Oral liquid for treating metabolic syndrome and preparation method thereof

Abstract

The invention relates to the technical field of oral liquid, in particular to oral liquid for treating metabolic syndrome and a preparation method of the oral liquid. Comprising the following raw materials in parts by weight: 12-18 parts of selenium-enriched yeast modified astragalus membranaceus, 10-14 parts of superfine grinding fermented coptis chinensis, 14-18 parts of gynostemma pentaphylla, 12-16 parts of hawthorn, 8-12 parts of rhizoma alismatis, 10-13 parts of turmeric, 6-8 parts of a cinnamon extract, 3-6 parts of coenzyme Q10 microspheres, 5-10 parts of a folium cortex eucommiae extract and 3-7 parts of a nuciferine extract. The preparation method of the oral liquid for treating the metabolic syndrome comprises the following preparation processes: S1, preparing selenium-enriched yeast modified astragalus membranaceus; s2, preparing superfine grinding fermented coptis chinensis; and S3, extracting the fiveleaf gynostemma herb. The traditional Chinese medicine composition can effectively improve insulin resistance and reduce oxidative damage in a synergistic manner in multiple aspects, and plays a key role in controlling blood sugar and blood fat of metabolic syndrome patients and preventing complications.

Description

Technical Field

[0001] The present invention relates to the technical field of oral liquids, and in particular to an oral liquid for treating metabolic syndrome and a preparation method thereof. Background Art

[0002] Metabolic syndrome (MS) has become an increasingly serious health problem worldwide. Its onset is closely related to changes in modern lifestyles, including high-calorie dietary intake, reduced physical activity, and long-term mental stress. MS is not a single disease, but a complex metabolic disorder syndrome, whose core features include a variety of cardiovascular disease risk factors such as obesity, hyperglycemia, hypertension, and dyslipidemia. These factors are interrelated and influence each other, greatly increasing the risk of patients suffering from type 2 diabetes, cardiovascular diseases (such as coronary heart disease, myocardial infarction, stroke, etc.) and other related complications, seriously affecting the quality of life of patients and placing a heavy burden on the social medical system.

[0003] At present, the clinical treatment strategy for metabolic syndrome mainly focuses on the intervention of each independent risk factor. In terms of drug treatment, various types of hypoglycemic drugs are commonly used to control hyperglycemia. For example, sulfonylurea drugs can lower blood sugar by stimulating pancreatic β cells to secrete insulin, but may increase the risk of hypoglycemia. Although biguanides can improve insulin sensitivity and reduce hepatic glucose output, they may cause gastrointestinal discomfort such as nausea, vomiting, and diarrhea. For the treatment of dyslipidemia, statins are widely used to lower cholesterol levels, but some patients may experience adverse reactions such as liver damage and muscle pain. When fibrates are used to regulate triglyceride levels, they may also cause gastrointestinal reactions and have a certain impact on liver and kidney function. In the treatment of hypertension, different types of antihypertensive drugs such as diuretics, β-blockers, angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARB) have different side effect spectra. For example, diuretics may cause electrolyte disorders, and β-blockers may affect heart rate and airway responsiveness. Although this single-target drug combination therapy model can alleviate patients' symptoms to a certain extent, it has obvious limitations.

[0004] On the one hand, due to the extremely complex pathogenesis of MS, which involves disorders of multiple physiological systems and signal pathways, single-target drugs can often only intervene in a specific risk factor or pathophysiological process, and it is difficult to comprehensively regulate the body's metabolic imbalance. This leads to less than ideal treatment effects, and it is difficult to effectively control the patient's various metabolic indicators at the same time, and the long-term prognosis of the disease is limited. On the other hand, the combined use of multiple drugs not only increases the difficulty of medication compliance for patients, but also the interactions between drugs may cause more adverse reactions, further increasing the patient's physical burden and potential health risks. Summary of the invention

[0005] The purpose of the present invention is to solve the shortcomings of the prior art and to propose an oral liquid for treating metabolic syndrome and a preparation method thereof.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] An oral liquid for treating metabolic syndrome, comprising the following raw materials by weight:

[0008] 12-18 parts of selenium-enriched yeast modified astragalus, 10-14 parts of ultrafinely crushed fermented coptis, 14-18 parts of gynostemma pentaphyllum, 12-16 parts of hawthorn, 8-12 parts of oriental arisaema, 10-13 parts of turmeric, 6-8 parts of cinnamon extract, 3-6 parts of coenzyme Q10 microspheres, 5-10 parts of eucommia leaf extract, and 3-7 parts of nuciferine extract.

[0009] The above-mentioned method for preparing an oral liquid for treating metabolic syndrome includes the following preparation process: S1, preparing selenium-enriched yeast-modified astragalus, soaking it in a culture solution containing selenium-enriched yeast, and culturing it for 36 hours at 29°C and pH 5.5 by shaking culture. After the culture is completed, using a continuous centrifuge to quickly separate the astragalus from the culture solution, then rinsing it with deionized water for 3 times, and then rinsing it with anhydrous ethanol for 2 times. The rinsed astragalus is freeze-dried to form a porous sponge-like structure, first pre-frozen at -40°C for 2-3 hours, and then dried to constant weight at a vacuum degree of 0.08-0.09MPa and a temperature of 30°C for standby use;

[0010] S2, preparing ultrafine grinding fermented Coptis chinensis, the Coptis chinensis is first frozen at -20 ° C for 2-3 hours, and then ground in an ultrafine grinder to a particle size of 40-100 μm, the ground Coptis chinensis is inoculated with Bifidobacterium, and fermented at 36 ° C and a relative humidity of 60%-70% for 4 days. During the fermentation process, an intelligent stirring system is used, stirring once every 12 hours, each stirring for 10 minutes, and the stirring speed is 50-60 rpm. After the fermentation is completed, the Coptis chinensis is made into a nanoparticle dispersion, and a high-pressure homogenization method is used to homogenize 3-5 times at a pressure of 100-150 MPa, so that the Coptis chinensis forms nanoparticles with a particle size of 20-50 nm and dispersed in water for standby use;

