CN1296080C - Liver clearing blood pressure lowering capsule nd its preparation method - Google Patents

Abstract

The invention discloses a new traditional Chinese medicine Qinggan Jiangya capsule for treating hypertension developed by using medicinal plants as raw materials. It is mainly composed of Prunella vulgaris, Polygonum multiflorum, Sophora japonica, Sangji, Pueraria lobata, Salvia miltiorrhiza, Alisma, thistle, polygala, and Achyranthes bidentata. Its preparation method: extract Polygonum multiflorum, Radix Puerariae, Alisma, and Achyranthes bidentata among the above ten herbs with 50-70% ethanol; extract Prunella vulgaris and Salvia miltiorrhiza with 60-95% ethanol; , Sangjisheng, Xiaoji and Polygala are extracted with water; the above three extracts are concentrated into a thick paste, combined and mixed; dried under reduced pressure, crushed, granulated, and filled into liver-clearing and hypotensive capsules. The medicine has remarkable and stable curative effect on treating hypertension, especially its antihypertensive effect on elevated diastolic blood pressure is better than that of commonly used traditional Chinese medicines at present, and it is safe to take and has no adverse reactions and side effects.

Description

Qinggan Jiangya capsule and preparation method thereof

Technical field

The invention is a new traditional Chinese medicine for treating hypertension developed by taking medicinal plants as raw materials.

Background technique

The pathogenesis of hypertension and its clinical symptoms survey results show that hypertension is caused by multiple factors. Clinical syndromes of traditional Chinese medicine will show hyperactivity of liver fire and deficiency of liver and kidney yin; arterial stenosis and lesions will appear in the human blood circulation system. wait. In the past, traditional Chinese medicine used cold and cool herbs to calm the liver and subdue yang in the treatment of hypertension, while Western medicine mainly used synthetic drugs to expand the cardiovascular system.

At present, in the clinical application of drugs for treating hypertension, most of them have certain adverse reactions or side effects. For example, the traditional Chinese medicine Niuhuang Jiangya Pills is cold in nature and is a sedative and antihypertensive drug. Because of its strong sedative effect, it often causes drowsiness. Because the main ingredients are artificial bezoar, antelope horn, pearls, etc., long-term use can cause diarrhea. Another example is the traditional Chinese medicine Songling Xuemaikang, which is salty and cold in nature. Long-term use can also affect the digestive system, causing adverse reactions such as diarrhea and epigastric fullness. Another example is that although chemical synthetic drugs such as Kaibotong and Norvasc can lower blood pressure, there are many adverse reactions such as dizziness, headache, heart palpitations, chest and back pain, angioedema, and insufficient blood supply after taking them. Long-term use will not only damage the liver and kidneys. Kidney, and dizziness, headache, heart palpitations, insomnia and other symptoms of hypertension itself can not be fundamentally improved.

Contents of the invention

The present invention adopts the method of nourishing the liver and kidney according to the understanding of traditional Chinese medicine on the pathogenesis characteristics of hypertension, "liver fire tends to flourish and kidney yin tends to lose"; Dilatation, according to the new idea of expanding the peripheral and distal blood vessels of the heart to treat hypertension, in order to protect the target organs; to achieve both symptoms and root causes, Qinggan Jiangya Capsules were developed. According to the theory of the same origin of the liver and kidney in traditional Chinese medicine, the prescription research is carried out for hypertension by clearing the liver yang to nourish the kidney yin, and nourishing the kidney yin to calm the liver fire. Qinggan Jiangya Capsules focuses on regulating the liver and kidneys, and regulates the liver and kidneys by clearing the liver and nourishing the kidneys. At the same time, it adopts the antihypertensive route of dilating the peripheral and distal blood vessels of the heart to reduce the peripheral blood supply resistance of the heart, so as to achieve The purpose of treating both symptoms and root causes.

1. Formulation and preparation method

1. Recipe

Prunella vulgaris 150～350g, Polygonum multiflorum 120～400g, Sophora japonica 100～300g, Sangji 150～350g, Pueraria 100～250g, Salvia miltiorrhiza 150～350g, Alisma 100～350g, Thistle 80～200g, Polygala 100～200g, Sichuan Achyranthes bidentata 100～250g.

Make 1000 grains, 0.5g/ grain.

2. Preparation method

Polygonum multiflorum, Radix Puerariae, Alisma, and Achyranthes bidentata in the above ten prescription medicinal materials are extracted 2 to 3 times with 6 to 10 times the amount of 50 to 70% ethanol for 1 to 3 hours each time, and the filtrates are combined to recover the ethanol and reduce Concentrate under pressure until the relative density is 1.20～1.35 (measured at 60°C) thick ointment for later use; Prunella vulgaris and Salvia miltiorrhiza are extracted 1～3 times with 8～12 times the amount of 60～95% ethanol under reflux, each time for 1～3 hours, and the filtrates are combined , recover ethanol, decompress and concentrate into the thick paste required above for later use; decoct Prunella vulgaris, Salvia miltiorrhiza dregs and Sophora japonica, Sangji, small thistle, Polygala 2-3 times with 10-14 times the water, 1-3 times each time. After 2 hours, the combined filtrates were concentrated under reduced pressure into the same thick paste as required for subsequent use. Combine all the thick pastes mentioned above, mix well, dry under reduced pressure, pulverize, add an appropriate amount of dextrin, granulate, and fill into 1000 capsules to obtain (see the preparation process flow chart of Qinggan Jiangya Capsules for details).

The medicinal properties of Qinggan Jiangya Capsule produced according to the above-mentioned preparation method and process are stable. Four years after Qinggan Jiangya Capsule was approved by the State Drug Administration as a new traditional Chinese medicine, its efficacy was tested again. According to the stability test of curative effect conducted by Tianjin Pharmaceutical Research Institute of the State Drug Administration on conscious spontaneously hypertensive rats, Qinggan Jiangya Capsules stored for 4 years have obvious antihypertensive effect, and the antihypertensive effect lasts for 3 hours, which is the same as the new one. Compared with the drugs produced, there is no significant difference in the antihypertensive effect, and the pharmacological activity is not reduced; there is no obvious change in the heart rate when the blood pressure is lowered.

2. Pharmacological effects

The pharmacological effects of Qinggan Jiangya Capsules are: tonify the liver and kidney, expand the peripheral and distal blood vessels of the heart, lower the total peripheral resistance and lower blood pressure, and improve the insufficient blood supply to the heart and brain. The pharmacodynamics test of the Tianjin Pharmaceutical Research Institute of the State Drug Administration proved that after administration of 4.0g crude drug/kg to the duodenum of dogs, the blood pressure decreased significantly, and the total peripheral resistance and left ventricular work decreased; There was no significant effect on the maximum rate of rise and fall of indoor pressure and the pumping function of the heart.

3. Functional Indications

Clearing away heat and calming the Liver, nourishing the Liver and Kidney. For hypertensive liver-fire hyperactivity, liver-kidney yin deficiency syndrome. Symptoms include dizziness, headache, red face, red eyes, irritability, dry mouth, bitter mouth, soreness of the waist and knees, palpitations, insomnia, tinnitus, forgetfulness, and constipation. Usage and dosage: take orally, 3 capsules at a time, 3 times a day, or follow the doctor's advice.

Four, curative effect characteristics

The drug has remarkable and stable therapeutic effect on hypertension, is safe to take, and has no adverse reaction and side effects. Five national clinical pharmacology bases, including the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine, Guang'anmen Hospital of China Academy of Traditional Chinese Medicine, Xiyuan Hospital of China Academy of Traditional Chinese Medicine, and Beijing Hospital of Traditional Chinese Medicine, adopted a randomized double-blind control method. A Phase II clinical study was conducted on the antihypertensive effect of Qinggan Jiangya Capsules; the number of test cases was 431 cases. The results showed that Qinggan Jiangya Capsule's antihypertensive curative effect was 51.5% and the total effective rate was 84.4%; the marked rate of TCM syndrome curative effect was 52.5% and the total effective rate was 91.7%. Compared with Songling Xuemaikang Capsules of the same type of traditional Chinese medicine, the comparison test showed that Qinggan Jiangya Capsules had significantly better antihypertensive effect than Songling Xuemaikang Capsules (P<0.01); the curative effect of improving TCM syndromes was also significantly better than Songling Xuemaikang Capsules (P<0.01). <0.01).

1. Protects Liver and Kidneys

Qinggan Jiangya Capsule has the function of nourishing the liver and kidney, and is superior to antihypertensive drugs that damage the liver and kidney, so it is suitable for long-term use. While effectively treating hypertension, the medicine also protects the liver and kidneys and prevents liver and kidney function failure caused by drug damage.

2. Protect the heart and prevent target organ damage

Qinggan Jiangya Capsule has the effect of dilating the peripheral and distal blood vessels of the heart, reduces the total peripheral resistance, and overcomes the disadvantages of myocardial dilatation caused by commonly used antihypertensive drugs to expand the cardiovascular system; it not only protects the heart but also prevents the failure of treating hypertension. Causes damage to target organs such as insufficient blood supply.

3. Significant curative effect in the treatment of elevated diastolic blood pressure

According to the expert argumentation organized by the Ministry of Health’s Bureau of Original Drugs, “Qinggan Jiangya Capsule’s antihypertensive effect on elevated diastolic blood pressure is superior to that of commonly used traditional Chinese medicine is its characteristic.” The curative effect is significantly better than similar drugs such as Songling Xuemaikang, Naoliqing and Yufeng Ningxin Tablets (respectively see "Qinggan Jiangya Capsule Phase II Clinical Trial Report", "Beijing Tiantan Hospital and Peking University First Hospital Clinical Observations, research reports"); thereby solving the problem of clinical medication that commonly used antihypertensive drugs have no obvious effect on reducing diastolic blood pressure, resulting in abnormal pressure differences.

4. It is safe to take and has no side effects

Qinggan Jiangya Capsules are safe and reliable to take, without adverse reactions and side effects. Toxicological studies have shown that there is no acute toxic reaction when it exceeds 450 times the clinical dosage; after 6 months of long-term toxicity test, no obvious toxic reaction was found in the growth, development, hematology, serum biochemistry and other aspects of the animals, and no pathological examination found any relationship with the drug. Relevant pathological changes (see "Qinggan Jiangya Capsule Long-Term Toxicity Test Report on Rats"). The safety test of Qinggan Jiangya Capsule Phase II clinical study showed that during the entire clinical trial process, no adverse reactions and side effects were found, and no adverse effects were found on heart, liver and kidney functions (see "Qinggan Jiangya Capsule Treatment Hypertension Phase II Clinical Trial Report"). Peking University First Hospital, the clinical research of Qinggan Jiangya Capsules in the treatment of diabetic and hypertensive patients showed that Qinggan Jiangya Capsules have significant and stable antihypertensive effect, are safe to take, have no toxic side effects, have no effect on heart rate, and have no effect on liver and kidney. There is no damage to the function, and there is no damage to the bloody urine and stool routine.

