Use of a pharmaceutical composition for preparing a medicament for bidirectional regulation of blood pressure

Abstract

The application belongs to the technical field of medicine, and relates to application of a pharmaceutical composition in preparation of a medicine for bidirectional regulation of blood pressure. The application provides application of a pharmaceutical composition in preparation of a medicine for bidirectional regulation of blood pressure, wherein the pharmaceutical composition comprises the following components: ginsenoside Rk1, ginsenoside Rg5, ginsenoside Rg3, ginsenoside Rh4, ginsenoside Rk3, a ginseng ethanol-water extract and a pharmaceutically acceptable carrier. The pharmaceutical composition can realize bidirectional regulation of blood pressure.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to the application of a pharmaceutical composition in the preparation of a drug for bidirectional regulation of blood pressure. Background Technology

[0002] Hypertension is the most common chronic disease in humans and a major risk factor for cardiovascular and cerebrovascular diseases. Currently used antihypertensive drugs have significant short-term blood pressure-lowering effects, but they do not address the underlying cause. Patients need to take medication long-term or even lifelong, which inevitably leads to target organ damage and drug resistance. Ginsenosides are sterol compounds mainly found in ginseng. They can participate in multiple cell signaling pathways, so their efficacy is complex. However, currently, there is a lack of highly effective ginseng-based drugs that can regulate blood pressure in both directions. Summary of the Invention

[0003] The purpose of this invention is to provide the use of a pharmaceutical composition in the preparation of a drug for bidirectional regulation of blood pressure. The pharmaceutical composition of this invention is capable of achieving bidirectional regulation of blood pressure.

[0004] This invention provides the use of a pharmaceutical composition in the preparation of a drug for bidirectional regulation of blood pressure, the pharmaceutical composition comprising the following components: ginsenoside Rk1, ginsenoside Rg5, ginsenoside Rg3, ginsenoside Rh4, ginsenoside Rk3, ginseng ethanol-water extract, and a pharmaceutically acceptable carrier.

[0005] The present invention also provides the use of a pharmaceutical composition in the preparation of a medicament for the prevention and / or treatment of hypertension and / or hypotension, the pharmaceutical composition comprising the following components: ginsenoside Rk1, ginsenoside Rg5, ginsenoside Rg3, ginsenoside Rh4, ginsenoside Rk3, ginseng ethanol-water extract, and a pharmaceutically acceptable carrier.

[0006] Preferably, in the pharmaceutical composition, the mass percentage of ginsenoside Rk1 is 5-12%, the mass percentage of ginsenoside Rg5 is 5-12%, the mass percentage of ginsenoside Rg3 is 5-12%, the mass percentage of ginsenoside Rh4 is 3-8%, the mass percentage of ginsenoside Rk3 is 2-6%, and the mass percentage of ginsenoside ethanol-water extract is 50-80%.

[0007] Preferably, the ginseng ethanol-water extract comprises the following components in weight percentage: 5-11.3% ginsenosides, 20-30% ginseng polysaccharides, 22-32.7% ginseng polypeptides, 1.0-2.0% ginseng polyphenols, and 2.0-4.0% ginseng flavonoids.

[0008] Preferably, the ginsenoside components include Rg1, Re, Rf, Rb1, Rc, Rd, and Rb2; the mass percentage of Rg1 in the ginseng ethanol-water extract is 2-3%, the mass percentage of Re in the ginseng ethanol-water extract is 1.0-2.5%, the mass percentage of Rf in the ginseng ethanol-water extract is 0.2-1.5%, the mass percentage of Rb1 in the ginseng ethanol-water extract is 0.5-1.5%, the mass percentage of Rc in the ginseng ethanol-water extract is 0.5-1.2%, the mass percentage of Rd in the ginseng ethanol-water extract is 0.5-0.8%, and the mass percentage of Rb2 in the ginseng ethanol-water extract is 0.3-0.8%.

[0009] Preferably, the ginseng ethanol-water extract is extracted from white ginseng, fresh ginseng, or red ginseng.

[0010] Preferably, the extraction method of the ginseng ethanol-water extract includes the following steps: drying and pulverizing ginseng to obtain pulverized ginseng; mixing the pulverized ginseng with an ethanol aqueous solution with a volume percentage of 75%, heating at 55°C for 3 hours, and filtering to obtain a first filtrate and a first filter residue; mixing the first filter residue with an ethanol aqueous solution with a volume percentage of 45%, heating at 55°C for 3 hours, and filtering to obtain a second filtrate and a second filter residue; mixing the second filter residue with water, heating at 80°C for 3 hours, and filtering to obtain a third filtrate; combining the first filtrate, the second filtrate, and the third filtrate, evaporating the solvent, and freeze-drying to obtain the ginseng ethanol-water extract.

