Application of traditional Chinese medicine composition in preparation of medicine for preventing and treating hypertension

Abstract

The invention relates to the technical field of traditional Chinese medicines, in particular to application of a traditional Chinese medicine composition in preparation of medicines for preventing and treating hypertension. The traditional Chinese medicine composition comprises sedum sarmentosum, seaweed, oyster, hawthorn, herba siegesbeckiae, schisandra chinensis and polygonum cuspidatum. The composition is found to be capable of remarkably inhibiting a renin-angiotensin-aldosterone system, regulating vascular active factors, relaxing vascular smooth muscles, protecting vascular endothelial functions, reducing heart left ventricular hypertrophy and effectively reducing systolic pressure and diastolic pressure. The traditional Chinese medicine composition is an existing Chinese patent medicine, medication is safe, and the preparation method is simple, rapid, efficient and easy to operate. The prepared mixture, tablet, capsule, pellet and the like are convenient to carry and take.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to the application of a traditional Chinese medicine composition in the preparation of medicines for preventing and treating hypertension. Background Art

[0002] Hypertension, also known as high blood pressure, is a phenomenon in which the pressure exerted by blood on the blood vessel walls when flowing in the blood vessels is continuously higher than normal.

[0003] Hypertension is generally divided into two types: primary hypertension and secondary hypertension. Primary hypertension, usually referred to as hypertension, refers to an increase in systolic and / or diastolic blood pressure at rest (>=140 / 90 mmHg), often accompanied by fat and sugar metabolism disorders and functional or organic changes in organs such as the heart, brain, kidney and retina. It is a systemic disease characterized by organ remodeling. Hypertension can be diagnosed when the blood pressure is >=140 / 90 mmHg measured more than 2 times on different days after resting for more than 5 minutes. Common complications of hypertension include coronary heart disease, diabetes, heart failure, hyperlipidemia, kidney disease, peripheral arterial disease, stroke, left ventricular hypertrophy, etc. Among the various complications of hypertension, damage to the heart, brain, and kidneys is the most significant.

[0004] Current medical science believes that essential hypertension is a lifelong disease. No drug can completely cure hypertension. People need to take antihypertensive drugs for life to achieve the best living conditions. Rational use of antihypertensive drugs according to the condition of the disease can maintain blood pressure at normal or near normal levels, which is effective in alleviating symptoms, delaying the progression of the disease, and preventing complications such as cerebrovascular accidents, heart failure, and renal failure.

[0005] There are many types of antihypertensive drugs, each with its own characteristics. Currently, there is a trend towards long-acting preparations or dosage forms that have a long-lasting effect and require fewer doses, so that patients can take them more easily. However, due to individual differences, current antihypertensive drugs have different side effects. In recent years, with the deepening of medical research, the treatment of hypertension has also been evolving. The field of traditional Chinese medicine should also actively intervene in the prevention and treatment of hypertension and develop prescriptions for the symptoms. Summary of the invention

[0006] In view of this, the technical problem to be solved by the present invention is to provide an application of a Chinese medicine composition in the preparation of a drug for preventing and treating hypertension.

[0007] The invention provides application of a traditional Chinese medicine composition in preparing medicine for preventing and treating hypertension.

[0008] In the present invention, the Chinese medicine composition comprises the following raw materials in parts by weight: 1-1000 parts of Creeping Herb, 1-500 parts of Seaweed, 1-1000 parts of Oyster, 1-500 parts of Hawthorn, 1-1000 parts of Siegesbeckia, 1-500 parts of Schisandrae Chinensis, and 1-800 parts of Polygonum Cuspidatum.

[0009] In the present invention, the prevention and treatment include: lowering blood pressure, lowering oxidative stress levels, alleviating left ventricular hypertrophy, inhibiting activation of the renin-angiotensin-aldosterone system and / or improving vasoactive factor levels.

[0010] In the present invention, the lowering of blood pressure includes lowering diastolic pressure and / or lowering systolic pressure. Experiments show that the Chinese medicine composition can effectively lower the systolic and diastolic pressure of rats. In addition, the Chinese medicine composition can significantly inhibit the activation of the RAAS system and reduce the production of Ang II; it can significantly increase the production of CAT and T-AOC, improve antioxidant capacity, and reduce the oxidative stress caused by L-NAME-induced rats.

[0011] The RAAS system, full name of the renin-angiotensin-aldosterone system, is an important endocrine system in the human body, mainly responsible for regulating blood pressure and water-salt balance, and participates in the functional regulation of multiple organs such as cardiovascular and kidneys by producing a series of hormones and enzymes. In the present invention, the inhibition of renin-angiotensin-aldosterone system activation includes reducing serum Renin, Ang II and / or ALD levels.

[0012] Endothelin (ET) and nitric oxide (NO) are vasoactive factors secreted by the vascular endothelium. ET is the strongest vasoconstrictor factor and has a significant vasoconstrictor effect on various organs of the human body; while NO is a vasodilator factor and has a significant effect on regulating vascular tension, improving blood circulation, etc. In the present invention, improving the level of vasoactive factors includes inhibiting the secretion of ET-1 and / or increasing the level of NO.

