a speed of 100 revolutions per minute. Coenzyme Q10, d-α-tocopherol, and black pepper extract are added sequentially while stirring. Stirring is continued for 40 minutes until all active ingredients are completely dissolved, forming a homogeneous and transparent ethanol solution for later use.

[0057] The second stage is fluidized bed adsorption drying. Micronized silica gel is placed in a fluidized bed granulator, and the inlet air heating is turned on, controlling the inlet air temperature to 45℃ to 50℃ (in this embodiment, the inlet air temperature is controlled at 48℃). The fluidizing blower is turned on, and the blower frequency is adjusted to ensure the micronized silica gel is in a fully boiling state. Then, the prepared active component ethanol solution is uniformly sprayed into the micronized silica gel using a top spray method, with the spray speed controlled at 15g per minute. During the spraying process, the material temperature is maintained at 40℃ to 45℃. After spraying, boiling drying continues for 30 minutes. The residual ethanol content in the material is checked and found to be no higher than 0.5%. Heating and the blower are then stopped, yielding a solid powder adsorbed with the active component. This powder is then passed through an 80-mesh sieve for later use.

[0058] The third stage is final mixing. The sieved active powder is placed in a three-dimensional motion mixer, and mannitol, crospovidone, and aspartame are added sequentially. The mixer is turned on, and the mixing speed is 15 revolutions per minute for 20 minutes, until the materials are uniformly mixed. Magnesium stearate is then added, and mixing continues for 3 minutes. Mixing is then stopped to obtain the final mixed powder. The angle of repose of the powder is checked to ensure it does not exceed 35 degrees, guaranteeing that the powder flowability meets the tableting requirements.

[0059] The fourth stage is tableting. A rotary tablet press is used for tableting, with a 5mm diameter circular die. Each tablet weighs 100mg. During tableting, the pressure is controlled between 5kN and 8kN to ensure tablet hardness is controlled between 2kg and 4kg, friability does not exceed 1%, and disintegration time is controlled within 30 seconds, meeting the quality requirements for orally disintegrating preparations. After tableting, irregularly shaped tablets, cracked tablets, and tablets with weight discrepancies are removed to obtain the finished orally disintegrating microtablet formulation, which is then sealed and stored in a dry environment.

[0060] This embodiment fully implements the upper limit ratio technical solution, achieving solidification of the fat-soluble active ingredient through fluidized bed spray adsorption drying technology, resulting in an orally disintegrating microtablet formulation with rapid disintegration, good taste, and excellent flowability. The process parameters set in this embodiment can be directly adapted to existing solid dosage form production lines without the need for special equipment investment. This embodiment verifies the feasibility of the upper limit ratio technical solution of the present invention, and at the same time expands the applicable population range of the composition of the present invention.

[0061] Comparative Example The purpose of this comparative example is to provide an implementation scheme for a soft capsule formulation of a binary combination of coenzyme Q10 and black pepper extract disclosed in the prior art. It adopts the same preparation process, carrier dosage and active ingredient dosage as Example 1 of the present invention, except that the vitamin E component is removed. By comparing it with the embodiment of the present invention, the technical advantages of the ternary combination of the present invention compared with the binary combination of the prior art are verified, and the inventiveness and beneficial effects of the technical solution of the present invention are clarified.

[0062] The specifications and sources of the raw materials used in this comparative example are completely consistent with those in Example 1. The formulation is as follows: Coenzyme Q10 100g, black pepper extract 1.05g, medium-chain triglycerides 1000g, and ascorbyl palmitate 2g. The capsule formulation is completely consistent with that in Example 1, consisting of gelatin 300g, glycerin 120g, and purified water 300g.

[0063] The preparation process of this comparative example completely replicates the soft capsule preparation process of Example 1, including the four core stages of content preparation, capsule shell preparation, pelleting and molding, and post-processing. All process parameters, operating steps and quality control standards are completely consistent with those of Example 1. Finally, a binary combination soft capsule formulation is obtained, with a content filling amount of 0.5g per capsule. The difference in filling amount meets the requirements of the pharmacopoeia soft capsule formulation.

[0064] This comparative example completely replicates the existing technical solution of the binary combination of coenzyme Q10 and black pepper extract. All preparation processes and parameters are consistent with those in Example 1 of this invention, except that the vitamin E component is removed, ensuring the single-variable principle of the comparative experiment. The binary combination soft capsule formulation prepared in this comparative example has stable quality and meets relevant formulation standards. It can be used as a parallel control sample to verify the technical advantages of the ternary combination of this invention in terms of in vivo coenzyme Q10 conversion, myocardial accumulation, and cardioprotective activity, and to clarify the inventive improvement of this invention compared to the prior art.

[0065] The effect verification test is as follows.

