Composition for treating cardiovascular and cerebrovascular diseases and preparation method thereof

Abstract

The present invention provides a composition for treating cardiovascular and cerebrovascular diseases and a preparation method thereof, and relates to the field of Chinese medicine compositions. The composition is composed of the following ingredients: chrysanthemum, oyster and cassia seed. Compared with the problems of complex ingredients and numerous flavors of Chinese medicine compositions with similar functions in the prior art, the composition of the present invention has only three flavors of Chinese medicine, specializes in the liver meridian and has comparable efficacy, has a certain efficacy on target organ damage caused by cardiovascular and cerebrovascular diseases, and saves costs.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine compositions, and in particular to a composition for treating cardiovascular and cerebrovascular diseases and a preparation method thereof. Background Art

[0002] Cardiovascular and cerebrovascular diseases in a broad sense are a group of circulatory system diseases mainly characterized by abnormalities of the heart and blood vessels, including heart and blood vessel diseases, pulmonary circulation diseases and cerebrovascular diseases, among which hypertension, stroke and coronary heart disease are the most serious. Studies have shown that there are four main causes of cardiovascular and cerebrovascular diseases: ① Vascular factors such as atherosclerosis, hypertensive arteriosclerosis, and arteritis; ② Hemodynamic factors such as hypertension; ③ Hemorheological abnormalities such as hyperlipidemia and diabetes; ④ Blood component factors such as leukemia, anemia, and thrombocytosis. At present, the treatment of cardiovascular and cerebrovascular diseases, in addition to appropriate exercise, surgical treatment, and rehabilitation treatment, is mainly drug treatment.

[0003] Taking hypertension as an example, hypertension refers to an increase in arterial systolic and (or) diastolic blood pressure at rest, often accompanied by functional or organic changes in organs such as the heart, brain, kidney, and retina, as well as fat and sugar metabolism disorders. It is divided into primary hypertension and secondary hypertension. The occurrence of hypertension is related to genetic factors on the one hand, and on the other hand, it can also be caused by acquired environmental, dietary, drug and other factors that cause functional disorders in the regulation of blood pressure by higher nerve centers. The clinical symptoms of hypertension are dizziness, headache, mental symptoms, and neurological symptoms. At present, the prevention or treatment methods for hypertension include not only a reasonable diet and avoiding cold stimulation, but also the use of antihypertensive drugs for conditioning and treatment. Traditional Chinese medicine is widely used in the treatment of hypertension due to its advantages such as a wide source of raw materials, systematic treatment and few side effects.

[0004] For example, the book: Yang Zengliang, Xie Haizhou's Clinical Prescriptions [M], Beijing: People's Military Medical Publishing House, 2012: 77. It discloses a blood pressure lowering prescription, which is composed of 15g of Prunella Vulgaris, 25g of Semen Cassiae (pre-decocted), 15g of Cassiae Seed, 10g of Kudingcha Tea, 10g of Wild Chrysanthemum, 10g of Scutellaria, 10g of Sophora japonica Bud, 10g of Citrus aurantium, and 15g of Cyathula officinalis. This prescription can treat hypertension and arteriosclerosis, and is mainly used to treat those with hyperactivity of liver yang or hyperactivity of yang transforming into fire, with emphasis on "purging the excess". Book: Gao Jiandong, Bai Zhijun, Practical Nephrology of Integrated Traditional Chinese and Western Medicine [M], Jinan: Shandong University Press, 2016:135. It discloses the prescription for Yin deficiency and Yang hyperactivity syndrome in the TCM syndrome differentiation and treatment of hypertensive renal damage, which is modified on the basis of Zhengan Xifeng Decoction. The prescription is 30g of Rehmannia glutinosa, 12g of Cornus officinalis, 15g of Asparagus cochinchinensis, 15g of Ophiopogon japonicus, 30g of Dioscorea batatas, 30g of Poria cocos, 12g of Alisma orientalis, 30g of Scrophularia ningpoensis, 12g of Tortoise shell, 30g of Calcined Oyster shell, 15g of Cyathula capitata, 12g of Viscum album, 10g of Lycium barbarum, and 15g of Chrysanthemum morifolium. This prescription is mainly used to treat symptoms such as headache and dizziness, heaviness of the head and lightness of the feet, restlessness and insomnia, and hot palms and soles.