[0011] Preferably, the sources of ginsenoside Rk1, ginsenoside Rg5, ginsenoside Rg3, ginsenoside Rh4 and ginsenoside Rk3 include natural extraction.

[0012] Preferably, the ginsenosides Rk1, Rg5, Rh4, Rg3, and Rk3 are extracted from wild ginseng, cultivated ginseng, American ginseng, Panax notoginseng, red ginseng, or white ginseng.

[0013] Preferably, the method for preparing the pharmaceutical composition includes the following steps:

[0014] Ginsenoside Rk1, ginsenoside Rg5, ginsenoside Rg3, ginsenoside Rh4, ginsenoside Rk3, ginseng ethanol-water extract, and a pharmaceutically acceptable carrier are mixed to obtain a pharmaceutical composition.

[0015] This invention provides the application of a pharmaceutical composition in the preparation of a drug for bidirectional regulation of blood pressure. The traditional Chinese medicine composition of this invention has an auxiliary effect in lowering blood pressure. It will provide a safe and reliable drug for millions of people with hypertension, while also providing new opportunities for the in-depth development and utilization of ginseng and the development of the ginseng industry in Jilin Province. The composition of this invention is more stable and easier to store, showing significant application prospects. Experimental results show that people with normal blood pressure can maintain normal and stable blood pressure after taking the pharmaceutical composition of this invention; patients with hypertension and hypotension can restore normal and stable blood pressure after taking the pharmaceutical composition of this invention. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0017] Figure 1 The results of the effects of the compositions 1-3 provided by the present invention on the regulation of systolic blood pressure in hereditary hypertension (SHR) rats are shown in the figure.

[0018] Figure 2 The results of the effects of the compositions 1-3 provided by the present invention on the regulation of diastolic blood pressure in hereditary hypertension (SHR) rats are shown in the figure.

[0019] Figure 3 The results of the effects of compositions 1-3 provided by the present invention on the regulation of systolic blood pressure in rats with hereditary hypotension (ACI) are shown in the figure.

[0020] Figure 4 The results of the effects of the compositions 1-3 provided by the present invention on the regulation of diastolic blood pressure in rats with hereditary hypotension (ACI) are shown in the figure. Detailed Implementation

[0021] This invention provides the use of a pharmaceutical composition in the preparation of a drug for bidirectional regulation of blood pressure. The pharmaceutical composition comprises the following components: ginsenoside Rk1, ginsenoside Rg5, ginsenoside Rg3, ginsenoside Rh4, ginsenoside Rk3, ginseng ethanol-water extract, and a pharmaceutically acceptable carrier. The composition of this invention exhibits extremely high safety; no LD50 was detected in acute toxicity tests. 50The pharmaceutical composition of this invention can achieve bidirectional regulation of blood pressure, treating both hypertension and hypotension. In addition to ginsenosides, the pharmaceutical composition contains other active ginseng substances such as ginseng polysaccharides, ginseng polypeptides, flavonoids, and polyphenols, improving drug safety. Acute toxicity tests show that it has high drug safety; after a single oral gavage dose of 22.9 g / kg BW, no abnormalities were observed in body posture, limb movement, respiration, or organs (heart, liver, lungs, and kidneys).

[0022] The present invention also provides the use of a pharmaceutical composition in the preparation of a medicament for the prevention and / or treatment of hypertension and / or hypotension, the pharmaceutical composition comprising the following components: ginsenoside Rk1, ginsenoside Rg5, ginsenoside Rg3, ginsenoside Rh4, ginsenoside Rk3, ginseng ethanol-water extract, and a pharmaceutically acceptable carrier.

[0023] In this invention, the pharmaceutical composition contains 5-12% ginsenoside Rk1, 5-12% ginsenoside Rg5, 5-12% ginsenoside Rg3, 3-8% ginsenoside Rh4, 2-6% ginsenoside Rk3, and 50-80% ginsenoside ethanol-water extract.

[0024] In this invention, the ginsenoside Rk1 in the pharmaceutical composition has a mass percentage of 5-12%, preferably 5.3-10.8%. In this invention, ginsenoside Rk1, chemical name: 3β,6α,12β-trihydroxydammar-20(21),24-diene-6-O-β-D-glucopyranoside, molecular formula C 42 H 70 O 12 It has a molecular weight of 767.0, is odorless, and is a white powder. It is soluble in methanol and ethanol, slightly soluble in ethyl acetate, poorly soluble in water, and insoluble in chloroform and diethyl ether. CAS No.: 494753-69-4. Its structural formula is shown in Formula I.

