FDP cyclic adenosine monophosphate compound drink for improving cardiomyopathy and preparation method thereof

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 cardiomyopathy and a preparation method of the FDP cyclic adenosine monophosphate compound drink. The invention discloses a red date health-care beverage, which is prepared from the following raw materials in a mass ratio: 8g of water, 2g of red date extracting solution, 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. Comprising the following steps: complexing charges; carrying out microencapsulation embedding; carrying out steady-state treatment; and performing freeze-drying treatment. According to the FDP cyclic adenosine monophosphate composite drink for improving cardiomyopathy and the preparation method of the FDP cyclic adenosine monophosphate composite drink, the FDP cyclic adenosine monophosphate composite drink is designed through scientific compounding of active ingredients and an innovative process, the stability, bioavailability and function synergy of core components are remarkably improved, and meanwhile the technical problems that the compatibility of multiple components is poor, and the targeted delivery efficiency is low are solved.

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 cardiomyopathy and its preparation method. Background Art

[0002] As a progressive heart dysfunction disease, cardiomyopathy seriously threatens human health. Its pathological characteristics are manifested as abnormal myocardial cell energy metabolism, oxidative stress injury, and fibrotic hyperplasia. Current clinical treatments mainly rely on drug intervention and surgery. However, long-term medication is prone to drug resistance and liver and kidney toxicity, while invasive treatments carry relatively high risks. With the development of nutritional medicine, supplementing myocardial energy metabolism substrates and regulating redox balance through functional foods has become a new direction for adjuvant treatment. However, there are still significant technical bottlenecks in the stability of active ingredients, bioavailability, and synergistic action mechanisms of existing products.

[0003] In the prior art, composite preparations for improving cardiomyopathy often face multiple challenges: First, the core active ingredients (such as fructose 1,6-diphosphate and peptide substances) are prone to degradation and inactivation during processing and storage due to their unstable molecular structures; second, traditional oral preparations are affected by the gastrointestinal environment, with low absorption rates of active ingredients and difficulty in meeting the requirements of targeted delivery; third, physical and chemical property conflicts are likely to occur during the compounding of multiple components, resulting in precipitation or phase separation and affecting the homogeneity of the product; fourth, the compatibility between flavoring agents and functional ingredients is poor, and the flavoring process may damage the activity of thermosensitive substances. Summary of the Invention

[0004] The present invention provides an FDP-cyclic adenosine monophosphate compound drink for improving cardiomyopathy and its preparation method. Through scientific compounding of active ingredients and innovative process design, the stability, bioavailability, and functional synergy of the core components are significantly improved, while also solving technical problems such as poor compatibility of multiple components and low targeted delivery efficiency.

[0005] The technical solution adopted by the present invention is: An FDP-cyclic adenosine monophosphate compound drink for improving cardiomyopathy, which is composed of the following raw materials in the following mass ratios: water accounts for 8 grams, red date extract accounts for 2 grams, trisodium fructose 1,6-diphosphate 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, and vitamin B6 accounts for 0.00003 gram.

[0006] As a further improvement of the present invention, the concentration of the red date extract is 20%.

[0007] As a further improvement of the present invention, it includes 0.005 - 0.015 grams of coenzyme Q10 micropowder. The coenzyme Q10 is prepared by supercritical CO2 fluid crystallization technology, with a particle size distribution D90 ≤ 80 nm and a specific surface area ≥ 25 m 2 / g.

[0008] As a further improvement of the present invention, natural flavoring agent components are added: 0.002 - 0.005 grams of mogroside, 0.001 - 0.003 grams of zinc citrate. After ultrasonic-assisted dissolution, it is sterilized through a 0.1 μm filter membrane.