[0011] S3, extracting Gynostemma pentaphyllum, washing and chopping Gynostemma pentaphyllum, using extrusion granulation technology to make it into particles with a diameter of 2-3mm, adding 8 times the amount of water to the Gynostemma pentaphyllum particles, soaking for 1 hour, heating to boiling, keeping slightly boiling for 2 hours, filtering with a ceramic membrane to obtain a primary filtrate, adding 6 times the amount of water to the residue, repeating the above operation to obtain a secondary filtrate, combining the two filtrates, concentrating under reduced pressure to a relative density of 1.1-1.2, adding 95% ethanol to make the alcohol content reach 70%, standing for 24 hours, filtering with a filter paper-filter cloth combination, recovering ethanol, and obtaining a Gynostemma pentaphyllum extract for standby use;

[0012] S4, Hawthorn extraction, wash the hawthorn, remove the core, crush it, mix it evenly with an appropriate amount of food-grade silicon dioxide powder, and then perform supercritical CO 2 Extraction: extract for 1-2 hours at a pressure of 20-30MPa and a temperature of 40-50°C, collect the extract, dissolve the extract with 6 times the amount of water, heat to boiling, keep it slightly boiling for 1.5 hours, filter it with a multi-layer stainless steel filter, collect the filtrate, add 4 times the amount of water to the residue, repeat the above operation, combine the two filtrates, and concentrate to an appropriate amount for standby use;

[0013] S5, extracting the oriental rhizome, after washing the oriental rhizome, adopting microwave-assisted treatment, placing the oriental rhizome in a microwave oven, and treating it at a power of 500-800W for 3-5 minutes to loosen the internal structure of the oriental rhizome, adding 7 times the amount of water to the treated oriental rhizome, soaking for 1 hour, heating to boiling, keeping slightly boiling for 1.5 hours, filtering to obtain a primary filtrate, adding 5 times the amount of water to the residue, repeating the operation to obtain a secondary filtrate, combining the two filtrates, concentrating to a suitable volume, and setting aside;

[0014] S6, turmeric extraction, turmeric is crushed into coarse powder, refluxed and extracted twice with 8 times the amount of 70% ethanol, each time for 2 hours, the extracts are combined, first filtered with a sand core funnel to remove most of the drug residues, then filtered with an ultrafiltration membrane, ethanol is recovered, and concentrated to an extract with a relative density of 1.05-1.10, and finally the turmeric extract is prepared into microcapsules by spray drying for standby use;

[0015] S7, preparing cinnamon extract, mixing cinnamon extract with cyclodextrin, stirring at 40-50° C. for 2-3 hours, so that the cinnamon extract is embedded in the cavity of cyclodextrin molecules to form a cinnamon-cyclodextrin inclusion complex, and setting aside;

[0016] S8, preparing coenzyme Q10 microspheres by emulsification-solvent evaporation method, and setting aside;

[0017] S9, preparing the Eucommia leaf extract, using a thin film dispersion method, dissolving the Eucommia leaf extract, phospholipids and cholesterol in an appropriate amount of an organic solvent, removing the organic solvent by rotary evaporation under reduced pressure to form a lipid film, then adding a phosphate buffer having a pH value of 7.4, and ultrasonically treating the mixture in a water bath ultrasonicator for 15-20 minutes to disperse the lipid film to form liposomes with a particle size of 80-120 nm, which are then set aside;

[0018] S10, preparing the nuciferine extract, using an emulsification-solvent evaporation method, dissolving the nuciferine extract in dichloromethane, mixing with an aqueous phase containing PLGA, stirring at high speed to form an emulsion, and evaporating the organic solvent to obtain nuciferine-PLGA nanoparticles;

[0019] S11, pre-mixing, respectively sieve the porous sponge-like selenium-enriched yeast modified astragalus, nano-coptis chinensis particle dispersion, Gynostemma pentaphyllum particle extract, hawthorn supercritical extract solution, oriental extract, turmeric microcapsule, cinnamon-cyclodextrin inclusion complex, coenzyme Q10 microspheres, Eucommia ulmoides leaf liposomes, and nuciferine-PLGA nanoparticles through an 80-mesh sieve to remove possible lumps or large particle impurities, ensure that the particle size of each component is uniform, weigh each raw material according to the proportion, first place the Gynostemma pentaphyllum particle extract, hawthorn supercritical extract solution, oriental extract, Eucommia ulmoides leaf liposomes, and nuciferine-PLGA nanoparticles in a three-dimensional mixer, and mix them at a speed of 10-15 rpm for 15-20 minutes;

[0020] S12, adding active ingredients and preliminary stirring;

[0021] S13, adding auxiliary materials and stirring finely;

[0022] S14. Filling.

[0023] Preferably, in step S1, the mass ratio of selenium-enriched yeast to astragalus in the culture solution is 1:10, and the shaking speed during shaking culture is 120-150 rpm.

[0024] Preferably, in step S2, the weight of the inoculated bifidobacterium is 7% of the weight of Coptis chinensis.

[0025] Preferably, in step S4, the mass ratio of hawthorn to food-grade silicon dioxide is 10:1.

[0026] Preferably, in step S6, during spray drying, the air inlet temperature is controlled to be 180-200°C, and the air outlet temperature is controlled to be 80-100°C.

[0027] Preferably, in step S7, the mass ratio of cinnamon extract to cyclodextrin is 1:3.

[0028] Preferably, in step S9, the mass ratio of the eucommia leaf extract, phospholipids and cholesterol is 1:3:1.

[0029] Preferably, in step S8, the specific operation of the emulsification-solvent evaporation method is: dissolving coenzyme Q10 in an organic solvent, mixing it with an aqueous phase containing an emulsifier, forming an emulsion at a stirring speed of 1000-1200 rpm, and then stirring at a speed of 200-300 rpm at 30°C to volatilize the organic solvent to form microspheres, and the microspheres are centrifuged at a speed of 5000-6000 rpm for 10 minutes, then washed 3 times with deionized water, and freeze-dried to form coenzyme Q10 microspheres.