[0025]

[0026] In this invention, the mass percentage of ginsenoside Rg5 in the pharmaceutical composition is 5-12%, preferably 6.1-10.5%. In this invention, ginsenoside Rg5, chemical name: beta-D-Glucopyranoside,(3beta,12beta,20E)-12-hydroxydammara-20(22),24-dien-3-yl2-O-beta-D-glucopyranosyl, molecular formula C 42H 70 O 12 Molecular weight: 767.0, odorless, white powder. Soluble in methanol and ethanol, slightly soluble in ethyl acetate, poorly soluble in water, insoluble in chloroform and diethyl ether. CAS number: 74964-14-0, structural formula as shown in Formula II.

[0027]

[0028] In this invention, the ginsenoside Rg3 in the pharmaceutical composition has a mass percentage of 5% to 12%, preferably 5.5% to 8.9%. In this invention, ginsenoside Rg3, chemically named 3-O-[β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl]-20(S)-protopanaxadiol, has the molecular formula: C 42 H 72 O 13 Molecular weight: 784.5, odorless, white powder. Soluble in methanol and ethanol, slightly soluble in ethyl acetate, poorly soluble in water, insoluble in chloroform and diethyl ether. CAS number: 14197-60-5. Structural formula as shown in Formula III.

[0029]

[0030] In this invention, the ginsenoside Rh4 in the pharmaceutical composition comprises 3-8% by mass, preferably 3.0-6.2%. In this invention, ginsenoside Rh4, scientifically known as 6-O-β-D-glucopyranosyl-20(-H2O)-trans-protopanaxatriol, has the molecular formula C2. 36 H 60 O8; Molecular weight: 620.4. Odorless, white powder. Soluble in methanol and ethanol, slightly soluble in ethyl acetate, poorly soluble in water, insoluble in chloroform and ether; CAS number: 174721-08-5, structural formula as shown in Formula IV.

[0031]

[0032] In this invention, the ginsenoside Rk3 in the pharmaceutical composition has a mass percentage of 2-6%, preferably 2.5-4.3%. In this invention, ginsenoside Rk3, scientifically known as Trihydroxydammar-20(21),24-diene-6-O-β-D-glucopyranoside, has the molecular formula C2. 36 H 60O8; Molecular weight: 620.87, odorless, white powder. Soluble in methanol and ethanol, slightly soluble in ethyl acetate, poorly soluble in water, insoluble in chloroform and diethyl ether; CAS number: 364779-15-7, structural formula as shown in Formula V.

[0033]

[0034] In this invention, the ginseng ethanol-water extract in the pharmaceutical composition comprises 50-80% by mass, preferably 63-75%. In this invention, the ginseng ethanol-water extract comprises the following components by mass percentage: 5-11.3% ginsenosides, 20-30% ginseng polysaccharides, 22-32.7% ginseng polypeptides, 1.0-2.0% ginseng polyphenols, and 2.0-4.0% ginseng flavonoids.

[0035] In this invention, the ginseng ethanol-water extract preferably comprises 5-11.3% ginsenosides, more preferably 7-9.3%, and more preferably 9%. In this invention, the ginsenosides preferably include Rg1, Re, Rf, Rb1, Rc, Rd, and Rb2; the mass percentage of Rg1 in the ginseng ethanol-water extract is 2-3%, preferably 2.4-2.7%, more preferably 2.6%; the mass percentage of Re in the ginseng ethanol-water extract is 1.0-2.5%, preferably 1.4-2.0%, more preferably 1.5%; the mass percentage of Rf in the ginseng ethanol-water extract is 0.2-1.5%, preferably 0.5-1.4%, more preferably 1.4%; and the mass percentage of Rb1 in the ginseng ethanol-water extract is... The ginseng ethanol-water extract contains 0.5-1.5% by mass, preferably 0.8-1.2%, more preferably 0.9% by mass; Rc contains 0.5-1.2% by mass, preferably 0.8-1.1%, more preferably 1.1% by mass; Rd contains 0.5-0.8% by mass, preferably 0.6-0.7%, more preferably 0.7% by mass; and Rb2 contains 0.3-0.8% by mass, preferably 0.5-0.8%, more preferably 0.8% by mass.

[0036] In this invention, the ginseng ethanol-water extract comprises 20-30% ginseng polysaccharides, preferably 29.3%. In this invention, the ginseng ethanol-water extract comprises 22-32.7% ginseng polypeptides, preferably 32.3%. In this invention, the ginseng ethanol-water extract comprises 1.0-2.0% ginseng polyphenols, preferably 1.3%. In this invention, the ginseng ethanol-water extract comprises 2.0-4.0% ginseng flavonoids, preferably 3.1%.

[0037] In this invention, the ginseng ethanol-water extract is extracted from white ginseng, fresh ginseng, or red ginseng.

