FDP cyclic adenosine monophosphate compound drink for improving myocardial energy metabolism

Abstract

The invention relates to the technical field of nutritional health-care drinks, in particular to an FDP cyclic adenosine monophosphate compound drink for improving myocardial energy metabolism. The invention relates to a red date beverage, which is composed of the following components by mass: 8 g of water, 2 g of a red date extract, 0.15 g of 1, 6-fructose diphosphate trisodium salt, 0.1 g of deer myocardial peptide powder, 0.1 g of anhydrous citric acid, 0.004 g of potassium sorbate, 0.00003 g of vitamin B1, 0.00003 g of vitamin B2, and 0.00003 g of vitamin B6. The preparation method comprises the following steps: high voltage pulse electric field treatment; constructing an ATP regeneration system: adding 0.03-0.04 g of L-carnitine and 0.006-0.008 g of creatine, carrying out ultrasonic-assisted dissolution, and then mixing with the pretreated red date extracting solution; performing energy steady-state concentration; and performing low-temperature stabilizing treatment. The invention provides the FDP cyclic adenosine monophosphate compound drink for improving myocardial energy metabolism, and the clinical application value and the market promotion potential of myocardial energy metabolism regulating products are improved.

Description

Technical Field

[0001] The present invention relates to the technical field of nutritional and health drinks, and particularly to an FDP cyclic adenosine monophosphate compound drink for improving myocardial energy metabolism. Background Art

[0002] Myocardial energy metabolism is the core physiological process maintaining normal cardiac function, which depends on the continuous supply of adenosine triphosphate (ATP) and the dynamic balance of metabolic pathways. With the influence of modern lifestyle and environmental factors, myocardial energy metabolism imbalance has become a potential inducement for various cardiovascular diseases. Currently, the intervention means for myocardial energy metabolism mainly focus on single energy substrate supplementation or metabolic enzyme regulation, such as exogenous supplementation of high-energy phosphate compounds or coenzyme substances. However, the energy metabolism network of myocardial cells has high complexity, and the mechanism of action of a single component is difficult to achieve multi-target synergistic effect, and there are significant limitations in terms of the stability of active ingredients, bioavailability, and the persistence of metabolic regulation.

[0003] In the prior art, products for improving myocardial energy metabolism often face the following problems: First, the component combination lacks systematic design, and the synergistic effects of energy substrates, metabolic cofactors, and antioxidant systems are not fully integrated, resulting in insufficient activation efficiency of metabolic pathways; Second, the preparation process has a high risk of degrading thermosensitive active ingredients (such as fructose diphosphate, peptide substances), and conventional sterilization or concentration techniques are likely to damage the molecular structure and affect the efficacy of the final product; Third, liquid preparations are prone to stratification, oxidation, or microbial contamination during storage, and the stability is difficult to meet the requirements for long-term preservation; Fourth, the oral absorption efficiency is limited by the molecular weight of the components and the transmembrane transport ability, and it is difficult to achieve targeted delivery and effective intracellular release. Summary of the Invention

[0004] The present invention provides an FDP cyclic adenosine monophosphate compound drink for improving myocardial energy metabolism, which improves the clinical application value and market promotion potential of products for regulating myocardial energy metabolism.

[0005] The technical solution adopted by the present invention is as follows: An FDP cyclic adenosine monophosphate compound drink for improving myocardial energy metabolism is composed of the following components in mass ratio: water accounts for 8 grams, red date extract accounts for 2 grams, trisodium 1,6-diphosphate fructose accounts for 0.15 grams, deer myocardial peptide powder accounts for 0.1 gram, anhydrous citric acid accounts for 0.1 gram, potassium sorbate accounts for 0.004 gram, vitamin B1 accounts for 0.00003 gram, vitamin B2 accounts for 0.00003 gram, vitamin B6 accounts for 0.00003 gram, and its preparation method includes the following steps:

[0006] S1, High-voltage pulsed electric field treatment: Apply a square wave pulse with a field strength of 15 - 28 kV / cm, a pulse width of 25 - 45 μs, a frequency of 100 - 200 Hz, and a treatment time of 5 - 8 minutes to the mixed solution;

[0007] S2, Construction of ATP regeneration system: Add 0.03 - 0.04 g of L-carnitine and 0.006 - 0.008 g of creatine, mix with the pretreated red date extract after ultrasonic-assisted dissolution;

[0008] S3, Energy homeostasis concentration: Concentrate to a solid content of 10 ± 1% at 40 - 45°C and a vacuum of -0.08 to -0.1 MPa using a rotary evaporator;

[0009] S4, Low-temperature stabilization treatment: Cool the concentrated solution to -30°C at a rate of 2 - 3°C / min, maintain for 2 hours, then quickly rewarm to 4°C, and cycle the treatment 3 times.

[0010] As a further improvement of the present invention, add 0.005 - 0.01 g of coenzyme Q10 nano-liposomes and 0.002 - 0.005 g of taurine, the particle size of the nano-liposomes ≤ 80 nm, and the encapsulation efficiency ≥ 95%.

[0011] As a further improvement of the present invention, the high-voltage pulsed electric field treatment is carried out in two stages, and the temperature is raised to 25 - 30°C at a rate of 1 - 2°C / min between the two stages,

[0012] First stage: Electric field strength 10 - 15 kV / cm, pulse width 40 - 50 μs, positive pulse;

[0013] Second stage: Electric field strength 25 - 30 kV / cm, pulse width 20 - 30 μs, bipolar pulse.

[0014] As a further improvement of the present invention, the L-carnitine and creatine are subjected to ultrafine grinding treatment, the D50 particle size ≤ 5 μm, the specific surface area ≥ 8 m 2 / g, and premixed with trisodium 1,6-diphosphate in a molar ratio of 1:3.

[0015] As a further improvement of the present invention, a freeze-drying protectant is added after the energy homeostasis concentration in step S3, the freeze-drying protectant includes 1 - 2% (w / w) of trehalose and 0.5 - 1% (w / w) of mannitol, and the mixed solution is aseptically filtered through a 0.22 μm filter and then subpackaged.

[0016] As a further improvement of the present invention, the freeze-drying procedure includes: cooling to -45°C at a rate of 4°C / min and holding for 3 hours, then sublimation drying for 18 hours under a vacuum of ≤ 5 Pa and a condenser temperature of -60°C, and finally the water activity ≤ 0.15.

[0017] Advantages of the present invention: (1) Through the scientific ratio of fructose-1,6-diphosphate trisodium salt (FDP), deer myocardial peptide powder, and vitamin B group, combined with the ATP regeneration system of L-carnitine and creatine, the present invention realizes the synergistic effect of energy substrate supply, coenzyme activation, and mitochondrial function regulation, significantly improving the activation efficiency of the myocardial cell metabolic pathway.

[0018] (2) The present invention adopts a high-voltage pulsed electric field treatment in stages and a low-temperature stabilization process. While avoiding the degradation of thermosensitive components (such as fructose diphosphate and peptides), it enhances the exposure of active sites through the optimization of molecular conformation induced by the electric field. Combining the ultra-fine grinding premixing technology and the nano-liposome encapsulation technology, it reduces the particle size of the components and increases the specific surface area, significantly improving the solubility and intestinal absorption efficiency, and ensuring the efficient release and utilization of active components in target cells.

[0019] (3) Through the combined application of energy homeostasis concentration and freeze-drying protectant, combined with the programmed freeze-drying technology, the present invention effectively inhibits the risks of oxidation stratification and microbial contamination of liquid preparations. The water activity of the final product is ≤0.15, and its physical and chemical properties can be stably maintained at room temperature for a long time. Specific embodiments

[0020] In order to make the technical problems, technical solutions, and advantages to be solved by the present application clearer, the following further details the present application with reference to embodiments. It should be understood that the embodiments described herein are only used to explain the present application and are not used to limit the present application.