[0009] A preparation method of an FDP cyclic adenosine monophosphate compound drink for improving cardiomyopathy includes the following steps:

[0010] Step 1, charge complexation: Form a complex of deer myocardial peptide powder and fructose-1,6-diphosphate trisodium salt in an alternating electric field with an electric field strength of 50 - 80 V / cm and a frequency of 20 - 50 Hz;

[0011] Step 2, microencapsulation embedding: After the charge complexation product and vitamin B components are homogenized by high-pressure microfluidics, they are encapsulated using a multi-layer embedding technology;

[0012] Step 3, stabilization treatment: Mix the embedded product with the pretreated red date extract under vacuum oscillation conditions with an oscillation frequency of 40 - 60 Hz and a vacuum degree of -0.06 to -0.08 MPa;

[0013] Step 4: Freeze-drying treatment: Pre-freeze the final product at a rate of 3 - 5 °C / min to -45 °C, maintain it for 2 - 4 hours, and then perform sublimation drying under a vacuum degree ≤ 5 Pa and a condenser temperature of -60 °C, controlling the moisture content ≤ 1.5%.

[0014] As a further improvement of the present invention, the alternating electric field adopts a pulse mode with a pulse width of 1 - 5 ms, a duty cycle of 30 - 50%, and the electric field direction automatically reverses every 10 seconds.

[0015] As a further improvement of the present invention, the multi-layer embedding technology includes an inner coating and an outer coating, with an embedding rate ≥ 92% and an in vitro simulated release rate reaching 80 - 85% in 6 hours,

[0016] Inner coating: Chitosan-sodium alginate composite membrane with a thickness of 50 - 80 nm;

[0017] Outer coating: Gelatin-pectin composite membrane with a thickness of 100 - 150 nm.

[0018] As a further improvement of the present invention, in Step 1, the charge complexation process is carried out in two stages, and gradient cooling is adopted between the two stages with a cooling rate ≤ 1 °C / min,

[0019] The first stage: pH 6.5 - 7.0, temperature 10 - 15 °C, time 30 - 45 minutes;

[0020] The second stage: pH 7.2 - 7.5, temperature 5 - 8 °C, time 60 - 90 minutes.

[0021] The beneficial effects of the present invention: Through the synergistic effect of charge complexation-induced molecular self-assembly and multi-layer embedding technology, the present invention realizes the directional compounding and targeted controlled release of active ingredients (fructose 1,6-diphosphate, cardiotrophin, and coenzyme Q10) at the nanoscale. Combined with the gradient steady-state process and cryogenic freeze-drying protection, it significantly improves the gastrointestinal stability of the core ingredients and the targeting efficiency of myocardial tissue. At the same time, through the regulation of the redox microenvironment, the spatio-temporal synergistic release of energy metabolism substrates and antioxidant components is achieved, enhancing the ATP synthesis rate of cardiomyocytes and restoring the mitochondrial membrane potential to near the normal level, ultimately achieving multi-dimensional synergistic effects in myocardial function repair and fibrosis inhibition. Specific embodiments

[0022] In order to make the technical problems, technical solutions, and beneficial effects to be solved by the present application clearer, the following further elaborates on the present application in combination with 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.

[0023] The present invention provides an FDP cyclic adenosine monophosphate compound drink for improving cardiomyopathy, which is composed of raw materials with the following mass ratios: water accounts for 8 grams, red date extract accounts for 2 grams, trisodium fructose 1,6-diphosphate accounts for 0.15 grams, deer cardiotrophin 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, and vitamin B6 accounts for 0.00003 gram.

[0024] The concentration of the red date extract in the present invention is 20%.

[0025] The present invention includes 0.005 - 0.015 grams of coenzyme Q10 micropowder. The coenzyme Q10 is prepared by supercritical CO2 fluid crystallization technology, with a particle size distribution D90 ≤ 80 nm and a specific surface area ≥ 25 m 2 / g.

[0026] The present invention adds natural flavoring agent components: mogroside 0.002 - 0.005 grams, zinc citrate 0.001 - 0.003 grams. After ultrasonic-assisted dissolution, it is sterilized through a 0.1 μm filter membrane.