[0038] In this invention, the extraction method of the ginseng ethanol-water extract includes the following steps: drying and pulverizing ginseng to obtain pulverized ginseng; mixing the pulverized ginseng with an ethanol aqueous solution with a volume percentage of 75%, heating at 55°C for 3 hours, and filtering to obtain a first filtrate and a first filter residue; mixing the first filter residue with an ethanol aqueous solution with a volume percentage of 45%, heating at 55°C for 3 hours, and filtering to obtain a second filtrate and a second filter residue; mixing the second filter residue with water, heating at 80°C for 3 hours, and filtering to obtain a third filtrate; combining the first filtrate, the second filtrate, and the third filtrate, evaporating the solvent, and freeze-drying to obtain the ginseng ethanol-water extract.

[0039] In this invention, the sources of ginsenoside Rk1, ginsenoside Rg5, ginsenoside Rg3, ginsenoside Rh4 and ginsenoside Rk3 include natural extraction.

[0040] This invention involves drying and pulverizing ginseng to obtain pulverized ginseng. The invention does not specify any particular method for drying and pulverizing; conventional drying and pulverizing methods well-known to those skilled in the art can be used.

[0041] After obtaining the pulverized ginseng, the present invention mixes the pulverized ginseng with an ethanol aqueous solution containing 75% by volume, heats at 55°C for 3 hours, and filters to obtain a first filtrate and a first filter residue. In the present invention, the volume ratio of the pulverized ginseng to the ethanol aqueous solution containing 75% by volume is preferably 1:(8-12), more preferably 1:10. In the present invention, the heating method is preferably a water bath heating method. In the present invention, the first filtrate is preferably stored in a refrigerator at 4°C.

[0042] After obtaining the first filter residue, the present invention mixes the first filter residue with an aqueous ethanol solution of 45% by volume, heats at 55°C for 3 hours, and filters to obtain a second filtrate and a second filter residue. In the present invention, the volume ratio of the first filter residue to the aqueous ethanol solution of 45% by volume is preferably 1:(8-12), more preferably 1:10. In the present invention, the heating method is preferably a water bath heating method. In the present invention, the second filtrate is preferably stored in a refrigerator at 4°C.

[0043] After obtaining the second filter residue, the present invention mixes the second filter residue with water, heats it at 80°C for 3 hours, and filters it to obtain the third filtrate. In the present invention, the volume ratio of the second filter residue to water is preferably 1:(8-12), more preferably 1:10. In the present invention, the heating method is preferably a water bath heating method. In the present invention, the second filtrate is preferably stored in a refrigerator at 4°C.

[0044] After obtaining the first, second, and third filtrates, this invention combines the three filtrates, evaporates the solvent, and freeze-dries them to obtain ginseng ethanol-water extract. This invention does not have a specific limitation on the solvent evaporation method; conventional methods are acceptable, such as using a rotary evaporator to remove the solvent. After evaporating the solvent, this invention preferably freeze-dries the concentrate. This invention does not have a specific limitation on the freeze-drying method; conventional freeze-drying methods are acceptable. After freeze-drying, this invention preferably grinds the freeze-dried solid into powder.

[0045] In this invention, the sources of ginsenosides Rk1, Rg5, Rg3, Rh4, and Rk3 preferably include natural extraction. In this invention, ginsenosides Rk1, Rg5, Rh4, Rg3, and Rk3 are extracted from wild ginseng, cultivated ginseng, American ginseng, Panax notoginseng, red ginseng, or white ginseng. In this invention, the extraction methods for ginsenosides Rk1, Rg5, Rg3, Rh4, and Rk3 preferably include one or more of the following: water extraction, organic solvent extraction, permeation, distillation, ultrasonic impregnation, extraction, and macroporous adsorption resin separation. In this invention, ginsenosides Rk1, Rg5, and Rg3 can preferably be obtained through the conversion of other diol-type ginsenosides. For example, ginsenosides Rk1 and Rg5 can be obtained by conversion of diol-type ginsenosides such as Rb1. In this invention, ginsenosides Rh4 and Rk3 are preferably obtained by conversion of other triol-type ginsenosides. For example, ginsenosides Rh4 and Rk3 can be obtained by conversion of triol-type ginsenoside Rg1. In this invention, the conversion method preferably includes enzymatic degradation. The sources of ginsenosides Rk1, Rg5, Rg3, Rh4, and Rk3 in this invention preferably also include direct purchase.

[0046] In this invention, the pharmaceutically acceptable carrier in the pharmaceutical composition preferably comprises 1-10% by mass. In this invention, the pharmaceutically acceptable carrier preferably includes one or more of the following: solvent, buffer, coating, isotonist, wetting agent, emulsifier, preservative, and antibacterial agent. In this invention, the dosage form of the pharmaceutical composition preferably includes: tablets, powder, suspension, emulsion, capsules, granules, sugar-coated tablets, pills, liquid, medicated solution, or syrup.

