A Chinese medicine composition for treating mild to moderate essential hypertension and its preparation method and application

Abstract

The present invention relates to a Chinese medicine composition for treating mild to moderate essential hypertension, a preparation method and an application thereof. The Chinese medicine composition for treating mild to moderate essential hypertension comprises the following raw material components by weight: 6-12 parts of Uncaria rhynchophylla, 10-12 parts of Paeonia suffruticosa, 3-5 parts of Coptis chinensis, 5-9 parts of Scutellaria baicalensis, 5-10 parts of Phellodendron chinense, 6-10 parts of Orientalis alisma, 5-12 parts of Ligustrum lucidum, 5-12 parts of Puerariae lobata and 1-3 parts of Hirudo. The Chinese medicine composition is prepared into granules by the preparation method of the present application, and has a good therapeutic effect on hypertension of liver yang hyperactivity type and yin deficiency yang hyperactivity type.

Description

Technical Field

[0001] The present invention relates to the medical field, and in particular to a Chinese medicine composition for treating mild to moderate essential hypertension, and a preparation method and application thereof. Background Art

[0002] Essential hypertension (EH) is one of the most common cardiovascular diseases worldwide. It is characterized by increased systemic arterial blood pressure (systolic blood pressure ≥140 mmHg and / or diastolic blood pressure ≥90 mmHg), which may be accompanied by clinical symptoms such as stroke, myocardial infarction, heart failure and renal failure. Hypertension is one of the most common chronic diseases and the most important risk factor for death from cardiovascular and cerebrovascular diseases. Although it is known that essential hypertension is related to environmental and genetic factors, its exact pathogenesis is still not fully understood.

[0003] At present, hypertension cannot be cured. Although Western medicine used to treat hypertension can quickly lower blood pressure in the short term, it requires clear dosage, combination of multiple drugs, and even lifelong use. It also has the characteristics of adverse reactions, unstable blood pressure control, and poor prevention of complications. Unlike Western medicine, Chinese medicine treats hypertension from a holistic perspective. It can not only stabilize blood pressure, balance internal organs and blood, protect target organs, coordinate internal organs and yin and yang, but also interfere with the occurrence and development of hypertension through multiple links, multiple pathways, and multiple targets. It can also improve clinical symptoms and quality of life such as dizziness, headache, insomnia, etc., reverse hypertension-related risk factors, and improve long-term survival rate. It has unique advantages in reducing adverse reactions and improving symptoms in patients with hypertension, and to a certain extent solves the problems of single target of Western medicine and many adverse reactions.

[0004] There is no exact description of the name of hypertension in traditional Chinese medicine. According to its symptoms such as "dizziness", "headache" and "stroke", it belongs to diseases such as "dizziness" and "headache" in traditional Chinese medicine, which is particularly common in clinical practice. Liver yang hyperactivity type is a common TCM syndrome of primary hypertension, which belongs to the syndrome of deficiency of the root and excess of the superficial symptoms. The imbalance of yin and yang and liver and kidney yin deficiency are the root of the disease. At present, some TCM theories use the method of calming the liver and suppressing yang, clearing heat and purging fire to treat primary hypertension, such as Tianma Gou Teng Granules and Tianzhi Granules. From the perspective of traditional Chinese medicine, there are 7 main types of hypertension: liver fire inflammation syndrome, phlegm and dampness internal obstruction syndrome, blood stasis internal obstruction syndrome, yin deficiency and yang hyperactivity syndrome, kidney essence deficiency syndrome, qi and blood deficiency syndrome and Chong and Ren disorders syndrome. Most of the Chinese patent medicines that have been marketed treat one syndrome. When used in combination with Western medicine, they can reduce adverse reactions and improve the quality of life, thereby achieving the purpose of long-term treatment. Summary of the invention

[0005] In order to make up for the deficiencies of the prior art, the present invention provides a Chinese medicine composition for treating mild to moderate essential hypertension, and a preparation method and application thereof, which has a good therapeutic effect on both liver yang hyperactivity type and yin deficiency yang hyperactivity type hypertension.

[0006] The technical solution adopted by the present invention to solve the above technical problems is:

[0007] A traditional Chinese medicine composition for treating mild to moderate essential hypertension comprises the following raw material components by weight: 6-12 parts of Uncaria rhynchophylla, 10-12 parts of Paeonia suffruticosa, 3-5 parts of Coptis chinensis, 5-9 parts of Scutellaria baicalensis, 5-10 parts of Phellodendron chinense, 6-10 parts of Alismatis orientalis, 5-12 parts of Ligustrum lucidum, 5-12 parts of Pueraria root and 1-3 parts of Leech.