[0005] Another example is patent CN113633727A, which discloses a Chinese medicine composition for treating hypertension, comprising the following parts by weight: 10-15 parts of oyster; 10-15 parts of kudzu root; 5-10 parts of wolfberry; 15-20 parts of wax gourd; 5-10 parts of hawthorn; 3-7 parts of cassia seed; 5-10 parts of chrysanthemum; 10-15 parts of yam; 10-15 parts of jujube; 3-6 parts of mint; 2-6 parts of corn silk; 4-9 parts of polygonatum; 1-4 parts of tangerine peel; 3-7 parts of malt extract; 5-10 parts of edible starch; 5-10 parts of xylitol; 1-2 parts of magnesium stearate; and 1-2 parts of ionized calcium. The Chinese medicine composition in the invention has the effects of promoting blood circulation and removing blood stasis, softening blood vessels, regulating qi and relieving pain, calming the liver and promoting yang, lowering blood pressure and quenching thirst, and enhancing human immunity. Taking the Chinese medicine composition of the present invention has a significant antihypertensive effect and is safe and has no side effects.

[0006] However, the above-mentioned prescriptions are relatively complex in composition, contain many medicinal ingredients and are costly. Therefore, it is necessary to find a composition for treating cardiovascular and cerebrovascular diseases with excellent therapeutic effect and simple ingredients and a preparation method thereof. Summary of the invention

[0007] In view of the problems existing in the prior art, the present invention provides a composition for treating cardiovascular and cerebrovascular diseases and a preparation method thereof. The composition is simple to use, specifically acts on the liver meridian and has a comparable therapeutic effect, has a certain therapeutic effect on target organ damage caused by cardiovascular and cerebrovascular diseases, and saves costs.

[0008] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0009] The invention provides a composition consisting of the following ingredients: chrysanthemum, oyster and cassia seed.

[0010] Furthermore, the chrysanthemum includes one or more of chrysanthemum strychnifolia, fetal chrysanthemum and tribute chrysanthemum, and the oyster includes calcined oyster and / or raw oyster.

[0011] Preferably, the chrysanthemum is chrysanthemum, and the oyster is calcined oyster.

[0012] Furthermore, the composition consists of the following ingredients in parts by weight: 8-12 parts of chrysanthemum, 12-18 parts of calcined oyster shells and 8-12 parts of cassia seeds.

[0013] Preferably, the composition consists of the following ingredients in parts by weight: 10 parts of chrysanthemum, 15 parts of calcined oyster shell and 10 parts of cassia seed.

[0014] Furthermore, the present invention also provides a method for preparing the above-mentioned composition, comprising the following steps:

[0015] (1) Grinding, sieving and mixing chrysanthemum, oyster and cassia seed respectively to obtain a mixed powder;

[0016] (2) adding the mixed powder to water, soaking, first boiling and extracting, and centrifuging to obtain a supernatant and a medicinal residue;

[0017] (3) adding water to the residue from step (2) for a second decoction and extraction, and centrifuging to obtain a supernatant;

[0018] (4) mixing the supernatants obtained in step (2) and step (3) to obtain a water extract;

[0019] (5) Concentrate and filter the water extract to obtain the product.

[0020] Furthermore, the volume of water added in step (2) is 5-20 times that of the mixed powder; and the volume of water added in step (3) is 5-20 times that of the medicinal residue.

[0021] Preferably, the volume of water added in step (2) is 10 times that of the mixed powder; and the volume of water added in step (3) is 8 times that of the medicinal residue.

[0022] Furthermore, the soaking time in step (2) is ≥30 minutes, the boiling time of the first decoction extraction is 0.5-2 hours, and the boiling time of the second decoction extraction is 0.5-2 hours.

