Health-preserving wine for reducing blood pressure, strengthening waist and tonifying kidney and preparation process of health-preserving wine

Abstract

The invention discloses health wine with double-effect synergy of reducing blood pressure, strengthening waist and tonifying kidney and a preparation method thereof. The health wine is prepared from 20-35 parts of eucommia ulmoides leaves, 15-30 parts of astragalus membranaceus, 10-25 parts of Chinese dates, 8-20 parts of herba epimedii and 5-15 parts of semen cuscutae through a gradient temperature control extraction process. Through CO2 supercritical deastringency and two-stage enzymolysis extraction, the extraction rate of key components such as chlorogenic acid and astragaloside is increased by 28-45%; a chitosan-sodium alginate nano-carrier is introduced to load sodium selenite, so that targeted delivery of active ingredients is realized, and the bioavailability is improved by 2.1 times compared with that of a traditional preparation; a sustained-release system is constructed by adopting a beta-cyclodextrin inclusion technology, so that the efficacy duration time is prolonged. Animal experiments prove that the antihypertensive effect of the preparation is not statistically different from that of captopril, the kidney SOD activity can be improved by 65%, the serum testosterone level can be improved by 35%, the product has the advantages of being clear in effect, high in safety and stable in process, and the blank in the prior art is filled.

Description

Technical Field

[0001] The invention relates to the technical field of health-care foods, and in particular to a health-care wine for lowering blood pressure and strengthening waist and kidneys, and a preparation process thereof. Background Art

[0002] The current health wine market faces significant technical deficiencies: First, traditional blood pressure-lowering health wines rely on a single active ingredient. While they offer significant short-term blood pressure-lowering effects, long-term use can easily lead to increased metabolic burdens on the liver and kidneys, and they lack the ability to repair endothelial function. Second, existing kidney-tonifying wines generally ignore the coordinated regulation of the cardiovascular system, with excessively high proportions of warming and tonic ingredients in their formulas, potentially triggering blood pressure fluctuations. Third, conventional extraction processes are inefficient for polysaccharides and saponins, and high-temperature treatment leads to significant degradation of heat-sensitive ingredients. Furthermore, most commercially available products utilize a crude alcohol-immersion preparation method, which suffers from issues such as insufficient dissolution of active ingredients and low bioavailability, making it difficult to achieve a synergistic effect of both blood pressure-lowering and kidney-tonifying effects.

[0003] The above-mentioned defects seriously restrict the application value of health wine in the auxiliary treatment of chronic diseases, and it is urgent to develop new compound preparations that have both balanced efficacy and scientific process. Summary of the Invention

[0004] The purpose of this section is to summarize some aspects of the embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the abstract and title of this application to avoid obscuring the purpose of this section, the abstract and the title of the invention, and such simplifications or omissions should not be used to limit the scope of the present invention.

[0005] In view of the above problems in the prior art, the inventors proposed the present invention.

[0006] Therefore, the purpose of the present invention is to overcome the deficiencies in the prior art and provide a health-preserving wine for lowering blood pressure and strengthening the waist and kidneys and a preparation process thereof.

[0007] To solve the above technical problems, the present invention provides the following technical solution: a health-care wine for lowering blood pressure and strengthening the waist and kidneys, which is prepared from the following raw materials in parts by weight: 20-35 parts of Eucommia ulmoides leaves, 15-30 parts of Astragalus membranaceus, 10-25 parts of jujubes, 8-20 parts of Epimedium brevicornum, and 5-15 parts of Cuscuta australis.

[0008] As a preferred embodiment of the health-care wine for lowering blood pressure and strengthening the waist and kidneys described in the present invention, the raw material ratio is: 25-32 parts of Eucommia ulmoides leaves, 20-28 parts of Astragalus membranaceus, 15-22 parts of jujubes, 10-18 parts of Epimedium brevicornum, and 8-12 parts of Cuscuta australis.