[0008] In one example, the following raw material components are included by weight: 12 parts of Uncaria rhynchophylla, 12 parts of Paeonia suffruticosa, 5 parts of Coptis chinensis, 9 parts of Scutellaria baicalensis, 9 parts of Phellodendron amurense, 9 parts of Alismatis orientalis, 9 parts of Ligustrum lucidum, 9 parts of Pueraria root, and 1.5 parts of Leech.

[0009] In one example, the Chinese medicine composition is prepared into tablets, capsules, granules, pills, powders, syrups, tinctures, mixtures, lozenges, decoctions, wines, dews, teas, fluid extracts and extracts.

[0010] The present application also provides a method for preparing the Chinese medicine composition for treating mild to moderate primary hypertension, comprising the following steps: first weighing each raw material component, adding 6-12 times the weight of water and soaking for half an hour; then heating to boiling and continuing to decoct for 1-3 hours, filtering to obtain a filtrate and a filter residue; then adding 4-11 times the weight of water and decoct for 0.5-2.5 hours, filtering, combining the two filtrates, and concentrating under reduced pressure at 60-80°C to prepare a clear paste with a relative density of 1.05-1.2.

[0011] Furthermore, the method comprises the following steps: first weighing each raw material component, adding 9 times the weight of water to soak for half an hour, heating to boiling and then continuing to boil for 2 hours, filtering to obtain a filtrate and a residue, then adding 7 times the weight of water to boil for 1.5 hours, filtering, combining the two filtrates, and concentrating under reduced pressure at 60-80°C to obtain the product.

[0012] In one example, a clear paste with a relative density of 1.05-1.2 is prepared after reduced pressure concentration at 60-80°C, which is then spray-dried to obtain a spray-dried powder, and then auxiliary materials are added and mixed evenly, and then granules are prepared by a dry method; the added auxiliary materials include sucralose, maltitol, corn starch, sodium chloride and microcrystalline cellulose, among which sucralose accounts for 0.05% of the weight of the spray-dried powder, maltitol accounts for 2% of the weight of the spray-dried powder, corn starch accounts for 10% of the weight of the spray-dried powder, sodium chloride accounts for 0.2% of the weight of the spray-dried powder, and microcrystalline cellulose accounts for 2% of the weight of the spray-dried powder.

[0013] In one example, the Chinese medicine composition for treating mild to moderate essential hypertension is used in the preparation of antihypertensive drugs.

[0014] The present invention adopts the above structure, and has the advantages of:

[0015] The Chinese medicine composition for treating mild to moderate essential hypertension provided by the present invention has the fundamental treatment method of calming the liver and suppressing yang, and also has the functions of promoting blood circulation and unblocking collaterals. Uncaria rhynchophylla and Paeonia suffruticosa are used as the main medicines, which are sweet and cool in nature and enter the liver and heart meridians, calm the wind and calm the convulsion, clear away heat and calm the liver, relax the muscles and activate the collaterals, and increasing the dosage of Uncaria rhynchophylla enhances the heat-clearing and liver-calming effects. Modern pharmacology shows that rhynchophylline can inhibit sympathetic nerve activity, reduce the excitability of vascular smooth muscle and other vascular system-related nerves, and then reduce nerve stimulation of vasoconstriction to lower blood pressure. Paeonia suffruticosa can clear away heat and cool blood, promote blood circulation and remove blood stasis, and is an important medicine for symptoms such as blazing blood heat, liver and kidney fire and blood stasis.

[0016] The present invention uses scutellaria baicalensis, phellodendron chinense, coptis chinensis and orientalis as ministerial drugs. Among them, scutellaria baicalensis is good at regulating the qi stagnation and disorder of heat syndrome, coptis chinensis can treat diseases of real fire accompanied by long-term diarrhea of ​​pus and blood and other internal organs deficiency, phellodendron chinense is mainly used to treat intestinal diseases, and the three yellows can clear away heat and dampness, purge fire and reduce blood pressure. Orientalis chinensis can promote diuresis and eliminate dampness, purge heat, clear turbidity and reduce lipids. The four medicines are all ministerial drugs to enhance the effect of clearing heat and purging fire.