[0023] Preferably, the soaking time in step (2) is 30 minutes, the boiling time of the first decoction extraction is 2 hours, and the boiling time of the second decoction extraction is 2 hours.

[0024] Furthermore, the above composition or the composition prepared by the above preparation method can be used in the preparation of drugs for treating cardiovascular and cerebrovascular diseases.

[0025] Furthermore, the cardiovascular and cerebrovascular diseases include hypertension, stroke, atherosclerosis, angina pectoris, myocardial infarction or coronary heart disease.

[0026] Preferably, the cardiovascular and cerebrovascular disease is hypertension.

[0027] Furthermore, the medicine also includes pharmaceutically acceptable excipients.

[0028] In some specific embodiments, the auxiliary material includes one or more of a diluent, a binder, a disintegrant, a lubricant and a preservative.

[0029] Furthermore, the dosage form of the drug includes tablets, granules, capsules, pastes, powders or pills.

[0030] The technical effects achieved by the present invention are:

[0031] 1. The composition of the present invention uses chrysanthemum as the main drug, which is one of the eight medicinal materials in Zhejiang. According to the Chinese Pharmacopoeia, chrysanthemum is slightly cold in nature, bitter and sweet in taste, and enters the lung and liver meridians. It has the effects of dispersing wind and clearing heat, calming the liver and improving eyesight, and clearing away heat and detoxifying. It is used for wind-heat cold, headache and dizziness, red and swollen eyes, blurred vision, sores, carbuncle and swelling. According to the Shennong's Herbal Classic, chrysanthemum "maintains all wind-induced dizziness, swelling and pain, loss of eyesight, dead skin, and rheumatism. Long-term use can promote qi, lighten the body, endure fatigue and prolong life." Cassia seed is used as the assistant drug. It is sweet, bitter, and salty, slightly cold in nature, and is good at entering the liver, kidney, and large intestine meridians. It has the effects of clearing the liver and improving eyesight, moistening the intestines and relieving constipation. The earliest "Shennong Bencao Jing" listed Cassia seed as a top grade, saying that it "can cure various eye diseases, improve eyesight over time, and lighten the body." Another adjuvant is calcined oyster, which is slightly cold in nature, salty in taste, and enters the liver, gallbladder, and kidney meridians. It can calm the mind, subdue yang and replenish yin, soften and disperse nodules. There are also those who are mainly deficient. "Taiping Huimin Heji Bureau Prescription" believes that calcined oyster can "cure various deficiencies and new diseases, sudden deficiency of body fluids, frequent spontaneous sweating, worse when lying down at night, and not stopping for a long time, thin and withered, frightened, short of breath and tiredness." This medicine is used as an assistant, one is to assist the other medicines to enter the liver meridian, and the other is to replenish the deficiency.

[0032] 2. The induced classic hypertensive mouse model in the present invention is induced by unilateral nephrectomy and subcutaneous implantation of doca particles to induce a hypertensive model. Through a 28-day administration study, it is found that the Chinese medicine composition of the present invention has a significant inhibitory effect on the increase in hypertension in the model group. At the same time, the composition can also alleviate morphological damage to kidney and heart tissues and alleviate renal fibrosis. The composition is based on the theory of monarch, minister, assistant and envoy in traditional Chinese medicine, and the components cooperate with each other to achieve an excellent use effect.