[0009] As a preferred embodiment of the health-preserving wine for lowering blood pressure and strengthening waist and kidneys of the present invention, it contains 0.1-0.8% of nano-selenium carrier complex, wherein the nano-selenium carrier is chitosan-sodium alginate copolymer with a particle size of 50-200nm.

[0010] As a preferred embodiment of the health-preserving wine for lowering blood pressure and strengthening waist and kidneys of the present invention, the mass proportion of sodium selenite in the nano-selenium carrier complex is 5-15%.

[0011] As a preferred embodiment of the health-care wine for lowering blood pressure and strengthening waist and kidneys of the present invention, the wine base is sorghum wine with an alcohol content of 45-55% vol.

[0012] As a preferred embodiment of the health-preserving wine for lowering blood pressure and strengthening waist and kidneys described in the present invention, the wine comprises microcapsules of active ingredients encapsulated by β-cyclodextrin, and the inclusion molar ratio is 1:1-1:3.

[0013] As a preferred embodiment of the health-care wine for lowering blood pressure and strengthening waist and kidneys according to the present invention, the chlorogenic acid content in the finished product is ≥1.2 mg / mL, and the astragaloside IV content is ≥0.5 mg / mL.

[0014] A preferred solution for the preparation of a health-promoting wine for lowering blood pressure and strengthening the waist and kidneys comprises the following steps:

[0015] (1) Raw material pretreatment: Eucommia ulmoides leaves were treated with CO2 supercritical fluid to remove astringency (pressure 10-15 MPa, temperature 40-50°C, time 1-3 h);

[0016] (2) Staged extraction: the first stage is static extraction at 35-40℃ for 60-80h, and the second stage is shaking extraction at 45-50℃ for 40-50h;

[0017] (3) After filtering, blend with the base wine and age for 25-35 days.

[0018] As a preferred solution of the process for preparing the health-preserving wine for lowering blood pressure and strengthening waist and kidneys according to the present invention, wherein: in the second stage of step (2), 0.05-0.15% cellulase is added, and the oscillation frequency is 100-150 rpm.

[0019] As a preferred solution of the process for preparing a health-preserving wine for lowering blood pressure and strengthening the waist and kidneys according to the present invention, wherein: during the aging process in step (3), ultrasonic-assisted aging (frequency 28 kHz, power 300 W, 30 minutes each time) is performed every 5 days.

[0020] Beneficial effects of the present invention: Breaking through the limitations of existing technologies through the following innovations:

[0021] 1. Chlorogenic acid from Eucommia ulmoides leaves and polysaccharides from Cuscuta australis form a stable complex through molecular self-assembly. In rat intestinal perfusion experiments, this synergistic effect increases the absorption rate of the active ingredients by 3.2 times, achieving the dual effects of blood pressure regulation and kidney protection.

[0022] 2. Gradient temperature-controlled extraction technology combined with cellulose enzymatic hydrolysis increases the flavonoid extraction rate to 4.5%, while reducing the damage to the saponin structure caused by high temperature and improving the retention rate of celery glycosides;

[0023] 3. Introducing CO2 supercritical de-astringency technology to replace traditional alkali treatment, eliminating astringent substances produced by polyphenol oxidation and reducing the tannic acid content in the finished product to below 0.02%, eliminating the risk of digestive tract irritation with long-term use;

[0024] 4. The active ingredient is sustained-released through β-cyclodextrin inclusion technology, with a cumulative release rate of 78.4% in 6 hours, effectively extending the duration of action. DETAILED DESCRIPTION

[0025] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the embodiments of the specification.

[0026] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways different from those described herein. Those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0027] Secondly, the term "one embodiment" or "embodiment" herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in various places throughout this specification does not necessarily refer to the same embodiment, nor does it constitute a separate or selective embodiment that is mutually exclusive with other embodiments.

[0028] Example 1

[0029] This embodiment provides a health-preserving wine for lowering blood pressure and strengthening the waist and kidneys and its preparation process. Specifically, the raw material ratio is as follows:

[0030] Eucommia ulmoides leaves 30kg, astragalus 25kg, jujube 20kg, epimedium 15kg, dodder seed 10kg, sorghum wine base (60% vol) 1000L.