[0017] In addition, the present invention uses Ligustrum lucidum, Pueraria root and leech as adjuvant drugs. Ligustrum lucidum nourishes the liver and kidney, can nourish the yin of the liver and kidney, can nourish water and contain wood, and improve the phase of yin deficiency and yang hyperactivity. Leech can break blood, remove blood stasis and dredge menstruation. Modern pharmacological research has confirmed that leech contains hirudin, polypeptide and other ingredients, which can significantly reduce blood viscosity and prevent the effect of thrombin on fibrinogen. Pueraria root can relieve muscle, reduce fever, raise yang and stop diarrhea, and can lower blood pressure through the endothelium-dependent and independent dilation function of mesenteric arteries. The medicinal flavors used in this prescription all have different degrees of heat-clearing effects, and are matched with yang-raising, blood-activating and collateral-dredging drugs, which have a stronger effect on treating liver yang hyperactivity type hypertension.

[0018] In summary, the Chinese medicine composition for treating mild to moderate essential hypertension provided by the present invention has a strict compatibility and a concise prescription. It can calm the liver and suppress yang, clear away heat and purge fire to treat the symptoms of hypertension patients, and warm the meridians, promote blood circulation and dredge the collaterals to treat the root cause. It is an effective prescription for treating mild to moderate primary hypertension. Clinical data show that the Chinese medicine extract provided by the present invention has a definite overall therapeutic effect, can significantly lower blood pressure, and has a good improvement on the symptoms of irritability, insomnia, soreness of waist and knees, bitter mouth, insomnia, dry mouth, and headache. It can significantly relieve the symptoms of mild to moderate primary patients and effectively improve the quality of life of patients. DETAILED DESCRIPTION

[0019] In order to clearly illustrate the technical features of this solution, the present invention is described in detail below through specific implementation methods.

[0020] 1. Explore the effects of the components and ratios of Chinese medicine compositions on experimental results through animal experiments

[0021] 1.1 The composition and dosage of the tested drug samples are as follows, wherein experimental samples 3 and 8 are samples of the present invention, and the remaining samples are samples with composition or dosage adjusted based on the experimental samples.

[0022] Comparative sample 1: Uncaria rhynchophylla 40g, Paeonia suffruticosa 120g, Coptidis chinensis 50g, Scutellaria baicalensis 90g, Phellodendron chinense 90g, Alisma orientalis 90g, Ligustrum lucidum 90g, Pueraria lobata 90g, Leech 15g.

[0023] Comparative sample 2: Uncaria rhynchophylla 40g, Paeonia suffruticosa 120g, Coptidis chinensis 50g, Scutellaria baicalensis 90g, Phellodendron chinense 90g, Alisma orientalis 90g, Ligustrum lucidum 90g, Pueraria lobata 90g, Leech 30g.

[0024] Experimental sample 3: Uncaria rhynchophylla 120g, Paeonia suffruticosa 120g, Coptidis chinensis 50g, Scutellaria baicalensis 90g, Phellodendron chinense 90g, Alisma orientalis 90g, Ligustrum lucidum 90g, Pueraria lobata 90g, Leech 15g.

[0025] Comparative sample 4: Uncaria rhynchophylla 120g, Paeonia suffruticosa 120g, Coptidis chinensis 50g, Chrysanthemum 90g, Phellodendron chinense 90g, Alisma orientalis 90g, Ligustrum lucidum 90g, Pueraria lobata 90g, Leech 15g.

[0026] Comparative sample 5: Uncaria rhynchophylla 120g, Paeonia suffruticosa 120g, Scutellaria baicalensis 140g, Phellodendron chinense 90g, Alismatis rhizome 90g, Ligustrum lucidum 90g, Pueraria root 90g, Leech 15g.

[0027] Comparative sample 6: 120g of Paeonia suffruticosa, 50g of Coptis chinensis, 90g of Scutellaria baicalensis, 90g of Phellodendron chinense, 90g of Alisma orientalis, 90g of Ligustrum lucidum, 90g of Pueraria lobata, and 15g of Leech.

[0028] Comparative sample 7: Uncaria rhynchophylla 120g, Paeonia suffruticosa 120g, Coptidis chinensis 50g, Scutellaria baicalensis 90g, Phellodendron chinense 90g, Alisma orientalis 90g, Ligustrum lucidum 90g, Pueraria root 90g, Leech 15g, Ligusticum chuanxiong 10.

[0029] Experimental sample 8: Uncaria rhynchophylla 120g, Paeonia suffruticosa 100g, Coptis chinensis 30g, Scutellaria baicalensis 60g, Phellodendron chinense 100g, Alisma orientalis 100g, Ligustrum lucidum 120g, Pueraria lobata 120g, Leech 30g.