[0033] 3. Compared with the problems of complex ingredients and numerous herbs in the prior art for Chinese medicine compositions with similar functions, the composition of the present invention contains only three herbs, which are specifically effective in the liver meridian and have comparable curative effects. It has certain curative effects on target organ damage caused by cardiovascular and cerebrovascular diseases and saves costs. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 The changes of systolic blood pressure (SBP) of mice in each group;

[0035] Figure 2 The mean blood pressure (MBP) changes of mice in each group;

[0036] Figure 3 The changes of diastolic blood pressure (DBP) of mice in each group;

[0037] Figure 4 The changes of heart rate (HR) of mice in each group;

[0038] Figure 5 Heart index of mice in each group;

[0039] Figure 6 Kidney index of mice in each group;

[0040] Figure 7 The 12h urine volume (12h Urinary Volume) of mice in each group;

[0041] Figure 8 Serum BUN of mice in each group;

[0042] Fig. 9 Serum creatinine of mice in each group;

[0043] Fig.10 The morphological damage of glomerular tissue (20 μm) in each group, wherein (a) is the blank control group, (b) is the model group, (c) is the high-dose group of Example 1, (d) is the low-dose group of Example 1, and (e) is the positive control group;

[0044] Fig.11 It is the glomerular injury index;

[0045] Fig.12 The morphological damage of the renal cortex (50 μm) in each group, wherein (a) is the blank control group, (b) is the model group, (c) is the high-dose group of Example 1, (d) is the low-dose group of Example 1, and (e) is the positive control group;

[0046] Fig.13The figures are the histomorphological damage of renal medulla (50 μm) in each group, wherein (a) is the blank control group, (b) is the model group, (c) is the high-dose group of Example 1, (d) is the low-dose group of Example 1, and (e) is the positive control group;

[0047] Fig.14 It is the renal tubular damage index;

[0048] Fig.15 The morphological damage of the heart (50 μm) in each group, wherein (a) is the blank control group, (b) is the model group, (c) is the high-dose group of Example 1, (d) is the low-dose group of Example 1, and (e) is the positive control group;

[0049] Fig.16 The cardiac injury index is:

[0050] Fig.17 The collagen fiber deposition in the glomerulus (20 μm) of each group, wherein (a) is the blank control group, (b) is the model group, (c) is the high-dose group of Example 1, (d) is the low-dose group of Example 1, and (e) is the positive control group;

[0051] Fig.18 The collagen fiber deposition in the renal cortex (50 μm) of each group, wherein (a) is the blank control group, (b) is the model group, (c) is the high-dose group of Example 1, (d) is the low-dose group of Example 1, and (e) is the positive control group;

[0052] Fig.19 The expression levels of TGF-β messenger RNA in mice of each group;

[0053] Fig. 20 The expression levels of α-SMA messenger RNA in mice of each group;

[0054] Fig.21 The expression levels of Collagen I messenger RNA in each group of mice;

[0055] Fig. 22 The expression levels of Collagen III messenger RNA in each group of mice;

[0056] Fig.23 The expression levels of NOX1 messenger RNA in each group of mice;

[0057] Fig.24 The expression levels of NOX2 messenger RNA in each group of mice;

[0058] Fig.25 The expression levels of NOX4 messenger RNA in each group of mice;

[0059] In the above figures, compared with the blank control group, #P<0.05, ##P<0.01; compared with the model group, *P<0.05, **P<0.01. DETAILED DESCRIPTION

[0060] The following describes the embodiments of the present invention through specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention.

[0061] Before further describing the specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terms used in the examples of the present invention are for describing specific embodiments rather than for limiting the scope of protection of the present invention.

[0062] When the embodiment gives a numerical range, it should be understood that, unless otherwise specified in the present invention, the two endpoints of each numerical range and any numerical value between the two endpoints can be selected. Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those of ordinary skill in the art to which the present invention belongs.

[0063] It is worth noting that the raw materials used in the present invention are all common commercially available products, so their sources are not specifically limited.

[0064] Example 1

[0065] A composition for treating cardiovascular and cerebrovascular diseases is composed of the following components in parts by weight: 10g of chrysanthemum, 15g of calcined oyster and 10g of cassia seed.

