A traditional Chinese medicine composition for treating hypertension, its preparation method and uses.

Abstract

This invention provides a traditional Chinese medicine composition for treating hypertension, prepared from the following raw materials in the indicated weight ratios: 8-12 parts of Achyranthes bidentata, 8-12 parts of Leonurus japonicus, 12-18 parts of Alisma plantago-aquatica, 8-12 parts of Scutellaria baicalensis, 8-12 parts of Paeonia lactiflora, 8-12 parts of Atractylodes lancea, and 4-6 parts of Carthamus tinctorius. This invention also provides a method for preparing the composition and its uses. This traditional Chinese medicine composition can effectively control blood pressure in young and middle-aged patients with hypertension diagnosed as damp-heat obstruction syndrome. By preparing a decoction from the seven herbs in the composition using specific dosages and traditional Chinese medicine processing techniques, it can clear heat and dry dampness, promote blood circulation and diuresis, and lower blood pressure. Simultaneously, it effectively improves clinical symptoms of damp-heat obstruction syndrome such as persistent fever and sweating, thirst without excessive drinking, epigastric fullness and nausea, restlessness, loose stools with yellow color, and scanty dark urine, providing a new medication option for clinical use.

Description

Technical Field

[0001] This invention relates to a traditional Chinese medicine composition for treating hypertension, its preparation method, and its uses, belonging to the pharmaceutical field. Background Technology

[0002] Hypertension in young and middle-aged adults refers to hypertension (blood pressure ≥140 / 90 mmHg) patients aged 18-65 years, who account for approximately 78% of the total hypertension population.

[0003] Characteristics of hypertension in young and middle-aged adults: 1) Diastolic hypertension is more common in young and middle-aged adults: Diastolic hypertension in young and middle-aged adults is predominantly characterized by elevated diastolic blood pressure, while systolic blood pressure is normal or only slightly elevated. This is because the arteries of young and middle-aged hypertensive patients still have good elasticity, and the elastic reservoir function of the arteries during diastole is relatively normal. They can absorb more pressure from the increased stroke volume, leading to increased total peripheral resistance and elevated diastolic blood pressure; while the stiffness of the large arteries is not severe, so systolic blood pressure does not increase significantly. 2) Hypertension in young and middle-aged adults often involves an increased heart rate. Activation of the sympathetic nervous system is an important mechanism in the occurrence and development of hypertension in young and middle-aged adults. High work and life pressures, mental stress, and dysfunction of the central nervous system in the brain lead to excessive activation of the sympathetic nervous system, resulting in a faster heart rate, stronger myocardial contraction, and elevated blood pressure. In the early stages of hypertension, elevated blood pressure in young and middle-aged adults is often accompanied by increased heart rate, which is one of the biological markers of sympathetic nervous system activation. Surveys show that 64% of hypertensive patients under 40 years of age have evidence of excessive sympathetic nervous system activation compared to normotensive individuals of the same age; while only 23% of hypertensive patients aged 40 and above have excessive sympathetic activation compared to normotensive individuals. 3) Most hypertensive patients in young and middle-aged adults are obese or have metabolic disorders. Among these patients, the incidence of unhealthy lifestyle-related diseases such as overweight / obesity, dyslipidemia, glucose metabolism disorders, and hyperuricemia is high. Studies show that among hypertensive patients under 55 years of age, 80.4% have dyslipidemia, 45.8% have abdominal obesity, over 70% have two or more risk factors, and approximately 50% have metabolic syndrome.

[0004] The main causes of hypertension in young and middle-aged adults are: 1) Overactivation of the sympathetic nervous system. Long-term high stress, tension, anxiety, depression, and other negative emotions, coupled with unhealthy lifestyle habits such as frequently staying up late, can disrupt the balance of the autonomic nervous system, leading to overactivation of the sympathetic nervous system. Increased sympathetic nerve excitability causes a series of changes, including vasoconstriction and increased heart rate, all of which are important reasons for elevated blood pressure, especially diastolic blood pressure; 2) Overactivity of the renin-angiotensin-aldosterone system. In daily life, many young and middle-aged adults experience poor rest, mental stress, excessive pressure, staying up late, irregular sleep patterns, long-term smoking and excessive alcohol consumption, and excessive fatigue. These unhealthy lifestyle habits can lead to excessive renin secretion and overactivation of the renin-angiotensin-aldosterone system. The normal regulatory mechanism of angiotensin is strengthened, leading to vasoconstriction and increased peripheral blood flow resistance, thus making high diastolic blood pressure more common. A domestic study has confirmed that plasma renin activity and angiotensin II levels gradually decrease with age. The renin-angiotensin levels differ between young and middle-aged patients and elderly patients with essential hypertension; the younger the patient, the higher the renin-angiotensin levels.