[0030] 1.2 Sample preparation method

[0031] Weigh each medicinal material according to the prescription ratio of the experimental sample and the control sample, add 9 times the weight of water to soak for half an hour, heat to boiling and continue to boil for 2 hours, filter to obtain the filtrate and residue, add 7 times the weight of water and boil for 1.5 hours, filter, combine the two filtrates, and concentrate under reduced pressure at 60-80°C to form a standard decoction. The concentration of each 1 ml of the standard decoction is equivalent to 1 g of the raw medicinal material. After packaging, store it in a frozen state at -20°C for later use.

[0032] 1.3 Experimental animals

[0033] 90 SHR male rats and 10 WKY male rats, SPF grade, were purchased from Beijing Weitonglihua Laboratory Animal Technology Co., Ltd. with license number SCXK (Beijing) 2020 0008.

[0034] 1.4 Grouping and Dosing

[0035] WKY and SHR rats were adaptively fed for one week. Ten WKY rats were selected as the normal group, and SHR rats were randomly divided into 9 groups, with 10 rats in each group, and their initial blood pressure was measured.

[0036] The dosage setting was calculated based on the clinical dosage. The irbesartan tablets group was 13.5 mg / kg, the control sample group 1 (dosage 1.09 g / kg), the control sample group 2 (dosage 1.12 g / kg), the experimental sample group 3 (dosage 1.22 g / kg), the control sample group 4 (dosage 1.22 g / kg), the control sample group 5 (dosage 1.22 g / kg), the control sample group 6 (dosage 1.03 g / kg), the control sample group 7 (dosage 1.39 g / kg), and the experimental sample group 8 (dosage 1.26 g / kg). Each medication group was given the corresponding drug by gavage at 10 mL / kg, and the normal group and the model group were given an equal volume of pure water, once a day, for 4 consecutive weeks, and blood pressure was measured at a fixed time each week (8:00 am-15:00 pm).

[0037] 1.5 Blood pressure measurement

[0038] Before measuring blood pressure, the rats were placed in a constant temperature box at 35°C for 10 minutes to preheat. The pressure sensor of the non-invasive blood pressure measuring instrument was placed at the base of the rat's tail, and data was obtained through the supporting software. The measurement was repeated 3 times for each rat when it was awake and quiet, and the average value was taken. Blood pressure values ​​were recorded before the start of the experiment, 14 days after administration, and 28 days after administration.

[0039] 1.6 Sample collection

[0040] After 4 weeks of drug intervention, blood was collected from the inferior vena cava, centrifuged and the supernatant was obtained, and renin and angiotensin were measured according to the instructions of the kit.

[0041] 1.7 Statistics

[0042] All data were expressed as mean ± standard deviation and analyzed using SPSS 21.0 statistical software package. ANOVA was used and the q test was used for comparison between groups. Differences were considered statistically significant when P < 0.05 or P < 0.01.

[0043] 1.8 Experimental Results

[0044]

[0045] As shown in Table 1, the systolic blood pressure of each group decreased to varying degrees after medication. The decrease in experimental samples 3 and 8 was the largest, which was significantly different from the model group (P < 0.01). The comparison samples 5 and 7 were also significantly different from the model group (P < 0.05). The blood pressure lowering effect of comparison sample 2, which reduced the dosage of Uncaria rhynchophylla and increased the dosage of leech, was not as good as that of experimental samples 3 and 8.

[0046]

[0047] As shown in Table 2, the diastolic blood pressure of the experimental sample was significantly lower than that of the model group, with a significant difference (P < 0.01). Secondly, there was a significant difference between the comparison sample 7 and the model group (P < 0.05). There was no significant difference in the diastolic blood pressure between the remaining comparison sample groups and the model group.

[0048]

[0049] Table 3 shows that compared with the normal group, the serum renin and angiotensin in the model group increased. After 4 weeks of administration, the serum renin and angiotensin levels of experimental sample 3, experimental sample 8 and comparative sample 7 decreased significantly. There was also a significant difference between the angiotensin of comparative sample 4 and the model group. Among them, the serum renin of experimental sample 8 decreased the most compared with the model group, and the angiotensin of experimental sample 3 decreased the most compared with the model group, with significant differences (P < 0.01).