[0066] The preparation method of the Chinese medicine compound comprises the following steps:

[0067] (1) Grind the above drugs into fine powder respectively, pass through No. 7 sieve and mix well;

[0068] (2) Add 10 times the volume of ultrapure water to the mixed powder for the first decoction extraction, soak for 30 minutes in advance, wait for the drug to completely absorb the water, boil for 2 hours, then centrifuge and take the supernatant;

[0069] (3) Add 8 times the volume of ultrapure water to the residue after the first extraction for a second decoction extraction for 2 h, then centrifuge and take the supernatant;

[0070] (4) mixing the supernatants of the two extractions to obtain a water extract;

[0071] (5) The water extract was subjected to rotary evaporation, and the filtrate was concentrated to 0.46 g / ml of crude drug at a constant temperature, filtered through a membrane, and the drug solution was divided into 15 ml centrifuge tubes and stored at -80 degrees Celsius.

[0072] Example 2

[0073] A composition for treating cardiovascular and cerebrovascular diseases, comprising the following components in parts by weight: 8g of chrysanthemum, 12g of calcined oyster and 8g of cassia seed.

[0074] The preparation method of the Chinese medicine compound comprises the following steps:

[0075] (1) Grind the above drugs into fine powder respectively, pass through No. 7 sieve and mix well;

[0076] (2) Add 5 times the volume of ultrapure water to the mixed powder for the first decoction extraction. Soak for 30 minutes in advance, wait until the drug completely absorbs the water, boil for 0.5 hours, centrifuge, and take the supernatant;

[0077] (3) Add 5 times the volume of ultrapure water to the residue after the first extraction for a second decoction extraction for 0.5 h, then centrifuge and take the supernatant;

[0078] (4) mixing the supernatants of the two extractions to obtain a water extract;

[0079] (5) The water extract was subjected to rotary evaporation, and the filtrate was concentrated to 0.46 g / ml of crude drug at a constant temperature, filtered through a membrane, and the drug solution was divided into 15 ml centrifuge tubes and stored at -80 degrees Celsius.

[0080] Example 3

[0081] A composition for treating cardiovascular and cerebrovascular diseases, comprising the following components in parts by weight: 12g of chrysanthemum, 18g of calcined oyster shell and 12g of cassia seed.

[0082] The preparation method of the Chinese medicine compound comprises the following steps:

[0083] (1) Grind the above drugs into fine powder respectively, pass through No. 7 sieve and mix well;

[0084] (2) Add 20 times the volume of ultrapure water to the mixed powder for the first decoction extraction, soak for 30 minutes in advance, wait for the drug to completely absorb the water, boil for 2 hours, then centrifuge and take the supernatant;

[0085] (3) Add 20 times the volume of ultrapure water to the residue after the first extraction for a second decoction extraction for 2 h, then centrifuge and take the supernatant;

[0086] (4) mixing the supernatants of the two extractions to obtain a water extract;

[0087] (5) The water extract was subjected to rotary evaporation, and the filtrate was concentrated to 0.46 g / ml of crude drug at a constant temperature, filtered through a membrane, and the drug solution was divided into 15 ml centrifuge tubes and stored at -80 degrees Celsius.

[0088] Example 4

[0089] A composition for treating cardiovascular and cerebrovascular diseases, comprising the following components in parts by weight: 10 g of fetal chrysanthemum, 15 g of raw oyster and 10 g of cassia seed.

[0090] The preparation method of the Chinese medicine compound comprises the following steps:

[0091] (1) Grind the above drugs into fine powder respectively, pass through No. 7 sieve and mix well;

[0092] (2) Add 10 times the volume of ultrapure water to the mixed powder for the first decoction extraction, soak for 30 minutes in advance, wait for the drug to completely absorb the water, boil for 2 hours, then centrifuge and take the supernatant;

[0093] (3) Add 8 times the volume of ultrapure water to the residue after the first extraction for a second decoction extraction for 2 h, then centrifuge and take the supernatant;

[0094] (4) mixing the supernatants of the two extractions to obtain a water extract;

[0095] (5) The water extract was subjected to rotary evaporation, and the filtrate was concentrated to 0.46 g / ml of crude drug at a constant temperature, filtered through a membrane, and the drug solution was divided into 15 ml centrifuge tubes and stored at -80 degrees Celsius.