[0030] Preferably, the organic solvent for dissolving coenzyme Q10 is ethyl acetate, and the emulsifier for the mixed aqueous phase is polyvinyl alcohol.

[0031] The present invention has the following beneficial effects:

[0032] 1. The oral liquid of the present invention integrates a variety of raw materials with specific pharmacological activities. Selenium-enriched yeast-modified Astragalus not only retains the efficacy of Astragalus itself in improving insulin sensitivity and regulating glucose and lipid metabolism, but the introduction of selenium also enhances the ability to resist oxidative stress, synergizing from multiple aspects such as improving insulin resistance and reducing oxidative damage, and plays a key role in controlling blood sugar and blood lipids and preventing complications in patients with metabolic syndrome. Ultrafine grinding and fermented Coptis chinensis regulates the function of intestinal flora and cooperates with other ingredients to improve the intestinal microenvironment, reduce endotoxin absorption, and alleviate metabolic disorders caused by intestinal flora imbalance. It synergizes with Gynostemma pentaphyllum to further enhance the body's ability to regulate glucose and lipid metabolism. Gynostemma pentaphyllum itself regulates blood lipids and enhances immunity. The two work together to improve symptoms related to obesity and dyslipidemia. Hawthorn helps digestion and strengthens the stomach, promotes qi and disperses blood stasis, while Alisma orientalis promotes urination and clears dampness and heat. The two synergistically promote digestion, regulate water and salt metabolism in the body, effectively lower blood lipids and blood pressure, and reduce edema. They work together with other ingredients to act on various symptoms of metabolic syndrome and improve the health of patients in all aspects.

[0033] 2. The astragalus root in the present invention is made into a porous sponge-like structure, which greatly increases the specific surface area, significantly improves the dissolution rate and extraction efficiency of the effective ingredients, and enables more active ingredients to be utilized, thereby enhancing its efficacy in regulating glucose and lipid metabolism and anti-oxidation;

[0034] 3. In the present invention, the Rhizoma Coptidis is made into a nanoparticle dispersion, and the nano-scale particle size makes it have a huge specific surface area, which can dissolve and release more quickly in the body, greatly improving the bioavailability, and ensuring that its role in regulating intestinal flora and lowering blood sugar is more efficiently exerted;

[0035] 4. The hawthorn and silicon dioxide in the present invention are mixed in supercritical CO 2 Extraction combined with subsequent water extraction not only improves the extraction rate of key active ingredients such as organic acids and flavonoids in hawthorn, but also silicon dioxide plays a filtering role in the water extraction process, improves the purity of the filtrate, and makes hawthorn more effective in digestion, stomach and lowering blood lipids. Microwave-assisted treatment of oriental radix destroys cell structure. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 The figure is a graph showing the changes in fasting blood glucose (FBG) values ​​of treatment group 1, treatment group 2 and control group within 4 months in Example 1;

[0037] Figure 2 This is a graph showing changes in 2-hour postprandial blood glucose (2hPG) values ​​of treatment group 1, treatment group 2 and control group within 4 months in Example 1;

[0038] Figure 3 This is a graph showing the changes in the values ​​of glycated hemoglobin (HbA1c) in treatment group 1, treatment group 2 and control group within 4 months in Example 1;

[0039] Figure 4 The figure is a graph showing the changes in the total cholesterol (TC) values ​​of treatment group 1, treatment group 2 and control group within 4 months in Example 1;

[0040] Figure 5 The figure is a graph showing the changes in triglyceride (TG) values ​​of treatment group 1, treatment group 2 and control group within 4 months in Example 1;

[0041] Figure 6 This is a graph showing the changes in high-density lipoprotein cholesterol (HDL-C) values ​​in treatment group 1, treatment group 2 and control group within 4 months in Example 1;

[0042] Figure 7 This is a graph showing the changes in low-density lipoprotein cholesterol (LDL-C) values ​​in treatment group 1, treatment group 2 and control group within 4 months in Example 1;

[0043] Figure 8 The figure is a graph showing the changes in systolic blood pressure (SBP) of treatment group 1, treatment group 2 and control group within 4 months in Example 1;

[0044] Fig. 9 This is a graph showing the changes in diastolic blood pressure (DBP) values ​​of treatment group 1, treatment group 2 and control group within 4 months in Example 1. DETAILED DESCRIPTION

[0045] The technical solutions in the embodiments of the present invention will be described clearly and completely below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments.

[0046] An oral liquid for treating metabolic syndrome, comprising the following raw materials by weight:

[0047] 12-18 parts of selenium-enriched yeast modified astragalus, 10-14 parts of ultrafinely crushed fermented coptis, 14-18 parts of gynostemma pentaphyllum, 12-16 parts of hawthorn, 8-12 parts of oriental arisaema, 10-13 parts of turmeric, 6-8 parts of cinnamon extract, 3-6 parts of coenzyme Q10 microspheres, 5-10 parts of eucommia leaf extract, and 3-7 parts of nuciferine extract.

[0048] The above-mentioned method for preparing an oral liquid for treating metabolic syndrome comprises the following preparation process:

[0049] S1. Prepare selenium-enriched yeast-modified astragalus, soak it in a culture solution containing selenium-enriched yeast, and culture it for 36 hours under the conditions of 29° C. and pH 5.5 by shaking culture. The mass ratio of selenium-enriched yeast to astragalus in the culture solution is 1:10, and the shaking speed during shaking culture is 120-150 rpm. After the culture is completed, use a continuous centrifuge to quickly separate the astragalus from the culture solution, then rinse it with deionized water for 3 times, and then rinse it with anhydrous ethanol for 2 times. The rinsed astragalus is freeze-dried to form a porous sponge-like structure, first pre-frozen at -40° C. for 2-3 hours, and then dried to constant weight under the conditions of vacuum degree of 0.08-0.09 MPa and temperature of 30° C. for standby use;