[0050] The above experiments show that the systolic and diastolic blood pressures of the rats in the hypertension treatment group were reduced to varying degrees compared with the model group. The dosage of Uncaria rhynchophylla in the comparison sample group 1 was small, and the blood pressure of the rats decreased less. The serum renin and angiotensin decreased compared with the model group, but there was no significant difference. The comparison sample group 6 removed Uncaria rhynchophylla, and the systolic and diastolic blood pressures decreased the least, indicating that Uncaria rhynchophylla plays a key role in this prescription. The amount of leeches in the comparison sample group 2 increased, and the blood pressure of the rats was not significantly different from that of the model group, and the mental state of the rats was not good. The comparison sample group 4 removed Scutellaria baicalensis and used Chrysanthemum instead. The antihypertensive effect was not as good as that of experimental samples 3 and 8. Although Scutellaria baicalensis and Chrysanthemum have the effect of clearing heat, the antihypertensive effect of Scutellaria baicalensis is stronger in the combination prescription. Although the dosage of Scutellaria baicalensis in the comparison sample 5 increased, the antihypertensive effect was not as good as that of Scutellaria baicalensis and Coptis chinensis, indicating that Coptis chinensis not only plays a role in clearing heat and detoxification, but also plays a synergistic role in the combination of multiple drugs in the prescription. Comparative sample 7 added Chuanxiong to experimental sample 3. Although it had a certain antihypertensive effect, the comprehensive effect of the prescription was not as good as that of experimental samples 3 and 8. Experimental sample 3 increased the dosage of Uncaria rhynchophylla and Coptis chinensis while reducing the dosage of Scutellaria baicalensis. The blood pressure dropped most significantly, and the rats' diet and mental state were relatively good. Compared with experimental sample 3, experimental sample 8 showed that experimental sample 3 was the best combination.

[0051] 2. Explore the influence of granule preparation method on its quality

[0052] The Chinese medicine composition for treating essential hypertension provided by the present invention contains a large amount of bitter and cold drugs, the extract is extremely bitter and difficult to swallow, the extract contains polysaccharides, and the spray-dried powder is easy to absorb moisture and stick together, resulting in a low preparation yield and difficulty in granulation. By adding different types and amounts of excipients to compare the effects of the excipients on the taste and hygroscopicity, and by comparing the effects of different excipient ratios on the granulation yield, fluidity, etc. of the granules, the best excipient ratio is screened.

[0053] 2.1 Preparation method of granule samples

[0054] Weigh each medicinal material, add 9 times the weight of water to soak for half an hour, heat to boiling and continue to boil for 2 hours, filter the filtrate and residue, add 7 times the weight of water and boil for 1.5 hours, filter, combine the two filtrates, and concentrate under reduced pressure at 60-80°C to make a clear paste with a relative density of 1.05-1.2, spray dry, add auxiliary materials and mix well, and then perform dry granulation.

[0055] 2.2 Investigate the effect of adding different excipients on the quality of granules

[0056] Using the preparation method of 2.1, on the basis of the raw material composition and dosage of Example 3 in 1.1, with the type of auxiliary materials as a variable, granule samples 1-11 were prepared, and taste evaluation and hygroscopicity experiments were performed on them. The results are shown in Table 4.

[0057]

[0058] Hypertension patients often occur in the middle-aged and elderly population, and the flavoring agents added to the excipients should be careful not to choose excipients that increase blood sugar. Through the comparative study of different excipient formulas in Table 4, it was found that the addition of three flavoring agents, sucralose, maltitol, and sodium chloride, can better cover up the extremely bitter taste of the granules. In addition, by comparing the effects of three fillers, maltodextrin, dextrin, and corn starch on the appearance of the granules, it was found that the addition of corn starch has lower hygroscopicity under the same conditions, and the combination with microcrystalline cellulose can better improve the hygroscopicity of the sample.

[0059] 2.2 Investigate the effect of different excipient ratios on the quality of granules

[0060] In order to further refine the effect of different proportions of auxiliary materials on particles, an experimental study on the auxiliary material ratio was conducted. The specific experimental methods are as follows: (1) Particle yield: record the mass of the spray-dried powder and the added auxiliary materials, weigh the mass of the particles with qualified particle size, and calculate the yield of qualified finished particles. Particle yield = [qualified particle mass / (solid content in the thick paste + auxiliary material mass)] × 100%. (2) Determination of repose angle: Injection method: slowly add particles from the top of the funnel, and the inclination angle of the conical accumulation formed by the material leaking from the bottom of the funnel on the horizontal plane is measured three times in parallel and the average value is calculated.