[0096] Comparative Example 1

[0097] The only difference from Example 1 is that only chrysanthemum is used (the preparation method is consistent with that of Example 1, and the raw materials added are adjusted according to the formulation situation).

[0098] Comparative Example 2

[0099] The only difference from Example 1 is that only calcined oyster is used (the preparation method is the same as that of Example 1, and the raw materials added are adjusted according to the formulation).

[0100] Comparative Example 3

[0101] The only difference from Example 1 is that only Cassia seed is used (the preparation method is the same as that of Example 1, and the raw materials added are adjusted according to the formulation conditions).

[0102] Comparative Example 4

[0103] A composition is composed of the following components in parts by weight: 10g of chrysanthemum, 15g of calcined oyster shell, 10g of cassia seed and 10g of polygonatum.

[0104] That is, the only difference from Example 1 is that the composition further contains 10 g of Polygonatum odoratum (the preparation method is consistent with that of Example 1, and the raw materials added are adjusted according to the formulation conditions).

[0105] Comparative Example 5

[0106] A composition is composed of the following components in parts by weight: 14g of chrysanthemum, 7g of calcined oyster shell and 14g of cassia seed (the preparation method is consistent with that in Example 1, and the raw materials added are adjusted according to the formulation conditions).

[0107] 1. Experimental study on the effect of the composition of the present invention on alleviating DOCA / Salt-induced hypertension

[0108] ① All experimental C57 mice were adaptively raised for one week before undergoing single kidney removal surgery.

[0109] ② One week after recovery from surgery, the mice were numbered and randomly grouped into: blank control group (Ctrl, n=7), model group (DOCA / Salt, n=7), DOCA / Salt plus Example 1 low-dose group of the composition in Example 1 (2.3 g / kg / d, n=7), DOCA / Salt plus Example 1 high-dose group of the composition in Example 1 (4.6 g / kg / d, n=7), DOCA / Salt plus Examples 2-4 and Comparative Examples 1-5 high-dose groups (4.6 g / kg / d, each group n=7), DOCA / Salt plus positive drug perindopril positive control group (Perindopril, 2 mg / kg / d, n=7), wherein n is the number of mice in each group.

[0110] About modeling: DOCA / Salt was used to induce a classic hypertension model, and each group of the Chinese medicine composition was given for intervention. Blood pressure was measured using the tail cuff method, and the blood pressure of the DOCA / Salt model group increased significantly throughout the experimental period, indicating that the modeling was successful.

[0111] ③ After collecting the basal blood pressure, the model group and each drug-treated group were subcutaneously implanted with DOCA sustained-release capsules (40 mg / mice), and the control group underwent sham surgery at the corresponding position. After the surgery, the drinking water of the model and each drug-treated group was replaced with 1% saline.

[0112] ④Start gavage administration from the day after the surgery. According to the clinical dosage of this Chinese medicine formula, the standard body weight is 70kg, the conversion coefficient is 9.1, and the corresponding dosage of mice is calculated to be 4.6g / kg / d. This is the high-dose group, and the low-dose group is half of it. The dosage of positive drugs is referenced in the literature. When gavage, the dosage volume is 0.1ml / 10g according to the weight of the mouse, and it is maintained for 4 weeks.

[0113] ⑤ In addition to collecting basal blood pressure, all mice were adaptively monitored for three consecutive days before formal data collection to reduce the stress response of mice when formal data collection was performed. The blood pressure of mice was monitored every 2-3 days for 4 weeks. When measuring blood pressure, keep the surrounding environment quiet. When collecting data, when the animal is quiet and the real-time blood pressure monitoring waveform is stable, record systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), and heart rate (HR). Each animal collects data from 5 stable states, and the average value is the data for this blood pressure monitoring.

[0114] ⑥After the experiment, collect mouse samples.