[0047] In this invention, the preparation method of the pharmaceutical composition includes the following steps:

[0048] Ginsenoside Rk1, ginsenoside Rg5, ginsenoside Rg3, ginsenoside Rh4, ginsenoside Rk3, ginseng ethanol-water extract, and a pharmaceutically acceptable carrier are mixed to obtain a pharmaceutical composition.

[0049] To further illustrate the present invention, the application of a pharmaceutical composition provided by the present invention in the preparation of a drug for bidirectional regulation of blood pressure is described in detail below with reference to the accompanying drawings and embodiments, but these should not be construed as limiting the scope of protection of the present invention.

[0050] Example 1

[0051] Preparation of the composition of the present invention

[0052] Ginsenoside Rk1, ginsenoside Rg5, ginsenoside Rh4, ginsenoside Rg3, ginsenoside Rh4, and ginsenoside Rk3 were all purchased from Shanghai Yuanye Biotechnology Co., Ltd. Their purity all met pharmaceutical standards. They were prepared according to the proportions shown in Tables 1 to 3 below.

[0053] Preparation method of ethanol-water extract:

[0054] 1. Dry the ginseng and grind it into powder;

[0055] 2. Heat ginseng powder with 10 times its volume of 75% ethanol in a 55°C water bath for 3 hours. Store the filtrate in a 4°C refrigerator.

[0056] 3. Heat the filter residue from the previous step with 10 times its volume of 45% ethanol in a 55°C water bath for 3 hours, and store the filtrate in a 4°C refrigerator.

[0057] 4. Heat the filter residue from the previous step with 10 times its volume of pure water in an 80°C water bath for 3 hours. Store the filtrate in a 4°C refrigerator and discard the filter residue.

[0058] 5. Combine the filtrates obtained in steps 2, 3 and 4, and use a rotary evaporator to evaporate most of the solvent;

[0059] 6. Freeze-dry the concentrated liquid, and grind the freeze-dried solid into powder.

[0060] The composition of the ginseng ethanol-water extract is shown in Table 4.

[0061] Ginsenoside Rk1, ginsenoside Rg5, ginsenoside Rg3, ginsenoside Rh4, ginsenoside Rk3, ginseng ethanol-water extract, and dextrin (Shanghai Yuanye Biotechnology Co., Ltd.) were mixed to obtain a pharmaceutical composition.

[0062] Table 1. Composition of the pharmaceutical composition

[0063]

[0064] Table 2 Composition of the pharmaceutical composition

[0065]

[0066]

[0067] Table 3. Composition of the pharmaceutical composition

[0068]

[0069] Table 4 Ethanol-water extracts

[0070]

[0071]

[0072] Example 2

[0073] Safety evaluation of the compositions of the present invention

[0074] The non-clinical safety evaluation of the compositions of the present invention is as follows:

[0075] 1. Acute oral toxicity test in mice

[0076] Mice were orally administered composition 1 of the present invention by gavage under the conditions of maximum dosing concentration and maximum dosing volume, and observed continuously for 14 days to obtain the maximum tolerated dose of the composition of the present invention >10.0 g / kg BW.

[0077] 2. Acute oral toxicity test in Beagle dogs

[0078] Composition 1 of the present invention was administered orally by gavage to Beagle dogs at the maximum dosing concentration and maximum dosing volume conditions, thereby obtaining a maximum tolerated dose of the composition of the present invention >2.0 g / kg BW.

[0079] 3. Long-term toxicity of oral administration to rats

[0080] A long-term toxicity test was conducted on SD rats using the composition 1 of the present invention via oral gavage for three months, followed by a four-week recovery period after drug withdrawal. The results showed: ① General condition: During the administration and recovery periods, the animals' food and water intake were normal, their weight increased, their fur was smooth, and their behavior was normal; ② Hematological and blood biochemical indicators: After the administration and recovery periods, all hematological and blood biochemical indicators fluctuated within the normal range, with no obvious abnormalities observed; ③ Bone marrow and urinalysis indicators: After the administration and recovery periods, no obvious abnormalities were observed in the bone marrow and urinalysis indicators; ④ Histopathological indicators: After the administration and recovery periods, no obvious abnormalities were observed in the organs of the animals, and there were no significant differences in organ weight and organ coefficients compared to the control group. No obvious pathological changes were observed in any organ. The results indicate that no significant toxic reactions were observed with long-term administration in SD rats.

