Thaflavin composition for treating hypertension as well as preparation method and application of theaflavin composition

Abstract

The invention provides a theaflavin composition for treating hypertension as well as a preparation method and application thereof, and relates to the technical field of medicines. The theaflavin composition comprises theaflavin, a celery seed extract, a gastrodia elata extract, a parasitic loranthus extract, a centella asiatica extract, a lotus leaf extract and a licorice extract. Wherein the theaflavin can regulate blood fat, inhibit atherosclerosis and improve the vascular endothelial function; the celery seed extract inhibits the activity of angiotensin converting enzyme, and cooperates with theaflavin to regulate blood pressure; the gastrodia elata extract can calm liver wind and improve cerebral circulation; the loranthus parasiticus extract has the effects of tonifying liver and kidney and regulating water sodium metabolism; the centella asiatica extract can resist inflammation and repair vascular endothelium; the lotus leaf extract can clear heat, promote diuresis, calm the liver and suppress yang; and the licorice extract harmonizes the medicines and resists oxidation. According to the invention, theaflavin is taken as a core, multi-dimensional effects of reducing blood pressure, protecting blood vessels and resisting inflammation and oxidation are realized, and a natural and comprehensive health management scheme is provided for hypertensive patients.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a theaflavin composition for treating hypertension, a preparation method thereof and an application thereof. Background Art

[0002] Hypertension, a common cardiovascular disease, poses a serious threat to human health. Hypertension is characterized by elevated systemic arterial pressure and increased peripheral arteriolar resistance, often accompanied by varying degrees of increased cardiac output and blood volume. Hypertensive patients often experience symptoms such as dizziness, headache, blurred vision, tinnitus, insomnia, and fatigue. Long-term hypertension can severely affect the structure and function of target organs such as the heart, brain, and kidneys, and may ultimately lead to serious consequences such as heart failure, renal failure, and stroke, significantly reducing the patient's quality of life and even endangering their lives.

[0003] Currently, the treatment of hypertension mainly includes lifestyle intervention and drug therapy. Lifestyle intervention includes weight control, reduced salt intake, increased exercise, etc. However, for many patients, it is difficult to effectively control blood pressure by relying solely on lifestyle changes, and medication is still needed. However, although existing antihypertensive drugs can control blood pressure to a certain extent, they have many side effects. For example, nifedipine sustained-release tablets may cause facial flushing and rapid heartbeat, and metoprolol tartrate tablets may cause bradycardia and fatigue. Long-term use may affect patient compliance and quality of life. Natural active ingredients, due to their high safety and minimal side effects, have attracted widespread attention in the prevention and treatment of hypertension. Theaflavins, a compound isolated from tea leaves, have garnered significant attention in recent years. Research has shown that theaflavins possess diverse biological activities, including antioxidant, anti-inflammatory, and lipid-lowering activities. Currently, there are relatively few products and research studies directly applying theaflavins to the treatment of hypertension, making it difficult to meet clinical needs.

[0004] Therefore, the development of a safe and effective theaflavin-based composition for the treatment of hypertension has important practical significance. It can not only provide new treatment options for hypertensive patients, but also reduce the side effects of traditional drugs and improve the quality of life of patients. Summary of the Invention

[0005] The object of the present invention is to provide a theaflavin composition for treating hypertension, a preparation method thereof and an application thereof. The theaflavin composition provided by the present invention can significantly lower blood pressure.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions: The present invention provides a theaflavin composition for treating hypertension, comprising the following components in parts by weight: 8-12 parts of theaflavin, 5-10 parts of celery seed extract, 3-8 parts of gastrodia elata extract, 3-8 parts of mistletoe extract, 3-8 parts of Centella asiatica extract, 3-8 parts of lotus leaf extract and 1-3 parts of liquorice extract.

[0007] The present invention also provides a method for preparing the above-mentioned theaflavins composition, comprising: mixing hydroxypropyl-β-cyclodextrin with water to obtain a hydroxypropyl-β-cyclodextrin solution, adding theaflavins, celery seed extract, Gastrodia elata extract, Morus alba extract, Centella asiatica extract, lotus leaf extract and licorice extract, performing ultrasonic inclusion complexation, and spray drying to obtain the theaflavins composition.

[0008] Preferably, the mass volume ratio of the hydroxypropyl-β-cyclodextrin solution is 15%-20%.

[0009] More preferably, the volume ratio of the total weight of theaflavins, celery seed extract, Gastrodia elata extract, Morus alba extract, Centella asiatica extract, lotus leaf extract and liquorice extract to the hydroxypropyl-β-cyclodextrin solution is 1:10-15.

[0010] Preferably, the celery seed extract is obtained by supercritical CO2 extraction.

[0011] Preferably, the Gastrodia elata extract and the Morus alba extract are obtained by ultrasonic enzymatic hydrolysis, hot water extraction, and alcohol precipitation.

[0012] Preferably, the Centella asiatica extract and the Licorice extract are obtained by ethanol ultrasonic extraction.

[0013] Preferably, the lotus leaf extract is obtained by fermentation.