[0115] like Figure 1-3 As shown in the figure, the high and low doses of Example 1 were used for intervention at the same time as the model group. Compared with the model group, the high and low doses of Example 1 delayed the increase of blood pressure (SBP, MBP, DBP) from the 6th day (P<0.05, P<0.01). The blood pressure of the positive control group increased slowly and was basically maintained at the normal blood pressure level. Figure 4 As shown, the heart rate of the Chinese medicine composition of Example 1 was significantly lower than that of the model group at week 4 (P<0.01). The results show that the Chinese medicine composition of the present invention has an inhibitory effect on DOCA / Salt-induced blood pressure increase and has a reducing effect on heart rate.

[0116] 2. Experimental study on the protection of renal function by the composition of the present invention

[0117] After the 4-week experiment, heart and kidney tissue samples were taken from the mice and compared with the body weight to calculate the heart index and kidney index (such as Figure 5-6 ), compared with the blank control group, the cardiorenal index of the model group was significantly increased (P<0.01), while the high-dose group of Example 1 of the present invention significantly reduced the increase of the cardiorenal index after administration (P<0.05); the mice were placed in metabolic cages to collect urine for 12 hours, and the 12-hour urine was quantified. Figure 7 It can be seen that the urine volume of the model group was significantly increased compared with the control group (P<0.01), and the high dose of the composition of Example 1 of the present invention improved this trend (P<0.05); serum creatinine and urea nitrogen levels are important indicators for evaluating renal function impairment, such as Figure 8-9 As shown, compared with the blank control group, the serum creatinine (Cr) and urea nitrogen (BUN) levels of the model group were significantly increased, indicating that hypertension impaired renal function, and the composition of the embodiment of the present invention significantly reduced the elevated serum creatinine and urea nitrogen levels of the model group after treatment. The above results show that the composition of the embodiment of the present invention can protect renal function. In comparison, there are significant differences in some indicators between the composition of each comparative example and the embodiment, and the effect of protecting renal function is relatively small.

[0118] The cardiac index, renal index, 12h urine volume and serum creatinine of each group of mice in the present invention are specifically shown in the following table:

[0119] Table 1 Cardiac index, renal index, 12h urine volume, urea nitrogen and serum creatinine of each group of mice in the present invention

[0120]

[0121]

[0122] (Note: Compared with the blank control group, #P<0.05, ##P<0.01; compared with the model group, *P<0.05, **P<0.01; compared with the high-dose group in Example 1, ▲ P<0.05, ▲▲ P<0.01. )

[0123] III. Experimental study on the effect of the composition of the present invention on the morphological damage of kidney and heart tissues in hypertensive mice

[0124] HE staining of kidney tissue Fig.10 , Fig.12 and Fig.13 As shown, in the kidney tissue of mice treated with DOCA / Salt, the glomerular boundaries were unclear, the basement membrane increased, the cell nuclei increased, the glomerular reticular structure was not obvious, and the glomerular damage and tubulointerstitial damage increased; Fig.11 , Fig.14 As shown in the results, after high and low doses of Example 1 were administered, the kidney tissue damage was significantly reduced (P<0.01); the cardiac tissue morphology results also showed a similar trend, that is, the model group showed pathological manifestations such as myocardial cell hypertrophy, widened and loose gaps, and disordered myocardial fiber arrangement ( Fig.15 ), the cardiac damage score was significantly increased, and the composition of the present invention significantly reduced the above abnormal cardiac tissue morphology indexes and reduced cardiac damage ( Fig.16 ); The above results show that the composition of the present invention can alleviate the morphological damage of kidney and heart tissues. In comparison, there are significant differences in some indicators between the composition of each comparative example and the embodiment, and the effect of alleviating the morphological damage of kidney and heart tissues is relatively small.