[0027] A preparation method of an FDP cyclic adenosine monophosphate compound drink for improving cardiomyopathy includes the following steps:

[0028] Step 1, Charge complexation: Complexes are formed between deer myocardial peptide powder and fructose-1,6-diphosphate trisodium salt in an alternating electric field with an electric field strength of 50 - 80 V / cm and a frequency of 20 - 50 Hz;

[0029] Step 2, Microencapsulation embedding: After the charge complexation product and vitamin B components are homogenized by high-pressure microfluidization, they are encapsulated using a multi-layer embedding technique;

[0030] Step 3, Stabilization treatment: The embedded product is mixed with pretreated red date extract under vacuum oscillation conditions with an oscillation frequency of 40 - 60 Hz and a vacuum degree of -0.06 to -0.08 MPa;

[0031] Step 4: Freeze-drying treatment: The final product is pre-frozen to -45°C at a rate of 3 - 5°C / min, maintained for 2 - 4 hours, and then sublimation-dried under a vacuum degree of ≤5 Pa and a condenser temperature of -60°C, controlling the moisture content to ≤1.5%.

[0032] In the present invention, the alternating electric field adopts a pulse mode with a pulse width of 1 - 5 ms, a duty cycle of 30 - 50%, and the electric field direction automatically reverses every 10 seconds.

[0033] In the present invention, the multi-layer embedding technique includes an inner coating and an outer coating, with an embedding rate ≥92% and an in vitro simulated release rate reaching 80 - 85% in 6 hours.

[0034] Inner coating: Chitosan-sodium alginate composite membrane with a thickness of 50 - 80 nm;

[0035] Outer coating: Gelatin-pectin composite membrane with a thickness of 100 - 150 nm.

[0036] In Step 1 of the present invention, the charge complexation process is carried out in two stages, and gradient cooling is used between the two stages with a cooling rate ≤1°C / min.

[0037] First stage: pH 6.5 - 7.0, temperature 10 - 15°C, time 30 - 45 minutes;

[0038] Second stage: pH 7.2 - 7.5, temperature 5 - 8°C, time 60 - 90 minutes.

[0039] Example 1 (Preparation of basic formula):

[0040] Step 1, Raw material preparation

[0041] Take 0.15 g of fructose-1,6-diphosphate trisodium salt, 0.1 g of deer myocardial peptide powder, 2 g of 20% red date extract, 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 8 g of water.

[0042] Step 2, Charge complexation

[0043] Dissolve deer myocardial peptide powder and fructose-1,6-diphosphate trisodium salt in phosphate buffer solution with pH 6.8 (concentration 5%), place it in an alternating electric field reactor (electric field strength 60 V / cm, frequency 35 Hz, pulse width 3 ms, duty cycle 40%), and reverse the electric field direction every 10 seconds. Treat it in two stages: (1) The first stage: maintain the temperature at 12°C and stir for 45 minutes; (2) The second stage: cool down to 6°C at a gradient (rate 0.8°C / min), adjust the pH to 7.3, and continue the reaction for 75 minutes.

[0044] Step 3, Microencapsulation embedding

[0045] Mix the charge complexation solution with vitamin B group, homogenize it by high-pressure microfluidics (pressure 150 MPa, circulate 3 times), and then adopt double-layer embedding: (1) Inner layer coating: spray chitosan-sodium alginate (mass ratio 3:1) composite solution to form a 60-nm thick film layer; (2) Outer layer coating: immerse it in gelatin-pectin (mass ratio 2:1) composite solution to form a 120-nm thick film layer, and the embedding rate is 93.5%.

[0046] Step 4, Steady-state treatment

[0047] Mix the embedded microcapsules with the pretreated red date extract (filtered through a 0.1-μm filter membrane), and oscillate in a vacuum oscillation tank (vacuum degree -0.07 MPa, frequency 50 Hz) for 30 minutes.

[0048] Step 5, Freeze-drying process

[0049] Pre-freeze to -45°C (rate 4°C / min), after maintaining for 3 hours, conduct sublimation drying at a vacuum degree of 4 Pa and a condenser temperature of -60°C for 24 hours, and the final moisture content is 1.2%.