[0014] The present invention also provides the use of the theaflavin composition in preparing a drug for treating hypertension.

[0015] Preferably, the hypertension is essential hypertension.

[0016] Compared with the prior art, the present invention has the following beneficial effects: The present invention provides a theaflavins composition for treating hypertension, comprising theaflavins, celery seed extract, Gastrodia elata extract, mistletoe extract, Centella asiatica extract, lotus leaf extract, and licorice extract. Theaflavins regulate blood lipids, inhibit atherosclerosis, and improve vascular endothelial function, directly intervening in hypertension. Celery seed extract inhibits angiotensin-converting enzyme activity and reduces the production of vasoconstrictor substances, synergizing with theaflavins to regulate blood pressure. Gastrodia elata extract calms the liver and extinguishes wind, improving cerebral circulation. Mulberry leaf extract nourishes the liver and kidneys and regulates water and sodium metabolism. Centella asiatica extract fights inflammation and repairs vascular endothelium. Lotus leaf extract clears heat and dampness, calms the liver and suppresses yang, promoting water metabolism and fat decomposition. Licorice extract harmonizes the various medicinal ingredients and acts as an antioxidant. With theaflavins as its core, the composition of the present invention achieves a multi-dimensional synergistic effect of lowering blood pressure, protecting blood vessels, and combating inflammation and oxidation, balancing symptom relief and complication prevention, providing a natural, comprehensive health management solution for patients with hypertension. DETAILED DESCRIPTION

[0017] The present invention provides a theaflavin composition for treating hypertension, comprising the following components in parts by weight: 8-12 parts of theaflavin, 5-10 parts of celery seed extract, 3-8 parts of gastrodia elata extract, 3-8 parts of mistletoe extract, 3-8 parts of Centella asiatica extract, 3-8 parts of lotus leaf extract and 1-3 parts of liquorice extract.

[0018] The theaflavins in the composition of the present invention play a core role in regulating blood lipids, inhibiting atherosclerosis, and improving vascular endothelial function. As the core active ingredient in black tea, theaflavins can directly intervene in the hyperlipidemia and vascular sclerosis associated with hypertension by reducing cholesterol absorption and inhibiting endocrine cholesterol synthesis. It is the core drug in the prescription for the main symptoms of high blood pressure.

[0019] The celery seed extract in the composition of the present invention plays an auxiliary role in lowering blood pressure, anti-oxidation, and improving vascular tension; the celery seed extract inhibits the activity of angiotensin-converting enzyme, reduces the production of vasoconstrictor substances, and cooperates with theaflavins to regulate blood pressure. At the same time, its antioxidant capacity can reduce the damage to blood vessels by free radicals, assisting theaflavins in strengthening the dual goals of "lowering blood pressure" and "protecting blood vessels."

[0020] The Gastrodia elata extract in the composition of the present invention can calm the liver and extinguish wind, improve cerebral circulation, and alleviate the symptoms of hyperactivity of liver yang such as dizziness and headache caused by hypertension by regulating the central nervous system and dilating cerebral blood vessels.

[0021] The mistletoe extract in the composition of the present invention nourishes the liver and kidneys, regulates water and sodium metabolism, improves the metabolic disorder of liver and kidney yin deficiency type hypertension, reduces water and sodium retention, and assists in lowering blood pressure.

[0022] The Centella asiatica extract in the composition of the present invention has anti-inflammatory and vascular endothelial repair effects, can inhibit the release of inflammatory factors, reduce vascular endothelial damage, and prevent hypertension complications.

[0023] The lotus leaf extract in the composition of the present invention clears away heat and dampness, calms the liver and suppresses yang, and can dilate blood vessels, lower blood lipids and assist in lowering blood pressure by promoting water metabolism and reducing visceral fat accumulation.

[0024] The liquorice extract in the composition of the present invention can harmonize various medicines and has anti-oxidation effect.

[0025] The present invention also provides a method for preparing the above-mentioned theaflavins composition, comprising: mixing hydroxypropyl-β-cyclodextrin with water to obtain a hydroxypropyl-β-cyclodextrin solution, adding theaflavins, celery seed extract, Gastrodia elata extract, Morus alba extract, Centella asiatica extract, lotus leaf extract and licorice extract, performing ultrasonic inclusion complexation, and spray drying to obtain the theaflavins composition.

[0026] The concentration of the hydroxypropyl-β-cyclodextrin solution of the present invention is preferably 15%-20% (w / v), more preferably 18% (w / v). The preparation method of the hydroxypropyl-β-cyclodextrin solution is preferably: mixing hydroxypropyl-β-cyclodextrin with water at 50-60°C to obtain a hydroxypropyl-β-cyclodextrin solution; the volume ratio of the total weight of the theaflavins, celery seed extract, Gastrodia elata extract, Morus alba extract, Centella asiatica extract, lotus leaf extract and licorice extract to the hydroxypropyl-β-cyclodextrin solution is preferably 1:10-15, more preferably 1:12. By encapsulating the active ingredients of the composition with hydroxypropyl-β-cyclodextrin, the solubility and stability of the active ingredients can be improved. The celery seed extract of the present invention is obtained by supercritical CO2 extraction. The preparation method of the celery seed extract preferably comprises drying the celery seeds to a moisture content of 3%-7%, crushing them through a 40-80 mesh sieve, and extracting them with supercritical CO2 for 30-40 minutes at a temperature of 30-40°C, a pressure of 20-30 MPa, and a CO2 flow rate of 3-5 kg / h to obtain the celery seed extract. More preferably, the celery seeds are dried to a moisture content of 5%, crushed through a 60 mesh sieve, and extracted with supercritical CO2 for 35 minutes at a temperature of 35°C, a pressure of 25 MPa, and a CO2 flow rate of 4 kg / h to obtain the celery seed extract.