[0005] Currently, the treatment of hypertension in young and middle-aged adults faces the following challenges: 1) Low awareness: Many young and middle-aged hypertension patients are unaware that they have hypertension, leading to low treatment and control rates; 2) Atypical symptoms: Young and middle-aged hypertension patients often lack typical clinical symptoms, such as dizziness and headaches, and therefore may not actively seek treatment; 3) Poor treatment adherence: Due to concerns about the side effects of long-term medication, insufficient understanding of the dangers of hypertension, or busy work schedules, patients may not follow medical advice and find it difficult to adhere to long-term treatment; 4) Multiple comorbidities: Young and middle-aged hypertension patients often have metabolic disorders such as overweight / obesity, dyslipidemia, and glucose metabolism disorders. 5) Difficulty in blood pressure control: especially diastolic blood pressure control. Young and middle-aged patients primarily experience elevated diastolic blood pressure, and existing treatments may struggle to effectively control it. 6) Difficulty in lifestyle changes: Young and middle-aged patients may find it difficult to change unhealthy lifestyle habits due to high work pressure and numerous social activities. These include quitting smoking and limiting alcohol consumption, reducing sodium intake, and increasing exercise, all crucial components of comprehensive hypertension treatment. 7) Long-term risk assessment: Young and middle-aged hypertensive patients may focus more on short-term treatment effects while neglecting long-term or lifelong risk assessment. Long-term risk management is essential. (Wang Xin, et al., Current Status of Hypertension Epidemiology and Treatment Control in Young and Middle-aged Populations in my country, Chinese Journal of Cardiovascular Diseases, December 2022, Vol. 50, No. 12)

[0006] Traditional Chinese medicine (TCM) treatment of hypertension in young and middle-aged people is based on TCM syndrome differentiation, which has different subtypes. The currently reported subtypes are roughly as follows: liver yang hyperactivity type, liver and kidney yin deficiency type, liver stagnation and spleen deficiency type, phlegm and dampness accumulation type, qi deficiency and blood stasis type, yin and yang deficiency type, blood stasis obstructing collaterals type, damp-heat obstruction type, and asymptomatic type. The TCM syndrome differentiation and treatment methods are also different according to different subtypes. Summary of the Invention

[0007] The technical solution of the present invention is to provide a traditional Chinese medicine composition for treating hypertension, especially for treating hypertension of the damp-heat obstruction type in young and middle-aged people. Another technical solution of the present invention is to provide a preparation method and uses of the traditional Chinese medicine composition.

[0008] This invention provides a traditional Chinese medicine composition for treating hypertension, which is prepared from the following raw materials in the indicated weight ratios:

[0009] 8-12 parts of Achyranthes bidentata, 8-12 parts of Leonurus japonicus, 12-18 parts of Alisma plantago-aquatica, 8-12 parts of Scutellaria baicalensis, 8-12 parts of Paeonia lactiflora, 8-12 parts of Atractylodes lancea, and 4-6 parts of Carthamus tinctorius.

[0010] More preferably, it is prepared from raw materials in the following weight ratio:

[0011] 10 parts of Achyranthes bidentata, 10 parts of Leonurus japonicus, 15 parts of Alisma plantago-aquatica, 10 parts of Scutellaria baicalensis, 10 parts of Paeonia lactiflora, 10 parts of Atractylodes lancea, and 5 parts of Carthamus tinctorius.

[0012] The traditional Chinese medicine composition of the present invention is prepared into a commonly used oral preparation by adding pharmaceutically acceptable excipients or auxiliary ingredients, using the raw medicinal powder, water or organic solvent extract of the raw material as the active ingredient.

[0013] The preparations mentioned above are tablets, capsules, pills, and oral liquids.

[0014] This invention provides a method for preparing the traditional Chinese medicine composition for treating hypertension, comprising the following steps:

[0015] a. Weigh the raw materials according to their respective weight ratios;

[0016] b. Powder, or extract with water or organic solvents, and add pharmaceutically acceptable excipients or auxiliary ingredients to prepare commonly used oral pharmaceutical preparations.

[0017] This invention provides the use of the aforementioned traditional Chinese medicine composition in the preparation of a medicament for hypertension.

[0018] The aforementioned drug is for treating hypertension of the damp-heat obstruction type.

[0019] The aforementioned drug is for treating hypertension of the damp-heat obstruction type in young and middle-aged adults.