The main pharmacodynamic test data related to the therapeutic effect of Qinggan Jiangya Capsules

Summary

After conscious spontaneous hypertensive rats took 2, 4, and 8 g (crude drug)/Kg of Qinggan Jiangya extract for a single oral administration, the blood pressure of the 8 g (crude drug)/Kg group decreased, and there was no significant change in heart rate; After oral Qinggan Jiangya extract 1, 2, 4g (crude drug)/Kg, 1g (crude drug)/Kg has no significant effect on blood pressure; 2, 4g (crude drug)/Kg can lower blood pressure, but has no significant effect on heart rate. Once a day, take Qinggan Jiangya extract orally for 14 consecutive days (2, 4, 8g (crude drug)/Kg/d for spontaneously hypertensive rats, 1, 2g (crude drug)/Kg/d for renal hypertensive dogs) blood pressure All decreased significantly, and the heart rate had no significant change; 2 to 4 days after stopping the drug, the blood pressure returned to the level of the control period, and the animal's body weight, food intake and behavior did not change significantly. After giving Qinggan Jiangya extract 2, 4g (crude medicine)/Kg to the duodenum of anesthetized open-chested dogs, the blood pressure decreased in a dose-dependent manner, and the heart rate did not change significantly; ±LVdp/dt _max did not change, and the left ventricular work decreased ; There was no significant change in the pumping function of the heart, and the total peripheral resistance decreased. Single and continuous administration of Qinggan Jiangya Extract 5, 10, 20g (crude drug)/Kg to mice does not affect the mice's autonomous activities, and has no synergistic effect with pentobarbital sodium.

Qinggan Jiangya Capsule has the functions of clearing away heat, calming the liver, and nourishing the liver and kidney. It is mainly used clinically for hypertensive patients with hyperactivity of liver fire and nourishing the liver and kidney at various stages. In this study, the antihypertensive effect was observed in spontaneously hypertensive rats and renally hypertensive dogs, and the heart hemodynamics of anesthetized open-chest dogs was studied, in order to provide experimental basis for clinical application.

Experimental Materials

1. Animals:

(1) Spontaneously hypertensive rats (SHR): purchased from the Department of Animal Experiments, Beijing Fuwai Hospital, Chinese Academy of Medical Sciences, meeting the first-class standard (certificate number: Yidongzi No. 01-1086). Raised in an observation room regulated by a central air-conditioning system, with a room temperature of 26±2°C and artificial lighting for 12 hours a day. Rats were reared in separate cages according to sex. The cages were 43×27×18cm, and 4 mice per cage had free access to drinking water. They were fed with high-protein lumps every day. Once, change to fresh tap water once, and the temperature of the manometer chamber is 26±2°C.

(2) Renal hypertensive dogs (RHD) formed in this laboratory: they were raised in a 2.5×1.5m single-room breeding room regulated by a central air-conditioning system, with a room temperature of 25±3°C and free drinking water. Feed pellet feed (provided by Beijing Aifen Company) once at 4 o'clock.

(3) Miscellaneous dogs: purchased from the suburbs of Tianjin and bred for more than two weeks for use.

(4) Kunming mice: Provided by the animal room of the hospital, which meets the first-class standard (certificate number: Jinshidong Facility Zhunzi No. 001).

2. Drugs and preparation:

(1) Qinggan Jiangya fluid extract (referred to as Qinggan Jiangya): brown viscous suspension, equivalent to 2.08 grams of crude drug per ml, provided by Beijing Hongtianli Medicine and Health Products Research Institute, batch number 960515, diluted with distilled water to form The medicinal liquid of 0.2, 0.4, 0.8g (crude drug)/ml is used for intragastric administration of SHR, diluted to 1, 2g (crude drug)/ml medicinal liquid for intragastric administration of RHD and duodenal administration of mixed dogs, diluted to 0.25, 0.5, 1.0g (crude drug)/ml, for intragastric administration of mice.

(2) Niuhuang Jiangya pills: commercially available, produced by Tianjin Darentang Pharmaceutical Factory, batch number 940204, each pill weighs 1.6g, ground into 0.05, 0.08, 0.2g pill weight/ml liquid medicine with distilled water, respectively for mice , SHR, RHD intragastric administration and duodenal administration in mixed dogs.

(3) Pentobarbital sodium: SERVA product, formulated with normal saline to 2.3 mg/ml, for intraperitoneal injection in mice.

      Experimental methods and results

1. Acute hypotensive test

1. Acute antihypertensive effect on SHR:

SHR is used for both sexes, with a body weight of 280±64g. Before measuring the pressure, put the rats in an electric thermostat at 36±1°C to warm up. After 10 minutes, use a CRS-III rat computer blood pressure and heart rate meter to indirectly measure the systolic pressure of the rat tail artery ( SBP) and heart rate (HR). Before the official experiment, the pressure was measured once a day for about two weeks. After the rats adapted to the environment and the blood pressure was stable, the experiment was carried out again. SHR was randomly divided into 5 groups according to blood pressure and body weight, with 8 rats in each group. Ointment 2, 4, 8g (crude drug)/Kg and positive control drug Niuhuang Jiangya Pill 0.8g/Kg, the volume is 1ml/100g, measure before administration and after administration 1,2,3,4,6,8 , 12, 24h systolic blood pressure and heart rate.

The results showed that there was no significant change in SBP and HR in the control group within 24 hours. Infusion of 2 and 4g (crude drug)/kg for clearing the liver and lowering blood pressure had no significant effect on SBP and HR. After the dose was increased to 8g (crude drug)/Kg, SBP began to decrease from 1h after taking the drug, reached the peak value at 2h, and the maximum blood pressure drop was 20±12mmHg, the effect is maintained for more than 3 hours after administration; HR has no significant change when reducing blood pressure. The SBP decreased significantly at 2 hours after feeding Niuhuang Jiangya Pills at 0.8g/Kg, and reached the maximum antihypertensive effect by 10±11mmHg, and had no significant effect on HR. The results are shown in Tables 1 and 2.

2. Acute antihypertensive effect on RHD:

5 dogs with renal vascular hypertension formed by the renal artery on one side of stenosis, weighing 19±4Kg, measured the blood pressure of the common carotid artery moved in the skin sheath by auscultation, measured the heart rate by palpation, and recorded the lead II electrocardiogram at the same time . Under the condition that the blood pressure remained stable for 5 days, administration was started according to an orthogonal design, the control group was filled with distilled water, and the treatment group was fed with different doses of liver-clearing and blood pressure-reducing 1, 2, 4, g (crude drug)/Kg, respectively. Positive control drug Niuhuang Jiangya Pill 0.2g/Kg, except that the administration volume of 4g (crude drug)/Kg group is 2ml/Kg, other each group volume is 1ml/Kg, measures before administration and after administration 1,2 , 3, 4, 6, 8h systolic blood pressure, diastolic blood pressure (DBP) and heart rate, the interval between two administrations is 5 days. The paired t test was used to compare the significance of the mean difference before and after administration.

The results showed that the blood pressure and heart rate of the control group did not change significantly within 8 hours. Taking 1g (crude drug)/Kg of clearing the liver and lowering blood pressure has no obvious effect on blood pressure. After giving 2, 4g (crude drug)/Kg, the blood pressure begins to drop about 1h, and reaches the maximum blood pressure reduction in 2h, and the blood pressure (SBP/DBP) drops to the maximum They were 10±4/8±3, 14±5/12±2mmHg respectively, and the effect was maintained for 3-4 hours, and the heart rate did not change significantly when the blood pressure was lowered. Blood pressure dropped significantly after 0.2g/Kg of Niuhuang Jiangya pills, and the drop was most obvious in 2-3 hours. The maximum blood pressure drop was 18±4/16±3mmHg, and the blood pressure reduction effect could be maintained for 6 hours. The results are shown in Tables 3 and 4.

Qinggan Jiangya Extract had no obvious effect on ECG waveform.

2. Experimental treatment trials

1. The antihypertensive effect of SHR administered continuously for 14 days:

After the blood pressure was stabilized in the 5-day control period, distilled water, Qinggan Jiangya 2, 4, 8g (crude drug)/Kg/d, and Niuhuang Jiangya pills 0.8g/Kg/d were given to SHR for 14 consecutive days, and the administration was determined. The results of SBP and HR before and 2 hours after administration are shown in Tables 5 and 6.

It can be seen from the table that the SBP and HR of the control group fluctuated little during the treatment period. There is no significant change in SBP and HR during the treatment period by taking 2g (crude drug)/Kg/d for clearing the liver and reducing blood pressure. The SBP before administration of 4.8g (crude drug)/Kg/d starts from the 3rd day, and the drop value Compared with the average value of the control period, there is a significant difference, with an average decrease of 7±5, 12±3mmHg in 14 days; the SBP 2h after daily administration is compared with the average value of the control period, and the average decrease of 14±10, 22±3mmHg in 14 days. 7mmHg, the blood pressure of each dose group recovered to the level of the control period 2 to 4 days after drug withdrawal; the positive control drug (Niuhuang Jiangya Pills) decreased by an average of 12 ± 6mmHg before the daily administration of the positive control drug (Niuhuang Jiangya Pills) during the 14-day treatment period; After that, the average drop was 19±9mmHg. During the whole treatment period, Qinggan Jiangya Extract and Niuhuang Jiangya Pills had no significant effect on heart rate. During the treatment, the body weight, diet and drinking water of the animals had no significant changes.

2. The antihypertensive effect of continuous administration of RHD for 14 days:

RHD orally cleared the liver and lowered blood pressure 1, 2g (crude drug)/Kg/d for 14 consecutive days, measured the blood pressure and heart rate before and 2-3 hours after administration, and the results are shown in Table 7.

The results showed that there were no significant changes in blood pressure and heart rate in the control period. After oral administration of 1, 2g (crude medicine)/Kg/d for clearing liver and lowering blood pressure, the blood pressure decreased significantly from the 11th and 7th day, respectively, and the blood pressure decreased by an average of 1±4/3±3, 9±9 respectively before administration on the 14th day /7±5mmHg, the average decrease after administration was 4±5/5±5, 15±7/12±5mmHg. Heart rate did not change significantly during the treatment period. During the treatment period, no abnormal animal behavior was observed, and there was no significant effect on body weight and food intake.

3. Effects on Cardiac Hemodynamics in Anesthetized Chest-opened Dogs

Healthy mixed-breed dogs weighing 16.9±2.2 (13.0-19.5) Kg, both male and female. Intravenous injection of 3% pentobarbital sodium 30mg/Kg anesthetized, endotracheal intubation connected to SC-3 type electric ventilator for artificial positive pressure breathing. Thoracotomy was performed at the left fourth intercostal space to expose the heart, the aortic root was separated, and an electromagnetic flowmeter probe with a diameter of 12 or 14mm (FC-120/140T) was attached, and the aortic flow was measured by a MFV-3200 square wave electromagnetic flowmeter. , which represents the cardiac output (CO); the apex of the heart is intubated into the left ventricle, and the left ventricular systolic pressure (LVSP) is measured through the TP-400T pressure transducer connected to the AP-641G blood pressure amplifier, and the LVSP electrical signal is input into the EQ -601G differentiator processing, measure the maximum rate of rise and fall of left ventricular pressure (±LVdp/dt _max ); separate the right femoral artery, intubate to the abdominal aorta, connect AP-641G blood pressure amplifier through TP-400T pressure transducer Measure systolic blood pressure (SBP) and diastolic blood pressure (DBP); insert needle electrodes subcutaneously in limbs, map standard lead II electrocardiogram (ECG II) through AC-601G ECG amplifier, and input ECG electrical signals into AT-601G heart rate monitor , to measure the heart rate (HR). The above observation indexes were simultaneously recorded on the RTA-1200 thermal array recorder of the RM-6300 eight-channel physiological recorder. At the same time, HR, SBP, DBP and LVSP are stored in the disk of the VM-187G memory, and the changes of heart rate and blood pressure during the experiment are dynamically observed and checked. Laparotomy was performed, and the duodenum was isolated and cannulated in preparation for drug administration. In addition, the left femoral vein was cannulated for fluid replacement.