[0027] The Gastrodia elata extract and the Morus alba extract of the present invention are obtained by ultrasonic enzymatic hydrolysis, hot water extraction, and alcohol precipitation. The preparation method of the Gastrodia elata extract is preferably as follows: the Gastrodia elata tuber is dried and crushed, passed through a 200-400 mesh sieve, mixed with 23-28 times the weight of water, and a complex enzyme is added to perform enzymatic hydrolysis at 42-46°C and a pH value of 5.5-6.6 for 40-60 minutes, the enzyme is inactivated, and the extract is extracted at 80-90°C for 1.5-2.5 hours, centrifuged at 400-600 rpm for 8-12 minutes, the supernatant is concentrated under reduced pressure to 1 / 3-1 / 5 of the supernatant volume, 3-5 times the volume of 90%-95% (v / v) ethanol solution is added, the extract is allowed to stand at 2-5°C for 10-15 hours, and centrifuged at 300-400 rpm for 13-18 minutes, and the precipitate is collected as the Gastrodia elata extract. More preferably, the tubers of Gastrodia elata are dried and crushed, passed through a 300-mesh sieve, mixed with 25 times the weight of water, and a complex enzyme is added for enzymatic hydrolysis at 44°C and pH 6 for 50 minutes, the enzyme is inactivated, extracted at 85°C for 2 hours, centrifuged at 500 rpm for 10 minutes, the supernatant is concentrated under reduced pressure to 1 / 4 of the volume of the supernatant, 4 times the volume of 93% (v / v) ethanol solution is added, the mixture is allowed to stand at 4°C for 12 hours, and centrifuged at 350 rpm for 15 minutes, and the precipitate is collected as the Gastrodia elata extract. The preparation method of the mistletoe extract is preferably as follows: drying and crushing the mistletoe, passing through a 150-250 mesh sieve, mixing with 20-25 times its weight of water, adding a complex enzyme, performing enzymatic hydrolysis at 42-46° C. and a pH value of 5.5-6.6 for 50-60 minutes, inactivating the enzyme, extracting at 92-96° C. for 1-2 hours, centrifuging at 500-600 rpm for 8-12 minutes, taking the supernatant and concentrating it under reduced pressure to 1 / 3-1 / 5 of the volume of the supernatant, adding 3-5 times the volume of 93%-97% (v / v) ethanol solution, standing at 2-5° C. for 10-15 hours, centrifuging at 400-500 rpm for 13-18 minutes, and collecting the precipitate as the mistletoe extract. More preferably, the mistletoe is dried and crushed, passed through a 200-mesh sieve, mixed with 23 times its weight of water, and a complex enzyme is added for enzymatic hydrolysis at 44°C and pH 6 for 55 minutes, the enzyme is inactivated, and the mixture is extracted at 93°C for 1.5 hours, centrifuged at 550 rpm for 10 minutes, the supernatant is concentrated under reduced pressure to 1 / 4 of the volume of the supernatant, 4 times the volume of 95% (v / v) ethanol solution is added, the mixture is allowed to stand at 4°C for 12 hours, and centrifuged at 450 rpm for 15 minutes, and the precipitate is collected as the mistletoe extract.The complex enzyme used in the preparation process of Gastrodia elata extract and Morus alba extract is preferably composed of cellulase and papain in a weight ratio of 2-5:1-3, more preferably 3:2. The cellulase has an enzymatic activity of 100,000 U / g and is purchased from Jiangsu Changjing Bioengineering Co., Ltd. with item number 101. The papain has an enzymatic activity of 100,000 U / g and is purchased from Heze Fengrui Biotechnology Co., Ltd. with item number FR-5466. The dosage of the complex enzyme is preferably 2%-5% of the mass of the Gastrodia elata tuber, more preferably 3%.

[0028] The Centella asiatica extract and the licorice extract of the present invention are obtained by ethanol ultrasonic extraction. The preparation method of the Centella asiatica extract preferably comprises: grinding the Centella asiatica through a 100-150 mesh sieve, adding 15-25 parts by weight of a 60%-70% (v / v) ethanol solution, ultrasonically extracting at 40-50°C and 45-55kHz for 1-3 times, each time for 30-60 minutes, combining the filtrates, concentrating the filtrates under reduced pressure to 1 / 2-1 / 4 of the volume of the filtrate, and drying to obtain the Centella asiatica extract. More preferably, the method comprises: grinding the Centella asiatica through a 120 mesh sieve, adding 20 parts by weight of a 65% (v / v) ethanol solution, ultrasonically extracting at 45°C and 50kHz for 2 times, each time for 40 minutes, combining the filtrates, concentrating the filtrates under reduced pressure to 1 / 3 of the volume of the filtrate, and drying to obtain the Centella asiatica extract.