[0081] 4. Long-term toxicity test of oral administration in Beagle dogs

[0082] A long-term toxicity test was conducted on Beagle dogs using the composition 1 of the present invention via oral gavage for three months, followed by a four-week recovery period after drug withdrawal. The results showed: ① General condition: During the administration and recovery periods, food and water intake and body temperature were normal, weight increased, fur was smooth, and behavior was normal; ② Hematological and blood biochemical indicators: After the administration and recovery periods, all hematological and blood biochemical indicators fluctuated within the normal range, with no obvious abnormalities observed; ③ Electrocardiogram indicators: After the administration and recovery periods, all electrocardiogram indicators fluctuated within the normal range, with no obvious abnormalities observed; ④ Bone marrow and ophthalmological examination: After the administration and recovery periods, bone marrow cells... No abnormalities were observed in cells and their taxa; ophthalmic examination revealed clear vascular patterns without hemorrhage or exudation in the fundus of all groups of animals, no edema in the optic disc, and normal arteriovenous ratios; ⑤ Immunological and urinary / fecal indicators: After the end of administration and during the recovery period, all immunological and urinary / fecal indicators fluctuated within the normal range, with no significant abnormalities observed; ⑥ Histopathological indicators: After the end of administration and during the recovery period, no significant abnormalities were observed in any of the animals' organs grossly, and there were no significant differences in organ weight and organ coefficients compared to the control group. No significant pathological changes were observed in any organ. The results indicate that long-term administration to Beagle dogs did not result in significant toxic reactions.

[0083] 5. General pharmacological tests

[0084] Oral administration of composition 1 of the present invention to anesthetized Beagle dogs via gavage had no significant effect on their blood pressure (diastolic and systolic), heart rate, P wave, T wave, R wave, QRS interval, PR interval, QT interval, respiratory rate, or respiratory amplitude. The composition of the present invention also had no significant effect on the Irwin's behavioral test score and pole climbing test score in mice. This indicates that the composition of the present invention does not affect the central nervous system, cardiovascular system, or respiratory system of animals.

[0085] 6. Mutagenicity test

[0086] Chromosomal aberration assays in cultured mammalian cells (CHL), Ames assays, and mouse micronucleus assays showed that composition 1 of the present invention had no mutagenic effect.

[0087] Example 3

[0088] Pharmacodynamics

[0089] The compositions of the present invention have a good regulatory effect on both hereditary hypertension (SHR) rats and hereditary hypotension (ACI) rats.

[0090] Materials: Hereditary hypertensive (SHR) rats, and compositions 1-9 obtained in Example 1 of this invention.

[0091] Method 1: Within one week of purchase, the rats underwent multiple blood pressure measurements to acclimatize them to the measurement environment. After one week, 100 SHR rats were randomly divided into 10 groups of 10 each to establish a hypertension model. The experiment included a model group, and groups for Composition 1, Composition 2, Composition 3, Composition 4, Composition 5, Composition 6, Composition 7, Composition 8, and Composition 9. Rats in each group were administered the drugs via gavage. The gavage dose for each composition was 150 mg / kg. The model group was administered drinking water via gavage. Rats in each group were treated with the drugs for 30 days, and all observation indicators were measured every 3 days. After the treatment period, observation continued for 12 days, with all indicators measured every 3 days.

[0092] result( Figure 1 , Figure 2 As shown in Tables 5-7, compositions 1-3 of the present invention have good antihypertensive effects in a rat model of hereditary hypertension (SHR). Compositions 4-9 of the present invention either do not contain ginsenoside Rh4, or ginsenoside Rg5, or ginsenoside Rk1, or ginsenoside Rg3, or replace the component of ginsenoside Rg3 with ginsenoside Rb1, or replace the component of ginsenoside Rk1 with ginsenoside Rb1, or replace the component of ginsenoside Rh4 with ginsenoside Rg1; their antihypertensive effects are far less than those of compositions 1-3.

[0093] Method 2: Within one week of purchasing hereditary hypotension (ACI) rats, their blood pressure was measured multiple times to allow them to acclimatize to the measurement environment. One week later, 100 ACI rats were randomly divided into 10 groups of 10 each to establish a hypotension model. The experiment included a model group, and groups for Composition 1, Composition 2, Composition 3, Composition 4, Composition 5, Composition 6, Composition 7, Composition 8, and Composition 9. Rats in each group were administered the drugs via gavage. The gavage dose for each composition was 150 mg / kg. The model group was administered drinking water via gavage. Rats in each group were treated with the drugs for 30 days, and all observation indicators were measured every 3 days. After the treatment period, observation continued for 12 days, with all indicators measured every 3 days.