The pre-drug values were recorded after the operation was completed and the indicators were stable. For duodenal administration, except for the 4g (crude drug)/Kg group whose administration volume is 2ml/Kg, the volume of other groups is 1ml/Kg.

The experiment was divided into 4 groups: (1) blank control group: distilled water 1ml/Kg; (2) liver-clearing and blood-pressure-reducing 2g (crude drug)/Kg group; (3) liver-clearing and blood-pressure reducing 4g (crude drug)/Kg group; (4 ) Positive drug control group: Niuhuang Jiangya pill 0.2g/Kg.

The above indicators were recorded at 0.5, 1, 1.5, 2, and 3 hours after administration, respectively. Calculate cardiac output (SV), cardiac index (CI), left ventricular work (LVW) and total peripheral resistance (TPR) according to formula derivation. The experimental data are expressed as mean ± standard deviation (X ± SD), and the significance of the mean difference before and after administration is compared by paired t test.

1. Effects on blood pressure, heart rate and electrocardiogram:

After bolus injection of distilled water in anesthetized open-chest dogs, there was no significant change in SBP, DBP, HR and ECG II within 3 hours.

After 0.5 to 2 hours after duodenal administration of 2 and 4 g (crude medicine)/Kg for clearing the liver and lowering blood pressure, a significant antihypertensive effect appeared, and the maximum decrease percentage SBP was 6.2 ± 2.8%, 10.3 ± 2.9% respectively (P < 0.01), DBP were 12.9±6.0% (P<0.01) and 15±5.0% (P<0.001), respectively. The antihypertensive effect was enhanced and the duration was prolonged as the dose increased (Table 8).

Cleaning the liver and lowering blood pressure had no significant effect on heart rate and ECG II waveform.

2. Effect on left ventricular work:

In the control group, there was no significant change in LVSP, ±LVdp/dt _max , and LVW within 3 hours after administration of distilled water.

One hour after administration of 2 and 4 g (crude drug)/Kg for clearing liver and reducing blood pressure, LVSP decreased significantly, and the maximum decrease percentages were 5.7±2.9% (P<0.05) and 12.5±2.5% (P<0.01), respectively.

Liver-clearing and blood-pressure-reducing 2 and 4g (crude drug)/Kg had no significant effect on ±LVdp/dt _max . However, LVW decreased significantly at 1-1.5 hours after administration, and the maximum decrease percentages were 11.1±7.0% (P<0.05) and 14.9±1.7% (P<0.01). The results are shown in Table 9.

3. Effects on cardiac pumping function and total peripheral resistance:

After the control group was given distilled water, CO, SV, CI and TPR basically had no significant changes within 3 hours.

Liver-clearing and blood-pressure-reducing 2, 4g (crude drug)/Kg also has no significant effect on CO, SV, CI. However, TPR decreased significantly, with the maximum reductions being 8.7±3.5% and 14.8±4.5% respectively (P<0.01). The results are shown in Table 10.

4. The positive control drug, Niuhuang Jiangya Pill, significantly lowered blood pressure and total peripheral resistance, did not change heart rate, reduced left ventricular work, and had no significant effect on heart pumping function.

4. Mice sedation experiment

(1) Effects of a single administration on the nervous system of mice:

1) Effects on autonomous activities of mice:

50 Kunming healthy mice, weighing 18-22g, male and female, were randomly divided into five groups according to body weight, with 10 mice in each group. According to the pharmacodynamic test results, the effective dose of the RHD antihypertensive test was 2g (crude drug)/Kg, Converted into mouse equivalent dose by body surface area is about 10.3g (crude drug)/Kg, this experiment selects the equivalent dose that is equivalent to pharmacodynamics, and according to this, the drug group is administered intragastrically to give liver-clearing and blood-pressure lowering 5, 10, 20g (crude drug)/Kg, blank control group ig equal volume distilled water, volume is 0.2ml/10g, positive control group ig Niuhuang Jiangya pill 1g (pill weight)/Kg, mouse is put into TDW 1h after administration -02 type universal animal activity recorder autonomous activity box, one for each box, record the number of mouse autonomous activities within 5 minutes, the results are shown in Table 11.

Table 11. Effect of single administration of Qinggan Jiangya Capsules on autonomous activities of mice (X±SD) drug Dose g/Kg Number of animals (only) Number of voluntary activities (times/5min) Percent change (%) Distilled water to clear liver and lower blood pressure, clear liver and lower blood pressure, Niuhuang Jiangya pills -510201 1010101010 647±161565±192626±166648±112504±159 --16.2-7.1-3.9-25.2

Note: 1. Compared with blank control group: P<0.05;

2. Dosage unit: Liver clearing and blood pressure lowering is calculated according to g/Kg of crude drug,

       Niuhuang Jiangya Pills are calculated in g/Kg of the preparation, the same below.

The results showed that 1 hour after administration, compared with the control group, the autonomous activities of the mice in each administration group had no significant change, while the administration of Niuhuang Jiangya Pills for 1 hour could significantly reduce the number of autonomous activities of the mice, and the number of activities decreased by 25.2% (P <0.05).

2) Effects on subthreshold sodium pentobarbital sleep:

Get above-mentioned mouse that measures autonomous activity, after medicine 70min ip subthreshold dose of pentobarbital sodium 23mg/Kg, with injecting pentobarbital sodium 15min inward righting reflex disappears more than 1min as falling asleep index, observes after administration. The number of animals falling asleep in each group was used to calculate the percentage falling asleep. The results are shown in Table 12.

Table 12. The effect of single administration of Qinggan Jiangya Capsules on sleep with subvalvular pentobarbital sodium drug Dose g/Kg Number of animals (only) Number of sleeping animals (only) Percentage of falling asleep (%) Distilled water to clear liver and lower blood pressure, clear liver and lower blood pressure, Niuhuang Jiangya pills -510201 1010101010 21015 20.210.0010.050.0

Note: There was no significant difference compared with the blank control group.

The results showed that 70 minutes after the administration, liver-clearing and blood-pressure reduction did not increase the number of animals falling asleep with subthreshold penobarbital sodium, and there was no synergistic effect with penobarbital sodium.

(2) The impact of continuous administration on the nervous system of mice:

Take 40 mice in the above-mentioned blank control group and the drug-administered group, once a day, for three consecutive days, and repeat the above two experiments 1 hour after the last drug administration. The results are shown in Tables 13 and 14.

Table 13. Effect of continuous administration of Qinggan Jiangya Capsules on autonomous activities in mice (X±SD) drug Dose g/Kg Number of animals (only) Number of voluntary activities (times/5min) Percent change (%) Distilled water clears liver and lowers blood pressure clears liver and lowers blood pressure clears liver and lowers blood pressure -51020 10101010 542±168571±193512±109505±95 -5.4-5.5-6.8

Note: There was no significant difference compared with the blank control group.

Table 14. Effect of single administration of Qinggan Jiangya Capsules on sleep with subvalvular pentobarbital sodium drug Dose g/Kg Number of animals (only) Number of sleeping animals (only) Percentage of falling asleep (%) Distilled water clears liver and lowers blood pressure clears liver and lowers blood pressure clears liver and lowers blood pressure -51020 10101010 1000 10.0000

Note: There was no significant difference compared with the blank control group.

The results showed that the continuous administration of liver-clearing and blood-pressure-reducing medicine did not affect the spontaneous activity of mice, and had no synergistic effect with pentobarbital sodium.

Summary

1. A single oral administration of Qinggan Jiangya extract 2g (crude drug)/Kg by SHR has no significant effect on blood pressure, and blood pressure drops significantly after administration of 4 and 8g (crude drug)/Kg, and the three doses have no significant effect on heart rate. RHD single oral administration of Qinggan Jiangya extract 1g (crude drug)/Kg has no obvious antihypertensive effect, 2, 4g (crude drug)/Kg has obvious antihypertensive effect, and there is no change in heart rate. Each dose group had no significant effect on ECG.

2. Qinggan Jiangya extract once a day, continuous administration for 14 days SHR2, 4, 8g (crude drug)/Kg/d, 2g (crude drug)/Kg/d antihypertensive effect is not obvious, 4, 8g (crude drug)/Kg/d Kg/d blood pressure began to decrease on the 5th and 3rd day respectively; RHD1, 2g (crude drug)/Kg/d blood pressure began to decrease on the 11th and 7th day of administration respectively; the heart rate had no obvious change, and the blood pressure decreased 2 to 4 days after stopping the drug. returned to the level of the control period.

3. After giving Qinggan Jiangya extract 2.4g (crude drug)/Kg to the duodenum of anesthetized open-chest dogs, the blood pressure (SBP, DBP) decreased, the total peripheral resistance (TPR) decreased, and the heart rate did not change significantly, ±LVdp /dt _max did not change significantly, left ventricular work (LVW) decreased, and cardiac pumping function (CO, CI) did not change significantly.

4. Single and continuous administration of 5, 10, and 20 g (crude drug)/Kg of Qinggan Jiangya Extract to mice showed no significant change in autonomous activity and no synergistic effect with pentobarbital sodium.

Experimental Unit: Tianjin Institute of Pharmaceutical Sciences, State Administration of Medicine

Experimenters: 1. RHD experiment: Xu Xiangwei, He Xiaoyun

2. SHR experiment: Yang Yi Xu Xiangwei

3. Cardiac hemodynamics experiment: Xu Xiangwei Yang Yi

4. Sedation experiment: Xu Xiangwei Liu Houxiao He Xiaoyun

Person in charge: Liu Houxiao

Experiment Date: 1996.4～1997.2

Original record keeping location:

  Hypertension Pharmacology Laboratory, Tianjin Institute of Pharmaceutical Research

Table 1. Effects of single administration of Qinggan Jiangya Capsules on SHR systolic blood pressure and heart rate (X±SD, n=8) index drug Dose (g/kg) Before administration After administration (h) 1 2 3 4 6 8 12 twenty four Systolic blood pressure mmHg Blank control Qinggan Jiangya Niuhuang Jiangya Pills -2.04.08.00.8 215±17218±12217±12216±10216±10 214±14216±12212±15202±13 ^** 213±10 216±13215±10210±15197±16 ^** 206±10 ^* 217±13215±12212±14204±15 ^* 208±12 ^* 218±15217±11215±10211±16209±13 ^* 215±13215±11217±14213±11214±9 216±16217±9215±13213±9213±10 214±15218±9214±11214±10212±8 218±15217±14217±13216±11215±11 heart rate bpm Blank control Qinggan Jiangya Niuhuang Jiangya Pills -2.04.08.00.8 379±23378±18381±22382±24386±20 386±28384±26377±27376±28379±25 382±27375±27385±28380±28376±28 377±25374±22380±17382±19385±22 375±25387±24375±24377±27382±24 371±24383±29387±23380±26386±25 374±18377±20382±23381±28375±25 380±26379±27380±28378±18383±28 381±24384±25379±27377±27379±25

Note: ^* P<0.05 ^** P<0.01 compared with before administration.