[0050] S2. Prepare ultrafine grinding and fermentation of Coptis chinensis. First, freeze Coptis chinensis at -20°C for 2-3 hours, then grind it in an ultrafine grinder to a particle size of 40-100 μm, inoculate the crushed Coptis chinensis with Bifidobacterium, and the weight of the inoculated Bifidobacterium is 7% of the weight of Coptis chinensis. Ferment for 4 days at 36°C and relative humidity of 60%-70%. Use an intelligent stirring system during the fermentation process, stir once every 12 hours, stir for 10 minutes each time, and stir at a speed of 50-60rpm. After the fermentation is completed, make Coptis chinensis into a nanoparticle dispersion, and use a high-pressure homogenization method to homogenize 3-5 times at a pressure of 100-150MPa, so that Coptis chinensis forms nanoparticles with a particle size of 20-50nm and disperses in water for later use;

[0051] S3, extracting Gynostemma pentaphyllum, washing and chopping Gynostemma pentaphyllum, using extrusion granulation technology to make it into particles with a diameter of 2-3mm, adding 8 times the amount of water to the Gynostemma pentaphyllum particles, soaking for 1 hour, heating to boiling, keeping slightly boiling for 2 hours, filtering with a ceramic membrane to obtain a primary filtrate, adding 6 times the amount of water to the residue, repeating the above operation to obtain a secondary filtrate, combining the two filtrates, concentrating under reduced pressure to a relative density of 1.1-1.2, adding 95% ethanol to make the alcohol content reach 70%, standing for 24 hours, filtering with a filter paper-filter cloth combination, recovering ethanol, and obtaining a Gynostemma pentaphyllum extract for standby use;

[0052] S4, hawthorn extraction, the hawthorn was washed, cored, crushed, and evenly mixed with an appropriate amount of food-grade silicon dioxide powder, wherein the mass ratio of hawthorn to food-grade silicon dioxide was 10:1, and then subjected to supercritical CO 2 Extraction: extract for 1-2 hours at a pressure of 20-30MPa and a temperature of 40-50°C, collect the extract, dissolve the extract with 6 times the amount of water, heat to boiling, keep it slightly boiling for 1.5 hours, filter it with a multi-layer stainless steel filter, collect the filtrate, add 4 times the amount of water to the residue, repeat the above operation, combine the two filtrates, and concentrate to an appropriate amount for standby use;

[0053] S5, extracting the oriental rhizome, after washing the oriental rhizome, adopting microwave-assisted treatment, placing the oriental rhizome in a microwave oven, and treating it at a power of 500-800W for 3-5 minutes to loosen the internal structure of the oriental rhizome, adding 7 times the amount of water to the treated oriental rhizome, soaking for 1 hour, heating to boiling, keeping slightly boiling for 1.5 hours, filtering to obtain a primary filtrate, adding 5 times the amount of water to the residue, repeating the operation to obtain a secondary filtrate, combining the two filtrates, concentrating to a suitable volume, and setting aside;

[0054] S6, turmeric extraction, turmeric is crushed into coarse powder, reflux extracted twice with 8 times the amount of 70% ethanol, each time for 2 hours, the extracts are combined, first filtered with a sand core funnel to remove most of the drug residues, then filtered with an ultrafiltration membrane, ethanol is recovered, and concentrated to an extract with a relative density of 1.05-1.10, and finally the turmeric extract is prepared into microcapsules by spray drying for standby use, and the air inlet temperature is controlled at 180-200°C and the air outlet temperature is controlled at 80-100°C during spray drying;

[0055] S7, preparation of cinnamon extract, taking cinnamon, crushing it and then performing steam distillation, collecting the distillate, extracting the distillate with petroleum ether, the extraction process is carried out in a separatory funnel, fully shaking for 5-10 minutes each time, standing and stratifying for 15-20 minutes, taking the petroleum ether layer, repeating the extraction 3-5 times, using new petroleum ether each time, recovering the petroleum ether, further purifying it by molecular distillation technology to obtain cinnamon extract, mixing the cinnamon extract with cyclodextrin, wherein the mass ratio of cinnamon extract to cyclodextrin is 1:3, stirring at 40-50° C. for 2-3 hours, so that the cinnamon extract is embedded in the cavity of cyclodextrin molecules to form a cinnamon-cyclodextrin inclusion complex, and set aside;

[0056] S8. Prepare coenzyme Q10 microspheres by emulsification-solvent evaporation method and set aside; the specific operation of the emulsification-solvent evaporation method is: dissolve coenzyme Q10 in an organic solvent (ethyl acetate is used as the organic solvent), mix it with an aqueous phase containing an emulsifier (polyvinyl alcohol is used as the emulsifier), and form an emulsion at a stirring speed of 1000-1200 rpm, and then stir at a speed of 200-300 rpm at 30°C to evaporate the organic solvent to form microspheres. The microspheres are centrifuged at a speed of 5000-6000 rpm for 10 minutes, then washed 3 times with deionized water, and freeze-dried to form coenzyme Q10 microspheres.

[0057] S9, preparation of Eucommia leaf extract, wash and dry Eucommia leaves, crush them, add 8-10 times the amount of 60% ethanol solution, and perform ultrasonic assisted extraction for 30-45 minutes at an ultrasonic power of 200-300W and a temperature of 50-60°C. The ultrasonic extraction process is carried out in a sealed container with a cooling jacket. After the extraction is completed, the filtrate is filtered, the residue is extracted again, the filtrate is combined, and then concentrated to a suitable volume under reduced pressure, and then separated by adsorption using a macroporous resin column, and water and 20%, 40%, 60%, 80% concentration gradient ethanol are used. The elution was performed with an alcohol solution, and the target eluate was collected and concentrated to obtain an eucommia leaf extract. Finally, the eucommia leaf extract was prepared into liposomes. The eucommia leaf extract, phospholipids and cholesterol were dissolved in an appropriate amount of an organic solvent by a thin film dispersion method. Specifically, the mass ratio of the eucommia leaf extract, phospholipids and cholesterol was 1:3:1. The organic solvent was removed by rotary evaporation under reduced pressure to form a lipid film. Then, a phosphate buffer having a pH value of 7.4 was added, and ultrasonic treatment was performed in a water bath ultrasonicator for 15-20 minutes to disperse the lipid film to form liposomes with a particle size of 80-120 nm, which were set aside.