[0029] The preparation method of the licorice extract preferably comprises: grinding the licorice through an 80-120 mesh sieve, adding 15-25 times by weight of a 70%-80% (v / v) ethanol solution, ultrasonically extracting at 45-55° C. and 50-60 kHz for 1-3 times, each time for 20-40 minutes, combining the filtrates, concentrating the filtrates under reduced pressure to 1 / 2-1 / 4 of the volume of the filtrate, and drying to obtain the licorice extract. More preferably, it comprises: grinding the licorice through a 100 mesh sieve, adding 20 times by weight of a 75% (v / v) ethanol solution, ultrasonically extracting at 50° C. and 55 kHz for 2 times, each time for 30 minutes, combining the filtrates, concentrating the filtrates under reduced pressure to 1 / 3 of the volume of the filtrate, and drying to obtain the licorice extract.

[0030] The lotus leaf extract of the present invention is obtained by fermentation. The preparation method of the lotus leaf extract of the present invention preferably comprises: drying and crushing the lotus leaves, passing through a 50-100 mesh sieve, mixing with 8-15 times the weight of distilled water, sterilizing, inoculating with 1%-3% of the composite bacterial solution, fermenting at 28-32°C, an initial pH of 6-7, and 120-170 rpm for 48-72 hours, sterilizing, centrifuging at 500-600 rpm for 10-15 minutes, taking the supernatant, concentrating under reduced pressure to 1 / 2-1 / 4 of the supernatant volume, and drying to obtain the lotus leaf extract. The preparation method of the lotus leaf extract more preferably comprises: drying and crushing the lotus leaves, passing through an 80 mesh sieve, mixing with 10 times the weight of distilled water, sterilizing, inoculating with 2% of the composite bacterial solution, fermenting at 30°C, an initial pH of 6.5, and 150 rpm for 60 hours, sterilizing, centrifuging at 500 rpm for 12 minutes, taking the supernatant, concentrating under reduced pressure to 1 / 3 of the supernatant volume, and drying to obtain the lotus leaf extract. The composite bacterial solution is preferably composed of Aspergillus niger solution and Bacillus subtilis solution in a volume ratio of 3-6:1-3, more preferably 5:2. The Aspergillus niger is Aspergillus niger HY4-2, purchased from Guangdong Provincial Microbial Culture Collection Center, with a deposit number of GDMCC No: 62851, disclosed in CN116041561A. The spore concentration of the Aspergillus niger solution is preferably (3-8)×10 8 / mL, more preferably 5×10 8 Bacillus subtilis CICC ® 10148, the spore concentration of the Bacillus subtilis liquid purchased from the China Industrial Microbiological Culture Collection Center is preferably (1-3)×10 9 / mL, more preferably 2×10 9 pieces / mL.

[0031] The present invention also provides the use of the above-mentioned theaflavins composition in the preparation of a drug for treating hypertension, wherein the hypertension is essential hypertension. The drug comprises the above-mentioned theaflavins composition and pharmaceutically acceptable excipients. The dosage form of the drug includes tablets, capsules, granules, pills, and oral liquid.

[0032] In the present invention, unless otherwise specified, all raw material components are commercially available products well known to those skilled in the art.

[0033] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions of the present invention. Obviously, the embodiments described are only some of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0034] In the following examples, unless otherwise specified, all methods are conventional.

[0035] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0036] The cellulase activity in the examples and comparative examples was 100,000 U / g, purchased from Jiangsu Changjing Bioengineering Co., Ltd., item number 101; the papain activity was 100,000 U / g, purchased from Heze Fengrui Biotechnology Co., Ltd., item number FR-5466; Aspergillus niger was Aspergillus niger HY4-2, purchased from Guangdong Provincial Microbiological Culture Collection Center, with a collection number of GDMCC No: 62851; Bacillus subtilis was Bacillus subtilis CICC ® 10148, purchased from China National Center for Industrial Culture Collection of Microorganisms; Aspergillus oryzae was Aspergillus oryzae CICC® 2359, purchased from China National Center for Industrial Culture Collection of Microorganisms; Bacillus thuringiensis was Bacillus thuringiensis CICC® 10059, purchased from China National Center for Industrial Culture Collection of Microorganisms; theaflavin was prepared according to Example 4 of invention patent CN117867052A, and the theaflavin content was 63.9% as determined by HPLC; hydroxypropyl-β-cyclodextrin was purchased from Xi'an Dongfeng Biotechnology Co., Ltd., item number DF5641.