Table 2. Effect of single administration of Qinggan Jiangya Capsules on SHR systolic blood pressure (X±SD, n=8, unit: %) drug Dose g/kg Base value before administration Percent change after administration 1 2 3 4 6 8 12 twenty four Blank control Qinggan Jiangya Niuhuang Jiangya Pills -2.04.08.00.8 215±17218±12217±12216±10216±10 -0.6±1.9-1.0±1.9-1.9±2.9-6.2±4.7 ^* -1.5±1.1 0.8±3.1-1.3±1.5-3.7±5.4-8.9±5.6 ^** -2.9±3.4 1.1±3.2-1.1±2.8-2.7±3.3-5.5±5.3 ^* -3.7±4.2 1.6±2.3-0.4±1.8-0.4±2.2-2.1±7.7-3.1±3.8 ^* 0.1±2.9-1.4±2.2-0.4±2.8-1.1±3.7-0.9±3.9 0.3±3.7-0.5±2.0-1.3±2.0-1.3±3.7-1.3±2.7 -0.2±2.1-0.3±2.3-1.7±2.8-1.0±3.0-1.4±2.7 0.3±2.6-0.4±2.5-0.2±1.90.4±2.1-0.5±2.8

Note: 1. The unit of the basic value before administration: mmHg;

2. Compared with the control group in the same period: ^* P<0.05, ^** P<0.01, ^*** P<0.001;

Table 3. The effect of a single oral administration of Qinggan Jiangya Capsules on blood pressure and heart rate in RHD (X±SD, n=5) index drug Dose (g/kg) Before administration After administration (h) 1 2 3 4 6 8 Systolic blood pressure mmHg Blank control Qinggan Jiangya Niuhuang Jiangya Pills -1.02.04.00.2 181±19185±24183±23182±27186±24 180±22185±30178±20173±28 ^** 176±22 ^** 182±18184±27173±19 ^** 168±28 ^** 173±21 ^* 182±20180±29177±22 ^** 174±30 ^* 172±24 ^*** 185±23182±24178±20174±26 ^* 175±22 ^* 186±19185±24184±20180±24180±24 ^* 185±21184±26182±20181±27186±22 Diastolic blood pressure mmHg Blank control Qinggan Jiangya Niuhuang Jiangya Pills -1.02.04.00.2 120±18124±25123±21123±25124±22 117±19124±28120±20 ^* 118±27 ^* 115±23 ^** 120±17124±28116±19 ^** 112±24 ^*** 113±21 ^** 119±16122±30118±22 ^** 115±26 ^** 112±26 ^* 122±23124±27119±21118±24 ^* 112±24 ^* 123±18124±25123±18125±27119±23 ^* 121±21126±28123±21126±30123±22 heart rate bpm Contrast Qinggan Jiangya Niuhuang Jiangya Pills -1.02.04.00.2 107±8103±12101±12101±9103±11 106±8102±1198±1597±15103±17 110±7103±10101±1595±16103±12 109±7100±9100±12100±13105±12 110±7103±14100±1298±6106±12 113±5102±10103±1497±11106±11 110±5104±14102±1298±13106±8

Note: Comparison before and after administration: ^* P<0.05, ^** P<0.01, ^*** P<0.001.

Table 4. Effect of single administration of Qinggan Jiangya Capsules on RHD blood pressure (X±SD, n=5 unit: %) index drug Dose g/kg Base value before administration Percent change after administration 1 2 3 4 6 8 systolic blood pressure Blank control Qinggan Jiangya Niuhuang Jiangya Pills -1.02.04.00.2 181±19185±24183±23182±27186±24 -0.6±1.8-0.4±4.0-2.7±2.1-5.0±2.2 ^** -5.0±1.9 ^** 0.5±2.2-1.0±4.8-5.4±1.3 ^*** -7.6±2.7 ^*** -6.9±3.1 ^** 0.3±2.8-3.3±5.7-3.3±1.2 ^* -4.9±3.2 ^* -7.5±1.9 ^*** 2.1±5.0-1.7±3.4-2.8±2.6-4.4±2.3 ^* -5.7±3.6 ^* 2.7±3.5-0.3±1.90.8±2.5-0.9±2.3-3.0±1.9 ^** 2.1±3.6-0.8±4.1-0.3±1.9-0.7±1.10.4±3.6 diastolic pressure Blank control Qinggan Jiangya Niuhuang Jiangya Pills -1.02.04.00.2 120±18124±25123±21123±25124±22 -1.9±1.8-0.4±5.1-3.1±2.0-4.5±3.2-8.1±3.7 ^* 0.3±3.1-0.5±7.5-5.6±2.2 ^** -8.9±2.2 ^*** -9.3±4.1 ^** -0.4±3.1-1.8±8.7-4.5±2.4 ^* -6.6±3.3 ^* -10.6±6.6 ^* 2.1±4.7-0.3±3.9-3.3±3.4-4.3±3.0-10.6±5.8 ^* 3.3±3.6-0.2±2.40.0±2.9-1.2±3.3-4.4±2.9 ^** 1.3±4.81.0±3.0-0.6±1.41.4±3.6-1.0±3.1

Note: 1. Base value unit before administration: mmHg:

2. Compared with the control group in the same period: ^* P<0.05, ^** P<0.01, ^*** P<0.001;

Table 5. Effect of long-term administration of Qinggan Jiangya Capsules (14d) on SHR systolic blood pressure (X±SD, n=8) drug Dose (g/kg) Control period (days) Dosing period (days) Withdrawal period (days) 1 2 3 4 5 x 1 2 3 5 7 9 11 13 14 1 2 3 4 Contrast Qinggan Jiangya Niuhuang Jiangya Pills --2.04.08.00.8 front and back front and back 216±17219±13216±10216±10216±12 218±13218±12218±12218±12214±13 217±16218±11217±11217±11217±11 218±16216±12214±11214±11216±10 215±14217±12215±10215±10217±11 217±15218±11217±12216±10216±11 217±15218±13218±11215±10217±12210±15216±10197±16 ^** 216±11208±9 ^* 215±15217±14217±13213±11215±10 219±14217±14216±11215±13214±12208±12 ^* 205±17 ^** 194±15 ^*** 207±13198±10 ^** 219±15218±14218±11216±10210±13 ^** 203±12 ^* 201±15 ^** 195±12 ^*** 201±14 ^** 192±13 ^*** 217±14220±12215±10212±10 ^** 208±12 ^** 202±10 ^** 203±9 ^*** 197±9 ^** 205±10 ^* 195±10 ^*** 217±11216±11215±9211±12 ^** 207±14 ^* 201±13 ^** 203±10 ^*** 192±13 ^*** 200±17 ^** 196±16 ^** 215±16218±17218±11213±12207±12 ^* 201±14 ^** 200±15 ^*** 192±8 ^*** 201±12 ^** 197±8 ^*** 219±14217±12214±10210±10 ^** 206±9 ^** 199±14 ^** 198±11 ^*** 190±11 ^*** 202±12 ^*** 193±10 ^*** 217±13215±11205±11 ^*** 196±10 ^*** 198±8 ^*** 216±11216±13205±9 ^*** 198±10 ^*** 200±11 ^*** 218±12216±13211±12 ^*** 203±7 ^** 208±13 219±15217±13213±14 ^* 208±8 ^* 214±13 217±14219±12217±9213±9216±15

Note: 1." X " refers to the average value of the control period, " before " refers to before administration every day, and " after " refers to 2 hours after administration every day,

2. Paired comparison with X: ^* P<0.05, ^** P<0,01, ^*** P<0.001;

Table 6. Effect of long-term administration of Qinggan Jiangya Capsules (14d) on SHR heart rate (X±SD, n=8) drug Dose (g/kg) Control period (days) Dosing period (days) Withdrawal period (days) 1 2 3 4 5 x 1 2 3 5 7 9 11 13 14 1 2 3 4 Contrast Qinggan Jiangya Niuhuang Jiangya Pills --2.04.08.00.8 front and back front and back 386±28386±20386±20383±29382±27 379±23379±23375±25379±23380±28 379±27384±18380±15373±25375±25 383±22373±25383±29383±22380±22 390±17378±20381±22381±22386±20 383±20380±19382±20379±17380±15 383±20376±24380±19381±22382±20381±24379±17377±19380±15378±23 380±22380±24379±21382±24379±25 379±29380±25379±32375±25382±24385±30379±32375±25389±23385±27 376±18371±24382±24378±28375±21378±19371±16381±22380±24384±23 373±23381±27380±24384±23373±23381±27386±25383±23379±32375±25 382±24385±30379±21376±27379±29380±25374±23387±23385±18377±19 378±19375±21373±23381±27382±24378±28378±17379±24372±24376±28 379±21376±273S2±24385±30379±32375±25379±29380±25382±24378±28 387±16381±24382±26387±16383±28 381±24375±27374±22381±26386±25 374±18380±20381±24375±17379±25 379±25373±23379±25382±26374±22 381±24382±24377±19381±24382±26

Note: 1. "X" refers to the average value of the control period, "before" refers to before the daily administration, and "after" refers to 2 hours after the daily administration;

2. There is no significant difference compared with X pairing.

Table 7. Effects of long-term administration of Qinggan Jiangya Capsules (14d) on RHD blood pressure and heart rate (X±SD, n=5) index drug Dose (g/kg) Control period (days) Dosing period (days) Recovery period (days) 1 2 3 4 5 x 1 2 3 5 7 9 11 13 14 1 2 3 Systolic blood pressure mmHg Clear liver and lower blood pressure 1.02.0 front and back 183±20188±23 187±21185±18 189±22188±19 193±21189±20 188±20185±19 188±20187±19 191±23189±22191±20183±17 ^* 190±24189±23 190±18188±20184±16176±15 ^* 189±22190±19184±17175±13 ^* 191±23187±19175±15 ^* 173±16 ^* 187±21182±19173±11 ^* 168±15 ^* 182±22 ^* 177±20 ^** 170±13 ^* 165±13 ^* 183±20 ^* 178±19 ^** 170±11 ^* 165±18 ^** 179±19 ^** 170±13 ^* 179±21 ^** 167±14 ^** 185±18178±17 ^* 191±21187±21 Diastolic blood pressure mmHg Clear liver and lower blood pressure 1.02.0 front and back 124±17125±22 124±17125±16 130±16123±15 131±14127±17 126±17123±17 127±14125±17 126±17124±21124±19119±15 ^* 127±21124±19 125±19125±21121±16116±16 ^* 126±21128±17123±15117±15 ^* 127±21124±16117±17 ^** 114±17 ^** 123±18120±19115±16 ^* 112±19 ^** 120±20115±18 ^** 111±17 ^* 107±16 ^** 122±17 ^* 116±17 ^** 114±13 ^** 107±18 ^** 118±20 ^* 111±14 ^*** 116±18 ^** 110±14 ^** 123±16117±15 ^* 126±18124±16 heart rate bpm Clear liver and lower blood pressure 1.02.0 front and back 111±7110±8 108±11110±12 108±8103±5 114±7107±9 108±11111±10 110±7108±7 107±9110±6108±10109±7 111±12107±10 112±12109±8114±9110±7 113±8110±14110±8105±8 109±7110±14108±12110±7 111±7110±12109±12108±9 111±10109±2110±13108±8 113±2110±4111±10110±13 110±4107±13 109±5112±8 110±7113±5 108±11109±12