[0061] Using the preparation method of 2.1, on the basis of the raw material composition and dosage of Example 3 in 1.1, granule samples 12-16 were prepared with the auxiliary material ratio as a variable. The ratio composition is shown in Table 5, and the experimental results are shown in Table 6.

[0062]

[0063]

[0064] The above experimental results show that the five excipients are mixed in different proportions to form granules, and sample 13 has the highest granulation yield, lower moisture absorption rate, stronger fluidity and better taste. The use of maltitol, microcrystalline cellulose and corn starch together can better prevent the granules from absorbing moisture and improve the stability of the granules. Compared with sample 12 and sample 16, there is a difference in taste between adding sodium chloride and not adding sodium chloride, indicating that the use of sucralose, maltitol and sodium chloride together can better mask the bitterness of the drug, and sweeteners and bitterness blockers work together. Compared with sample 13 and sample 15, increasing the proportion of sucralose will excessively increase the sweetness of the granules. Therefore, sample 13 can be used for subsequent experiments.

[0065] 3. Clinical trials

[0066] The sample of the present invention was used to conduct a clinical efficacy study on patients with mild to moderate hypertension due to liver yang hyperactivity and yin deficiency and yang hyperactivity. A total of 120 patients with mild to moderate hypertension who met the inclusion criteria were included in this trial. The patients had symptoms such as headache, insomnia, and dizziness to varying degrees for a long time.

[0067] 3.1 Clinical samples

[0068] Take the sample raw material of Example 3, add 9 times the weight of water, boil for 2 hours, filter to obtain a residue and a filtrate; then add 7 times the weight of water and boil for 1.5 hours, filter to obtain a residue and a filtrate; combine the two filtrates, concentrate the filtrate under reduced pressure at 60-80° C. to make a clear paste with a relative density of 1.05-1.2, spray dry to obtain a spray-dried powder, add 10% times the weight of corn starch, 0.05% sucralose, 2% maltose, 0.2% sodium chloride, and 2% microcrystalline cellulose, mix evenly, dry granulate, and bag, 9 g / bag. The above-mentioned medicine can be referred to as Uncaria rhynchophylla antihypertensive granules in the following clinical experiments.

[0069] 3.2 Diagnostic criteria

[0070] 3.2.1 Standards of TCM Syndrome Differentiation

[0071] (1) Hyperactivity of Liver Yang

[0072] Main symptoms: dizziness, headache, irritability, insomnia;

[0073] Secondary symptoms: flushed face, red eyes, dry mouth, bitter taste in the mouth, tinnitus, sore waist and knees; tongue and pulse: red tongue with yellow coating, stringy or rapid pulse

[0074] (2) Yin deficiency and Yang hyperactivity type

[0075] Main symptoms: dizziness, headache, back pain, weak knees, and fever in the five parts of the body.

[0076] Secondary symptoms: palpitations, insomnia, tinnitus, forgetfulness, red tongue, less coating. Tongue and pulse: stringy, thin and rapid pulse. If one of the above main symptoms and two of the secondary symptoms are present, combined with tongue and pulse, this syndrome can be diagnosed.

[0077] 3.2.2 Western medicine diagnostic criteria

[0078] The main diagnostic basis for office blood pressure is formulated with reference to the National Primary Hypertension Prevention and Management Guidelines (2020 Edition): If the systolic blood pressure is ≥140mmHg and / or the diastolic blood pressure is ≥90mmHg at the first visit, it is recommended to recheck twice within 4 weeks. If the above diagnostic thresholds are reached for 3 measurements on different days, the diagnosis can be confirmed. Systolic blood pressure ≥140mmHg and / or diastolic blood pressure ≥90mmHg "and / or" means that there are 3 situations: systolic blood pressure ≥140mmHg and diastolic blood pressure ≥90mmHg, systolic blood pressure ≥140mmHg and diastolic blood pressure <90mmHg, and systolic blood pressure ≤140mmHg and diastolic blood pressure ≥90mmHg.

[0079] Hypertension is divided into grades 1, 2, and 3 according to the classification of blood pressure levels in the 1999 hypertension guidelines of WHO / ISH (World Health Organization and International Hypertension League), as shown in Table 7 for details.

[0080]

[0081] 3.3 Inclusion, exclusion, elimination, and termination criteria

[0082] 3.3.1 Inclusion and Exclusion Criteria

[0083]

[0084] 3.3.2 Rejection and shedding criteria

[0085] (1) Patients who met the inclusion criteria but did not take medication after inclusion were excluded.