[0037] Example 1 Preparation of theaflavin composition (1) Preparation of celery seed extract Celery seeds were dried to a moisture content of 5%, crushed and passed through a 60-mesh sieve, and subjected to supercritical CO2 extraction for 35 min at a temperature of 35°C, a pressure of 25 MPa, and a CO2 flow rate of 4 kg / h to obtain celery seed extract; (2) Preparation of Gastrodia elata extract and Morus alba extract The tubers of Gastrodia elata were dried and crushed, passed through a 300-mesh sieve, mixed with 25 times the weight of water, and a composite enzyme of 3% by weight of the tubers of Gastrodia elata was added. The mixture was enzymatically hydrolyzed at 44° C. and pH 6 for 50 min, the enzyme was inactivated, and the mixture was extracted at 85° C. for 2 h. The mixture was centrifuged at 500 rpm for 10 min, the supernatant was concentrated under reduced pressure to 1 / 4 of the volume of the supernatant, 4 times the volume of 93% (v / v) ethanol solution was added, the mixture was allowed to stand at 4° C. for 12 h, and centrifuged at 350 rpm for 15 min. The precipitate was collected as the Gastrodia elata extract; The mistletoe extract was dried and crushed, passed through a 200-mesh sieve, mixed with 23 times the weight of water, and a complex enzyme was added, which was 3% by weight of the mistletoe, and enzymatically hydrolyzed at 44°C and pH 6 for 55 minutes, and the enzyme was inactivated. The extract was extracted at 93°C for 1.5 hours, and then centrifuged at 550 rpm for 10 minutes. The supernatant was concentrated under reduced pressure to 1 / 4 of the volume of the supernatant, and 4 times the volume of 95% (v / v) ethanol solution was added. The extract was allowed to stand at 4°C for 12 hours, and centrifuged at 450 rpm for 15 minutes. The precipitate was collected as the mistletoe extract. The complex enzyme used in the preparation of Gastrodia elata extract and Morus alba extract consists of cellulase and papain in a weight ratio of 3:2; (3) Preparation of Centella asiatica extract and Licorice extract The Centella asiatica was crushed and passed through a 120-mesh sieve, 20 times the weight of a 65% (v / v) ethanol solution was added, and ultrasonic extraction was performed twice at 45° C. and 50 kHz for 40 minutes each time. The mixture was filtered, and the filtrates were combined, and the filtrates were concentrated under reduced pressure to 1 / 3 of the volume of the filtrate, and dried to obtain the Centella asiatica extract. Grind the liquorice through a 100-mesh sieve, add 20 times the weight of a 75% (v / v) ethanol solution, and ultrasonically extract twice at 50° C. and 55 kHz for 30 minutes each time, filter, combine the filtrates, and concentrate the filtrates under reduced pressure to 1 / 3 of the volume of the filtrate, and dry to obtain the liquorice extract; (4) Lotus leaf extract The lotus leaf was dried and crushed, passed through an 80-mesh sieve, mixed with 10 times the weight of distilled water, sterilized, inoculated with 2% (w / w) composite bacterial solution, fermented at 30°C, initial pH 6.5, and 150 rpm for 60 hours, sterilized, centrifuged at 550 rpm for 12 minutes, and the supernatant was concentrated under reduced pressure to 1 / 3 of the volume of the supernatant, and dried to obtain the lotus leaf extract; The composite bacterial solution is composed of Aspergillus niger solution and Bacillus subtilis solution in a volume ratio of 5:2, and the spore concentration of Aspergillus niger solution is 5×10 8 / mL, and the spore concentration of Bacillus subtilis was 2×10 9 / mL; (5) Preparation of theaflavins composition Accurately weigh 10 parts by weight of theaflavins, 8 parts by weight of celery seed extract, 5 parts by weight of Gastrodia elata extract, 5 parts by weight of Morus alba extract, 5 parts by weight of Centella asiatica extract, 5 parts by weight of lotus leaf extract, and 2 parts by weight of liquorice extract; Hydroxypropyl-β-cyclodextrin was mixed with distilled water at 55°C to obtain a 18% (w / v) hydroxypropyl-β-cyclodextrin solution, to which theaflavins, celery seed extract, Gastrodia elata extract, Morus alba extract, Centella asiatica extract, lotus leaf extract, and licorice extract were added, and the mixture was stirred at 55°C and 400 rpm for 2 h, and spray-dried to obtain a theaflavins composition. The volume ratio of the total weight of theaflavins, celery seed extract, Gastrodia elata extract, Morus alba extract, Centella asiatica extract, lotus leaf extract and licorice extract to the hydroxypropyl-β-cyclodextrin solution is 1:12 g / mL.