[0058] S10, preparation of nuciferol extract, washing and drying lotus leaves, crushing them, soaking them in 70% ethanol for 2-3 hours, and then loading them into a macroporous resin column, eluting them with deionized water, 20% ethanol solution, and 50% ethanol solution in sequence, using a peristaltic pump to control the flow rate within the range of 1-2 mL / min during the elution process, collecting the 50% ethanol eluate, and concentrating it to obtain nuciferol extract, and synthesizing the nuciferol extract with PLGA to prepare nanoparticles, dissolving the nuciferol extract in dichloromethane by an emulsification-solvent evaporation method, mixing it with an aqueous phase containing PLGA, stirring it at a high speed to form an emulsion, and evaporating the organic solvent to obtain nuciferol-PLGA nanoparticles;

[0059] S11, pre-mixing, respectively sieve the porous sponge-like selenium-enriched yeast modified astragalus, nano-coptis chinensis particle dispersion, Gynostemma pentaphyllum particle extract, hawthorn supercritical extract solution, oriental extract, turmeric microcapsule, cinnamon-cyclodextrin inclusion complex, coenzyme Q10 microspheres, Eucommia ulmoides leaf liposomes, and nuciferine-PLGA nanoparticles through an 80-mesh sieve to remove possible lumps or large particle impurities, ensure that the particle size of each component is uniform, weigh each raw material according to the proportion, first place the Gynostemma pentaphyllum particle extract, hawthorn supercritical extract solution, oriental extract, Eucommia ulmoides leaf liposomes, and nuciferine-PLGA nanoparticles in a three-dimensional mixer, and mix them at a speed of 10-15 rpm for 15-20 minutes;

[0060] S12, adding active ingredients and preliminary stirring, slowly adding the porous sponge-like selenium-enriched yeast modified astragalus, nano-coptis granule dispersion, turmeric microcapsules, cinnamon-cyclodextrin inclusion compound, and coenzyme Q10 microspheres into the above mixer, and continuing to stir at a speed of 20-25rpm for 20-30 minutes. During the stirring process, adding a small amount of anhydrous ethanol three times, wherein the amount of anhydrous ethanol added each time is 0.5%-1% of the total weight of the mixed material;

[0061] S13, adding auxiliary materials and fine stirring: after the above mixture is stirred evenly, xylitol, sodium benzoate and sodium citrate are dissolved in appropriate amount of deionized water respectively, and after preparing the solution, slowly add it into the mixer, stir at a speed of 30-35rpm for 30-40 minutes, and finally transfer the mixed materials to a vacuum stirring tank, and stir for 10-15 minutes under the condition of vacuum degree of 0.06-0.08MPa;

[0062] S14, filling, the prepared liquid is filled into brown glass bottles using an automated oral liquid filling machine in a Class 100 clean environment, 10 ml per bottle, and the filling speed is 30 bottles / minute. After filling, it is immediately sealed using an electromagnetic induction sealing machine to prevent contamination.

[0063] Embodiment 1:

[0064] Thirty patients diagnosed with metabolic syndrome, aged between 35 and 60 years old, were randomly divided into three groups with 10 people in each group on average. The treatment group 1 took the oral liquid prepared by the above-mentioned method disclosed in the present invention, 10 ml each time, 3 times a day;

[0065] The treatment group 2 took the powder prepared by mixing astragalus extract, coptis extract, gynostemma pentaphyllum extract, hawthorn extract, alisma extract, turmeric extract, cinnamon extract, coenzyme Q10, eucommia ulmoides leaf extract, and lotus leaf alkaloid extract in proportion but not through the preparation method process proposed in the present invention. The extraction method adopted the currently conventional means and was taken orally with warm water. The dose was the same as that after conversion of the corresponding component content in the oral liquid;

[0066] The control group took a placebo.

[0067] The treatment period was 4 months. The fasting blood glucose (FBG), 2-hour postprandial blood glucose (2hPG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP) of the patients were detected before and after treatment respectively. The values at the end of each month were recorded (the average value of each group was taken), and the obtained results are shown in Figure 1-8 。

[0068] Specifically, from Figure 1-8 It is not difficult to see that within 4 months, in treatment group 1, FBG ( Figure 1 ), 2hPG ( Figure 2 ), HbA1c ( Figure 3 ), TC ( Figure 4 ), TG ( Figure 5 ), LDL-C ( Figure 7 ), SBP ( Figure 8 ), DBP ( Fig. 9) showed a relatively obvious downward trend, and there was a steady decline in the monthly detection, indicating that the oral liquid of the present invention can continuously and effectively regulate fasting blood sugar levels, effectively cope with the increase of postprandial blood sugar, improve the body's ability to handle postprandial sugar load, and have a positive effect on long-term blood sugar control. It can effectively reduce the risk of chronic damage to various organs of the body caused by high blood sugar, and has a good regulatory effect on the total cholesterol level in blood lipid metabolism, which helps to reduce the risk of cardiovascular disease, effectively reduce the lipid content in the blood, reduce blood viscosity, and significantly reduce the level of low-density lipoprotein cholesterol, which is crucial to reducing the formation of atherosclerotic plaques and reducing the risk of cardiovascular disease. Blood pressure has been significantly controlled. This shows that the oral liquid has a positive regulatory effect on the cardiovascular system, and can effectively reduce blood pressure levels and reduce the risk of hypertension-related complications through multi-target mechanisms, such as improving endothelial function and regulating the renin-angiotensin-aldosterone system;

[0069] For HDL-C, refer to Figure 6 , HDL-C in treatment group 1 was 1.0±0.2mmol / L before treatment, and increased to 1.3±0.2mmol / L after 4 months of treatment. HDL-C has an anti-atherosclerotic effect, and its increase in level indicates that the oral solution can not only reduce harmful blood lipid components, but also have a positive effect on beneficial blood lipid components.