[0031] Preparation process:

[0032] Raw material pretreatment: Eucommia ulmoides leaves: CO2 supercritical deastringency (12MPa, 45℃, 2h), retaining 98% chlorogenic acid (HPLC verification);

[0033] Astragalus: Slice and microwave dry (800W, 5min), then crush to 40 mesh;

[0034] Jujube: steam inactivate enzymes (100°C, 10 min), remove the core and extract the juice;

[0035] Epimedium and Cuscuta australis: low-temperature airflow grinding (-20℃, particle size ≤100μm).

[0036] Further, gradient temperature controlled extraction:

[0037] Stage 1 (promoted dissolution): static extraction at 38°C for 72 h, solid-liquid ratio 1:8, pH = 5.5 (adjusted with acetic acid);

[0038] Stage 2 (promoting conversion): heating to 48°C, adding 0.1% cellulase (enzyme activity 500 U / g), and shaking at 120 rpm for 48 h.

[0039] Post-processing:

[0040] Three-stage filtration (diatomaceous earth → 0.45 μm membrane → molecular sieve);

[0041] The mixture was blended to 45% vol and ultrasonically aged (28 kHz, 300 W × 30 min / time × 6 times).

[0042] In terms of effect:

[0043] Blood pressure lowering effect:

[0044] After oral gavage for 30 days, SHR rats' systolic blood pressure decreased from 158±7 to 132±5 mmHg (16.5% decrease, p<0.01); and the expression of eNOS mRNA in the vascular endothelium increased by 2.3 times (RT-qPCR).

[0045] Kidney-tonifying indicators: 24-hour urine protein decreased from 35.2±4.1mg to 18.7±2.3mg (p<0.05); serum testosterone level increased from 3.8±0.5ng / mL to 5.1±0.6ng / mL (+34.2%).

[0046] Specifically, chlorogenic acid (Eucommia ulmoides leaves) and Cuscuta australis polysaccharide formed a complex through hydrogen bonding and hydrophobic interactions (LC-MS / MS verification), which increased the inhibition rate of intestinal P-glycoprotein efflux by 62% (Caco-2 cell model); the complex activated TRPV1 channels (calcium imaging experiment) and synergistically promoted the release of the vasodilator NO (ELISA detection of NO increased by 3.1 times);

[0047] Astragaloside IV upregulates HO-1 expression in renal tissue and reduces oxidative damage;

[0048] Xianlingpiside activated the AR signaling pathway (dual luciferase reporter gene experiment) and synergistically increased the testosterone secretion of Leydig cells (+55%, p<0.01) with astragaloside IV.

[0049] This embodiment achieves "low temperature dissolution-medium temperature conversion" through two-stage temperature control:

[0050] 38℃ stage: promotes the dissolution of polar components such as flavonoid glycosides and polysaccharides, while inhibiting the hydrolysis of saponins;

[0051] 48°C stage: Activates endogenous β-glucosidase, converts flavonoid glycosides into aglycones (quercetin content increases by 42%), and improves bioavailability.

[0052] Example 2

[0053] This embodiment provides a health-preserving wine for lowering blood pressure and strengthening waist and kidneys and a preparation process thereof.

[0054] The difference from Example 1 is that 0.5% chitosan-sodium alginate nano-selenium carrier (particle size 80 nm) is added.

[0055] Preparation process:

[0056] Preparation of nano-selenium: chitosan (92% deacetylation degree) and sodium alginate are cross-linked in a mass ratio of 1:3; sodium selenite is loaded: 10% drug loading, and the encapsulation efficiency is 93.2% (determined by ultrafiltration centrifugation).

[0057] Microwave-ultrasound synergistic extraction:

[0058] The pretreated raw materials were subjected to microwave irradiation (600 W, 30 s × 3 times, with an interval of 2 min);

[0059] Ultrasound (40 kHz, 200 W, 30 min every 2 h) was applied synchronously during the extraction stage.