Note: 1. "X" refers to the average value of the control period, "before" refers to before the daily administration, "after" refers to 2 to 3 hours after the daily administration,

2. Compared with X: ^* P<0.05, ^** P<0.01, ^*** P<0.001;

Table 8. Effect of Qinggan Jiangya Capsules on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in anesthetized open chest dogs

and heart rate (HR) (X±SD, n=5) index drug Dose (g/kg) Before administration After administration (h) 0.5 1 1.5 2 3 SBP Blank control Qinggan Jiangya Niuhuang Jiangya Pills -2.04.00.2 110±5110±7113±8107±14 112±5(1.8)108±7(-1.8)107±8 ^* (-5.3)101±16 ^** (-5.6) 111±5(0.9)104±8 ^* (-5.5)107±8 ^** (-5.3)100±16 ^* (-6.5) 112±4(1.8)105±7 ^** (-4.5)105±8 ^** (-7.1)96±18 ^** (-10.3) 111±7(0.9)110±7(0)105±10 ^* (-7.1)98±14 ^*** (-8.4) 110±5(0)112±7(1.8)106±10(-6.2)100±13 ^* (-6.5) DBP Blank control Qinggan Jiangya Niuhuang Jiangya Pills -2.04.00.2 72±577±477±973±11 74±6(2.8)74±6(-3.9)71±11(-7.8)65±11 ^*** (-11.0) 73±5(1.4)89±6(-10.4)71±11 ^* (-7.8)65±11 ^** (-11.0) 72±4(0)70±5 ^* (-9.1)88±9 ^*** (-11.7)62±10 ^*** (-15.1) 72±8(0)71±4(-7.8)68±11 ^* (-11.7)64±11 ^** (-12.3) 70±7(-2.8)74±4(-3.9)71±11(-7.8)64±14 ^* (-12.3) HR Blank control Qinggan Jiangya Niuhuang Jiangya Pills -2.04.00.2 154±35143±17144±23148±15 155±35(0.6)144±16(0.7)146±18(1.4)150±20(1.4) 154±36(0)143±19(0)146±20(1.4)152±16(2.7) 156±38(1.3)141±19(-1.4)146±17(1.4)148±20(0) 151±36(-1.9)142±17(-0.7)142±20(-1.4)146±17(-1.4) 153±36(-1.6)144±15(0.7)143±20(-0.7)114±19(-2.7)

Note: 1) Comparison before and after administration: ^* P<0.05, ^** P<0.01, ^*** P<0.001;

2) Brackets indicate the percentage change after administration, unit: %;

3) Unit: SBP, DBP: mmHg;

HR: beats/min.

Table 9. Qinggan Jiangya Capsules on the left ventricular pressure (LVSP) and the maximum rate of change of left ventricular pressure (±dp/dt _max ) in anesthetized open-chest dogs

and left ventricular work (LVW) (X±SD, n=5) index drug Dose (g/kg) Before administration After administration (h) 0.5 1 1.5 2 3 LVSP Blank control Qinggan Jiangya Niuhuang Jiangya Pills -2.04.00.2 125±10122±8125±10122±4 128±13(2.4)123±7(0.8)116±15(-7.2)118±5 ^* (-3.3) 127±12(1.6)118±6(-3.3)114±6 ^** (-8.8)115±6 ^** (-5.7) 128±11(2.4)119±12(-2.5)113±6 ^** (-9.6)111±8 ^** (-9.0) 128±11(0.8)122±6(0)116±11 ^** (-7.2)112±8 ^** (-8.2) 127±11(1.6)125±8(2.5)118±10(-5.6)116±9 ^* (-4.9) +dp/dt Blank control Qinggan Jiangya Niuhuang Jiangya Pills -2.04.00.2 3080±9122810±4092800±3232832±577 3192±1007(3.6)2910±517(3.6)2648±350(-5.4)2982±528(5.3) 3112±829(1.0)2830±541(0.7)2608±358(-6.9)2834±386(0.1) 3158±797(2.5)2802±555(0.3)2642±484(-5.6)2678±447(-5.4) 3108±861(0.9)2816±582(0.2)2744±444(-2.0)2710±501(-4.3) 3096±805(0.5)2892±402(2.9)2898±620(3.5)2656±393(-6.2) -dp/dt Blank control Qinggan Jiangya Niuhuang Jiangya Pills -2.04.00.2 2290±5832150±4842262±4032050±241 2354±583(2.8)2232±487(3.8)2266±331(0.2)1946±285(-5.1) 2298±817(0.3)1970±253(-8.4)2222±293(-1.8)1894±474(-7.6) 2366±618(3.3)2080±296(-3.3)2196±417(-2.9)1798±270(-12.3) 2324±620(1.5)2160±407(0.5)2222±383(-1.8)1888±237(-7.9) 2256±543(-1.5)2270±334(5.6)2388±307(5.6)1872±336(-8.7) LVW Blank control Qinggan Jiangya Niuhuang Jiangya Pills -2.04.00.2 3.03±0.833.31±1.073.35±1.123.39±1.02 3.14±0.87(3.6)3.34±1.09(0.9)3.12±0.98(-6.9)3.23±1.06 ^* (-4.7) 3.10±0.85(2.3)3.15±1.14(-4.8)3.11±1.05 ^* (-7.2)3.06±1.09 ^** (-9.7) 3.08±0.90(1.7)3.00±0.97 ^* (-9.4)2.98±0.94 ^* (-11.0)2.93±1.07 ^** (-13.6) 3.00±0.83(-1.0)3.13±1.06(-5.4)2.99±1.04 ^** (-10.7)3.04±1.02 ^* (-10.3) 2.95±0.80(-2.6)3.19±1.07(-3.6)3.17±1.23(-5.4)3.11±1.16(-8.3)

Note: 1) Comparison before and after administration: ^* P<0.05, ^** P<0.01, ^*** P<0.001;

2) Brackets indicate the percentage change after administration, unit: %;

3) Unit: LVSP: mmHg;

±dp/dt _max : mmHg/s;

LVW: kg·m/min/m ² .

Table 10. Effects of Qinggan Jiangya Capsules on Cardiac Output (CO), Stroke Volume (SV), and Cardiac Index (CI) in anesthetized open-chest dogs

and total peripheral resistance (TPR) (X±SD, n=5) index drug Dose (g/kg) Before administration After administration (h) 0.5 1 1.5 2 3 CO Blank control Qinggan Jiangya Niuhuang Jiangya Pills -2.04.00.2 1.84±0.531.83±0.671.96±0.771.99±0.49 1.87±0.56(1.6)1.85±0.69(1.1)1.97±0.76(0.5)2.05±0.50(3.0) 1.84±0.54(0)1.86±0.72(1.6)1.96±0.76(0)1.97±0.53(-1.0) 1.85±0.55(0.5)1.78±0.70(-2.7)1.95±0.74(-0.5)1.98±0.52(-0.5) 1.81±0.53(-1.6)1.78±0.70(-2.7)1.97±0.76(0.5)2.00±0.49.(0.5) 1.81±0.53(-1.6)1.76±0.68(-3.8)1.99±0.76(1.5)1.99±0.49(0) SV Blank control Qinggan Jiangya Niuhuang Jiangya Pills -2.04.00.2 11.9±2.412.4±4.813.5±5.013.4±3.4 12.0±2.7(0.8)12.4±5.0(0)13.4±4.9(-0.7)13.7±3.4(2.2) 12.0±2.8(0.8)12.6±5.3(1.6)13.3±5.0(-1.5)13.0±3.5(-3.0) 11.8±2.6(-0.8)12.3±5.2(-0.8)13.5±5.3(0)13.4±3.5(0) 12.1±2.7(1.7)12.0±5.0(-3.2)13.9±5.4(3.0)13.7±3.2(2.2) 11.9±2.7(0)12.0±5.0(-3.2)13.6±4.9(0.7)13.9±3.1(4.5) CI Blank control Qinggan Jiangya Niuhuang Jiangya Pills -2.04.00.2 2.66±0.742.77±0.892.72±0.802.86±0.46 2.69±0.78(1.1)2.82±0.90(1.8)2.73±0.77(0.4)2.95±0.54(3.1) 2.65±0.75(-0.4)2.82±0.98(1.8)2.72±0.78(0)2.84±0.58(-0.7) 2.66±0.79(0)2.70±0.94(-2.5)2.71±0.73(-0.4)2.84±0.57(-0.7) 2.60±0.73(-2.3)2.69±0.92(-2.9)2.74±0.79(0.7)2.87±0.52(0.3) 2.61±0.73(-1.9)2.67±0.92(-3.6)2.77±0.79(1.8)2.87±0.53(0.3) TPR Blank control Qinggan Jiangya Niuhuang Jiangya Pills -2.04.00.2 3955±12433690±8133616±10163565±577 4032±1372(1.9)3614±881(-2.1)3370±946(-6.8)3188±497 ^** (-10.6) 4065±1361(2.8)3416±770 ^* (-7.4)3379±941 ^* (-6.6)3266±487 ^* (-8.4) 4067±1470(2.8)3651±1065(-1.1)3262±889 ^* (-9.8)3196±751 ^* (-10.4) 4058±1188(2.6)3768±962(2.1)3223±1035 ^* (-10.9)3187±583 ^*** (-10.6) 3986±1204(0.8)3899±999(5.7)3239±781(-10.4)3221±472 ^** (-9.6)

Note: 1) Comparison before and after administration: ^* P<0.05, ^** P<0.01, ^*** P<0.001;

2) Brackets indicate the percentage change after administration, unit: %;

3) Unit: CO: l/min;

SV: ml/beats;

CI: l/min/m ² ;

TPR mmHg/ml/s.