[0020] This invention relates to a traditional Chinese medicine composition primarily for the treatment of hypertension in young and middle-aged adults due to damp-heat obstruction in the middle jiao (middle burner). The pathogenesis of this condition is the mutual binding of damp-heat in the middle jiao, leading to dysfunction of the spleen and stomach's ascending and descending functions. The formula uses Achyranthes bidentata and Alisma plantago-aquatica as the chief herbs. Achyranthes bidentata, with its sour taste, enters the liver meridian and effectively guides blood (fire) downwards. Alisma plantago-aquatica primarily clears turbidity, lowers lipids, promotes urination, and eliminates dampness, allowing damp-heat to be expelled through urination. The two herbs work together to clear liver heat. Leonurus japonicus and Paeonia lactiflora are the assistant herbs. Both herbs enter the liver meridian. Leonurus japonicus is a holy herb for the blood aspect of the Jueyin meridian. It is bitter, pungent, and slightly cold, and can both calm the liver and descend rebellious qi, as well as invigorate blood, promote urination, and clear heat. Paeonia lactiflora calms liver yang, nourishes blood, and astringes yin, and also has the effect of clearing heat. The two herbs work together to calm and soften the liver, allowing heat to be expelled through urination. Scutellaria baicalensis and Atractylodes lancea are the adjuvant herbs. One clears heat and detoxifies, while the other strengthens the spleen and dries dampness. The two herbs work together to dry dampness and resolve phlegm. Hypertension is a disease of Qi and blood. In its early stages, it enters the meridians; in its later stages, it enters the collaterals. Safflower is used as an adjuvant to invigorate blood, remove blood stasis, and unblock the collaterals. Looking at the seven herbs, the combination of Alisma plantago-aquatica and Leonurus japonicus enhances the diuretic effect of this formula. The formula contains many heat-clearing herbs: some clear heat and detoxify, others clear heat and dry dampness, and still others nourish Yin and clear heat. The combination of these three types enhances the heat-clearing effect without harming Yin. Achyranthes bidentata guides the other herbs downwards, leading the entire formula to expel damp-heat pathogens through urination, thus achieving the effect of lowering blood pressure. The combination of the principal, assistant, and adjuvant herbs is appropriate, achieving the therapeutic effect of lowering blood pressure through clearing heat and drying dampness, invigorating blood, and promoting diuresis.

[0021] The herbal composition of this invention can effectively control blood pressure in young and middle-aged patients with hypertension diagnosed with damp-heat obstruction syndrome. The seven herbs in the composition are prepared into a decoction using specific dosages and traditional Chinese medicine processing techniques. This decoction has the effects of clearing heat and drying dampness, promoting blood circulation and diuresis, and lowering blood pressure. Simultaneously, it effectively improves clinical symptoms of damp-heat obstruction syndrome such as persistent fever and sweating, thirst without excessive drinking, epigastric fullness and nausea, restlessness, loose stools with yellow color, and scanty dark urine, providing a new medication option for clinical use. Detailed Implementation

[0022] Example 1: Preparation of the drug mixture of the present invention

[0023] Weigh out the following raw materials: 10g of Achyranthes bidentata, 10g of Leonurus japonicus, 15g of Alisma plantago-aquatica, 10g of Scutellaria baicalensis, 10g of Paeonia lactiflora, 10g of Atractylodes lancea, and 5g of Carthamus tinctorius. Add water, decoct, and concentrate to prepare a compound.

[0024] Example 2: Preparation of the drug granules of the present invention

[0025] Weigh out the raw materials: 8g of Achyranthes bidentata, 8g of Leonurus japonicus, 12g of Alisma plantago-aquatica, 8g of Scutellaria baicalensis, 8g of Paeonia lactiflora, 8g of Atractylodes lancea, and 4g of Carthamus tinctorius. Add water to decoct and concentrate the mixture. Add starch, granulate and shape the mixture to prepare granules.

[0026] Example 3: Preparation of the drug capsule of the present invention

[0027] Weigh out the raw materials as follows: 12g of Achyranthes bidentata, 12g of Leonurus japonicus, 18g of Alisma plantago-aquatica, 12g of Scutellaria baicalensis, 12g of Paeonia lactiflora, 12g of Atractylodes lancea, and 6g of Carthamus tinctorius. Grind them directly into powder, fill them into capsules, and obtain capsules.

[0028] The beneficial effects of the present invention are demonstrated below through clinical trials and pharmacodynamic studies.

[0029] Example 1: Clinical trial of the pharmaceutical composition of the present invention for treating hypertension in young and middle-aged adults.

[0030] This invention provides a drug treatment for hypertension in young and middle-aged adults, which can improve blood pressure indicators and prevent cardiovascular diseases.

[0031] 1. Experimental Objective

[0032] To evaluate the clinical efficacy, safety, and mechanism of action of the drug of this invention in treating hypertension in young and middle-aged adults (damp-heat obstruction type), and to explore traditional Chinese medicine treatment options for hypertension in young and middle-aged adults.

[0033] 2. Materials and Methods

[0034] 2.1 Case inclusion criteria

[0035] 2.1.1 Western Medicine Diagnostic Criteria: Based on the "Chinese Guidelines for the Prevention and Treatment of Hypertension 2018 Revised Edition"

[0036] 2018 ESC / ESH Hypertension Management Guidelines

[0037] 2017 ACC / AHA / AAPA / ABC / ACPM / AGS / APhA / ASH / ASPC / NMA / PCNA Guidelines for the Prevention, Detection, Assessment and Management of Hypertension in Adults

[0038] ① Males or females aged 19 to 59.