[0013] Experiments show that the Chinese medicine composition can significantly inhibit the renin-angiotensin-aldosterone system, regulate vasoactive factors, relax vascular smooth muscles, protect vascular endothelial function, reduce left ventricular hypertrophy, and effectively reduce systolic and diastolic blood pressure.

[0014] The hypertension that the Chinese medicine composition of the present invention is used to prevent and treat is hypertension caused by vasoconstriction or hypertension caused by increased sodium ion concentration. In an embodiment of the present invention, the hypertension caused by vasoconstriction is hypertension induced by L-NAME. The hypertension caused by increased sodium ion concentration is hypertension induced by a high-salt diet.

[0015] In the embodiment of the present invention, the mass proportions of the components in the traditional Chinese medicine composition are: 923 parts of Creeping Herb, 308 parts of Seaweed, 923 parts of Oyster, 308 parts of Crataegus Pinnatifida, 923 parts of Siegesbeckia scabra, 308 parts of Schisandra chinensis, and 618 parts of Polygonum cuspidatum.

[0016] In a specific embodiment, the preparation method of the Chinese medicine composition comprises: adding water to reflux extraction of Siegesbeckia sibiricum, Herba Lysimachiae, Seaweed, Oyster, Hawthorn, Polygonum cuspidatum, and Schisandra chinensis, and concentrating and drying the filtrate. In this embodiment, in the reflux extraction, the mass ratio of water to the Chinese medicine composition is (4-12):1, and the reflux extraction is performed 1-3 times, each time for 1-2 hours, and the density of the extract is 1.25-1.30.

[0017] Preferably, the extraction method comprises: taking Siegesbeckia sibiricum, Herba Lysimachiae, seaweed, oyster, hawthorn, Polygonum cuspidatum and Schisandra chinensis, adding 8 times the amount of water, refluxing and extracting twice, each time for 1.5 hours, filtering, decompressing and concentrating to an extract with a relative density of 1.25 to 1.30 (60±5°C), and then concentrating and drying. The drying adopts belt vacuum drying, and then further comprises the steps of crushing, sieving, adding sucralose and an appropriate amount of cyclodextrin, mixing, and granulating.

[0018] The present invention also provides a medicine for preventing and treating hypertension, which comprises pharmaceutically acceptable excipients and the following raw materials in parts by weight: 1-1000 g of Herba Creepers, 1-500 g of Seaweed, 1-1000 g of Oyster, 1-500 g of Hawthorn, 1-1000 g of Siegesbeckia, 1-500 g of Schisandrae Chinensis, and 1-800 g of Polygonum Cuspidatum.

[0019] The dosage form of the drug of the present invention includes but is not limited to decoction, granules, capsules, tablets, oral liquids, pills, tinctures, syrups, suppositories, gels, sprays and / or injections.

[0020] In some embodiments provided by the present invention, the capsule is a hard capsule or a soft capsule.

[0021] In some embodiments provided herein, the tablet is an oral tablet or an oral tablet.

[0022] Oral tablets refer to tablets for oral administration. Most of the drugs in such tablets are absorbed through the gastrointestinal tract to exert their effects, and some of the drugs in tablets exert their effects locally in the gastrointestinal tract. In some embodiments provided by the present invention, the oral tablets are ordinary compressed tablets, dispersible tablets, effervescent tablets, chewable tablets, coated tablets or sustained-release tablets.

[0023] The pharmaceutically acceptable excipients include one or a mixture of two or more of fruit powder, edible flavors, sweeteners, acidulants, fillers, lubricants, preservatives, suspending agents, edible pigments, diluents, emulsifiers, disintegrants or plasticizers.

[0024] The medicine described in the present invention also includes other drugs for treating hypertension, and the other drugs for treating hypertension include: at least one of enalapril, hydrochlorothiazide, indapamide, betaxolol, metoprolol, nifedipine, losartan, valsartan and telmisartan.

[0025] In the present invention, in the medicine, the Chinese medicine composition and other therapeutic agents may exist independently of each other or may exist in combination, and the present invention does not limit this.

[0026] Furthermore, the present invention also provides a method for preventing and treating hypertension, which comprises administering the drug of the present invention.

[0027] The administration of the drug includes, but is not limited to, oral administration, spray inhalation, rectal administration, nasal administration, buccal administration, vaginal administration, topical administration. Or non-enteral administration, such as subcutaneous, intravenous, intramuscular, intraperitoneal, intrathecal, intraventricular, intrasternal or intracranial injection or infusion; or administration via an explanted reservoir. Preferably, the administration is oral, intraperitoneal or intravenous.

[0028] In the present invention, when the medicine includes a Chinese medicine composition and other therapeutic agents, two or more medicines can be administered simultaneously or sequentially, and the present invention is not limited to this.