[0125] The glomerular injury index, tubular injury index and cardiac injury index of each group of mice in the present invention are specifically shown in the following table:

[0126] Table 2 Glomerular injury index, tubular injury index and cardiac injury index of each group of mice in the present invention

[0127]

[0128] (Note: Compared with the blank control group, #P<0.05, ##P<0.01; compared with the model group, *P<0.05, **P<0.01; compared with the high-dose group in Example 1, ▲ P<0.05, ▲▲ P<0.01. )

[0129] IV. Experimental study on the effect of the composition of the present invention on reducing renal fibrosis in hypertensive mice

[0130] Masson staining was used to observe the collagen fiber deposition in the cortex and medulla of mouse kidneys. Fig.17 As shown, the composition of Example 1 of the present invention significantly reduced the collagen deposition caused by DOCA / Salt after administration.

[0131] In order to explore the specific mechanism of action of the composition of the present invention on renal fibrosis, the mRNA expression of fibrosis markers α-SMA, Collagen I, and Collagen III in the kidney and the mRNA expression of TGF-β, a key mediator of fibrosis regulation, were detected. The results showed that (see Figure 18-22 ), the level of fibrosis markers in the DOCA / Salt model group was significantly increased, while the composition of Example 1 of the present invention significantly reduced the expression of fibrosis markers α-SMA, Collagen I, and Collagen III in the kidneys of hypertensive mice, and inhibited the expression of TGF-β, a key mediator of fibrosis regulation. The above results show that the composition of the present invention can alleviate renal fibrosis in hypertensive mice.

[0132] V. Experimental study on reducing the expression of NOXs in kidney tissue of hypertensive mice by the composition of the present invention

[0133] Further analysis of the expression of NOX1, NOX2, and NOX4 genes in the kidney showed that (see Figure 23-25 ), the expressions of NOX1, NOX2 and NOX4 in the DOCA / Salt model group increased significantly, the high-dose group of Example 1 of the present invention significantly reduced the expression of NOX2 in kidney tissue (P<0.05), while NOX4 showed a downward trend, but without statistical significance.

[0134] The above experimental results show that the Chinese medicine composition of the present invention can delay the increase in blood pressure caused by DOCA / Salt hypertensive mice and improve the protective effect of kidney and heart tissue damage caused by hypertension. The Chinese medicine composition of the present invention is expected to be used as a potential therapeutic drug for target organ damage of hypertension.

[0135] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A composition, Features: The invention is composed of the following ingredients by weight: 8-12 parts of chrysanthemum, 12-18 parts of calcined oyster shell and 8-12 parts of cassia seed.

2. The composition according to claim 1, Features: The invention is composed of the following ingredients by weight: 10 parts of chrysanthemum, 15 parts of calcined oyster shell and 10 parts of cassia seed.

3. A method for preparing a composition according to any one of claims 1 to 2, Features: The following steps are involved: (1) respectively crushing, sieving and mixing chrysanthemum, calcined oyster shell and cassia seed to obtain a mixed powder; (2) adding the mixed powder to water, soaking, first boiling and extracting, and centrifuging to obtain a supernatant and a medicinal residue; (3) adding water to the residue from step (2) for a second decoction and extraction, and centrifuging to obtain a supernatant; (4) mixing the supernatants obtained in step (2) and step (3) to obtain a water extract; (5) Concentrate and filter the water extract to obtain the product.

4. The preparation method according to claim 3, Features: The volume of water added in step (2) is 5-20 times that of the mixed powder; and the volume of water added in step (3) is 5-20 times that of the medicinal residue.

5. The preparation method according to claim 3, Features: The soaking time in step (2) is ≥30 minutes, the boiling time of the first decoction extraction is 0.5-2 hours, and the boiling time of the second decoction extraction is 0.5-2 hours.

6. Use of the composition according to any one of claims 1 to 2 or the composition prepared by the preparation method according to any one of claims 3 to 5 in the preparation of a drug for treating cardiovascular and cerebrovascular diseases, Features: The cardiovascular and cerebrovascular disease is hypertension.

7. The use according to claim 6, Features: The drug also includes pharmaceutically acceptable excipients.

8. The use according to claim 6, Features: The dosage form of the drug includes tablets, granules, capsules, pastes, powders or pills.

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