[0050] Example 2 (Coenzyme Q10 optimized formula):

[0051] (I) Raw material supplementation

[0052] Add 0.01 g of coenzyme Q10 micropowder (D90 = 75 nm, specific surface area 28 m 2 / g, prepared by supercritical CO2 crystallization, pressure 12 MPa, temperature 40°C) on the basis of Example 1.

[0053] (II) Flavoring agent treatment

[0054] Add 0.003 g of mogroside and 0.002 g of zinc citrate, dissolve it by ultrasonic assistance (power 200 W, frequency 40 kHz, treat for 10 minutes), and then sterilize it through a 0.1-μm filter membrane.

[0055] (III) Targeted Release Verification

[0056] In vitro simulated gastrointestinal fluid release experiments showed that the cumulative release amount reached 83.5% in 6 hours, and the myocardial cell uptake efficiency was increased by 2.1 times compared with the ordinary preparation (determined by fluorescence labeling method).

[0057] Example 3 (Process Parameter Limit Test):

[0058] (I) Charge Complexation Enhancement

[0059] Using an electric field strength of 80 V / cm (pulse width 5 ms, duty cycle 50%), the two-stage treatment time was extended to 60 minutes in the first stage and 100 minutes in the second stage. Finally, the particle size of the complex decreased from the conventional 120 nm to 85 nm (determined by dynamic light scattering method).

[0060] (II) Lyophilization Accelerated Experiment

[0061] The final product was stored at 40°C / 75% RH for 3 months. The retention rate of fructose-1,6-diphosphate was ≥95% (detected by HPLC), and there was no significant change in the secondary structure of deer myocardial peptide (analyzed by circular dichroism spectroscopy).

[0062] Control Example (Traditional Mixing Process):

[0063] Omitting the charge complexation and embedding steps, all raw materials were directly mixed and then lyophilized. After testing: (1) The degradation rate of fructose-1,6-diphosphate in the gastrointestinal simulation fluid was 42% in 6 hours (the degradation rate in Example 1 was 23%); (2) The ATP synthesis rate of myocardial cells was only increased by 21% (the increase in Example 1 was 68%).

[0064] Effect Verification Data

[0065] (I) Animal Model Test

[0066] In the rat myocardial ischemia model, after 4 weeks of treatment in the Example 2 group: (1) The left ventricular ejection fraction (LVEF) was restored from 45% ± 3% to 62% ± 4%; (2) The myocardial fibrosis area was reduced by 58% (quantified by Masson staining); (3) The mitochondrial membrane potential was restored to 87% of the normal group (JC-1 fluorescent probe method).

[0067] (II) Stability Comparison [[ID=�8]]

[0068] The accelerated test (40°C / 75% RH, 6 months) showed that: (1) The retention rate of coenzyme Q10 micropowder content: 91% in the Example 2 group vs 67% in the traditional liposome embedding group; (2) The photolysis rate of vitamin B1: 8% in the Example 1 group vs 35% in the unembedded control group.

[0069] Examples 1-3 and the comparative examples above confirm that the FDP-cyclic adenosine monophosphate compound drink for improving cardiomyopathy provided by the present invention and its preparation method have significantly improved in terms of the stability of active ingredients, bioavailability, and functional synergy compared with traditional methods, and can more effectively address the many problems faced in the treatment of cardiomyopathy, providing a more reliable and effective solution for the adjuvant treatment of cardiomyopathy.

[0070] In summary, the FDP-cyclic adenosine monophosphate compound drink for improving cardiomyopathy and its preparation method according to the present invention have achieved a breakthrough in the technical bottlenecks related to the treatment of cardiomyopathy through scientific and reasonable raw material ratios, innovative preparation processes, and rigorous experimental verification. Its unique charge complexation, microencapsulation embedding, stabilization treatment, freeze-drying process, etc. not only improve the stability of active ingredients, enhance bioavailability, but also optimize the synergistic action mechanism among multiple components. From the test results of animal models, it can effectively improve myocardial function and inhibit myocardial fibrosis; the stability comparison also shows that the retention rate of key components is higher and the degradation rate is lower under different conditions. These advantages bring new hope to cardiomyopathy patients, are expected to play an important role in future clinical applications, further promote the development of the cardiomyopathy treatment field, and provide high-quality and effective treatment options for more patients.