[0029] For example, the Chinese medicine composition in the medicine is administered no longer than 6 hours, preferably no longer than 5 hours, more preferably no longer than 4 hours, even more preferably no longer than 3 hours, more preferably no longer than 2 hours and most preferably no longer than 1 hour before the administration of other therapeutic agents and / or no longer than 6 hours, preferably no longer than 5 hours, more preferably no longer than 4 hours, even more preferably no longer than 3 hours, more preferably no longer than 2 hours and most preferably no longer than 1 hour after the administration of other therapeutic agents.

[0030] In the present invention, when the medicine includes a Chinese medicine composition and other therapeutic agents, the administration frequency of two or more medicines may be the same or different, and the present invention is not limited to this.

[0031] For example, the administration frequency of two or more of the drugs is independently selected from 4 times / day, 3 times / day, 2 times / day or 1 time / day, wherein the administration frequency of the Chinese medicine composition is 4 times / day, 3 times / day, 2 times / day or 1 time / day.

[0032] In the present invention, the medicine includes a Chinese medicine composition, and the dosage is not less than the effective dose. If the medicine includes a Chinese medicine composition and other therapeutic agents, the dosage of the Chinese medicine composition is lower than the effective dose, or not lower than the effective dose; the dosage of other therapeutic agents is lower than the effective dose, or not lower than the effective dose.

[0033] In the present invention, the effective dose includes a "therapeutically effective amount" or a "prophylactically effective amount", which refers to an amount that is sufficient to treat or prevent a patient's disease but low enough to avoid serious side effects (at a reasonable benefit / risk ratio) within the scope of reasonable medical judgment. The preventive or therapeutic effective amount of a drug will vary depending on the specific drug selected (e.g., considering the efficacy, effectiveness and half-life of the drug), the selected route of administration, the disease to be prevented or treated, the severity of the disease to be prevented or treated, the age, size, weight and physical illness of the patient to be prevented or treated, the medical history of the patient to be prevented or treated, the duration of prevention or treatment, the nature of concurrent therapy, the desired preventive or therapeutic effect, and other factors, but can still be routinely determined by those skilled in the art.

[0034] In the present invention, the prevention and treatment includes prevention and / or treatment, which is a preventive and therapeutic measure for hypertension. This includes a method for preventing the occurrence of hypertension, the purpose of which is to prevent, slow down (reduce) undesirable physiological changes or lesions in the treatment subject, and the beneficial or desired clinical results include but are not limited to avoiding the occurrence of hypertension, alleviating hypertension symptoms, reducing the degree of hypertension, stabilizing the hypertensive state (i.e., not worsening), delaying or slowing the progression of hypertension, improving or relieving the hypertensive state, and alleviating (whether partially or completely), whether detectable or undetectable. Subjects in need of treatment include subjects who already have a condition or disease, as well as subjects who are susceptible to a condition or disease or subjects who intend to prevent a condition or disease.

[0035] In the present invention, the object of prevention and treatment is a human or a mammal, and the mammal includes bovines, equines, ovines, porcines, canines, felines, rodents, and primates.

[0036] The Chinese medicine composition of the present invention comprises Herba Lycopodii, seaweed, oyster, hawthorn, Herba Siegesbeckiae, Fructus Schisandrae Chinensis and Polygonum Cuspidati. The present invention finds that the composition can significantly inhibit the renin-angiotensin-aldosterone system, regulate vasoactive factors, relax vascular smooth muscle and protect vascular endothelial function, reduce left ventricular hypertrophy of the heart, and effectively reduce systolic and diastolic blood pressure. Moreover, the Chinese medicine composition is an existing Chinese patent medicine, safe for use, and the preparation method is simple, fast, efficient and easy to operate. The prepared mixture, tablets, capsules, pellets, etc. are easy to carry and convenient to take. DETAILED DESCRIPTION

[0037] The present invention provides the use of a Chinese medicine composition in the preparation of a drug for preventing and treating hypertension. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters to achieve it. It is particularly important to point out that all similar replacements and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the method and application of this article without departing from the content, spirit and scope of the present invention to realize and apply the technology of the present invention.

[0038] The present invention proposes an application of a Chinese medicine composition in the preparation of a drug for treating hypertension, wherein the Chinese medicine composition comprises: 1 to 1000 parts of Herba Creepersii, 1 to 500 parts of Seaweed, 1 to 1000 parts of Oyster, 1 to 500 parts of Crataegus, 1 to 1000 parts of Siegesbeckia, 1 to 1000 parts of Schisandrae Chinensis, and 1 to 800 parts of Polygonum Cuspidatum. The application may be any method that is beneficial to improving the corresponding symptoms of the patient, including treatment or prevention. The composition of the present invention may be directly ground into powder, or may be an extract obtained by conventional means in the art. The Chinese medicine used in the composition of the present invention may also be used in the form of direct grinding into powder, extract, or other processed forms.

[0039] Furthermore, the Chinese medicine composition includes: 1-1000 parts of Creeping Jasmine, 1-500 parts of seaweed, 1-1000 parts of oyster, 1-500 parts of hawthorn, 1-1000 parts of Siegesbeckia, 1-500 parts of Schisandra chinensis, and 1-800 parts of Polygonum cuspidatum.