[0070] The values ​​of treatment group 2 changed less, and the degree of improvement was significantly lower than that of treatment group 1, indicating that the powder without special treatment and optimized formulation process had poor effects in all aspects, while the placebo in the control group had almost no change, and the therapeutic effect was almost zero.

[0071] In summary, through the analysis of fasting blood sugar, 2-hour postprandial blood sugar, glycosylated hemoglobin, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, systolic blood pressure and diastolic blood pressure and other indicators of the three groups of patients, it can be concluded that the oral liquid of the present invention has significant multi-target synergistic beneficial effects in the treatment of metabolic syndrome. It can comprehensively and effectively regulate blood sugar, blood lipids and blood pressure levels, improve the metabolic disorders of patients with metabolic syndrome, and reduce the risk of complications such as cardiovascular diseases. In contrast, the single-ingredient mixed powder without special treatment and optimized formulation process is obviously inferior in therapeutic effect, while the placebo has almost no therapeutic effect. This fully proves the effectiveness and superiority of the unique formula design and preparation process of the oral liquid of the present invention in the treatment of metabolic syndrome, and provides a potential new option for the clinical treatment of metabolic syndrome.

[0072] Embodiment 2:

[0073] 50 patients with metabolic syndrome were selected and randomly divided into two groups, 25 people in each group. The treatment group took the oral liquid of the present invention, 10 ml each time, 3 times a day; the control group took conventional drugs for the treatment of metabolic syndrome (chosen according to the specific conditions of the patients, hypoglycemic, lipid-lowering, and antihypertensive drugs). The treatment cycle was 3 months. At the same time, fecal samples of patients before and after treatment were collected for intestinal flora analysis, and insulin sensitivity was assessed using the insulin resistance homeostasis model assessment method (HOMA-IR).

[0074] The HOMA-IR values ​​of the treatment group and the control group before and after treatment, and the changes in the number of beneficial bacteria (such as bifidobacteria and lactobacilli) and harmful bacteria (such as Escherichia coli and enterococci) in the intestinal flora were recorded. The results are shown in the following tables:

[0075] Table 1: Changes in HOMA-IR values ​​of the treatment group and the control group within 3 months in Example 2

[0076] Serial number Before treatment First Month Second month Third month Treatment Group 5.0±1.0 4.5±0.9 3.8±0.8 3.0±0.8 Control group 4.9±1.1 4.7±1.0 4.5±0.9 4.0±0.9

[0077] Table 2: Changes in the number of bifidobacteria (logCFU / g) in the treatment group and the control group within 3 months in Example 2

[0078] Serial number Before treatment First Month Second month Third month Treatment Group 7.5±1.5 8.0±1.6 8.5±1.7 9.4±1.8 Control group 7.6±1.4 7.7±1.3 7.8±1.2 8.0±1.1

[0079] Table 3: Changes in the number of lactobacilli (logCFU / g) in the treatment group and the control group within 3 months in Example 2

[0080] Serial number Before treatment First Month Second month Third month Treatment Group 6.8±1.2 7.2±1.3 7.8±1.4 8.8±1.5 Control group 6.9±1.3 7.0±1.2 7.1±1.1 7.5±1.0

[0081] Table 4: Changes in the number of Escherichia coli (logCFU / g) in the treatment group and the control group within 3 months in Example 2

[0082] Serial number Before treatment First Month Second month Third month Treatment Group 8.0±1.8 7.5±1.6 6.8±1.4 5.2±1.0 Control group 7.9±1.7 7.8±1.6 7.6±1.5 7.0±1.3

[0083] Table 5: Changes in the number of enterococci (logCFU / g) in the treatment group and the control group within 3 months in Example 2

[0084] Serial number Before treatment First Month Second month Third month Treatment Group 7.2±1.5 6.8±1.3 6.0±1.2 4.3±0.8 Control group 7.1±1.6 7.0±1.5 6.9±1.4 6.5±1.2

[0085] Combined with Tables 1 to 5, it is not difficult to see that in terms of insulin sensitivity, the HOMA-IR value of the treatment group continued to decline during the 3-month treatment period, from 5.0±1.0 to 3.0±0.8, indicating that the oral liquid of the present invention can effectively improve the patient's insulin resistance and gradually improve the body's sensitivity to insulin. The HOMA-IR value of the control group decreased relatively little, from 4.9±1.1 to only 4.0±0.9, indicating that the effect of conventional therapeutic drugs in improving insulin sensitivity is not as significant as the oral liquid of the present invention. This reflects that the synergistic effect of the oral liquid of the present invention has unique advantages in regulating the insulin signaling pathway, promoting the uptake and utilization of glucose by cells, etc., which helps to restore the normal glucose metabolism function of the body, thereby having a positive impact on the blood sugar control of patients with metabolic syndrome.

[0086] In terms of intestinal flora regulation, the number of beneficial bacteria Bifidobacterium and Lactobacillus in the treatment group continued to increase during the treatment process, with Bifidobacterium increasing from 7.5±1.5logCFU / g to 9.4±1.8logCFU / g and Lactobacillus increasing from 6.8±1.2logCFU / g to 8.8±1.5logCFU / g. At the same time, the number of harmful bacteria Escherichia coli and Enterococcus decreased significantly, with Escherichia coli decreasing from 8.0±1.8logCFU / g to 5.2±1.0logCFU / g and Enterococcus decreasing from 7.2±1.5logCFU / g to 4.3±0.8logCFU / g. This shows that the oral liquid can effectively regulate the composition and structure of intestinal flora, promote the growth and reproduction of beneficial bacteria, and inhibit the growth of harmful bacteria. The intestinal flora of the control group changed relatively little, with only a slight increase in the number of beneficial bacteria and a limited reduction in the number of harmful bacteria. This indicates that the oral liquid of the present invention may affect the intestinal microenvironment through the synergistic effect of multiple ingredients, such as regulating the intestinal pH value, providing prebiotic substances, etc., thereby improving the ecological balance of the intestinal flora, and further affecting systemic metabolism through pathways such as the gut-liver axis, and playing an important auxiliary role in improving metabolic disorders in patients with metabolic syndrome. This is also one of the important manifestations of its multi-target treatment of metabolic syndrome.