[0038] Example 2 Preparation of theaflavin composition (1) Celery seeds were dried to a moisture content of 3%, crushed and passed through a 40-mesh sieve, and subjected to supercritical CO2 extraction for 40 min at a temperature of 30°C, a pressure of 20 MPa, and a CO2 flow rate of 3 kg / h to obtain celery seed extract; (2) Preparation of Gastrodia elata extract and Morus alba extract The tubers of Gastrodia elata were dried and crushed, passed through a 200-mesh sieve, mixed with 23 times the weight of water, and a composite enzyme of 2% by weight of the tubers of Gastrodia elata was added. The mixture was enzymatically hydrolyzed at 42° C. and a pH value of 5.5 for 60 min, the enzyme was inactivated, and the mixture was extracted at 80° C. for 2.5 h, centrifuged at 400 rpm for 12 min, the supernatant was concentrated under reduced pressure to 1 / 3 of the volume of the supernatant, 3 times the volume of 95% (v / v) ethanol solution was added, the mixture was allowed to stand at 2° C. for 10 h, and centrifuged at 300 rpm for 18 min. The precipitate was collected as the Gastrodia elata extract; The mistletoe extract was dried and crushed, passed through a 150-mesh sieve, mixed with 20 times the weight of water, and a complex enzyme was added, and enzymatic hydrolysis was carried out at 42° C. and a pH value of 5.5 for 60 minutes, the enzyme was inactivated, and extraction was carried out at 92° C. for 2 hours, followed by centrifugation at 500 rpm for 12 minutes. The supernatant was concentrated under reduced pressure to 1 / 3 of the volume of the supernatant, 3 times the volume of 97% (v / v) ethanol solution was added, and the mixture was allowed to stand at 2° C. for 10 hours, and centrifuged at 400 rpm for 18 minutes. The precipitate was collected as the mistletoe extract; The complex enzyme used in the preparation of Gastrodia elata extract and Morus alba extract consists of cellulase and papain in a weight ratio of 2:1; (3) Preparation of Centella asiatica extract and Licorice extract The Centella asiatica was crushed and passed through a 100-mesh sieve, 15 times the weight of a 70% (v / v) ethanol solution was added, and ultrasonic extraction was performed three times at 40° C. and 45 kHz for 30 minutes each time. The mixture was filtered, and the filtrates were combined and concentrated under reduced pressure to 1 / 2 of the volume of the filtrate, and dried to obtain the Centella asiatica extract. Grind the licorice root through an 80-mesh sieve, add 15 times the weight of an 80% (v / v) ethanol solution, and extract it three times with ultrasound at 45° C. and 50 kHz for 20 minutes each time. Filter, combine the filtrates, and concentrate the filtrates under reduced pressure to 1 / 2 of the volume of the filtrate, and dry to obtain the licorice extract; (4) Lotus leaf extract The lotus leaf was dried and crushed, passed through a 50-mesh sieve, mixed with 8 times its weight of distilled water, sterilized, inoculated with 1% (w / w) composite bacterial solution, fermented at 32° C., initial pH 7, and 120 rpm for 48 hours, sterilized, centrifuged at 500 rpm for 15 minutes, and the supernatant was concentrated under reduced pressure to 1 / 2 of the volume of the supernatant, and dried to obtain the lotus leaf extract; The composite bacterial solution is composed of Aspergillus niger solution and Bacillus subtilis solution in a volume ratio of 3:1, and the spore concentration of Aspergillus niger solution is 8×10 8 / mL, and the spore concentration of Bacillus subtilis was 3×10 9 / mL; (5) Preparation of theaflavins composition Accurately weigh 8 parts by weight of theaflavins, 5 parts by weight of celery seed extract, 3 parts by weight of Gastrodia elata extract, 3 parts by weight of Morus alba extract, 3 parts by weight of Centella asiatica extract, 3 parts by weight of lotus leaf extract, and 1 part by weight of liquorice extract; Hydroxypropyl-β-cyclodextrin was mixed with distilled water at 50°C to obtain a 15% (w / v) hydroxypropyl-β-cyclodextrin solution, to which theaflavins, celery seed extract, Gastrodia elata extract, Morus alba extract, Centella asiatica extract, lotus leaf extract, and licorice extract were added, and the mixture was stirred for inclusion at 50°C and 300 rpm for 3 hours, and spray-dried to obtain a theaflavins composition; The volume ratio of the total weight of theaflavins, celery seed extract, Gastrodia elata extract, Morus alba extract, Centella asiatica extract, lotus leaf extract and licorice extract to the hydroxypropyl-β-cyclodextrin solution is 1:10 g / mL.