[0040] Furthermore, the Chinese medicine composition comprises: 500-1000 parts of Herba Creepers, 200-400 parts of Seaweed, 500-1000 parts of Oyster, 200-400 parts of Hawthorn, 500-1000 parts of Siegesbeckia, 200-400 parts of Schisandrae Chinensis, 300-700 parts of Polygonum Cuspidatum

[0041] Preferably, the Chinese medicine composition comprises: 700-950 parts of Creeping Jasmine, 200-350 parts of seaweed, 700-950 parts of oysters, 200-350 parts of hawthorn, 700-950 parts of Siegesbeckia, 200-350 parts of Schisandra chinensis, and 500-650 parts of Polygonum cuspidatum.

[0042] Most preferably, the Chinese medicine composition comprises: 923 parts of Siegesbeckia serrata, 923 parts of Creeping Herb, 308 parts of Sargassum, 923 parts of Oyster, 308 parts of Crataegus pinnatifida, 618 parts of Polygonum cuspidatum, and 308 parts of Schisandra chinensis.

[0043] Specifically, the drug for treating hypertension is selected from oral dosage forms, injection dosage forms or external administration preparations.

[0044] Specifically, the drug for treating hypertension is selected from decoctions, tablets, capsules, granules, pills, injections, decoctions, suspensions, dispersants, syrups, suppositories, gels, aerosols, patches, and oral liquids.

[0045] Among them, the composition of the present invention described above can be directly ground into powder by traditional methods, or it can be obtained by conventional means to obtain extracts so as to be made into different dosage forms, obtain better therapeutic effects and be more conducive to the preparation of modern pharmaceutical dosage forms.

[0046] The present invention also provides a method for preparing any of the aforementioned Chinese medicine compositions, the preparation method comprising:

[0047] Add water to reflux extraction of Siegesbeckia scabra, Creeping Herb, Sargassum, Calcined Oyster, Crataegus pinnatifida, Polygonum cuspidatum and Schisandra chinensis, adding 8 times the amount of water each time, extracting for 1.5 hours, filtering, and concentrating the filtrate under reduced pressure at no higher than 80°C to an extract with a relative density of 1.25-1.30 (60±5°C), belt vacuum drying, crushing and sieving, adding sucralose and dextrin to mix well, and obtaining granules.

[0048] The compound combination medicine for treating hypertension of the present invention can significantly inhibit the activation of the RAAS system and reduce the generation of Ang II; can significantly increase the generation of CAT and T-AOC, improve the antioxidant capacity, and reduce the oxidative stress caused by L-NAME induction in rats; can inhibit the secretion of ET-1 in vascular endothelial cells of rats with a high-salt diet, and increase the level of vasodilator factor NO in serum; can reduce left ventricular hypertrophy of the heart, and effectively reduce the systolic and diastolic blood pressure of rats. Moreover, the preparation method of the compound combination medicine for treating hypertension is simple, rapid, efficient, and easy to operate. The prepared mixture, tablets, capsules, pellets, etc. are easy to carry and convenient to take.

[0049] The test materials used in the present invention are all common commercial products and can be purchased in the market.

[0050] The following experiments, if no specific conditions are specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The APIs or excipients, reagents or instruments used, if the manufacturer is not specified, are all conventional products that can be purchased commercially. Unless otherwise specified, all percentages, ratios, proportions or parts are by weight.

[0051] Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein can be applied to the present invention. The present invention is further described below in conjunction with the embodiments:

[0052] Example 1 Preparation of Chinese medicine composition

[0053] Seven herbs in total, 923 g of Siegesbeckia sibiricum, 923 g of Creeping Herb, 308 g of Sargassum, 923 g of Oyster, 308 g of Crataegus pinnatifida, 618 g of Polygonum cuspidatum and 308 g of St. Vincent's Apple, are extracted twice with water by reflux, with 8 times the amount of water added each time. The extraction is carried out for 1.5 hours, and the extract is filtered. The filtrate is concentrated under reduced pressure at a temperature not higher than 80°C to an extract with a relative density of 1.25-1.30 (60±5°C), belt vacuum dried, crushed and sieved to obtain a composite intermediate, to which 2 g of sucralose and an appropriate amount of dextrin are added, and the mixture is mixed to obtain 1000 g of granules.

[0054] Experimental Example 2 Therapeutic effect of Chinese medicine composition on L-NAME-induced hypertension rat model

[0055] 1. Experimental Materials

[0056] 1.1 Animals

[0057] Wistar rats, male, SPF grade, weighing 180-200 g, were purchased from Beijing Weitonglihua Experimental Animal Technology Co., Ltd.

[0058] Breeding environment: room temperature 20-26°C, relative humidity controlled at 40%-70%, animal breeding density 4 per cage.