[0094] result( Figure 3 , Figure 4As shown in Tables 8-10, the compositions of the present invention have good blood pressure-raising effects in a rat model of hereditary hypotension (ACI). Blood pressure-raising drugs are very rare. Compositions 1-3 provided by the present invention have good regulatory effects on both hereditary hypertension (SHR) rats and hereditary hypotension (ACI) rats. In compositions 4-9 of the present invention, either ginsenoside Rh4, ginsenoside Rg5, ginsenoside Rk1, or ginsenoside Rg3 are not present, or the component of ginsenoside Rg3 is replaced with ginsenoside Rb1, or the component of ginsenoside Rk1 is replaced with ginsenoside Rb1, or the component of ginsenoside Rh4 is replaced with ginsenoside Rg1, and their blood pressure-raising effects are far less than those of compositions 1-3.

[0095] Table 5. Effects on blood pressure values ​​in hereditary hypertension (SHR) rats.

[0096]

[0097] Table 6. Effects on blood pressure values ​​in hereditary hypertension (SHR) rats.

[0098]

[0099] Table 7 Effects on blood pressure values ​​in hereditary hypertension (SHR) rats

[0100]

[0101] Table 8. Effects on blood pressure values ​​in rats with hereditary hypotension (ACI).

[0102]

[0103] Table 9. Effects on blood pressure values ​​in hereditary hypotension (ACI) rats.

[0104]

[0105] Table 10 Effects on blood pressure values ​​in hereditary hypotension (ACI) rats

[0106]

[0107] Example 4

[0108] Case 1: Li X (male, 90 years old, Han nationality, ID number 2201xxxxxxxxxx3518), a retired deputy director-level cadre, was diagnosed with hypertension in 1962 (blood pressure was 160 / 100 at that time, with a 60-year history of hypertension). He has been taking composition 3 in Example 1 of this invention for a long time, taking 2.4g every day. Currently, his blood pressure has reached normal (140 / 75) and remains stable. It has also significantly improved his sleep quality, maintained his energy, and made it easy for him to complete a weighted walking exercise for more than 2 hours.

[0109] Case 2: Ms. Chen (female, 60 years old, Manchu, ID number 2224xxxxxxxxx0218), before taking the pharmaceutical composition of this invention, had a blood pressure of 150 / 100 and a 15-year history of hypertension. After long-term use of composition 2 in Example 1 of this invention, at a dose of 2.4g per day, her blood pressure has now reached normal (120 / 80), her blood pressure is stable, her physical strength has significantly improved, and her sleep has noticeably improved.

[0110] Case 3: Ma X (male, 50 years old, Han nationality, ID number 2224xxxxxxxxx0327), whose blood pressure was 150 / 100 before taking the drug composition of this invention, had a 10-year history of hypertension. He started taking composition 5 from Example 1 in 2021. After 3 months, his blood pressure did not improve, so he switched to composition 2 from Example 1 of this invention, taking 2.4g daily. After one month, his blood pressure approached the normal range (130 / 80) and stabilized, significantly improving his physical strength and sleep.

[0111] Case 4: Gu Ximing (male, 60 years old, Manchu, ID number 2224xxxxxxxxx1273), before taking the pharmaceutical composition of this invention, had a blood pressure of approximately 160 / 100 and a 20-year history of hypertension. He started taking composition 7 from Example 1 of this invention in 2020, but his blood pressure did not improve significantly after two months. He then switched to composition 2 from Example 1 of this invention, taking 2.4g daily. Currently, his blood pressure has reached normal (130 / 80), is stable, and he has experienced significant improvements in physical strength and sleep.

[0112] Case 5: Park X-chan (male, 62 years old, Korean ethnicity, ID number 2224xxxxxxxxx1218), whose blood pressure was 160 / 100 before taking the pharmaceutical composition of this invention, had a 28-year history of hypertension. Since 2018, he has been taking Composition 1 of Example 1 of this invention, 2.4g daily. Currently, his blood pressure has reached normal (130 / 80), is stable, has significantly improved physical strength and sleep, and he is able to play tennis for more than 1 hour daily.

[0113] Case 6: Liu Xili (female, 36 years old, Han nationality, ID number 2201xxxxxxxxx2524) suffered from long-term low blood pressure (blood pressure 80 / 50). She started taking composition 5 in Example 1 of this invention in 2020. After 2 months, her blood pressure did not improve. She then switched to taking composition 1 in Example 1 of this invention, taking 2.4g daily. Currently, she maintains a stable normal blood pressure of 100 / 68, and her physical strength and sleep have significantly improved.