[0039] Example 3 Preparation of theaflavin composition (1) Celery seeds were dried to a moisture content of 7%, crushed and passed through an 80-mesh sieve, and subjected to supercritical CO2 extraction for 30 min at a temperature of 40°C, a pressure of 30 MPa, and a CO2 flow rate of 5 kg / h to obtain celery seed extract; (2) Preparation of Gastrodia elata extract and Morus alba extract The tubers of Gastrodia elata were dried and crushed, passed through a 400-mesh sieve, mixed with 28 times the weight of water, and a composite enzyme of 5% by weight of the tubers of Gastrodia elata was added. The mixture was enzymatically hydrolyzed at 46° C. and a pH value of 6.5 for 40 minutes, the enzyme was inactivated, and the mixture was extracted at 90° C. for 1.5 hours, centrifuged at 600 rpm for 10 minutes, and the supernatant was concentrated under reduced pressure to 1 / 5 of the volume of the supernatant. 5 times the volume of 90% (v / v) ethanol solution was added, and the mixture was allowed to stand at 5° C. for 15 hours, and centrifuged at 400 rpm for 13 minutes. The precipitate was collected as the Gastrodia elata extract; The mistletoe extract was dried and crushed, passed through a 250-mesh sieve, mixed with 25 times the weight of water, and a complex enzyme was added, which was 5% by weight of the mistletoe, and enzymatically hydrolyzed at 46°C and pH 6.5 for 50 minutes, and the enzyme was inactivated. The mixture was extracted at 96°C for 1 hour, and then centrifuged at 600 rpm for 19 minutes. The supernatant was concentrated under reduced pressure to 1 / 5 of the volume of the supernatant, and 5 times the volume of 93% (v / v) ethanol solution was added. The mixture was allowed to stand at 5°C for 15 hours, and centrifuged at 500 rpm for 13 minutes. The precipitate was collected as the mistletoe extract. The complex enzyme used in the preparation of Gastrodia elata extract and Morus alba extract consists of cellulase and papain in a weight ratio of 5:3; (3) Preparation of Centella asiatica extract and Licorice extract The centella asiatica was crushed and passed through a 150-mesh sieve, 25 times the weight of a 60% (v / v) ethanol solution was added, and ultrasonic extraction was performed at 50° C. and 55 kHz for 60 minutes. The mixture was filtered, and the filtrate was concentrated under reduced pressure to 1 / 4 of the volume of the filtrate, and dried to obtain the centella asiatica extract. Grind the licorice root through a 120-mesh sieve, add 25 times the weight of a 70% (v / v) ethanol solution, extract with ultrasound at 55° C. and 60 kHz for 40 minutes, filter, combine the filtrates, concentrate the filtrates under reduced pressure to 1 / 4 of the volume, and dry to obtain the licorice extract; (4) Lotus leaf extract The lotus leaf was dried and crushed, passed through a 100-mesh sieve, mixed with 15 times the weight of distilled water, sterilized, inoculated with 3% (w / w) composite bacterial solution, fermented at 28° C., initial pH 6, and 170 rpm for 72 h, sterilized, centrifuged at 600 rpm for 10 min, and the supernatant was concentrated under reduced pressure to 1 / 4 of the volume of the supernatant, and dried to obtain the lotus leaf extract; The composite bacterial solution is composed of Aspergillus niger solution and Bacillus subtilis solution in a volume ratio of 2:1, and the spore concentration of Aspergillus niger solution is 3×10 8 / mL, and the spore concentration of Bacillus subtilis was 1×10 9 / mL; (5) Preparation of theaflavins composition Accurately weigh 12 parts by weight of theaflavins, 10 parts by weight of celery seed extract, 8 parts by weight of Gastrodia elata extract, 8 parts by weight of Morus alba extract, 8 parts by weight of Centella asiatica extract, 8 parts by weight of lotus leaf extract, and 3 parts by weight of liquorice extract; Hydroxypropyl-β-cyclodextrin was mixed with distilled water at 60°C to obtain a 20% (w / v) hydroxypropyl-β-cyclodextrin solution, to which theaflavins, celery seed extract, Gastrodia elata extract, Morus alba extract, Centella asiatica extract, lotus leaf extract, and licorice extract were added, and the mixture was stirred for inclusion at 60°C and 400 rpm for 1.5 h, and spray-dried to obtain a theaflavins composition; The volume ratio of the total weight of theaflavins, celery seed extract, Gastrodia elata extract, Morus alba extract, Centella asiatica extract, lotus leaf extract and licorice extract to the hydroxypropyl-β-cyclodextrin solution is 1:15 g / mL.

[0040] Comparative Example 1 This comparative example is the same as Example 1, except that "10 parts by weight of theaflavins and 8 parts by weight of celery seed extract" are replaced by "18 parts by weight of theaflavins".

[0041] Comparative Example 2 This comparative example is the same as Example 1, except that "10 parts by weight of theaflavins and 8 parts by weight of celery seed extract" are replaced by "18 parts by weight of celery seed extract".

[0042] Comparative Example 3 This comparative example is the same as Example 1, except that the preparation method of the celery seed extract is as follows: the celery seeds are dried to a water content of 5% (w / w), crushed through a 60-mesh sieve, 15 times the weight of distilled water is added, and reflux extraction is performed at 100° C. twice, each time for 1.5 h, filtered, the filtrates are combined, concentrated under reduced pressure to 1 / 3 of the volume of the filtrate, and dried to a water content of 3% (w / w) to obtain the celery seed extract.

[0043] Comparative Example 4 This comparative example is the same as Example 1, except that the 65% (v / v) ethanol solution in the preparation of the Centella asiatica extract and the Glycyrrhiza uralensis extract in step (3) is replaced with distilled water.

[0044] Comparative Example 5 This comparative example is the same as Example 1, except that the composite bacterial solution in the preparation method of lotus leaf extract in step (4) is composed of Aspergillus oryzae solution and Bacillus thuringiensis solution in a volume ratio of 5:2, and the spore concentration of Aspergillus oryzae solution is 5×10 8 / mL, and the spore concentration of Bacillus thuringiensis was 2×10 9 The parameters remain unchanged.