[0021] The present invention provides an FDP cyclic adenosine monophosphate compound drink for improving myocardial energy metabolism, which is composed of the following components in mass ratio: 8 grams of water, 8 grams of red date extract, 0.15 grams of fructose-1,6-diphosphate trisodium salt, 0.1 gram of deer myocardial peptide powder, 0.1 gram of anhydrous citric acid, 0.004 gram of potassium sorbate, 0.00003 gram of vitamin B1, 0.00003 gram of vitamin B2, and 0.00003 gram of vitamin B6. Its preparation method includes the following steps:

[0022] S1, High-voltage pulsed electric field treatment: Apply a square wave pulse with a field strength of 15 - 28 kV / cm, a pulse width of 25 - 45 μs, a frequency of 100 - 200 Hz, and a treatment time of 5 - 8 minutes to the mixed solution;

[0023] S2, Construction of the ATP regeneration system: Add 0.03 - 0.04 grams of L-carnitine and 0.006 - 0.008 grams of creatine, and after ultrasonic-assisted dissolution, mix them with the pretreated red date extract;

[0024] S3, Energy homeostasis concentration: Concentrate to a solid content of 10 ± 1% at 40 - 45°C and a vacuum degree of -0.08 to -0.1 MPa using a rotary evaporator;

[0025] S4, Low-temperature stabilization treatment: The concentrated solution is cooled to -30°C at a rate of 2-3°C / min, maintained for 2 hours, and then rapidly rewarmed to 4°C. This cycle is repeated 3 times.

[0026] The present invention adds 0.005-0.01 g of coenzyme Q10 nanoliposomes and 0.002-0.005 g of taurine. The particle size of the nanoliposomes is ≤80 nm, and the encapsulation efficiency is ≥95%.

[0027] The high-voltage pulsed electric field treatment of the present invention is carried out in two stages. The temperature is increased to 25-30°C at a rate of 1-2°C / min between the two stages.

[0028] First stage: The electric field strength is 10-15 kV / cm, the pulse width is 40-50 μs, and the forward pulse.

[0029] Second stage: The electric field strength is 25-30 kV / cm, the pulse width is 20-30 μs, and the bipolar pulse.

[0030] The L-carnitine and creatine of the present invention are ultra-finely pulverized. The D50 particle size is ≤5 μm, the specific surface area is ≥8 m 2 / g, and premixed with trisodium 1,6-diphosphate in a molar ratio of 1:3.

[0031] The present invention adds a freeze-drying protectant after the energy steady-state concentration in step S3. The freeze-drying protectant includes 1-2% (w / w) of trehalose and 0.5-1% (w / w) of mannitol. The mixed solution is aseptically filtered through a 0.22 μm filter and then sub-packed.

[0032] The freeze-drying procedure of the present invention includes: cooling to -45°C at a rate of 4°C / min and holding for 3 hours, then sublimation drying for 18 hours under the conditions of a vacuum degree ≤5 Pa and a condenser temperature of -60°C, and finally the water activity ≤0.15.

[0033] Example:

[0034] Raw material preparation: Accurately weigh according to the mass ratio: 8 g of water, 2 g of red date extract, 0.15 g of trisodium 1,6-diphosphate, 0.1 g of deer myocardial peptide powder, 0.1 g of anhydrous citric acid, 0.004 g of potassium sorbate, 0.00003 g of vitamin B1, 0.00003 g of vitamin B2, 0.00003 g of vitamin B6, and the freeze-drying protectant: 1.5% (w / w) of trehalose, 0.8% (w / w) of mannitol.