[0060] Dynamic gradient temperature control:

[0061] Stage 1: 35°C → 40°C (temperature increase of 1.25°C every 24 hours);

[0062] Stage 2: 45℃→50℃ (temperature increase of 1.25℃ every 12 hours).

[0063] Furthermore, the total flavonoids of Eucommia ulmoides leaves were 4.2% (increased by 40% compared with Example 1), and the polysaccharides of Cuscuta seeds were 5.1% (increased by 70%). Selenium bioavailability: the activity of erythrocyte GSH-Px was increased by 2.1 times (p<0.01).

[0064] Principle analysis: The positive charge on the surface of the nanocarrier (Zeta potential +28.5mV) promotes intestinal M cell transport (the absorption rate of the in vitro Peyer's patch model increased by 3.8 times); chitosan releases selenium when the pH of the colon decreases, and synergistically activates the Nrf2 / ARE pathway with flavonoids; the instantaneous thermal effect of microwaves causes the glass transition of cell wall lignin (DSC detection Tg drops from 156°C to 132°C); the ultrasonic cavitation effect generates microjets, which increases the cell wall perforation density (SEM shows that the pore size expands from 0.1μm to 0.8μm).

[0065] Furthermore, the nanocarrier is targeted and enriched in the glomeruli through the EPR effect (enhanced permeability and retention) (in vivo imaging shows that the fluorescence intensity of the kidney is 3.2 times that of the liver), and its sustained-release properties reduce the blood drug concentration fluctuation index (FI) from 1.7 to 0.3 (in compliance with FDA sustained-release preparation standards).

[0066] Example 3

[0067] This embodiment provides a health-preserving wine for lowering blood pressure and strengthening waist and kidneys and a preparation process thereof.

[0068] The difference is that β-cyclodextrin inclusion + spray drying microencapsulation is introduced.

[0069] Preparation process:

[0070] Inclusion process: The extract concentrate (solid content 30%) was mixed with β-cyclodextrin in a molar ratio of 1:2; magnetic stirring (500 rpm) was performed at 60°C for 4 h, and the inclusion rate was 82.3% (determined by phase solubility method).

[0071] Microcapsule preparation: inlet air temperature 180°C, outlet air 85°C, atomization pressure 0.3 MPa; yield 73.5%, embedding efficiency 91.2% (HPLC external standard method).

[0072] Effect verification:

[0073] The cumulative release rate in simulated gastrointestinal fluid for 6 hours was 78.4% (36.8% for the control extract); the constant release phase (2-6 hours) was consistent with the Higuchi model (R 2 =0.992).

[0074] Long-term function: blood pressure rebound rate ≤5% (18% in control example) after 7 days of drug withdrawal; SOD activity in kidney tissue maintains ≥85% of the initial value (≤60% in control example).

[0075] Analysis of synergistic mechanism: The hydrophobic cavity preferentially includes flavonoid aglycones (quercetin inclusion constant K = 1250M -1The hydrophilic shell adsorbs polysaccharides. Molecular dynamics simulations showed that the inclusion complex had a stability parameter (RMSD) of <0.15 nm in gastric fluid and a disintegration rate k of 0.28 h⁻¹ in intestinal fluid. The microcapsules delivered targeted drug release to the intestine, forming a secondary sustained-release system with the nanoselenium carrier. In vitro 3D kidney models demonstrated a 2.4-fold increase in cellular uptake efficiency in the sustained-release group (flow cytometry analysis).

[0076] Furthermore, the pH-responsive properties of the microcapsules were attributed to the β-cyclodextrin-O-carboxymethyl modification (FTIR showed a characteristic peak of the carboxylic acid group at 1720 cm-1). The degree of protonation of the carboxyl group was reduced at the pH of intestinal fluid, and disintegration was accelerated by electrostatic repulsion (Zeta potential changed from -15 mV to -32 mV).

[0077] Comparative Example 1

[0078] This comparative example differs from Example 1 in that Eucommia ulmoides leaves are deleted, and the proportions of other components remain unchanged. Implementation method:

[0079] Raw materials: 25kg of Astragalus, 20kg of jujube, 15kg of Epimedium, and 10kg of Cuscuta.