Treatment of Hypertension with Qinggan Jiangya Capsules

  (Excessive Liver Fire, Liver and Kidney Yin Deficiency Type) Phase II Clinical Trial Report

The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine

Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine

    Guang'anmen Hospital, China Academy of Traditional Chinese Medicine

       Xiyuan Hospital, China Academy of Traditional Chinese Medicine

          Beijing Hospital of Traditional Chinese Medicine

Summary

Qinggan Jiangya Capsule is a three-class new traditional Chinese medicine drug developed by Beijing Hongtianli Medical and Health Products Research Institute for the treatment of hypertension (excessive liver fire, liver and kidney yin deficiency syndrome), approved by the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Beijing Traditional Chinese Medicine Five hospitals, Dongzhimen Hospital of the University, Guang'anmen Hospital of the Academy of Traditional Chinese Medicine, Xiyuan Hospital of the Academy of Traditional Chinese Medicine, and Beijing Hospital of Traditional Chinese Medicine observed a total of 431 cases, including 161 cases in the experimental group, 130 cases in the control group, and 140 cases in the open group. The results showed that the effective rate of antihypertensive efficacy test group was 49.7%, and the total effective rate was 82.6%. Compared with the control group: P<0.01, there was a very significant difference. The total effective rate of the treatment group was 51.5%, and the total effective rate was 84.4%. Compared with the control group: P<0.01, there was a very significant difference. The effective rate of the TCM syndrome test group was 52.8%, and the total effective rate was 89.4%. Compared with the control group, P<0.01, there was a very significant difference. The total effective rate of the treatment group was 52.5%, and the total effective rate was 91.7%. Compared with the control group: P<0.01, there was a very significant difference. No toxic side effects and adverse reactions were found during the test.

Test purposes

According to the approval document (98) ZL-033 of the Pharmaceutical Administration Bureau of the Ministry of Health and the "Guiding Principles for Clinical Research of New Drugs of Traditional Chinese Medicine", phase II clinical trials of Qinggan Jiangya Capsules in the treatment of hypertension (excessive liver-fire, liver-kidney yin deficiency) were formulated Plan, and from April to December 1998, Phase II clinical observation of Qinggan Jiangya Capsules in the treatment of hypertension was carried out, mainly to investigate its efficacy and safety.

normal information

A total of 431 inpatients and outpatients were selected, including 301 patients in the experimental group, 140 inpatients, accounting for 46.51%, 161 outpatients, accounting for 53.49%; 130 patients in the control group, 68 inpatients, accounting for 52.31% , 62 outpatients, accounting for 47.69%. There was no significant difference between the test group and the control group in terms of gender, age, course of disease, disease condition and hypertension type, stage, symptoms, tongue pulse, etc. before treatment. P>0.05, comparable, see Table 1-9 for details.

Table 1 Gender distribution of patients group Number of cases male female male: female example (%) example (%) Experimental group, control group, total treatment group 161130301 9567148 (59.00)(51.54)(49.17) 6663153 (41.00)(48.46)(50.83) 1.44:11.06:10.97:1

Statistical processing results: X ² =1.63 P>0.05 compared with the control group and X ² =0.20 P>0.05 in the total treatment group compared with the control group.

Table 2 Age distribution of patients group Number of cases 18～30 ~40 ~50 ~60 ~70 Experimental group, control group, total treatment group 161130301 111 13719 241651 373986 8667144

In the test group, the oldest was 70 years old and the youngest was 22 years old.

The oldest in the control group was 70 years old and the youngest was 34 years old.

Statistical processing results: comparison between the test group and the control group X ² =2.54 P>0.05;

X ² =2.23 P>0.05 compared between the total treatment group and the control group.

Table 3 Distribution of disease course in patients group Number of cases Disease course (year) <I 1～ 3～ 5～ 10～ Experimental group, control group, total treatment group 161130301 9616 231650 221349 292762 7868124

The longest duration of disease in the test group was 30 years, and the shortest was half a year.

The longest course of disease in the control group was 27 years, and the shortest was half a year.

Statistical processing results: comparing the test group with the control group, X ² =5.51, P>0.05;

Compared with the control group, X ² =6.71 in the total treatment group, P>0.05.

Table 4 The patient's degree of TCM condition group Number of cases mild Moderate severe example (%) example (%) example (%) Experimental group, control group, total treatment group 161130301 101133 (6.21)(8.46)(10.96) 6963114 (42.86)(48.46)(37.87) 8256154 (50.93)(43.08)(51.16)

Statistical processing results: X ² =2.30 P>0.05 compared between the test group and the control group;

X ² =4.24 P>0.05 compared between the total treatment group and the control group.

Table 5 Western medicine classification of patients with hypertension group Number of cases mild moderate to severe pure systole example (%) example (%) example (%) Experimental group, control group, total treatment group 161130301 9366163 (57.76)(50.77)(54.15) 4946116 (30.43)(35.38)(38.54) 191822 (11.80)(13.85)(7.30)

Statistical processing results: X ² =1.42 P>0.05 compared between the test group and the control group;

X ² =4.42 P>0.05 compared between the total treatment group and the control group.

Table 6 Stages of hypertension in patients group Number of cases Phase I Phase II Phase III example (%) example (%) example (%) Experimental group, control group, total treatment group 161130301 291861 (18.01)(13.85)(20.27) 124103210 (77.02)(79.23)(69.77) 8930 (4.97)(6.92)(9.97)

Statistical processing results: X ² =1.29 P>0.05 compared between the test group and the control group;

X ² =4.09 P>0.05 compared between the total treatment group and the control group.

Table 7 Patients' high blood pressure (mmHg) group Number of cases systolic blood pressure diastolic pressure X±S X±S Experimental group, control group, total treatment group 161130301 164.60±14.43165.05±16.08166.18±15.00 97.40±9.5097.47±8.6798.66±11.40

Statistical processing results: comparison between the test group and the control group

Systolic blood pressure t＝0.2486 P＞0.05

Diastolic blood pressure t＝0.3936 P＞0.05

      Comparison of the total treatment group with the control group

Systolic blood pressure t＝0.6848 P＞0.05

Diastolic blood pressure t＝0.6873 P＞0.05

Table 8 Distribution of patient symptoms (example) group Number of cases dizziness Headache irritable dry mouth Soreness of the waist and knees heart palpitations insomnia tinnitus forgetful red face dry Experimental group, control group, total treatment group, comparison between experimental group and control group X ² total treatment group, comparison with control group X ² 161130301 1451152710.190.24 124982320.110.14 1251012381.040.10 125992400.090.69 122982380.010.72 92751790.010.12 104772040.882.92 79701530.660.33 121881951.980.34 102791840.200.004 98811900.060.03

Statistical results show that: the experimental group and the control group P>0.05

      The total treatment group and the control group P>0.05

Table 9 Tongue pulse distribution of patients (example) group Number of cases red tongue yellow moss Abnormal pulse condition (string, thin, number) Experimental group, control group, total treatment group, comparison between experimental group and control group X ² P comparison between total treatment group and control group, X ² P 162130301 1471152730.61＞0.050.23＞0.05 1321022410.55>0.050.15>0.05 1591252962.14>0.051.94>0.05

Selection of subjects

1. Diagnostic criteria and basis

(1) Western medicine diagnostic criteria

1. Diagnostic criteria for hypertension (refer to the criteria formulated by the National Symposium on Cardiovascular Epidemiology and Population Prevention in 1979).

The systolic blood pressure is equal to or higher than 160mmHg (21.3Kpa) and the diastolic blood pressure is equal to or higher than 95mmHg (12.7Kpa). If one of the two is verified, the diagnosis can be confirmed.

Those who have a history of hypertension in the past without treatment for a long time (more than 3 months) and have normal blood pressure in this examination are not classified as hypertensive. If you have been taking medicine for treatment, those with normal blood pressure in this examination will still be classified as high blood pressure. If you have doubts, you can re-examine and make a diagnosis after stopping the medicine for 1 month.

2. Clinical staging standard (according to the 1993 WHO/ISH standard).

(1) Stage I hypertension: the blood pressure has reached the level of diagnosed hypertension, and there is no clinical manifestation of heart, brain and kidney complications.

(2) Stage II hypertension: blood pressure reaches the level of diagnosed hypertension, and one of the following:

X-ray, electrocardiogram or ultrasonography showed left ventricular hypertrophy; fundus examination showed general or partial narrowing of fundus arteries; proteinuria or/and plasma creatinine concentration slightly increased (106-177mmol/L); ultrasound or X-ray There is atherosclerotic plaque.

(3) Stage III hypertension: the blood pressure reaches the determined hypertension level, and the clinical manifestations of organ damage appear:

Heart: angina pectoris, myocardial infarction, heart failure.

Brain: transient ischemic attack (TIA), stroke, hypertensive encephalopathy.

Fundus: Retinal hemorrhage, exudate with or without papilledema.

Kidney: serum creatinine>177mmol/L, renal failure.

Blood vessels: arterial dissection, arterial occlusive disease.

3. Hypertension classification:

SBP DBP Kpa(mmHg) Kpa(mmHg) Normal 18.7 (140) Mild 18.7～24 (140～180) Subtype: Borderline 18.7～21.3 (140～160) Moderately severe > 24 (180) Pure systolic > 21.6 (160) Subtype: Borderline systolic 18.7～21.3(140～160) and <12 (90) and (or) 12 to 14 (90 to 105) and (or) 12 to 12.7 (90 to 95) and (or) >14 (105) and (or) <12 (90) and < 12(90)

(WHO/ISH, 1993)

(2) TCM diagnostic criteria

Dialectical basis:

Refer to the "Guiding Principles for Clinical Research of New Chinese Medicines" Guiding principles for clinical research of new Chinese medicines for the treatment of hypertension: hyperactivity of liver fire, deficiency of liver and kidney yin.

Main symptoms: ① dizziness, headache.

Secondary symptoms: ②Red face, red eyes, irritability, constipation, dry mouth and bitter mouth.

③Soreness of waist and knees, palpitation, insomnia, tinnitus and forgetfulness.

④Tongue pulse: red tongue, yellow coating, stringy and thin pulse (or stringy, thin, and few)

①, ②, and ③ each have one or more items, which can be identified as this syndrome by referring to the tongue pulse.

2. Case selection criteria

(1) Consistent with the diagnosis of hypertension

1. Under the premise of ensuring the safety of the patient's life, the blood pressure reached the diagnostic criteria for hypertension after 2 weeks of stopping the drug.

2. Those who did not take medication in the past, had blood pressure measured 3 times on different days within a week, reached the diagnostic level of hypertension, and those whose TCM syndromes belonged to hyperactivity of liver fire and deficiency of liver and kidney yin, could be included in the experimental cases.

(2) Taking stage II hypertension as the main observation object.

(3) Essential hypertension.

(4) Systolic blood pressure <200mmHg, diastolic blood pressure <115mmHg.

3. Case exclusion criteria (including incompatibility or exclusion criteria)

(1) Those who are under 18 years old or over 70 years old, pregnant or breastfeeding women, who are allergic to this drug.

(2) Secondary hypertension.

(3) Systolic blood pressure ≥ 200mmHg, diastolic blood pressure ≥ 115mmHg.

(4) The TCM syndrome differentiation of hypertension does not conform to the syndrome of hyperactivity of liver fire and deficiency of liver and kidney yin.

(5) Patients with severe primary diseases of the heart, brain, liver, kidney and hematopoietic system, and mental illness.

(6) Anyone who does not meet the inclusion criteria, does not take medication as prescribed, cannot judge the curative effect or has incomplete data, etc., which affects the judgment of curative effect or safety.

experiment method

1. Grouping method

In this experiment, a test group, a control group and an open group were set. Among them, the test group and the control group were dosed in groups by random double-blind control method. There were 161 cases in the test group, 130 cases in the control group, and 140 cases in the open group, a total of 431 cases.