[0059] 1.2 Drugs

[0060] Chinese medicine composition: the intermediate prepared according to Example 1, Jiangsu Kangyuan Pharmaceutical Co., Ltd.; N-nitro-L-arginine methyl ester (L-NAME, Dalian Meilun Biotechnology Co., Ltd., batch number: J0609C); enalapril maleate (Dalian Meilun Biotechnology Co., Ltd., batch number: M1108A); pentobarbital sodium (Beijing Chemical Reagent Company, batch number: 211122); physiological saline (Chenxin Pharmaceutical Co., Ltd., batch number: 2101282721).

[0061] 1.3 Instruments

[0062] Refrigerator (Haier Company, model: BCD-216SZ); electronic balance (Sartorius Scientific Instruments Company, model: BSA224S-CW); purified water instrument (Millipore Company, Germany, model: Milli-QPlus); animal weight scale (Shanghai Xiangchuan Electronic Scale Co., Ltd., model: CX-SC-DA); multi-function microplate reader (MD Company, USA, model: Flexstation 3); high-speed refrigerated centrifuge (KeDa Innovation Co., Ltd., model: KDC-160HR); non-invasive blood pressure measurement system (Shanghai Alcott Biotechnology Co., Ltd., model: ALC-NIBP).

[0063] 2. Dosage design

[0064] The daily dosage of the Chinese medicine composition is 8.62 g of crude drug / day. According to the body surface area conversion method, the equivalent dose for rats is 8.62 g / 60 kg × 6.3 = 0.90 g of crude drug / kg. According to the 1 / 4:1 / 2:1 dosing method, the low dose is 0.225 g of crude drug / kg and the medium dose is 0.45 g of crude drug. The drug is administered by gavage, 1 mL / 100 g, once a day.

[0065] The daily dosage of enalapril maleate is 15 mg / day. According to the body surface area conversion method, the equivalent dose for rats is 15 mg / 60 kg×6.3=1.6 mg / kg.

[0066] 3. Experimental Methods

[0067] Wistar rats were adaptively fed for 3 days, with free access to feed and water, and were randomly divided into a normal control group, a model control group, an enalapril control group, and a high, medium, and low dose group of the Chinese medicine composition according to body weight, with 10 rats in each group. Except for the normal control group, all animals were gavaged with L-NAME (40 mg / kg) every day, and the blank control group rats were gavaged with an equal volume of normal saline for 28 days. From the 14th day, the drug administration group rats were gavaged with positive drugs and corresponding low, medium, and high doses of Chinese medicine compositions (0.225 g / kg, 0.45 g / kg, 0.90 g / kg). The normal group and the model group were given normal saline under the same conditions, once a day, for 14 consecutive days. The tail vein systolic blood pressure (SBP) and diastolic blood pressure (DBP) of each group of rats were measured weekly using the ALC-NIBP non-invasive blood pressure measurement system, and the data of each group were recorded. After the experiment, the rats were euthanized, blood samples were taken from the abdominal aorta, and the serum was separated after centrifugation at 3500 rpm for 15 minutes at 4°C. The rat heart was taken out and washed in cold saline, dried with qualitative filter paper, and the left and right atria were removed along the atrioventricular ring, and the right ventricular free wall was removed along the ventricular septum to obtain the left ventricle of the heart. The left ventricular mass index (LVMI) was calculated to evaluate the degree of left ventricular hypertrophy: LVMI = left ventricular weight (mg) / body weight (g).

[0068] 4. Statistical methods

[0069] The results were statistically analyzed using t-test.

[0070] 5. Experimental Results

[0071] 5.1 Effects on systolic and diastolic blood pressure in L-NAME-induced hypertensive rat model

[0072] After 14 days of L-NAME induction by intragastric administration, the SBP of rats except the normal control group was greater than 160 mmHg, indicating that the hypertensive rat model was successfully established. The SBP and DBP of the model group rats were significantly increased compared with those of the normal group (P<0.001). After 7 days of intragastric administration, compared with the model group, the SBP of the enalapril group and the high- and medium-dose groups of the Chinese medicine composition was significantly reduced (P<0.001, P<0.01, P<0.05); compared with the model group, the DBP of the enalapril group and the medium-dose group of the Chinese medicine composition was significantly reduced (P<0.001, P<0.05). After 14 days of intragastric administration, compared with the model group, the SBP of the enalapril group, the high-dose group, the medium-dose group, and the low-dose group of the Chinese medicine composition was significantly reduced (P<0.001, P<0.001, P<0.01, P<0.05); compared with the model group, the DBP of the enalapril group, the high-dose group and the medium-dose group of the Chinese medicine composition was significantly reduced (P<0.001, P<0.001, P<0.05). This indicates that the Chinese medicine composition has a good antihypertensive effect on the L-NAME-induced hypertension model in rats. The results are shown in Tables 1 and 2.