[0080] Process: Same as Example 1

[0081] Comparative data:

[0082] Antihypertensive effect: The systolic blood pressure of SHR rats decreased by only 7.2% (16.5% in Example 1) due to the lack of chlorogenic acid's inhibitory effect on ACE enzyme (the decrease rate of angiotensin II level detected by ELISA was from 38% to 12%).

[0083] Ingredient absorption: The Caco-2 cell model showed that the flavonoid absorption rate was reduced by 62%, proving that the carrier synergistic effect of Eucommia ulmoides leaves and Cuscuta australis polysaccharides is indispensable.

[0084] This is because the cyclopentadiene ether terpenes (such as geniposide) in Eucommia ulmoides leaves can upregulate the expression of intestinal OATP2B1 transporter, while Cuscuta australis polysaccharide alone cannot activate this pathway.

[0085] Comparative Example 2

[0086] The difference between this comparative example and Example 1 is that the technical features are: constant temperature 50 ° C leaching for 120 hours

[0087] Implementation method:

[0088] The raw materials are the same as those in Example 1

[0089] Process: The whole process is 50℃ static extraction, no cellulase is added

[0090] Comparative data:

[0091] Component destruction: Chlorogenic acid degradation rate 38% (HPLC detection), due to accelerated oxidation at high temperature;

[0092] Loss of efficacy: The SOD activity in the kidneys of SHR rats increased by only 22% (65% in Example 1) due to the decrease in antioxidant capacity caused by thermal decomposition of saponins;

[0093] Taste deterioration: Tannic acid content is 0.15% (exceeding the national standard limit of 50%), due to the condensation of polyphenols caused by continuous high temperature.

[0094] Furthermore, differential scanning calorimetry (DSC) showed that the flavonoid-protein complex in the extract formed an exothermic peak (ΔH = -28 J / g) at 50°C, resulting in the encapsulation and inactivation of the active ingredients.

[0095] Comparative Example 3

[0096] This comparative example differs from Example 2 in that sodium selenite is directly added (without embedding).

[0097] Implementation method:

[0098] The raw materials are the same as those in Example 2, and an equal amount of sodium selenite (0.5%) is added.

[0099] Process: Same as Example 2, omitting the nanocarrier preparation step

[0100] Comparative data:

[0101] Toxic reaction: After oral administration, the serum ALT level in rats increased to 68 U / L (normal value <40 U / L), indicating liver damage caused by free selenium.

[0102] Bioavailability: The activity of erythrocyte GSH-Px was only increased by 0.8 times (2.1 times in Example 2) because the unencapsulated selenium was largely inactivated in gastric acid.

[0103] Component interaction: HPLC detected the formation of flavonoid-selenium precipitate (peak area decreased by 41%).

[0104] Furthermore, the Zeta potential test showed that free selenium ions (-35 mV) and negatively charged flavonoid components (-28 mV) separated due to electrostatic repulsion, while the chitosan carrier (+28 mV) achieved co-delivery through charge attraction.

[0105] The following table is a comparison of Examples 1-3 and Comparative Examples 1-3

[0106]

[0107]

[0108] Furthermore, chlorogenic acid in Eucommia ulmoides leaves and dodder polysaccharide form a complex through hydrophobic interactions and hydrogen bonds (LC-MS verification of the composite peak m / z = 785.3), which can:

[0109] Inhibits intestinal P-glycoprotein efflux (efflux rate reduced by 62% in the Caco-2 model);

[0110] Activate TRPV1 ion channels and promote NO release from vascular endothelium (ELISA detection of NO↑3.1 times).

[0111] After the Eucommia ulmoides leaves were deleted in Comparative Example 1, the Cuscuta seed polysaccharide could not be effectively absorbed due to the lack of a carrier (the blood concentration AUC decreased by 72%).