[0071] 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 described 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 cardiomyopathy, characterized in that, It consists of raw materials 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 heart myopeptide powder accounts for 0.1 gram, anhydrous citric acid accounts for 0.1 gram, potassium sorbate accounts for 0.004 grams, vitamin B1 accounts for 0.00003 grams, vitamin B2 accounts for 0.00003 grams, and vitamin B6 accounts for 0.00003 grams.

2. The FDP cyclic adenosine monophosphate compound drink for improving cardiomyopathy according to claim 1, characterized in that, The concentration of the red date extract is 20%.

3. The FDP cyclic adenosine monophosphate compound drink for improving cardiomyopathy according to claim 1, wherein, It includes 0.005 - 0.015 grams of coenzyme Q10 micropowder. The coenzyme Q10 is prepared by supercritical CO2 fluid crystallization technology, with a particle size distribution D90 ≤ 80 nm and a specific surface area ≥ 25 m 2 / g.

4. The FDP cyclic adenosine monophosphate compound drink for improving cardiomyopathy according to claim 1, wherein Add natural flavoring agent components: mogroside 0.002 - 0.005 grams, zinc citrate 0.001 - 0.003 grams. After ultrasonic-assisted dissolution, it is sterilized through a 0.1μm filter membrane.

5. A preparation method of FDP cyclic adenosine monophosphate compound drink for improving cardiomyopathy, characterized in that, It includes the following steps: Step 1, charge complexation: Form a complex of deer heart myopeptide powder and fructose-1,6-diphosphate trisodium salt in an alternating electric field with an electric field strength of 50 - 80 V / cm and a frequency of 20 - 50 Hz. Step 2, microencapsulation embedding: After homogenizing the charge complexation product and vitamin B components by high-pressure microfluidization, use a multi-layer embedding technique for encapsulation. Step 3, stabilization treatment: Mix the embedded product with the pretreated red date extract under vacuum oscillation conditions with an oscillation frequency of 40 - 60 Hz and a vacuum degree of -0.06 to -0.08 MPa. Step 4: Freeze-drying treatment: Pre-freeze the final product at a rate of 3 - 5 °C / min to -45 °C, maintain it for 2 - 4 hours, and then perform sublimation drying under a vacuum degree ≤ 5 Pa and a condenser temperature of -60 °C, controlling the moisture content ≤ 1.5%.

6. The preparation method of an FDP cyclic adenosine monophosphate compound drink for improving cardiomyopathy according to claim 5, characterized in that, The alternating electric field adopts a pulse mode with a pulse width of 1 - 5 ms, a duty cycle of 30 - 50%, and the electric field direction automatically reverses every 10 seconds.

7. The preparation method of an FDP-cyclic adenosine monophosphate compound drink for improving cardiomyopathy according to claim 5, characterized in that, The multi-layer embedding technique includes an inner coating and an outer coating, with an embedding rate ≥ 92% and an in vitro simulated release rate reaching 80 - 85% in 6 hours. Inner coating: chitosan-sodium alginate composite membrane with a thickness of 50 - 80 nm. Outer coating: gelatin-pectin composite membrane with a thickness of 100 - 150 nm.

8. The preparation method of an FDP-cyclic adenosine monophosphate compound drink for improving cardiomyopathy according to claim 5, wherein, In Step 1, the charge complexation process is carried out in two stages, and gradient cooling is used between the two stages with a cooling rate ≤ 1 °C / min. First stage: pH 6.5 - 7.0, temperature 10 - 15 °C, time 30 - 45 minutes. Second stage: pH 7.2 - 7.5, temperature 5 - 8 °C, time 60 - 90 minutes.