[0086] (2) Patients who fail to take medication as prescribed, have serious adverse events, or have special physiological changes and are not suitable to continue the trial are considered dropouts.

[0087] 3.3.3 Termination criteria:

[0088] (1) Those whose symptoms or signs worsen after taking the medication and refuse to continue taking the medication

[0089] (2) Subjects with poor medication compliance and unsuitable to continue the trial

[0090] (3) Those who have adverse reactions and are not suitable to continue the trial.

[0091] If one of the above criteria is met, the case trial can be terminated.

[0092] 3.4 Treatment

[0093] The enrolled hypertensive patients were treated with the same sample of the present invention, taken with boiled water, twice a day, 1 bag each time, 9 g / bag, for 28 consecutive days.

[0094] 3.5 Evaluation Metrics

[0095] 3.5.1 Main symptoms and signs

[0096] 3.5.1.1 Blood pressure

[0097] Correlation statistical analysis methods were used to analyze the changes in blood pressure after treatment.

[0098] 3.5.1.2 TCM Syndrome

[0099] The TCM syndrome score registration form for liver-yang hyperactivity type hypertension was developed with reference to the "Expert Consensus on TCM Diagnosis and Treatment of Hypertension" (2019) and "Chinese Internal Medicine" (2017 edition).

[0100]

[0101] Refer to the "Guidelines for Clinical Research on New Chinese Medicines for the Treatment of Hypertension" to develop a TCM Syndrome Points Registration Form for Yin Deficiency and Yang Hyperactivity Type Hypertension:

[0102]

[0103] 3.5.2 Biochemical detection indicators

[0104] Four blood lipids (TC, TG, LDL, HDL)

[0105] 3.5.3 Safety evaluation

[0106] Safety indicators: liver function, kidney function, blood sugar

[0107] 3.6 Efficacy determination

[0108] 3.6.1 Criteria for determining efficacy

[0109] 3.6.1.1 Blood pressure

[0110] Compare whether there is a significant difference in systolic and diastolic blood pressure before and after enrollment

[0111] 3.6.1.2 TCM Syndrome Efficacy

[0112] Markedly effective: The symptom efficacy rate after treatment is ≥70%.

[0113] Effective: The symptom efficacy rate after treatment is ≥30% and <70%.

[0114] Ineffective: The symptom efficacy rate after treatment is <30%.

[0115] Note: Calculation formula using the nimodipine method: TCM syndrome efficacy (n) = (TCM syndrome score before treatment - TCM syndrome score after treatment) / TCM syndrome score before treatment × 100

[0116] 3.6.1.3 Therapeutic effect of single TCM syndrome

[0117] Markedly effective: The symptom efficacy rate after treatment is ≥70%.

[0118] Effective: The symptom efficacy rate after treatment is ≥30% and <70%.

[0119] Ineffective: The symptom efficacy rate after treatment is <30%.

[0120] Note: Calculation formula using the nimodipine method: TCM syndrome efficacy (n) = (TCM syndrome score before treatment - TCM syndrome score after treatment) / TCM syndrome score before treatment × 100

[0121] 3.7 Results

[0122] Among the 178 patients with essential hypertension who met the inclusion criteria of this clinical study, 36 cases dropped out, with a dropout rate of 20.22%, and 22 cases were excluded, with a exclusion rate of 12.36%.

[0123] 3.7.1 Efficacy results

[0124] 3.7.1.1 Blood pressure

[0125]

[0126] It can be seen from the above table that there are significant differences in systolic and diastolic blood pressure before and after treatment (P value < 0.05), indicating that the Chinese medicine composition Uncaria rhynchophylla antihypertensive granules protected by the present application has a therapeutic effect on blood pressure in patients with mild to moderate liver yang hyperactivity type.

[0127]

[0128] It can be seen from the above table that the systolic and diastolic blood pressures decreased significantly after treatment, indicating that the Chinese medicine composition Uncaria rhynchophylla antihypertensive granules protected by the present application has a therapeutic effect on the blood pressure of patients with mild to moderate Yin deficiency and Yang hyperactivity type.

[0129] 3.7.1.2 TCM Syndrome

[0130] The statistics of TCM syndromes were completed for 120 people, with 34 people showing marked effects, 58 people showing effective effects, and 28 people showing ineffective effects. The total effective rate of the two groups was 76.7%.

[0131] The two groups of patients were subjected to paired t-tests before and after single TCM syndrome treatment, and the results were as follows:

[0132]

[0133] As shown in the table above, there was a significant difference in the TCM syndrome scores before and after medication (P < 0.05), and the best effect was achieved in improving insomnia and headache in patients with liver yang hyperactivity type, and headache symptoms in patients with yin deficiency and yang hyperactivity type.