[0087] Embodiment three:

[0088] A total of 40 obese patients with metabolic syndrome (body mass index (BMI) ≥ 28 kg / m 2), randomly divided into two groups, 20 people in each group. The treatment group took the oral solution of the present invention, 10 ml each time, 3 times a day; the control group took a placebo and performed diet control (reducing calorie intake by about 300 kcal per day). The treatment cycle was 5 months. The patient's weight, waist circumference, and average levels of serum inflammatory factors (such as C-reactive protein CRP, tumor necrosis factor-αTNF-α) were measured before treatment and in the first, second, third, fourth, and fifth months after treatment. The various parameters were recorded as a table, as shown below:

[0089] Table 6: Changes in weight, waist circumference, and average serum inflammatory factors of patients in the treatment group within 5 months in Example 3

[0090] Serial number Before treatment First Month Second month Third month Fourth month Fifth month Weight(kg) 90.5 88.0 86.0 85.0 84.5 84.0 Waist circumference (cm) 105 102 100 98 97.5 97 CRP level (mg / L) 10.0 8.5 7.0 6.0 5.5 5.0 TNF-α level (pg / ml) 12.0 10.5 9.0 8.5 8.2 8.0

[0091] Table 7: Changes in weight, waist circumference, and average serum inflammatory factors of the control group patients in Example 3 within 5 months

[0092]

[0093] Combined with Table VI and Table VII, the weight and waist circumference of the patients in the treatment group showed a continuous downward trend during the 5-month treatment period. The weight dropped from 90.5kg to 84.0kg, and the waist circumference dropped from 105cm to 97cm, indicating that the oral liquid of the present invention has a significant weight loss and fat reduction effect on patients with obese metabolic syndrome, and can effectively reduce fat accumulation in the body. While the control group only controlled the diet, although the weight and waist circumference decreased to a certain extent, the amplitude was significantly smaller than that of the treatment group, indicating that the effect of the oral liquid in weight loss does not only rely on the control of calorie intake, but through the synergistic effect of multiple ingredients, regulating the body's energy metabolism, promoting fat decomposition and metabolism, etc. to achieve the effect of reducing obesity, which is of great significance for improving the body composition and metabolic function of patients with metabolic syndrome.

[0094] The serum CRP level in the treatment group dropped from 10.0mg / L to 5.0mg / L, and the TNF-α level dropped from 12.0pg / ml to 8.0pg / ml, both of which decreased significantly, indicating that the oral liquid can effectively reduce the inflammatory response in patients. Obesity is closely related to chronic inflammatory state. Inflammatory factors can interfere with insulin signal transduction and affect lipid metabolism. The oral liquid helps to improve metabolic disorders such as insulin sensitivity and blood lipid metabolism in patients with metabolic syndrome by reducing the level of inflammation. Although the inflammatory indexes in the control group decreased slightly, the changes were not significant, which further highlighted the unique advantages of the oral liquid of the present invention in regulating obesity-related inflammation. Its multi-target mechanism of action involves inhibiting the activation of inflammatory cells, regulating the secretion of inflammatory factors, and other links, thereby having a positive impact on the overall health of patients with metabolic syndrome and reducing the risk of obesity-related complications.

[0095] As described above, it is only a preferred specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention, according to the technical solution and inventive concept of the present invention, making equivalent substitutions or changes, should be covered within the protection scope of the present invention.

Claims

1. An oral solution for treating metabolic syndrome, characterized in that: The raw material composition includes the following components by weight: 12-18 parts of selenium-enriched yeast modified astragalus, 10-14 parts of ultrafinely crushed fermented coptis, 14-18 parts of gynostemma pentaphyllum, 12-16 parts of hawthorn, 8-12 parts of oriental arisaema, 10-13 parts of turmeric, 6-8 parts of cinnamon extract, 3-6 parts of coenzyme Q10 microspheres, 5-10 parts of eucommia leaf extract, and 3-7 parts of nuciferine extract.