[0073] Table 1 Effects on systolic blood pressure (SBP) (mmHg) in L-NAME-induced hypertension rat model

[0074] Group Before modeling Week 1 Week 2 Week 3 Week 4 Normal group 127.59±9.65 129.38±10.24 131.42±2.66 131.57±7.35 130.89±13.48 Model Group 126.51±7.7 153.07±9.12### 182.98±3.58### 182.31±10.53### 179.98±3.58### Low dose 128.3±8.17 152.2±5.68 180.63±6.7 168.84±17.86 160.6±12.75* Medium dose 129.26±8.26 152.32±9.37 185.16±10.17 165.61±8.08* 155.91±18.85** High dose 129.99±4.17 149.78±11.74 182.1±13.21 160.8±12.39** 148.21±14.79*** Enalapril 129.29±5.68 151.25±7.86 183±9.33 152.89±10.74*** 145.89±9.26***

[0075] Note: Compared with the normal group, ###P<0.001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001.

[0076] Table 2 Effects on diastolic blood pressure / DBP (mmHg) in L-NAME-induced hypertensive rat model

[0077] Group Before modeling Week 1 Week 2 Week 3 Week 4 Normal group 88.32±3.89 86.38±6.46 88±5.22 86.76±6.66 88.24±4.96 Model Group 89.72±5.02 113.07±4.78### 128.36±5.68### 131.18±7.43### 128.34±6.66### Low dose 89±4.78 112.39±5.3 130.08±7.32 123.97±10.24 122±8.76 Medium dose 90.15±5.12 113.99±6.83 128.36±4.88 120.01±10.35 117.04±12* High dose 89±5.57 112.39±4.56 129.1±5.12 113.16±13.84* 99.4±3.83*** Enalapril 90.69±7.18 113.48±4.87 129.54±5.22 106.89±13.67*** 97.89±4.44***

[0078] Note: Compared with the normal group, ###P<0.001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001.

[0079] 5.2 Effects on oxidative stress levels in L-NAME-induced hypertensive rat model

[0080] Compared with the normal control group, the T-AOC and CAT activities in the serum of the model group rats were significantly decreased (P<0.001). Compared with the model group, the T-AOC activity of the enalapril group and the high-dose Chinese medicine composition group was significantly increased (P<0.01, P<0.05); compared with the model group, the CAT activity of the enalapril group and the high-dose Chinese medicine composition group was significantly increased (P<0.001, P<0.01). It shows that the Chinese medicine composition has a good regulatory effect on the oxidative stress of the L-NAME-induced hypertension model in rats. The results are shown in Table 3.

[0081] Table 3 Effects on oxidative stress level in L-NAME-induced hypertensive rat model

[0082]

[0083] Note: Compared with the normal group, ###P<0.001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001.

[0084] 5.3 Effects on LVMI in L-NAME-induced hypertensive rat model

[0085] Compared with the normal control group, the left ventricular mass index of the model group rats increased significantly (P<0.001). Compared with the model group, the left ventricular mass index of the enalapril group and the high and medium dose groups of the Chinese medicine composition decreased significantly (P<0.001, P<0.001, P<0.05). This shows that the Chinese medicine composition has a good improvement effect on left ventricular hypertrophy in the L-NAME-induced rat hypertension model. The results are shown in Table 4.

[0086] Table 4 Effects on LVMI in L-NAME-induced hypertensive rat model

[0087]

[0088] Note: Compared with the normal group, ###P<0.001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001.

[0089] 6. Experimental conclusion

[0090] The Chinese herbal composition at 0.45 g / kg and 0.90 g crude drug / kg can significantly regulate the oxidative stress in the L-NAME-induced hypertensive rat model and reduce left ventricular hypertrophy, and effectively reduce the systolic and diastolic blood pressure of rats, indicating that the Chinese herbal composition has a certain therapeutic effect on the L-NAME-induced hypertensive rat model.

[0091] Experimental Example 3 Therapeutic effect of Chinese medicine composition on high-salt diet-induced hypertension rat model

[0092] 1. Experimental Materials

[0093] 1.1 Animals

[0094] SD rats, male, SPF grade, weighing 180-220 g, were purchased from Hangzhou Medical College.

[0095] Breeding environment: room temperature 20-26℃, relative humidity controlled at 40-70%, and breeding density of 4 per cage.

[0096] 1.2 Drugs

[0097] Chinese medicine composition: the intermediate prepared according to Example 1, provided by Jiangsu Kangyuan Pharmaceutical Co., Ltd.; captopril (Dalian Meilun Biotechnology Co., Ltd., batch number: A0411A); pentobarbital sodium (Beijing Chemical Reagent Company, batch number: 211122); physiological saline (Chenxin Pharmaceutical Co., Ltd., batch number 2101282721).

[0098] 1.3 Instruments

[0099] Electronic balance (Sartorius Scientific Instruments, model BS224S); low-temperature centrifuge (eppendorf, Germany, model 5804R); purified water instrument (Millipore, Germany, model: Milli-Q Plus); animal weighing scale (Shanghai Xiangchuan Electronic Scale Co., Ltd., model: CX-SC-DA); microplate reader (Megu Molecular, USA, model: Flexstation3); non-invasive blood pressure measurement system (Shanghai Alcott Biotechnology Co., Ltd., model: ALC-NIBP).