[0134] 3.7.2 Comparison of main biochemical indicators before and after treatment

[0135] Before and after treatment, the changes in four blood lipids and blood sugar levels are shown in the following table:

[0136]

[0137] As shown in Table 14, there were significant differences in the total cholesterol and high-density lipoprotein cholesterol values ​​before and after the patients were enrolled (P < 0.05), indicating that the drug has the effect of lowering cholesterol.

[0138] The results listed in the above table show that the total effective rate of the comprehensive treatment of mild to moderate hypertension of the present invention is 76.7%, which has a good effect of improving clinical symptoms, indicating that the present invention has a therapeutic effect on hypertension of liver yang hyperactivity type and yin deficiency yang hyperactivity type.

[0139] The above specific implementations cannot be used as limitations on the scope of protection of the present invention. For those skilled in the art, any replacement, improvement or change made to the implementations of the present invention falls within the scope of protection of the present invention. The parts not described in detail in the present invention are all known technologies to those skilled in the art.

Claims

1. A Chinese medicine composition for treating mild to moderate essential hypertension, characterized in that: The composition comprises the following raw materials in parts by weight: 6-12 parts of Uncaria rhynchophylla, 10-12 parts of Paeonia suffruticosa, 3-5 parts of Coptis chinensis, 5-9 parts of Scutellaria baicalensis, 5-10 parts of Phellodendron amurense, 6-10 parts of Alismatis orientalis, 5-12 parts of Ligustrum lucidum, 5-12 parts of Pueraria root and 1-3 parts of Leech.

2. The Chinese medicine composition for treating mild to moderate essential hypertension according to claim 1, characterized in that: The composition is composed of the following raw material components by weight: 12 parts of Uncaria rhynchophylla, 12 parts of Paeonia suffruticosa, 5 parts of Coptis chinensis, 9 parts of Scutellaria baicalensis, 9 parts of Phellodendron amurense, 9 parts of Alismatis rhizome, 9 parts of Ligustrum lucidum fruit, 9 parts of Pueraria root, and 1.5 parts of Leech.

3. The Chinese medicine composition for treating mild to moderate essential hypertension according to claim 1, characterized in that: Made into tablets, capsules, granules, pills, powders, syrups, tinctures, mixtures, lozenges, decoctions, wines, dews, teas, fluid extracts and extracts.

4. A method for preparing the Chinese medicine composition for treating mild to moderate essential hypertension according to any one of claims 1 to 3, characterized in that: The method comprises the following steps: firstly weighing each raw material component, adding 6-12 times the weight of water and soaking for half an hour; then heating to boiling and continuing to decoct for 1-3 hours, filtering to obtain filtrate and filter residue; then adding 4-11 times the weight of water and decoct for 0.5-2.5 hours, filtering, combining the two filtrates, and concentrating under reduced pressure at 60-80°C to obtain the product.

5. The method for preparing the Chinese medicine composition for treating mild to moderate essential hypertension according to claim 4, characterized in that: The method comprises the following steps: firstly weighing each raw material component, adding 9 times the weight of water to soak for half an hour, heating to boiling and then continuing to boil for 2 hours, filtering to obtain filtrate and filter residue, then adding 7 times the weight of water to boil for 1.5 hours, filtering, combining the two filtrates, and concentrating under reduced pressure at 60-80°C to obtain the product.

6. The method for preparing the Chinese medicine composition for treating mild to moderate essential hypertension according to claim 4, characterized in that: The method also includes the following steps: concentrating under reduced pressure at 60-80°C to prepare a clear paste with a relative density of 1.05-1.2, spray drying to obtain a spray-dried powder, adding auxiliary materials, mixing evenly, and then preparing granules by a dry method. The added auxiliary materials include sucralose, maltitol, corn starch, sodium chloride and microcrystalline cellulose; wherein sucralose accounts for 0.05% of the weight of the spray-dried powder, maltitol accounts for 2% of the weight of the spray-dried powder, corn starch accounts for 10% of the weight of the spray-dried powder, sodium chloride accounts for 0.2% of the weight of the spray-dried powder, and microcrystalline cellulose accounts for 2% of the weight of the spray-dried powder.

7. Use of the Chinese medicine composition for treating mild to moderate essential hypertension according to any one of claims 1 to 3 in the preparation of antihypertensive drugs.

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