[0035] Step 1, High-voltage pulsed electric field treatment in stages

[0036] Premix FDP, deer myocardial peptide powder and red date extract, and inject them into the pulse treatment chamber (electrode spacing 5 mm). First stage: Apply a forward square wave pulse with a field strength of 12 kV / cm, a pulse width of 45 μs, a frequency of 150 Hz, and a treatment time of 3 minutes. During this period, the solution temperature rises from 20 °C to 25 °C. Second stage: Heat up to 28 °C at a rate of 1.5 °C / min, switch to a bipolar pulse with a field strength of 28 kV / cm and a pulse width of 25 μs, a frequency of 200 Hz, and a treatment time of 5 minutes.

[0037] Step 2, construction of the ATP regeneration system

[0038] Premix L-carnitine and creatine at a molar ratio of 1:3 (0.035 g:0.007 g), and use a jet mill (pressure 0.8 MPa) to process until D50 = 4.0 μm and the specific surface area is 8.5 m 2 / g. Add the ultrafine powder, coenzyme Q10 nanoliposomes, and taurine to the premixed solution, and disperse for 15 minutes under 40 kHz ultrasonic waves (power 300 W) to form a homogeneous colloid.

[0039] Step 3, energy steady-state concentration

[0040] Use a rotary evaporator (Buchi R-300), set the vacuum degree to -0.09 MPa and the temperature to 42 °C, and concentrate to a solid content of 10.2%. Add freeze-drying protectants (1.5% trehalose, 0.8% mannitol), and filter aseptically through a 0.22 μm PVDF membrane.

[0041] Step 4, programmed freeze-drying

[0042] Subpackage into 5 mL vials, with 3 mL in each vial. Pre-freezing stage: Cool down to -45 °C at a rate of 4 °C / min and maintain for 3 hours to form a glassy state. Sublimation drying: Vacuum degree 4.8 Pa, condenser -60 °C, the heating plate is heated with a gradient (0 → 25 °C / 8 h), and continue for 18 hours. Desorption drying: Keep at 35 °C for 2 hours, the final water activity is 0.13, and the water content ≤ 1.5%.

[0043] Step 5, low-temperature stabilization treatment

[0044] After re-dissolving the freeze-dried powder, cool down to -30 °C at a rate of 2.5 °C / min, maintain for 2 hours, and then place in a 4 °C water bath (rewarm within 30 seconds), and cycle 3 times to form a stable micelle structure.

[0045] Performance verification

[0046] Stability test: (1) Accelerated test (40°C / 75% RH, 3 months): The retention rate of FDP was 98.2%, and the retention rate of coenzyme Q10 was 94.5%, without stratification or oxidation discoloration. (2) Solubility: The lyophilized powder was completely dissolved in water at 37°C within 30 seconds, and the dispersion coefficient (PDI) ≤ 0.15.

[0047] Cell experiment: An H9C2 cardiomyocyte hypoxia model (1% O2, 24 h) was used: (1) ATP level: The ATP level in the experimental group was increased by 2.8 times compared with the control group (p < 0.01); (2) Mitochondrial membrane potential: The ratio of red to green fluorescence of JC-1 was increased by 67% (ΔΨm was restored to 82% of the normal level).

[0048] Animal experiment: SD rats (n = 30) were given intragastric administration (50 mg / kg·d, 4 weeks): (1) Myocardial ischemia-reperfusion injury model: The infarct area in the experimental group was reduced by 41%, and the serum LDH was decreased by 58%; (2) Echocardiogram: The left ventricular ejection fraction (LVEF) was increased from 45.3 ± 3.2% to 62.1 ± 4.1%.

[0049] As can be seen from the above examples, the FDP cyclic adenosine monophosphate compound drink of the present invention exhibits excellent performance in terms of stability, solubility, cell level, and animal experiments. It can effectively increase the ATP level of cardiomyocytes, restore the mitochondrial membrane potential, significantly reduce the myocardial infarction area, and improve cardiac function, and truly provides an efficient and stable nutritional and health drink solution for the prevention and treatment of diseases related to myocardial energy metabolism imbalance.