[0039] ② Meets at least one of the following criteria:

[0040] 1. In the absence of antihypertensive medication, the office systolic blood pressure is 130 ≤ (SBP) ≤ 159 mmHg and / or diastolic blood pressure is 80 ≤ (DBP) ≤ 99 mmHg;

[0041] 2. Patients with systolic blood pressure ≤130 (SBP) ≤159 mmHg and / or diastolic blood pressure ≤80 (DBP) ≤99 mmHg in the clinic, who are already taking antihypertensive medication but whose blood pressure is not at target, meet the inclusion criteria and refuse to change or add Western medicine.

[0042] 2.1.2 Traditional Chinese Medicine Diagnostic Criteria: Based on the classification criteria of the "National Basic Guidelines for the Prevention and Management of Hypertension 2020 Edition," "Expert Consensus on the Diagnosis and Treatment of Hypertension with Traditional Chinese Medicine," and "Clinical Application Guidelines for the Treatment of Primary Hypertension with Traditional Chinese Medicine (2021)":

[0043] ① Damp-heat obstruction syndrome:

[0044] Main symptoms: fever with persistent sweating, thirst but no desire to drink much, epigastric fullness and nausea, restlessness, loose and yellow stools, and scanty and dark urine;

[0045] Tongue and pulse: Yellow and greasy tongue coating, soft and rapid pulse;

[0046] 2.1.3 Inclusion criteria: ① Meets the Western medicine diagnostic criteria for hypertension and the TCM syndrome (damp-heat obstruction syndrome) diagnostic criteria; ② Primary hypertension, with blood pressure measured 3 times on different days within 1 week, with office systolic blood pressure 130 ≤ (SBP) ≤ 159 mmHg and / or diastolic blood pressure 80 ≤ (DBP) ≤ 99 mmHg; ③ Age between 20 and 59 years old; ④ No history of systematic use of: (1) hormone drugs; (2) central nervous system drugs; (3) non-steroidal anti-inflammatory drugs; (4) Chinese herbal medicines or other drugs that affect blood pressure within the past 2 weeks; Exclude those currently taking Western medicine for hypertension but whose blood pressure is still not up to standard, with systolic blood pressure 130 ≤ (SBP) ≤ 159 mmHg and / or diastolic blood pressure 80 ≤ (DBP) ≤ 99 mmHg; ⑤ Those who have signed informed consent forms.

[0047] 2.2 Patient Information

[0048] The selected subjects were all outpatients who met the diagnostic criteria from the Department of Cardiovascular Medicine II and its affiliated medical consortium of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine between January 2023 and January 2024, totaling 60 cases.

[0049] 2.3 Experimental Grouping

[0050] The patients were randomly divided into a control group and a treatment group. The control group consisted of 30 patients, including 20 males and 10 females, with a mean age of 28-59 years. The treatment group consisted of 30 patients, including 16 males and 14 females, with a mean age of 30-59 years. There were no statistically significant differences in age and sex between the two groups (P > 0.05), making them comparable.

[0051] 2.4 Treatment methods

[0052] 2.4.1 Control group:

[0053] The study used Songling Xuemaikang capsules, a commonly used and recognized treatment for hypertension, and a lifestyle intervention control group. Songling Xuemaikang capsules (0.5g, Chengdu Kanghong) 1.5g tid.

[0054] 2.4.2 Intervention measures for the treatment group:

[0055] After being randomly assigned to different groups, this group of patients received the drug of this invention, which has been shown to have substantial efficacy in extensive and repeated clinical trials, for the treatment of hypertension of the damp-heat obstruction type.

[0056] Formula: 10g of Achyranthes bidentata, 10g of Leonurus japonicus, 15g of Alisma plantago-aquatica, 10g of Scutellaria baicalensis, 10g of Paeonia lactiflora, 10g of Atractylodes lancea, and 5g of Carthamus tinctorius. Using traditional Chinese medicine preparation technology, each herb in the formula is prepared into a 100ml / bottle mixture according to type and dosage. Dosage: Oral administration, 15ml three times a day; (each ml contains 0.7g of raw herbs, each 15ml dose contains 10.5g of raw herbs, and the daily intake is 31.5g of raw herbs).

[0057] 2.5 treatment courses: 8 weeks.

[0058] 2.6 Observation Indicators

[0059] (1) Clinical efficacy. Criteria for judging efficacy: Marked effect: SBP decrease ≥20 mmHg or DBP decrease ≥10 mmHg; Effective: SBP decrease between 10 and 20 mmHg or DBP decrease <10 mmHg; Ineffective: Blood pressure decrease does not meet the effective criteria. Total effective rate = Marked effect rate + Effective rate.