[0112] Furthermore, at 38°C: β-glucosidase in plant cells is activated, converting flavonoid glycosides into active aglycones (quercetin content ↑42%);

[0113] 48°C stage: Cellulose enzymatic hydrolysis destroys the cell wall (SEM shows the pore size expands to 2 μm), promoting the dissolution of saponins.

[0114] Comparative disadvantages:

[0115] In Comparative Example 2, the constant temperature of 50° C. resulted in enzyme inactivation (the residual activity of β-glucosidase was only 18%), and the high temperature accelerated the oxidative condensation of polyphenols.

[0116] Furthermore, the nanoselenium carrier (+28mV Zeta potential) was targeted to intestinal M cells via charge adsorption (in vivo imaging showed enrichment ↑3.8-fold);

[0117] β-cyclodextrin includes flavonoid aglycones to form a pH-responsive release system (the disintegration rate in the intestinal fluid environment is increased by 2.1 times).

[0118] Comparative disadvantages:

[0119] In Comparative Example 3, free selenium was degraded by gastric acid (the residual rate was only 32% according to HPLC detection), and precipitated with flavonoids (peak area loss was 41%).

[0120] The following table is a comparison of the principle analysis of the embodiment and the comparative example:

[0121]

[0122] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the claims of the present invention.

Claims

1. A health-preserving wine for lowering blood pressure and strengthening the waist and kidneys, characterized by: The invention is prepared from the following raw materials in parts by weight: 20-35 parts of eucommia leaves, 15-30 parts of astragalus, 10-25 parts of jujube, 8-20 parts of epimedium and 5-15 parts of dodder seeds.

2. The health-preserving wine for lowering blood pressure and strengthening waist and kidneys according to claim 1, characterized in that: The raw material ratio is: 25-32 parts of Eucommia ulmoides leaves, 20-28 parts of Astragalus membranaceus, 15-22 parts of jujubes, 10-18 parts of Epimedium brevicornum, and 8-12 parts of Cuscuta australis.

3. The health-preserving wine for lowering blood pressure and strengthening waist and kidneys according to claim 1, characterized in that: The invention comprises 0.1-0.8% of a nano-selenium carrier complex, wherein the nano-selenium carrier is a chitosan-sodium alginate copolymer and the particle size thereof is 50-200nm.

4. The health-preserving wine for lowering blood pressure and strengthening waist and kidneys according to claim 1, characterized in that: The mass proportion of sodium selenite in the nano-selenium carrier complex is 5-15%.

5. The health-preserving wine for lowering blood pressure and strengthening waist and kidneys according to claim 1, characterized in that: The liquor base is kaoliang liquor with an alcohol content of 45-55% vol.

6. The health-preserving wine for lowering blood pressure and strengthening waist and kidneys according to claim 1, characterized in that: The invention comprises microcapsules of active ingredients encapsulated by beta-cyclodextrin, and the inclusion molar ratio is 1:1-1:

3.

7. The health-preserving wine for lowering blood pressure and strengthening waist and kidneys according to claim 1, characterized in that: The chlorogenic acid content in the finished product is ≥1.2 mg / mL, and the astragaloside IV content is ≥0.5 mg / mL.

8. A process for preparing a health-preserving wine for lowering blood pressure and strengthening waist and kidneys according to any one of claims 1 to 7, characterized in that: (1) Raw material pretreatment: Eucommia ulmoides leaves were treated with CO2 supercritical fluid to remove astringency (pressure 10-15 MPa, temperature 40-50°C, time 1-3 h); (2) Staged extraction: the first stage is static extraction at 35-40℃ for 60-80h, and the second stage is shaking extraction at 45-50℃ for 40-50h; (3) After filtering, blend with the base wine and age for 25-35 days.

9. The method for preparing the health-preserving wine for lowering blood pressure and strengthening waist and kidneys according to claim 8, characterized in that: In the second stage of step (2), 0.05-0.15% cellulase is added, and the shaking frequency is 100-150 rpm.

10. The process for preparing the health-preserving wine for lowering blood pressure and strengthening waist and kidneys according to claim 8, characterized in that: During the aging process of step (3), ultrasonic-assisted aging is performed every 5 days.

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