[0045] Test Example 1 100 SPF-grade male spontaneously hypertensive rats (SHR) weighing 200-220g were selected, and 10 SPF-grade male Wistar rats weighing 200-220g were used as blank control groups. Within 7 days before the experiment, the rats were subjected to repeated blood pressure measurements using the tail pulse method to adapt to the pressure measurement environment. The SHR rats were divided into 10 groups, 10 in each group: experimental group, model control group and positive control group. The experimental group was gavaged with the compositions of embodiment 1-3 and comparative example 1-5 according to 2g / kg dosage respectively, and the positive group was gavaged with 10mg / kg metoprolol tartrate tablets, which were gavaged with 10mL / kg capacity, once a day. The model control group and the blank control group were gavaged with equal amounts of normal saline. The systolic and diastolic blood pressures were measured before and after 4 weeks of gavage respectively for 4 weeks. The results are shown in Table 1 and Table 2.

[0046] Table 1 Effects of each group on systolic blood pressure Group Before medication (mmHg) After 4 weeks of medication (mmHg) Blank control group 120.6±12.7 123.8±12.5 Model control group 174.9±32.5 178.4±33.2 Positive control group 173.5±31.5 137.7±17.0 Example 1 175.2±30.9 139.2±15.9 Example 2 172.8±33.1 144.5±20.3 Example 3 173.4±28.0 142.0±24.8 Comparative Example 1 171.7±36.3 155.9±27.6 Comparative Example 2 170.9±32.6 156.1±25.4 Comparative Example 3 175.1±29.2 150.3±22.1 Comparative Example 4 174.3±34.7 149.6±25.7 Comparative Example 5 176.0±31.4 148.4±24.2

[0047] Table 2 Effects of each group on diastolic blood pressure Group Before medication (mmHg) After 4 weeks of medication (mmHg) Blank control group 77.0±8.5 81.8±7.8 Model control group 122.4±14.7 129.3±15.6 Positive control group 120.7±15.3 85.4±8.6 Example 1 123.3±12.9 88.2±9.5 Example 2 122.9±17.2 89.9±11.4 Example 3 124.5±13.8 91.7±13.2 Comparative Example 1 120.9±14.6 100.5±10.9 Comparative Example 2 122.1±13.4 107.0±12.0 Comparative Example 3 124.6±18.0 97.3±9.3 Comparative Example 4 121.4±14.7 95.1±8.7 Comparative Example 5 123.2±16.1 92.6±12.1 As shown in the results of Tables 1 and 2, both the experimental and positive control groups demonstrated good antihypertensive effects for both systolic and diastolic blood pressure. Compared to the positive control group, Examples 1-3 demonstrated comparable antihypertensive effects, indicating that the theaflavins compositions of Examples 1-3 exhibit similar antihypertensive effects as metoprolol tartrate tablets. The data from Example 1 and Comparative Examples 1-2 demonstrate that theaflavins and celery seed extract exhibit a synergistic effect in lowering blood pressure. The data from Example 1 and Comparative Examples 3-5 demonstrate that varying the extraction method, solvent type, and fermentation microorganism type can affect the efficacy of the compositions to varying degrees.

[0048] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A theaflavin composition for treating hypertension, characterized in that: The invention comprises the following components in parts by weight: 8-12 parts of theaflavins, 5-10 parts of celery seed extract, 3-8 parts of gastrodia elata extract, 3-8 parts of mistletoe extract, 3-8 parts of centella asiatica extract, 3-8 parts of lotus leaf extract and 1-3 parts of liquorice extract.

2. A method for preparing the theaflavin composition according to claim 1, characterized in that: include: Hydroxypropyl-β-cyclodextrin is mixed with water to obtain a hydroxypropyl-β-cyclodextrin solution, and theaflavin, celery seed extract, gastrodia elata extract, mistletoe extract, centella asiatica extract, lotus leaf extract and liquorice extract are added, ultrasonic inclusion is performed, and spray drying is performed to obtain the theaflavin composition.

3. The preparation method according to claim 2, characterized in that The mass volume ratio of the hydroxypropyl-β-cyclodextrin solution is 15%-20%.

4. The preparation method according to claim 2 or 3, characterized in that The volume ratio of the total weight of theaflavins, celery seed extract, gastrodia elata extract, mistletoe extract, centella asiatica extract, lotus leaf extract and liquorice extract to the hydroxypropyl-β-cyclodextrin solution is 1:10-15.

5. The preparation method according to claim 2, characterized in that The celery seed extract is obtained by supercritical CO2 extraction.

6. The preparation method according to claim 2, characterized in that The gastrodia elata extract and the mistletoe extract are obtained through ultrasonic enzymatic hydrolysis, hot water extraction and alcohol precipitation.

7. The preparation method according to claim 2, characterized in that The Centella asiatica extract and the liquorice extract are obtained by ethanol ultrasonic extraction.

8. The preparation method according to claim 2, characterized in that The lotus leaf extract is obtained by fermentation.

9. Use of the theaflavin composition according to claim 1 or the theaflavin composition obtained by the preparation method according to any one of claims 2 to 8 in the preparation of a drug for treating hypertension.

10. The use according to claim 9, characterized in that The hypertension is essential hypertension.