[0100] 2. Dosage design

[0101] The daily dosage of the Chinese medicine composition is 8.62 g of crude drug / day. According to the body surface area conversion method, the equivalent dose for rats is 8.62 g / 60 kg × 6.3 = 0.90 g of crude drug / kg. According to the 1 / 4:1 / 2:1 dosing method, the low dose is 0.225 g of crude drug / kg and the medium dose is 0.45 g of crude drug. The drug is administered by gavage, 1 mL / 100 g, once a day.

[0102] The dosage of Captopril is 13.5 mg / day. According to the body surface area conversion method, the equivalent dose for rats is 13.5 mg / 60 kg×6.2=1.4 mg / kg.

[0103] 3. Experimental Methods

[0104] SD rats were adaptively fed for 3 days, with free access to feed and water, and were randomly divided into normal control group, model control group, captopril control group, high, medium and low dose groups of Chinese medicine composition according to body weight, with 8 rats in each group. The control group rats were fed with ordinary feed, and the rats in other groups were given 8% NaCl high salt feed (7.5% NaCl + 92.5% ordinary feed) for 4 weeks, with free drinking water during the period. From the 5th week, the drug administration group rats were gavaged with positive drugs and corresponding low, medium and high doses of Chinese medicine composition (0.225g / kg, 0.45g / kg, 0.90g / kg), once a day, for 2 weeks. The tail vein systolic blood pressure (SBP) and diastolic blood pressure (DBP) of each group of rats were detected every two weeks using the ALC-NIBP non-invasive blood pressure measurement system, and the data of each group were recorded. After the experiment, the rats were euthanized, blood samples were taken from the abdominal aorta, and the serum was separated after centrifugation at 3500 rpm for 15 minutes at 4°C. The rat heart was taken out and washed in cold saline, dried with qualitative filter paper, and the left and right atria were removed along the atrioventricular ring, and the right ventricular free wall was removed along the ventricular septum to obtain the left ventricle of the heart. The left ventricular mass index (LVMI) was calculated to evaluate the degree of left ventricular hypertrophy: LVMI = left ventricular weight (mg) / body weight (g).

[0105] 4. Statistical methods

[0106] The results were statistically analyzed using t-test.

[0107] 5. Experimental Results

[0108] 5.1 Effects on systolic and diastolic blood pressure in a high-salt diet-induced hypertensive rat model

[0109] After 28 days of high-salt diet induction, SBP of rats except the normal control group was greater than 160 mmHg, indicating that the hypertensive rat model was successfully established. SBP and DBP of rats in the model group were significantly higher than those in the normal group (P<0.001). After 7 days of intragastric administration, SBP of the captopril group and the high- and medium-dose groups of the Chinese medicine composition were significantly lower than those in the model group (P<0.001, P<0.001, P<0.01); DBP of the captopril group and the high-, medium- and low-dose groups of the Chinese medicine composition were significantly lower than those in the model group (P<0.001, P<0.001, P<0.01, P<0.05). After 14 days of intragastric administration, compared with the model group, the SBP of the captopril group, the high, medium and low dose groups of the Chinese medicine composition were significantly reduced (P<0.001, P<0.001, P<0.001, P<0.001); compared with the model group, the DBP of the captopril group, the high, medium and low dose groups of the Chinese medicine composition were significantly reduced (P<0.001, P<0.001, P<0.001, P<0.001). This shows that the Chinese medicine composition has a good antihypertensive effect on the high salt diet-induced hypertension model in rats. The results are shown in Tables 5 and 6.

[0110] Table 5 Effects on systolic blood pressure in a high-salt diet-induced hypertensive rat model

[0111]

[0112]

[0113] Note: Compared with the normal group, ##P<0.01; ###P<0.001; compared with the model group, **P<0.01, ***P<0.001.

[0114] Table 6 Effects on diastolic blood pressure in high-salt diet-induced hypertensive rat model

[0115]

[0116] Note: Compared with the normal group, ###P<0.001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001.

[0117] 5.2 Effects on the RAAS system in a high-salt diet-induced hypertensive rat model

[0118] Compared with the normal control group, the activity of RAAS system in the model group was significantly enhanced, and the levels of Renin, Ang II and ALD in serum were significantly increased (P<0.001); compared with the model group, the level of Renin in the captopril group and the high-dose Chinese medicine combination group was significantly increased (P<0.01, P<0.01); compared with the model group, the level of Ang II in the captopril group and the high-dose Chinese medicine combination group was significantly increased (P<0.01, P<0.01); compared with the model group, the level of ALD in the captopril group and the high-, medium- and low-dose Chinese medicine combination groups was significantly increased (P<0.001, P<0.001, P<0.01, P<0.05); the results are shown in Table 7.

[0119] Table 7 Effects on RAAS system in high salt diet-induced hypertension rat model

[0120]

[0121] Note: Compared with the normal group, ###P<0.001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001.