[0050] In summary, the FDP cyclic adenosine monophosphate compound drink for improving myocardial energy metabolism of the present invention solves many problems existing in the prior art in improving myocardial energy metabolism products through a unique component ratio and an advanced preparation process. It has a significant synergistic effect, good stability of active ingredients, high bioavailability, and long-lasting metabolic regulation, providing a new effective way for the prevention and treatment of cardiovascular diseases and is expected to achieve good results in clinical application and market promotion.

[0051] The above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions recorded in the foregoing embodiments, or perform equivalent replacements for some of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. An FDP cyclic adenosine monophosphate compound drink for improving myocardial energy metabolism, characterized in that It is composed of components with the following mass ratios: water accounts for 8 grams, red date extract accounts for 2 grams, fructose 1,6-diphosphate trisodium salt accounts for 0.15 grams, deer myocardial peptide powder accounts for 0.1 gram, anhydrous citric acid accounts for 0.1 gram, potassium sorbate accounts for 0.004 gram, vitamin B1 accounts for 0.00003 gram, vitamin B2 accounts for 0.00003 gram, vitamin B6 accounts for 0.00003 gram, and its preparation method includes the following steps: S1, High-voltage pulsed electric field treatment: Apply a square wave pulse with a field strength of 15 - 28 kV / cm, a pulse width of 25 - 45 μs, a frequency of 100 - 200 Hz, and a treatment time of 5 - 8 minutes to the mixed solution; S2, Construction of ATP regeneration system: Add 0.03 - 0.04 grams of L-carnitine and 0.006 - 0.008 grams of creatine, and after ultrasonic-assisted dissolution, mix with the pretreated red date extract; S3, Energy homeostasis concentration: Concentrate to a solid content of 10 ± 1% at 40 - 45°C and a vacuum degree of -0.08 to -0.1 MPa using a rotary evaporator; S4, Low-temperature stabilization treatment: Cool the concentrated solution at a rate of 2 - 3°C / min to -30°C, maintain for 2 hours, and then quickly rewarm to 4°C, and cycle the treatment 3 times.

2. The FDP cyclic adenosine monophosphate compound drink for improving myocardial energy metabolism according to claim 1, characterized in that, Add 0.005 - 0.01 grams of coenzyme Q10 nanoliposomes and 0.002 - 0.005 grams of taurine, and the particle size of the nanoliposomes is ≤80 nm, and the encapsulation efficiency is ≥95%.

3. The FDP cyclic adenosine monophosphate compound drink for improving myocardial energy metabolism according to claim 1, characterized in that The high-voltage pulsed electric field treatment is carried out in two stages, and the temperature is raised to 25 - 30°C at a rate of 1 - 2°C / min between the two stages, The first stage: The field strength is 10 - 15 kV / cm, the pulse width is 40 - 50 μs, and it is a positive pulse; The second stage: The field strength is 25 - 30 kV / cm, the pulse width is 20 - 30 μs, and it is a bidirectional pulse.

4. The FDP cyclic adenosine monophosphate compound drink for improving myocardial energy metabolism according to claim 1, wherein The L-carnitine and creatine are subjected to ultrafine comminution treatment, with a D50 particle size ≤ 5 μm, a specific surface area ≥ 8 m 2 / g, and premixed with trisodium 1,6-diphosphate in a molar ratio of 1:

3.

5. The FDP cyclic adenosine monophosphate compound drink for improving myocardial energy metabolism according to claim 1, wherein Add a freeze-drying protectant after the energy homeostasis concentration in step S3. The freeze-drying protectant includes 1 - 2% (w / w) of trehalose and 0.5 - 1% (w / w) of mannitol. The mixed solution is aseptically filtered through a 0.22 μm filter and then sub-packed for treatment.

6. The FDP cyclic adenosine monophosphate compound drink for improving myocardial energy metabolism according to claim 5, characterized in that The freeze-drying procedure includes: Cooling to -45°C at a rate of 4°C / min and maintaining for 3 hours, then sublimation drying for 18 hours under a vacuum degree of ≤5 Pa and a condenser temperature of -60°C, and finally the water activity is ≤0.15.