2. Medication method

The test group took Qinggan Jiangya Capsules, 3 times a day, 3 capsules each time orally.

The control group took Songling Xuemaikang Capsules, 3 times a day, 3 capsules each time orally.

The open group took Qinggan Jiangya Capsules, 3 times a day, 3 capsules each time orally.

Qinggan Jiangya Capsules are produced by Beijing Hongtianli Medicine and Health Products Research Institute, batch number is 970926;

Songling Xuemaikang Capsules are produced by Chengdu Kanghong Pharmaceutical Co., Ltd., the batch number is 980314.

Three, course of treatment

Four weeks is a course of treatment, observe a course of treatment.

4. Matters needing attention

1. Measure blood pressure 2-3 times a week, preferably at 9-10 am, sitting. Measure the same upper limb every time. Blood pressure values are in mmHg. Rest for 20-30 minutes before the pressure measurement.

2. During the clinical trial period, it is not allowed to take other Chinese and Western medicines for the treatment of this disease, or adopt other treatment methods. If the blood pressure is ≥200/115mmHg, you can temporarily take nifedin 5mg sublingually, but the dosage needs to be recorded.

5. Observation indicators

1. Diagnostic tests

(1) Chest X-ray examination

(2) Echocardiography

(3) fundus examination

(4) Electrocardiogram

2. Curative effect observation

(1) Observe the changes of TCM symptoms, tongue and pulse before and after treatment.

(2) Changes in blood pressure before and after treatment.

3. Security check

(1) Routine laboratory tests of blood, urine and stool.

(2) Liver and kidney function tests.

(3) ECG examination.

6. Statistical Analysis Methods

Count data were analyzed by X ² test, rank data were analyzed by Ridit, and measurement data were analyzed by t or u test.

7. Efficacy standard and basis:

(1) Antihypertensive efficacy evaluation standard (refer to the standard formulated by the National Symposium on Cardiovascular Epidemiology and Population Prevention and Control in 1979)

1. Significant effect: <1> Diastolic blood pressure drops by 10mmHg (1.3Kpa) and above, and reaches the normal range; <2> Diastolic blood pressure has dropped by 20mmHg (2.7Kpa) or above although it has not dropped to normal. Must have one of them.

2. Effective: <1> Diastolic blood pressure drops less than 10mmHg (1.3Kpa), but has reached the normal range; <2> Diastolic blood pressure drops 10-19mmHg (1.3-2.5Kpa) compared with before treatment, but does not reach the normal range; <3 >Systolic blood pressure decreased by 30mmHg (4Kpa) or more than before treatment. Must have one of them.

3. Ineffective: Those who do not meet the above standards and those who automatically stop taking the medicine without lowering blood pressure after 2 weeks of taking the medicine.

(2) Criteria for evaluating curative effect of TCM syndromes:

1. Significantly effective: the clinical symptom score is reduced by two-thirds or more.

2. Effective: the clinical symptom score is reduced by one-third or more, and less than two-thirds.

3. Invalid: Those who do not meet the above standards.

Attachments: (1) TCM Syndrome Grading and Scoring Method:

1. Vertigo: a. Conscious dizziness, no sense of rotation of self or scenery or 2 points

    A sense of shaking; or simple dizziness without affecting work.

b. Conscious dizziness, and a sense of self-rotation or shaking, but it does not affect 4 points

Life; or simple dizziness that affects activities, but can persist in work

c. Consciously dizzy, and have a sense of rotation of oneself and the scene, and the head and body dare not 6 points

Turning around; or simply dizzy, distracted, and unfit for work

2. Headache: a, tolerable, does not affect work and study 2 points

                      4 points

                                             

3. Irritable and irritable: a. Slight 1 point

b. heavier 2 points

c, serious 3 points

4. Dry mouth and bitter mouth: a. Dry mouth is unbearable, drinking water is normal 1 point

                                                                                       , 

c. Unbearable dry mouth, drinking water frequently 3 points

5. Weak waist and knees: a. Does not affect work and study 1 point

b. Affect work and study 2 points

c. Unable to persist in work and study 3 points

6. Palpitations: a. Occasional palpitations 1 point

b. More than 3 times a day 2 points

c. Severe heart palpitations need to be treated with medication 3 points

7. Insomnia: a. Difficulty falling asleep but within 1 hour 1 point

Able to fall asleep and sleep for up to 6 hours

                                                                  

Or take 2 tablets of diazepam

c. Time to fall asleep must be more than 2 hours 3 points

        Or need to use more than 2 tablets of diazepam

8. Tinnitus: a. Occasional tinnitus 1 point

                                  

c. Persistent tinnitus, inability to work and study 3 points

9. Forgetfulness: a, mild 1 point

b. heavier 2 points

c, serious 3 points

10. Red face and red eyes: a. Slight 1 point

                                  

C. Noodles are like heavy jujube, 3 points of congestion with sclera membrane

11. Dry: a. 1 row per 2 days 1 point

                                      

c. For more than 3 days, medication is required 3 points

Tongue appearance: red tongue 1 point

                                                                                   

                                                                                                                                                

The disappearance of the above symptoms is 0 points.

(2) Classification of disease severity in traditional Chinese medicine: mild ≤ 10 points

             Moderate  ≥11 points <18 points

Severe ≥18 points

test results

1. Curative effect analysis

1. Efficacy of hypertension: see Table 10.

Table 10 Efficacy of hypertension in patients group Number of cases markedly effective efficient invalid total effective rate example (%) example (%) example (%) (%) Experimental group, control group, total treatment group 161130301 8040155 (49.7)(30.8)(51.5) 535499 (32.9)(41.5)(32.9) 283647 (17.4)(27.7)(15.6) 82.672.384.4

Statistical processing results: Ridit analysis,

Comparing the test group with the control group U＝3.06 P＜0.01

The comparison between the total treatment group and the control group U＝3.85 P＜0.01

Statistical results showed that the antihypertensive effect of the test drug was significantly better than that of the control group.

2. Comparison of the curative effect of each observation hospital in the total treatment group: see Table 11.

Table 11 total treatment group curative effect in each observation hospital Hospital Number of cases markedly effective efficient invalid total effective rate example (%) example (%) example (%) example (%) Tianjin First Affiliated Hospital of Traditional Chinese Medicine Dongzhimen Hospital Guang'anmen Hospital Xiyuan Hospital Beijing Hospital of Traditional Chinese Medicine 5150608060 2625294728 (50.98)(50.00)(48.30)(58.75)(46.67) 1816192719 (35.29)(32.00)(31.70)(33.75)(31.67) 7912613 (13.73)(18.00)(20.00)(7.500)(21.67) 4441487447 (86.27)(82.00)(80.00)(92.50)(78.33)

Statistical processing results: Ridit analysis, X ² =3.8215 P>0.05

The statistical results showed that there was no significant difference in the antihypertensive efficacy among the observation hospitals.

3. Changes in blood pressure before and after treatment: see Table 12 and Table 13.

Table 12 Changes in blood pressure before and after treatment in each group (mmHg) group Number of cases systolic blood pressure diastolic pressure pre-treatment after treatment pre-treatment after treatment X±S X±S X±S X±S Experimental group, control group, total treatment group 161130301 164.60±14.43165.05±16.08166.18±15.00 143.8±15.72146.60±16.70145.7±14.55 97.14±9.5097.47±8.6798.66±11.40 85.98±9.2489.07±7.6286.38±8.59

Statistical processing results: comparison of each group before and after treatment

Experimental group systolic blood pressure t=12.32 P<0.01, diastolic blood pressure t=10.9 P<0.01

Control group systolic blood pressure t=9.2 P<0.01, diastolic blood pressure t=8.15 P<0.01

The total treatment group systolic blood pressure t＝8.27 P＜0.01, diastolic blood pressure t＝1.45 P＜0.01

Statistics show that:

Both the test drug and the control drug had significant hypotensive effects on the systolic and diastolic blood pressure of hypertensive patients.

Table 13 Comparison of blood pressure difference before and after treatment in each group group Number of cases Difference before and after treatment Systolic blood pressure (X±S) Diastolic blood pressure (X±S) Experimental group, control group, total treatment group 161130301 20.81±13.6418.45±12.8120.48±13.08 11.16±9.78.40±7.29 12.28±8.30

Statistics show that:

Compared with the control group, the systolic pressure difference t＝1.77 P＞0.05

Diastolic pressure difference t＝2.93 P＜0.01

The difference between the total treatment group and the control group Systolic pressure difference t＝1.50 P＞0.05

Diastolic pressure difference t＝4.61 P＜0.01

Statistics show that:

The experimental drug was significantly better than the control group in reducing diastolic blood pressure.

4. Comparison of onset time in the treatment of hypertension: see Table 14.

Table 14 Comparison of the onset time of treatment of hypertension in each group group Number of cases Effective time (days) X±S Experimental group, control group, total treatment group 13394255 9.46±3.1112.70±4.117.33±4.26

The statistical results show that: compared with the control group, t=6.76 P<0.01

    Compared between the total treatment group and the control group t=10.53 P＜0.01

The results showed that the onset time of the test drug was faster than that of the control group, and the onset time was obviously better than that of the control group.

5. Efficacy of different types of hypertension in the total treatment group: see Table 15.

Table 15 total treatment group different types of hypertension curative effect Classification Number of cases markedly effective efficient invalid Total effective rate (%) example (%) example (%) example (%) Mild to moderate to severe pure systole 16311622 102467 (62.6)(39.7)(31.8) 474210 (28.8)(36.2)(45.5) 14285 (8.60)(24.1)(22.7) 91.475.977.3

Statistical processing results: Ridit analysis, X ² =17.56 P<0.01

Statistical results show that: this drug has better curative effect on mild hypertension than moderate to severe one.

6. Efficacy of TCM syndromes: see Table 16.

Table 16 The curative effect of TCM syndromes in each group group Number of cases markedly effective efficient invalid Total effective rate (%) example (%) example (%) example (%) Experimental group, control group, total treatment group 161130301 8543158 (52.8)(33.1)(52.5) 5956118 (36.6)(43.0)(39.2) 173125 (10.6)(23.9)(8.3) 89.476.191.7

Statistical processing results: Ridit analysis,

Compared with the control group U＝3.30 P＜0.01

The comparison between the total treatment group and the control group U＝2.75 P＜0.01

The statistical results show that the experimental drug is better than the control group in improving the TCM syndromes of hypertensive patients.