[0060] (2) Comparison of 24-hour ambulatory blood pressure. Compare the DBP and SBP levels before and after treatment in the two groups.

[0061] (3) TCM symptom scores. A scoring table was developed with reference to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines" (2002) [Zheng Xiaoyu, ed. Guiding Principles for Clinical Research of New Traditional Chinese Medicines (Trial) [M]. Beijing: China Medical Science and Technology Press, 2002: 151-155.]. Scores were taken once before and once after treatment for both groups.

[0062] 2.7 Data Processing

[0063] SPSS 26.0 software was used to perform statistical analysis on the collected and organized data. Count data were analyzed using...

[0064] χ 2 Tests; use mean ± standard deviation for continuous data. The independent samples t-test was used for comparisons between groups of normally distributed continuous data, and the paired samples t-test was used for comparisons within groups of normally distributed continuous data. The rank-sum test was used for comparisons of ordinal data. P < 0.05 indicates that the difference is statistically significant.

[0065] 2.7.1 Comparison of efficacy evaluation between the control group and the treatment group after 8 weeks of treatment:

[0066] After 8 weeks of treatment, in the control group, 12 cases showed significant improvement, 13 cases showed improvement, and 7 cases showed no improvement, with a total effective rate of 83.33%; in the treatment group, 10 cases showed significant improvement, 19 cases showed improvement, and 1 case showed no improvement, with a total effective rate of 96.67%. See Table 1 for details.

[0067] 2.7.2 Comparison of 24-hour ambulatory blood pressure

[0068] Before treatment, there was no significant difference in the 24-hour average systolic and diastolic blood pressures between the two groups of patients (P > 0.05); after treatment, the 24-hour average systolic and diastolic blood pressures of both groups decreased, and the 24-hour average systolic and diastolic blood pressures of the treatment group were lower than those of the control group, with a statistically significant difference, as shown in Table 2 for details.

[0069] 2.7.3 TCM Syndrome Scores

[0070] Before treatment, there was no statistical significance in the TCM syndrome scores between the two groups of patients (P > 0.05). After treatment, the TCM syndrome scores of both groups were significantly lower than those before treatment (P < 0.01), and the TCM syndrome scores of the treatment group were lower than those of the control group (P < 0.05), as shown in Table 3 for details.

[0071] Table 1 Comparison of Clinical Efficacy between Two Groups [n(%)]

[0072]

[0073] Table 2 Comparison of 24-hour Ambulatory Blood Pressure between Two Groups before and after Treatment

[0074]

[0075] Table 3 Comparison of TCM Syndrome Scores between Two Groups

[0076] Group Number of examples Before treatment After treatment control group 30 18.13±3.71 <![CDATA[7.77±3.16 ab ]]> Treatment group 30 16.71±2.69 <![CDATA[11.26±3.14 ab ]]>

[0077] Note: Comparison within the group before and after treatment a P < 0.01, comparison between groups after treatment b P < 0.05

[0078] The test results showed that the drug of the present invention could significantly improve the blood pressure of young and middle-aged hypertensive patients, which was significantly better than the control group, with a statistically significant difference. Overall comprehensive evaluation, the drug composition described in the present invention may have a certain effect on the long-term prevention of cardiovascular diseases, especially for the early intervention of young and middle-aged hypertensive patients, reducing the risk of cardiovascular events.

[0079] Test Example 2 Test on the Hypotensive Mechanism of the Drug of the Present Invention

[0080] A hypertensive rat model was induced by N-nitro-L-arginine methyl ester hydrochloride (L-NAME). A blank group, a model group, a Songling Xumai Kang group, a low-dose group of the drug of the present invention, a medium-dose group of the drug of the present invention, and a high-dose group of the drug of the present invention were set up; continuous intragastric administration was carried out for 4 weeks, and the blood pressure of the rats was measured once a week, and the blood pressure of the rats was measured 1 hour after the last administration; anesthesia was performed by intraperitoneal injection, and samples were taken. Serum, serum ET, vWF, TNF-α, MMP-9, and NO contents were measured.

[0081] This experiment investigated the effects of the drug of this invention on blood pressure in hypertensive rats induced by NO deficiency due to N-nitro-L-arginine methyl ester hydrochloride (L-NAME) and explored the related mechanisms of action, providing a reference for clinical drug use. Sixty SPF-grade male Wistar rats, weighing 200–250 g, were used. The animals were acclimatized for one week with free access to food and water. The experimental procedures adhered to ethical requirements for laboratory animals and strictly followed the "Regulations on the Management of Laboratory Animals" of the People's Republic of China.