[0122] 5.2 Effects on vasoactive factors in a high-salt diet-induced hypertensive rat model

[0123] Compared with the normal control group, the level of vasoactive factor NO in the serum of rats in the model group was significantly increased (P<0.001), and the level of ET-1 was significantly decreased (P<0.001). Compared with the model group, the NO level in the captopril group and the high-dose group of the Chinese medicine composition was significantly increased (P<0.01, P<0.05); compared with the model group, the ET-1 level in the captopril group and the high-, medium-, and low-dose groups of the Chinese medicine composition was significantly decreased (P<0.001, P<0.001, P<0.001, P<0.001). The results are shown in Table 8.

[0124] Table 8 Effects on vasoactive factors in the high-salt diet-induced hypertensive rat model

[0125]

[0126] Note: Compared with the normal group, ###P<0.001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001.

[0127] 5.3 Effects on LVMI in a high-salt diet-induced hypertensive rat model

[0128] Compared with the normal control group, the left ventricular mass index of the model group rats increased significantly (P<0.001). Compared with the model group, the left ventricular mass index of the captopril group and the high-dose Chinese medicine composition group decreased significantly (P<0.001, P<0.001). This shows that the Chinese medicine composition has a good improvement effect on left ventricular hypertrophy in the high-salt diet-induced hypertension model rat heart.

[0129] Table 9 Effects on LVMI in the high-salt diet-induced hypertensive rat model

[0130]

[0131] Note: Compared with the normal group, ###P<0.001; compared with the model group, ***P<0.001.

[0132] 6. Experimental conclusion

[0133] The Chinese medicine composition at 0.45g / kg and 0.90g crude drug / kg can significantly inhibit the activation of the RAAS system in the high-salt diet-induced hypertensive rat model, reduce serum Renin, Ang II and ALD levels, inhibit the secretion of ET-1 in rat vascular endothelial cells, increase the level of vasodilator factor NO in serum, and reduce left ventricular hypertrophy of the heart, and effectively reduce the systolic and diastolic blood pressure of rats, indicating that the Chinese medicine composition has a certain therapeutic effect on the high-salt diet-induced hypertensive rat model.

[0134] The above are only preferred embodiments 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 the scope of protection of the present invention.

Claims

1. Application of Chinese medicine composition in the preparation of medicine for preventing and treating hypertension; The Chinese medicine composition comprises the following raw materials in parts by weight: 1-1000 parts of Creeping Herb, 1-500 parts of seaweed, 1-1000 parts of oyster, 1-500 parts of hawthorn, 1-1000 parts of Siegesbeckia, 1-500 parts of Schisandra chinensis, and 1-800 parts of Polygonum cuspidatum.

2. The use according to claim 1, characterized in that: The prevention and treatment include: lowering blood pressure, lowering oxidative stress levels, alleviating left ventricular hypertrophy, inhibiting activation of the renin-angiotensin-aldosterone system and / or improving vasoactive factor levels.

3. The use according to claim 2, characterized in that: The lowering of blood pressure includes lowering diastolic blood pressure and / or lowering systolic blood pressure; The inhibiting of renin-angiotensin-aldosterone system activation comprises reducing serum Renin, Ang II and / or ALD levels; The improvement of vasoactive factor levels includes inhibiting the secretion of ET-1 and / or increasing NO levels.

4. The use according to any one of claims 1 to 3, characterized in that: The hypertension is hypertension caused by vasoconstriction or hypertension caused by increased sodium ion concentration.

5. The use according to claim 4, characterized in that: The hypertension caused by vasoconstriction is L-NAME-induced hypertension; The hypertension caused by the increased sodium ion concentration is hypertension induced by a high-salt diet.

6. The use according to any one of claims 1 to 5, characterized in that: The preparation method of the traditional Chinese medicine composition comprises: adding water to extract siegesbeckia, scutellaria baicalensis, seaweed, oyster, hawthorn, knotweed and schisandra chinensis, adding 5-10 times the mass of water each time, extracting for 2-4 hours, filtering, concentrating the filtrate under reduced pressure at a temperature not higher than 80° C. to an extract with a relative density of 1.25-1.30 (60±5° C.), and then concentrating and drying.

7. The use according to claim 67, characterized in that In the reflux extraction, reflux extraction was performed twice, each time for 1.5 hours.

8. A drug for preventing and treating hypertension, comprising pharmaceutically acceptable excipients and the following raw materials in parts by weight: 1-1000 parts of Creeping Peony, 1-500 parts of seaweed, 1-1000 parts of oyster, 1-500 parts of hawthorn, 1-1000 parts of Siegesbeckia, 1-500 parts of Schisandrae Chinensis, and 1-800 parts of Polygonum cuspidatum.

9. The drug according to claim 8, characterized in that Other drugs for treating hypertension are also included, and the other drugs for treating hypertension include: at least one of enalapril, hydrochlorothiazide, indapamide, betaxolol, metoprolol, nifedipine, losartan, valsartan, and telmisartan.

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