[0114] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. The use of a pharmaceutical composition in the preparation of a drug for bidirectional regulation of blood pressure, said pharmaceutical composition comprising the following components: ginsenoside Rk1, ginsenoside Rg5, ginsenoside Rg3, ginsenoside Rh4, ginsenoside Rk3, ginsenoside ethanol-water extract, and a pharmaceutically acceptable carrier; wherein the pharmaceutical composition comprises 5-12% by mass of ginsenoside Rk1, 5-12% by mass of ginsenoside Rg5, 5-12% by mass of ginsenoside Rg3, 3-8% by mass of ginsenoside Rh4, 2-6% by mass of ginsenoside Rk3, and 50-80% by mass of ginsenoside ethanol-water extract; The ginseng ethanol-water extract comprises the following components in weight percentage: 5-11.3% ginsenosides, 20-30% ginseng polysaccharides, 22-32.7% ginseng polypeptides, 1.0-2.0% ginseng polyphenols, and 2.0-4.0% ginseng flavonoids; The ginsenoside components include Rg1, Re, Rf, Rb1, Rc, Rd, and Rb2; Rg1 has a mass percentage of 2-3% in the ginseng ethanol-water extract, Re has a mass percentage of 1.0-2.5% in the ginseng ethanol-water extract, Rf has a mass percentage of 0.2-1.5% in the ginseng ethanol-water extract, Rb1 has a mass percentage of 0.5-1.5% in the ginseng ethanol-water extract, Rc has a mass percentage of 0.5-1.2% in the ginseng ethanol-water extract, Rd has a mass percentage of 0.5-0.8% in the ginseng ethanol-water extract, and Rb2 has a mass percentage of 0.3-0.8% in the ginseng ethanol-water extract.

2. The use of a pharmaceutical composition in the preparation of a medicament for the prevention and / or treatment of hypertension and / or hypotension, said pharmaceutical composition comprising the following components: ginsenoside Rk1, ginsenoside Rg5, ginsenoside Rg3, ginsenoside Rh4, ginsenoside Rk3, ginsenoside ethanol-water extract, and a pharmaceutically acceptable carrier; wherein the pharmaceutical composition comprises 5-12% by mass of ginsenoside Rk1, 5-12% by mass of ginsenoside Rg5, 5-12% by mass of ginsenoside Rg3, 3-8% by mass of ginsenoside Rh4, 2-6% by mass of ginsenoside Rk3, and 50-80% by mass of ginsenoside ethanol-water extract; The ginseng ethanol-water extract comprises the following components in weight percentage: 5-11.3% ginsenosides, 20-30% ginseng polysaccharides, 22-32.7% ginseng polypeptides, 1.0-2.0% ginseng polyphenols, and 2.0-4.0% ginseng flavonoids; The ginsenoside components include Rg1, Re, Rf, Rb1, Rc, Rd, and Rb2; Rg1 has a mass percentage of 2-3% in the ginseng ethanol-water extract, Re has a mass percentage of 1.0-2.5% in the ginseng ethanol-water extract, Rf has a mass percentage of 0.2-1.5% in the ginseng ethanol-water extract, Rb1 has a mass percentage of 0.5-1.5% in the ginseng ethanol-water extract, Rc has a mass percentage of 0.5-1.2% in the ginseng ethanol-water extract, Rd has a mass percentage of 0.5-0.8% in the ginseng ethanol-water extract, and Rb2 has a mass percentage of 0.3-0.8% in the ginseng ethanol-water extract.

3. The application according to claim 1 or 2, characterized in that, The ginseng ethanol-water extract is extracted from white ginseng, fresh ginseng, or red ginseng.

4. The application according to claim 1, characterized in that, The extraction method of the ginseng ethanol-water extract includes the following steps: drying and pulverizing ginseng to obtain pulverized ginseng; mixing the pulverized ginseng with an ethanol aqueous solution with a volume percentage of 75%, heating at 55°C for 3 hours, and filtering to obtain a first filtrate and a first filter residue; mixing the first filter residue with an ethanol aqueous solution with a volume percentage of 45%, heating at 55°C for 3 hours, and filtering to obtain a second filtrate and a second filter residue; mixing the second filter residue with water, heating at 80°C for 3 hours, and filtering to obtain a third filtrate; combining the first, second, and third filtrates, evaporating the solvent, and freeze-drying to obtain the ginseng ethanol-water extract.

5. The application according to claim 1 or 2, characterized in that, The sources of the ginsenosides Rk1, Rg5, Rg3, Rh4, and Rk3 include natural extraction.

6. The application according to claim 5, characterized in that, The ginsenosides Rk1, Rg5, Rh4, Rg3, and Rk3 are extracted from wild ginseng, cultivated ginseng, American ginseng, Panax notoginseng, red ginseng, or white ginseng.

7. The application according to claim 1 or 2, characterized in that, The method for preparing the pharmaceutical composition includes the following steps: Ginsenoside Rk1, ginsenoside Rg5, ginsenoside Rg3, ginsenoside Rh4, ginsenoside Rk3, ginseng ethanol-water extract, and a pharmaceutically acceptable carrier are mixed to obtain a pharmaceutical composition.

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