[0082] Sixty rats were randomly divided into six groups: model group (L-NAME 50mg / kg), high-dose group (L-NAME 50mg / kg + drug of the present invention 12g / kg), medium-dose group (L-NAME 50mg / kg + drug of the present invention 9g / kg), low-dose group (L-NAME 50mg / kg + drug of the present invention 6g / kg), positive control group (L-NAME 50mg / kg + Songling Xuemaikang 10mg / kg), and blank group, with 10 rats in each group. The rats were administered the drug by gavage once a day for four consecutive weeks.

[0083] Rats were kept in a constant temperature and quiet cage at 37℃. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were measured using a non-invasive blood pressure analyzer. Blood pressure was measured once a week, with 5 consecutive measurements taken each time, and the average value was recorded.

[0084] Table 4 Comparison of blood pressure and heart rate results in rats of different groups

[0085]

[0086] Note: Compared with the blank control group, *P<0.05, **P<0.01;

[0087] Compared with the model group, the remaining groups showed P < 0.05 and P < 0.01.

[0088] Serum marker testing:

[0089] 4 mL of blood was drawn from the abdominal aorta and injected into a regular vacuum blood collection tube. After standing for 30 min, the tube was centrifuged at 4000 r / min for 15 min. The serum was collected and the levels of ET, vWF, TNF-α, MMP-9, and NO were detected by ELISA. All data were measured three times and the average value was taken. The experiment was performed strictly in accordance with the kit instructions.

[0090] Table 5 Comparison of serum index results among different groups of rats

[0091]

[0092]

[0093] Note: Compared with the blank control group, *P<0.05, **P<0.01;

[0094] Compared with the model group, the remaining groups showed P < 0.05 and P < 0.01.

[0095] in conclusion:

[0096] The drug of this invention has a good effect on intervening in systolic blood pressure, diastolic blood pressure, oxidative stress and inflammatory response in rats. Nitric oxide (NO) signaling produced by endothelial nitric oxide synthase (eNOS) plays an important role in maintaining vascular homeostasis. The L-NAME-induced hypertension model makes the body prone to oxidative stress and inflammatory response when lacking NO. NO mainly lowers blood pressure by dilating blood vessels and inhibiting the proliferation of smooth muscle cells. NO can also prevent the adhesion between blood cells and between blood cells and endothelial cells, so as to ensure smooth blood flow [WU Y, DING Y, RAMPRASATH T, et al. Oxidative Stress, GTPCH1, and Endothelial Nitric Oxide Synthase Uncoupling in Hypertension[J]. Antioxid Redox Signal, 2021, 34(9):750-64.]. ET is an important factor in regulating cardiovascular function, maintaining baseline vascular tone and cardiovascular system stability. When vascular endothelial function is impaired, ET synthesis by vascular endothelial cells increases, leading to dysregulation of vascular tone regulation and vascular remodeling [CLOZEL M. Aprocitentan and the endothelin system in resistant hypertension[J]. Can J Physiol Pharmacol, 2022, 100(7):573-83.]. Studies have found that ET levels are positively correlated with 24-hour blood pressure and are higher than those in healthy individuals, suggesting that ET may be another major factor contributing to elevated blood pressure. vWF is secreted by vascular endothelial cells and is used as a highly specific and sensitive marker of vascular endothelial injury. It is one of the main glycoproteins in the process of thrombosis and hemostasis, and has vascular endothelial cell specificity. Therefore, it is considered an effective marker of endothelial injury [MANZ XD, BOGAARD ​​HJ, AMAN J. Regulation of VWF (Von Willebrand Factor) in Inflammatory Thrombosis [J]. ArteriosclerThrombVasc Biol, 2022, 42(11): 1307-20.].

[0097] The drug treatment group of this invention showed statistically significant differences compared to the model group, indicating that L-NAME-induced hypertension has a significant impact on blood vessels, causing vascular wall thickening, vascular damage, and even vascular remodeling. The drug of this invention has a protective effect on blood vessels. The drug of this invention can significantly increase the NO content in rats and decrease the serum ET and vWF content. MMP-9 is closely related to cardiac remodeling in the course of hypertension, mainly manifested in myocardial hypertrophy and myocardial fibrosis. Jing Yan et al. studied the pathogenesis of MMP-9 in hypertension and found that specific inhibition of MMP-9 expression can effectively reduce blood pressure in hypertensive rats and is also associated with vascular remodeling, suggesting that MMP-9 is an important cause of hypertension [YAN J, LID, LIU Q, et al. Effect of YiqiHuayuPingganZishen Formula Combined with Valsartan in the Treatment of Hypertension and Its Effect on MMP-9,Ang II, and MCP-1[J].ComputMathMethodsMed,2022,2022:798-2023.]. Therefore, the antihypertensive mechanism of the drug of this invention may be related to the inhibition of cardiac MMP-9 expression. TNF-α is one of the important indicators of inflammatory response. Research results show that inflammatory damage is a phenomenon that runs through the entire process of hypertension development and is an important link in the development of hypertension. TNF-α is a pro-inflammatory factor in the inflammatory cytokine family. [ Liu Zhenyue, Zhang Jianzhong. Effects of phlegm-blood stasis syndrome on hs-CRP, TNF-α, IL-4, IL-6 and ICAM-1 levels in patients with prehypertension [J]. Liaoning Journal of Traditional Chinese Medicine, 2014, 41(7):3. ] The TNF-α level in the model group was significantly higher than that in the treatment group with the drug of this invention, indicating that inflammation existed in the rats in the model group. The inflammatory process is related to the occurrence of hypertension. Therefore, detecting the TNF-α level is beneficial to exploring the degree of inflammatory damage in hypertension. The drug of this invention can reduce the expression of TNF-α.