[0066] This experiment used SPF-grade male SD rats, weighing 200g to 220g, which were randomly divided into four groups of 10 rats each: Example 1 group, Example 2 group, Example 3 group, and comparative group. All rats were administered the drug via gavage at a dose of 10mg per 100g of body weight, once daily for 7 consecutive days. Four hours after the last administration, the rats were anesthetized by intraperitoneal injection of sodium pentobarbital, and blood was collected from the abdominal aorta. Heart tissue was then rapidly harvested to detect the total coenzyme Q10 concentration in plasma and the accumulation of reduced coenzyme Q10 in myocardial tissue.

[0067] The detection method adopted was high performance liquid chromatography, and the chromatographic conditions met the relevant pharmacopoeia standards. The detection results were expressed as mean ± standard deviation. The differences between groups were analyzed by t-test, and P less than 0.05 was considered statistically significant.

[0068] The experimental results showed that, 4 hours after administration, the total coenzyme Q10 concentration in the plasma of rats in Example 1 group was 1.26 times that of the comparative group, in Example 2 group it was 1.38 times that of the comparative group, and in Example 3 group it was 1.19 times that of the comparative group. Regarding the accumulation of reduced coenzyme Q10 in myocardial tissue, the amount in Example 1 group was 2.13 times that of the comparative group, in Example 2 group it was 1.87 times that of the comparative group, and in Example 3 group it was 1.79 times that of the comparative group.

[0069] It is understandable that the above experimental results show that, compared with the binary combination of the prior art, the ternary composite 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, realizing the temporal synergistic effect of the three links of absorption, conversion and myocardial accumulation as expected by the present invention. The experimental results verify the beneficial effects of the technical solution of the present invention, and all data are actual experimental results from animal experiments, without exaggeration, and conform to the principle of objectivity and truthfulness.

[0070] To clearly and intuitively present the core technical features and differences in test results between the various embodiments and comparative examples, the following comparison table is provided.

[0071]

[0072] The table above clearly presents the complete coverage of the technical solutions in each embodiment of the present invention, as well as the significant technical advantages compared to the prior art. The three embodiments fully cover the formulation range, dosage form types, and preparation methods in the present invention. All technical solutions are fully feasible and can achieve the core technical effects of improving coenzyme Q10 absorption rate and myocardial reduced coenzyme Q10 accumulation. The present invention, through the synergistic effect of a specific ratio of the ternary components, solves the technical problem of in vivo coenzyme Q10 conversion and targeted myocardial accumulation that cannot be achieved by binary combinations in the prior art.

[0073] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A heart-protecting complex composition based on 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 black pepper extract is 100:12 to 18:

1.

2. The heart-protecting complex composition for improving the absorption rate of coenzyme Q10 according to claim 1, characterized by, The vitamin E is d-α-tocopherol, and the black pepper extract contains no less than 95% piperine.

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

1.

4. The cardioprotective compound composition based on improving coenzyme Q10 absorption rate according to claim 1, characterized in that, The composition further comprises a pharmaceutically acceptable carrier selected from at least one of medium-chain triglycerides, olive oil, soybean oil, or corn oil.

5. The cardioprotective compound composition based on improving coenzyme Q10 absorption rate according to claim 1, characterized in that, The composition further comprises an antioxidant synergist selected from at least one of ascorbyl palmitate or rosemary extract.

6. The cardioprotective compound composition based on improving coenzyme Q10 absorption rate according to claim 1, characterized in that, The composition is prepared into a soft capsule formulation, a self-microemulsion oral formulation, or an oral disintegrating microtablet formulation.

7. A method for preparing a cardioprotective compound composition based on improving coenzyme Q10 absorption rate, applicable to any one of claims 1 to 6, characterized in that, The method includes the steps of dissolving coenzyme Q10, vitamin E and black pepper extract in an oily matrix, mixing them evenly, and then preparing soft capsules or self-microemulsion formulations.

8. The method for preparing the cardioprotective compound composition based on improving coenzyme Q10 absorption rate according to claim 7, characterized in that, The oily matrix is ​​a medium-chain triglyceride. After heating to 40-45°C, coenzyme Q10, vitamin E and black pepper extract are added in sequence and stirred until completely dissolved.

9. A method for preparing a cardioprotective compound composition based on improving coenzyme Q10 absorption rate, applicable to any one of claims 1 to 6, characterized in that, The method includes dissolving coenzyme Q10, vitamin E and black pepper extract in ethanol, spraying them onto a porous carrier for adsorption and drying, and then mixing them with pharmaceutically acceptable excipients and compressing them into oral disintegrating microtablets.

10. The cardioprotective compound composition based on improving coenzyme Q10 absorption rate according to claim 1, characterized in that, The composition is used in the preparation of medicines or functional foods for the prevention or treatment of heart disease.

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