2. The method for preparing an oral liquid for treating metabolic syndrome according to claim 1, characterized in that: The preparation process includes the following: S1. Prepare selenium-enriched yeast-modified astragalus, soak it in a culture solution containing selenium-enriched yeast, and culture it at 29°C and pH 5.5 for 36 hours by shaking culture. After the culture, use a continuous centrifuge to quickly separate the astragalus from the culture solution, then rinse it with deionized water for 3 times, and then rinse it with anhydrous ethanol for 2 times. The rinsed astragalus is freeze-dried to form a porous sponge-like structure, first pre-frozen at -40°C for 2-3 hours, and then dried to constant weight at a vacuum degree of 0.08-0.09MPa and a temperature of 30°C for standby use; S2, preparing ultrafine grinding fermented Coptis chinensis, the Coptis chinensis is first frozen at -20 ° C for 2-3 hours, and then ground in an ultrafine grinder to a particle size of 40-100 μm, the ground Coptis chinensis is inoculated with Bifidobacterium, and fermented at 36 ° C and a relative humidity of 60%-70% for 4 days. During the fermentation process, an intelligent stirring system is used, stirring once every 12 hours, each stirring for 10 minutes, and the stirring speed is 50-60 rpm. After the fermentation is completed, the Coptis chinensis is made into a nanoparticle dispersion, and a high-pressure homogenization method is used to homogenize 3-5 times at a pressure of 100-150 MPa, so that the Coptis chinensis forms nanoparticles with a particle size of 20-50 nm and dispersed in water for standby use; S3, extracting Gynostemma pentaphyllum, washing and chopping Gynostemma pentaphyllum, using extrusion granulation technology to make it into particles with a diameter of 2-3mm, adding 8 times the amount of water to the Gynostemma pentaphyllum particles, soaking for 1 hour, heating to boiling, keeping slightly boiling for 2 hours, filtering with a ceramic membrane to obtain a primary filtrate, adding 6 times the amount of water to the residue, repeating the above operation to obtain a secondary filtrate, combining the two filtrates, concentrating under reduced pressure to a relative density of 1.1-1.2, adding 95% ethanol to make the alcohol content reach 70%, standing for 24 hours, filtering with a filter paper-filter cloth combination, recovering ethanol, and obtaining a Gynostemma pentaphyllum extract for standby use; S4, hawthorn extraction, wash the hawthorn, remove the core, crush it, mix it evenly with an appropriate amount of food-grade silicon dioxide powder, and then perform supercritical CO2 extraction, extract it at a pressure of 20-30MPa and a temperature of 40-50°C for 1-2 hours, collect the extract, dissolve the extract with 6 times the amount of water, heat it to boiling, keep it slightly boiling for 1.5 hours, filter it with a multi-layer stainless steel filter, collect the filtrate, add 4 times the amount of water to the residue, repeat the above operation, combine the two filtrates, and concentrate them to an appropriate amount for standby use; S5, extracting the oriental rhizome, after washing the oriental rhizome, adopting microwave-assisted treatment, placing the oriental rhizome in a microwave oven, and treating it at a power of 500-800W for 3-5 minutes to loosen the internal structure of the oriental rhizome, adding 7 times the amount of water to the treated oriental rhizome, soaking for 1 hour, heating to boiling, keeping slightly boiling for 1.5 hours, filtering to obtain a primary filtrate, adding 5 times the amount of water to the residue, repeating the operation to obtain a secondary filtrate, combining the two filtrates, concentrating to a suitable volume, and setting aside; S6, turmeric extraction, turmeric is crushed into coarse powder, refluxed and extracted twice with 8 times the amount of 70% ethanol, each time for 2 hours, the extracts are combined, first filtered with a sand core funnel to remove most of the drug residues, then filtered with an ultrafiltration membrane, ethanol is recovered, and concentrated to an extract with a relative density of 1.05-1.10, and finally the turmeric extract is prepared into microcapsules by spray drying for standby use; S7, preparing cinnamon extract, mixing cinnamon extract with cyclodextrin, stirring at 40-50° C. for 2-3 hours, so that the cinnamon extract is embedded in the cavity of cyclodextrin molecules to form a cinnamon-cyclodextrin inclusion complex, and setting aside; S8, preparing coenzyme Q10 microspheres by using an emulsification-solvent evaporation method, and setting aside; S9, preparing the Eucommia leaf extract, using a thin film dispersion method, dissolving the Eucommia leaf extract, phospholipids and cholesterol in an appropriate amount of an organic solvent, removing the organic solvent by rotary evaporation under reduced pressure to form a lipid film, then adding a phosphate buffer having a pH value of 7.4, and ultrasonically treating the mixture in a water bath ultrasonicator for 15-20 minutes to disperse the lipid film to form liposomes with a particle size of 80-120 nm, which are then set aside; S10, preparing the nuciferine extract, using an emulsification-solvent evaporation method, dissolving the nuciferine extract in dichloromethane, mixing with an aqueous phase containing PLGA, stirring at high speed to form an emulsion, and evaporating the organic solvent to obtain nuciferine-PLGA nanoparticles; S11, pre-mixing, respectively sieve the porous sponge-like selenium-enriched yeast modified astragalus, nano-coptis chinensis particle dispersion, Gynostemma pentaphyllum particle extract, hawthorn supercritical extract solution, oriental extract, turmeric microcapsule, cinnamon-cyclodextrin inclusion complex, coenzyme Q10 microspheres, Eucommia ulmoides leaf liposomes, and nuciferine-PLGA nanoparticles through an 80-mesh sieve to remove possible lumps or large particle impurities, ensure that the particle size of each component is uniform, weigh each raw material according to the proportion, first place the Gynostemma pentaphyllum particle extract, hawthorn supercritical extract solution, oriental extract, Eucommia ulmoides leaf liposomes, and nuciferine-PLGA nanoparticles in a three-dimensional mixer, and mix them at a speed of 10-15 rpm for 15-20 minutes; S12, adding active ingredients and preliminary stirring; S13, adding auxiliary materials and stirring finely; S14. Filling.

3. The method for preparing an oral liquid for treating metabolic syndrome according to claim 2, characterized in that: In the step S1, the mass ratio of selenium-enriched yeast to astragalus in the culture solution is 1:10, and the shaking speed during shaking culture is 120-150 rpm.

4. An oral liquid for treating metabolic syndrome and a preparation method according to claim 2, characterized in that: In the step S2, the weight of the inoculated bifidobacterium is 7% of the weight of Coptis chinensis.

5. The method for preparing an oral liquid for treating metabolic syndrome according to claim 2, characterized in that: In step S4, the mass ratio of hawthorn to food-grade silicon dioxide is 10:

1.

6. The method for preparing an oral liquid for treating metabolic syndrome according to claim 2, characterized in that: In step S6, during spray drying, the air inlet temperature is controlled to be 180-200°C and the air outlet temperature is controlled to be 80-100°C.

7. The method for preparing an oral liquid for treating metabolic syndrome according to claim 2, characterized in that: In the step S7, the mass ratio of cinnamon extract to cyclodextrin is 1:

3.

8. The method for preparing an oral liquid for treating metabolic syndrome according to claim 2, characterized in that: In the step S9, the mass ratio of the eucommia leaf extract, phospholipids and cholesterol is 1:3:

1.

9. The method for preparing an oral liquid for treating metabolic syndrome according to claim 2, characterized in that: In step S8, the specific operation of the emulsification-solvent evaporation method is as follows: dissolving coenzyme Q10 in an organic solvent, mixing it with an aqueous phase containing an emulsifier, forming an emulsion at a stirring speed of 1000-1200 rpm, and then stirring at a speed of 200-300 rpm at 30°C to volatilize the organic solvent to form microspheres. The microspheres are centrifuged at a speed of 5000-6000 rpm for 10 minutes, then washed 3 times with deionized water, and freeze-dried to form coenzyme Q10 microspheres.

10. The method for preparing an oral liquid for treating metabolic syndrome according to claim 9, characterized in that: Ethyl acetate is used as the organic solvent for dissolving coenzyme Q10, and polyvinyl alcohol is used as the emulsifier for the mixed water phase.

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