[0098] In summary, the results of this animal experiment suggest that the drug of this invention can improve inflammatory damage, protect blood vessels, and dilate blood vessels by increasing the expression of NO, decreasing the expression of ET, vWF, MMP-9 and TNF-α, thereby lowering blood pressure.

[0099] Experimental Example 2: Typical Case of Traditional Chinese Medicine in this Invention

[0100] Case 1

[0101] Patient Zhang, male, 35 years old, presented on October 21, 2023, with a complaint of "dizziness and headache for over a month." He also reported loss of appetite, abdominal distension and discomfort, and occasional nausea and vomiting. His tongue was red with a yellow, greasy coating, and his pulse was slippery and rapid. His blood pressure was measured at 154 / 96 mmHg in the clinic. A Holter monitor test revealed:

[0102] 1. 43 effective pressure measurements were taken, for a total of 43 pressure measurements.

[0103] 2. The average systolic blood pressure during the day was 140 mmHg (reference value <135), and the average diastolic blood pressure was 83 mmHg (reference value <85).

[0104] 3. The average systolic blood pressure at night was 135 mmHg (reference value <120), and the average diastolic blood pressure was 77 mmHg (reference value <70);

[0105] 4. Systolic blood pressure daytime blood pressure load was 70.37%, and nighttime blood pressure load was 93.75%; diastolic blood pressure daytime blood pressure load was 48.15%, and nighttime blood pressure load was 87.50%.

[0106] 5. The rate of decline in blood pressure at night was 3.00% for systolic blood pressure (non-dipper) and 7.00% for diastolic blood pressure (non-dipper).

[0107] 6. Average morning blood pressure: systolic pressure 148 mmHg (reference value <135), diastolic pressure 91 mmHg (reference value <85).

[0108] The Western medicine diagnosis was hypertension in young and middle-aged adults, while the traditional Chinese medicine diagnosis was: dizziness and damp-heat obstruction syndrome.

[0109] The patient was given a traditional Chinese medicine decoction (10g of Achyranthes bidentata, 10g of Leonurus japonicus, 15g of Alisma plantago-aquatica, 10g of Scutellaria baicalensis, 10g of Paeonia lactiflora, 10g of Atractylodes lancea, and 5g of Carthamus tinctorius) in 15 doses, which were then prepared using traditional Chinese medicine preparation technology and packaged into 15 bottles, each containing 100ml. The patient was instructed to take 15ml orally three times a day.

[0110] One month later, at a follow-up visit, the patient reported that the dizziness and headache symptoms had improved, and the original prescription was continued. Two months later (December 29, 2023), a follow-up ambulatory blood pressure check showed: 1. A total of 40 measurements were taken in 24 hours, of which 40 were valid; 2. The 24-hour blood pressure pattern was dipper-shaped; 3. The 24-hour average blood pressure was: systolic pressure 135 mmHg; diastolic pressure 81 mmHg; the highest daytime systolic pressure was 169 mmHg (20:10), and the highest diastolic pressure was 109 mmHg (09:11); the highest nighttime systolic pressure was 136 mmHg (09:11). The highest diastolic blood pressure was 87 mmHg (3:10) mmHg; the average daytime systolic blood pressure was 138 mmHg (reference value <135), and the average diastolic blood pressure was 83 mmHg (reference value <85); the average nighttime systolic blood pressure was 121 mmHg (reference value <120), and the average diastolic blood pressure was 74 mmHg (reference value <70). The 24-hour systolic and diastolic blood pressure loads were abnormal; the nighttime blood pressure drop rate was normal. The patient reported that symptoms such as loss of appetite and abdominal distension had significantly improved after taking the medication.

[0111] In summary, the patient's blood pressure decreased significantly before and after taking the medication, as observed by ambulatory blood pressure monitoring. The patient's subjective symptoms also improved, indicating that this traditional Chinese medicine composition has good clinical efficacy.

[0112] Case 2

[0113] Ms. Wang, female, 47 years old, presented to the outpatient clinic on February 23, 2024, with a history of "elevated blood pressure for 1+ days." The patient complained of poor appetite, lethargy, irritability, thirst but no desire to drink much, and burning urination. Physical examination revealed a yellow, greasy tongue coating and a soft, rapid pulse. Her blood pressure in the clinic was 168 / 102 mmHg. A Holter monitor was performed.

[0114] 1. A total of 40 measurements were taken in 24 hours, of which 40 were valid measurements;

[0115] 2. 24-hour blood pressure morphology: non-configurable:

[0116] 3. 24-hour average blood pressure: Systolic pressure is 121 mmHg; Diastolic pressure is 73 mmHg; The highest daytime systolic pressure is 144 (20:56) mmHg, and the highest diastolic pressure is 90 (20:56) mmHg; The highest nighttime systolic pressure is 128 (05:27) mmHg, and the highest diastolic pressure is 77 (04:27) mmHg.

[0117] 4. Abnormal 24-hour systolic blood pressure load, normal diastolic blood pressure load: excessive nighttime blood pressure drop rate. Western medicine diagnosis: hypertension in young and middle-aged adults; Traditional Chinese medicine diagnosis: dizziness, damp-heat obstruction syndrome.

[0118] A traditional Chinese medicine (TCM) composition (10g of Achyranthes bidentata, 10g of Leonurus japonicus, 15g of Alisma plantago-aquatica, 10g of Scutellaria baicalensis, 10g of Paeonia lactiflora, 10g of Atractylodes lancea, and 5g of Carthamus tinctorius) was prescribed for 15 doses, prepared using TCM preparation technology and packaged into 15 bottles of 100ml each. The patient was instructed to take 15ml orally three times a day. One month later, at a follow-up visit, the patient reported a significant decrease in home blood pressure and a clinic blood pressure of 138 / 88 mmHg. The current medication showed a significant antihypertensive effect, and the original prescription was continued for another month. At the second follow-up visit (May 27, 2024), another ambulatory blood pressure monitoring was performed, showing: 1. A total of 41 measurements were taken over 24 hours, of which 39 were valid; the morphology of the 24-hour blood pressure was non-structural. 3. 24-hour average blood pressure: Systolic pressure is 116 mmHg; Diastolic pressure is 69 mmHg; Highest daytime systolic pressure is 147 mmHg (08:05), Highest diastolic pressure is 90 mmHg (08:05); Highest nighttime systolic pressure is 122 mmHg (22:34), Highest diastolic pressure is 77 mmHg (22:34): 24-hour systolic pressure load exceeds the standard, diastolic pressure load is normal: 4, 5. Nighttime blood pressure drop rate exceeds the standard.

[0119] Based on the patient cases, ambulatory blood pressure monitoring showed a significant decrease in blood pressure levels before and after medication. Therefore, the traditional Chinese medicine composition of this invention has good clinical efficacy.

Claims

1. A traditional Chinese medicine composition for treating hypertension of the damp-heat obstruction type, characterized in that: It is prepared from the following raw materials in the indicated weight ratios: 8-12 parts of Achyranthes bidentata, 8-12 parts of Leonurus japonicus, 12-18 parts of Alisma plantago-aquatica, 8-12 parts of Scutellaria baicalensis, 8-12 parts of Paeonia lactiflora, 8-12 parts of Atractylodes lancea, and 4-6 parts of Carthamus tinctorius.

2. The traditional Chinese medicine composition for treating hypertension of the damp-heat obstruction type according to claim 1, characterized in that: It is prepared from the following raw materials in the indicated weight ratios: 10 parts of Achyranthes bidentata, 10 parts of Leonurus japonicus, 15 parts of Alisma plantago-aquatica, 10 parts of Scutellaria baicalensis, 10 parts of Paeonia lactiflora, 10 parts of Atractylodes lancea, and 5 parts of Carthamus tinctorius.

3. The traditional Chinese medicine composition for treating hypertension of the damp-heat obstruction type according to claim 1 or 2, characterized in that: It is prepared into a commonly used oral formulation by adding pharmaceutically acceptable excipients or auxiliary ingredients, using the original drug powder, water or organic solvent extract as the active ingredient.

4. The traditional Chinese medicine composition for treating hypertension of the damp-heat obstruction type according to claim 3, characterized in that: The oral preparations mentioned are tablets, capsules, pills, or oral liquids.

5. A method for preparing the traditional Chinese medicine composition for treating hypertension of the damp-heat obstruction type as described in any one of claims 1-4, characterized in that: It includes the following steps: a. Weigh the raw materials according to the specified weight ratio; b. Powder, or extract with water or organic solvents, and add pharmaceutically acceptable excipients or auxiliary ingredients to prepare commonly used oral pharmaceutical preparations.

6. The use of the traditional Chinese medicine composition according to any one of claims 1-4 in the preparation of a medicament for treating hypertension of the damp-heat type.

7. The use according to claim 6, characterized in that: The medication described is for treating hypertension of the damp-heat obstruction type in young and middle-aged adults.

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