7. Curative effect of TCM symptoms tongue and pulse: see Table 17.

Table 17 TCM symptoms and curative effect of tongue and pulse in each group group total treatment group control group X ² = P dizziness Number of cases before treatment Number of cases disappeared after treatment (%) 271135136 (50.2) 1156649 (42.6) X ² =1.86 P＞0.05 Headache Number of cases before treatment Number of cases disappeared after treatment (%) 23296136 (58.6) 985048(48.98) X ³ =2.75 P＞0.05 irritable Number of cases before treatment Number of cases disappeared after treatment (%) 238132106(44.54) 1017328 (27.7) X ³ =8.44 P<0.01 dry mouth Number of cases before treatment Number of cases disappeared after treatment (%) 240114126 (52.5) 994851 (51.5) X ² =2.72 P＞0.05 Soreness of the waist and knees Number of cases before treatment Number of cases disappeared after treatment (%) 23814593 (39.1) 987622 (22.4) X ² =8.52 P<0.01 heart palpitations Number of cases before treatment Number of cases disappeared after treatment (%) 17973106(59.22) 753639 (52.0 0) X ² =1.12 P＞0.05 insomnia Number of cases before treatment Number of cases disappeared after treatment (%) 204104100 (49.02) 774928 (36.4) X ² =3.53 P＞0.05 tinnitus Number of cases before treatment Number of cases disappeared after treatment (%) 1538172 (47.1) 703733 (47.1) X ² =1.33 P＞0.05 forgetful Number of cases before treatment Number of cases disappeared after treatment (%) 19514352 (26.7) 887018 (20.5) X ² =1.26 P＞0.05 red face Number of cases before treatment Number of cases disappeared after treatment (%) 18482102 (55.43) 794435 (44.3) X ² =2.61 P＞0.05

Group test group control group dry Number of cases before treatment Number of cases disappeared after treatment (%) 19063127(66.8) 814041(50.6) X ² =6.04 P<0.01 red tongue Number of cases before treatment Number of cases after treatment Number of cases disappeared 27318192(33.7) 1157540(34.78) X ² =0.06 P＞0.05 yellow moss Number of cases before treatment Number of cases disappeared after treatment (%) 241103138(57.3) 1024260(58.8) X ³ =0.07 P＞0.05 Abnormal pulse condition (string, thin, number) Number of cases before treatment Number of cases disappeared after treatment (%) 29626234(11.5) 12510817(13.6) X ² =0.37 P＞0.05

The statistical results show that the experimental drug has a good curative effect on improving TCM syndromes, especially on irritability, soreness of the waist and knees, and dry stool, which is better than that of the control group.

8. The relationship between the degree of TCM syndrome and the curative effect of the syndrome in the total treatment group: see Table 18.

Table 18 The relationship between the degree of TCM syndrome and the curative effect of the syndrome in the total treatment group degree Number of cases markedly effective efficient invalid Total effective rate (%) example (%) example (%) example (%) mild moderate severe 33114154 177566 (51.5)(65.8)(42.9) 143074 (42.4)(26.3)(48.1) 2914 (6.1)(7.9)(9.1) 93.992.190.9

Statistical processing results: Ridit analysis, X ² =9.17 P>0.05

Statistical results show that there is no significant difference in the curative effect of the experimental drug on different degrees of TCM syndromes.

2. Observation of safety indicators: See Tables 19 and 20.

Table 19 Routine changes of blood, urine and stool in patients before and after treatment group blood routine urine routine Routine Number of cases normal abnormal aggravate Number of cases normal abnormal aggravate Number of cases normal abnormal aggravate Experimental group, control group, open group Before treatment After treatment Before treatment After treatment Before treatment After treatment 160160125125297297 160160125125297297 000000 000 157157125125293293 125142109115233257 321516106026 000 119119104104225225 119119104104225225 000000 000

Table 20 Changes of heart, liver and kidney function in patients before and after treatment group liver function kidney function electrocardiogram GPT Gr BUN Number of cases normal abnormal Number of cases normal abnormal Number of cases normal abnormal Number of cases normal abnormal Experimental group, control group, total treatment group Before treatment After treatment Before treatment After treatment Before treatment After treatment 157157125125293293 157157125125286289 000074 98989595234234 96969595234234 000000 158158125125295295 150150120120283284 68551211 160160130130296296 56583334119125 1041029796177171

Tables 19 and 20 suggest that taking the test drug has no obvious damage to the patient's blood, urine, stool routine, liver and kidney functions, and individual patients have improved. Whether the drug has an effect remains to be further investigated.

3. Analysis of adverse reactions:

The experimental group observed 301 cases of patients, no adverse reactions were found.

4. Analysis of the reasons for the exclusion of cases:

A total of 20 cases were excluded from the observation group, of which 18 cases were lost to follow-up, and 2 cases were excluded because they were taking other drugs and could not evaluate the curative effect. 2 cases in the control group were excluded due to lack of reexamination.

Typical cases

Example 1: Patient Yang ××, male, 66 years old, cadre, hospital number 64715

Date of first visit August 8, 1998 Serial number 80

The patient was admitted to the hospital for one week mainly due to dizzy head, dizzy head, red face and red eyes. Past medical history of hypertension for 6 years. Orally take Fujiang tablet intermittently, the blood pressure is maintained at 180/100mmHg, and he has not taken any antihypertensive drug in the past six months. Symptoms on admission include dizziness, mild headache, flushed face, memory loss, upset and chest tightness, irritability, dry stool, red tongue with yellow coating, stringy pulse.

Physical examination showed: T36.7℃, P 70 beats/min, BP 180/100mmHg, fundus examination showed arterial narrowing, veins tortuous A.V intersection, diagnosed as hypertension stage II, after admission, TCM diagnosis was vertigo, hyperactivity of liver fire type, western medicine Diagnosed as hypertension IT stage, in line with the selected cases. Randomly included in the test group, they were given Qinggan Jiangya Capsules, 3 capsules each time, 3 times a day, orally. After taking the medicine for three days, the symptoms of dizziness and drowsiness were significantly relieved, mild dry mouth, no bitterness in the mouth, normal stool behavior once a day, blood pressure was 160/95mmHg, and the blood pressure was 160/90mmHg after one week. After two weeks, all symptoms were relieved , no dizziness, no headache, blood pressure at 140/80mmHg, continued to take this medicine, blood pressure remained stable at 140/80mmHg, red tongue with yellow coating turned to light red tongue, thin white coating, irritability and depression symptoms disappeared. After treatment, blood, urine, stool routine, liver function and kidney function were all normal. The curative effect of TCM syndrome was evaluated as markedly effective, and the curative effect of blood pressure was markedly effective.

Example 2: Dong ××, male, 68 years old, worker, hospital number: 61115, first visit period: October 6, 1998.

Chief complaint: frequent dizziness, headache, dizziness worsened in 2 weeks.

History of present illness: The patient had a history of hypertension for 10 years. In the past 2 weeks, dizziness and headache were obvious, accompanied by irritability, red face, red eyes, forgetfulness, dry mouth and soreness of waist and knees. Body of the tongue is dark red, fur is yellow, stringy and thready pulse. The symptom score is 24 points.

Physical examination: T36.5℃, R: 20 beats/min, P 78 beats/min, BP: 160/105mmHg.

TCM diagnosis: vertigo

TCM Syndrome Differentiation: Hyperactivity of Liver Fire, Liver and Kidney Yin Deficiency

Western medicine diagnosis: hypertension

Western Medicine Staging: Phase II

The patient began to take Qinggan Jiangya Capsules on October 6, 1998, 3 capsules/time, 3 times/day. During the medication, the compliance was good, and there was no missed drug situation in the treatment process. After taking the medicine for one week, the blood pressure began to drop, and after two weeks, the blood pressure dropped and remained at 120/80mmHg. The clinical symptoms, tongue and pulse conditions were significantly improved, and the score was 6 points. Both the antihypertensive and syndrome curative effects were markedly effective. The safety test showed that all indexes were normal before and after treatment, and the electrocardiogram showed T wave changes before treatment, but there was no change after treatment. During the observation process, no obvious adverse reactions were found in the patients.

discuss

1. The First Affiliated Hospital of Tianjin College of Traditional Chinese Medicine, Beijing Dongzhimen Hospital, Guang'anmen Hospital, Beijing Hospital of Traditional Chinese Medicine, and Xiyuan Hospital jointly carried out Qinggan Jiangya Capsules to treat hypertension (liver fire) from April to December 1998. Hyperactivity, Liver and Kidney Yin Deficiency Type) Phase II clinical trial. 301 patients were selected for the test group, and 130 patients were selected for the control group. The results of the clinical trials showed that the effective rate of antihypertensive effect in the test group was 49.7%, the total effective rate was 82.6%, the total effective rate in the treatment group was 51.5%, and the total effective rate was 84.4%. The efficacy of the experimental drug was better than that of the control group. The effective rate of TCM syndrome curative effect test group was 52.8%, the total effective rate was 89.4%, the total effective rate was 52.5%, and the total effective rate was 91.7%. medicine.

2. Clinical observations show that Qinggan Jiangya Capsules can improve the TCM syndromes of hypertensive patients with hyperactivity of liver-fire and liver-kidney yin deficiency, among which symptoms such as sore waist and knees, irritability, dry stool, and yellow fur There is an obvious improvement effect, which is better than that of the control group.

3. During the observation process, no adverse reactions and side effects were found, and no adverse effects on liver and kidney functions were found.

4. Clinical observations show that the drug has reliable curative effect, reasonable clinical application, easy administration, and no side effects. It is suitable for hypertensive patients with hyperactivity of liver fire and deficiency of liver and kidney yin. It is suggested that the functions and indications be defined as: clearing away heat and calming the liver, nourishing the liver and kidney. For hypertension hyperactivity of liver fire, liver and kidney yin deficiency syndrome. Symptoms include dizziness, headache, red face, red eyes, irritability, dry mouth, bitter mouth, soreness of waist and knees, heart palpitations, insomnia, tinnitus, forgetfulness, constipation and yellowish hypertensive patients.

in conclusion

According to the observation of clinical trials, this drug has obvious antihypertensive effect on hypertension (excessive liver-fire, liver-kidney yin deficiency syndrome) stage II, especially has a good antihypertensive effect on diastolic blood pressure of hypertensive patients, and it is easy to take clinically. It is safe and reliable, has no toxic and side effects, and has promotional value.

Experimental Design Unit: The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine

Experimental designer: Zhao Jianguo, Chief Physician Li Yan

The person in charge of the experiment: Zhao Jianguo, Chief Physician Li Yan

Test date: April 1998-December 1998

Original data storage place: The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine

Contact person, phone number: Han Li 022-27383144

Seal of the test unit:

Clinical Study of Qinggan Jiangya Capsules in Treating Diabetic and Hypertensive Patients

Feng ^{Jinguang1Li Wenhua2Wang Xinfang2}

Abstract: Objective To observe the curative effect and safety of Qinggan Jiangya Capsules in patients with diabetes and hypertension. Methods: 60 patients with diabetes mellitus and hypertension (stage I or stage II) were randomly divided into a treatment group (cleaning the liver and lowering blood pressure group) of 30 cases, and a control group (Yuefeng Ningxin group) of 30 cases for 4 weeks. Results: (1) The total effective rates of Qinggan Jiangya Capsules and Yufeng Ningxin Tablets were 70% and 46.7%; there was a significant difference between the two groups (P<0.001); Liver and kidney function damage, blood, urine, stool routine without damage, (3) no adverse reactions, no side effects. Conclusion: Qinggan Jiangya Capsules is better than Yufeng Ningxin Tablets in lowering blood pressure, and it is safe and has no side effects.

Keywords: Qinggan Jiangya Capsules Yufeng Ningxin Tablets

                           

1 Department of Internal Medicine, The First Hospital of Beijing Medical University

2 Trainee Physician, The First Hospital of Beijing Medical University

Qinggan Jiangya Capsule is a compound preparation developed according to the theory of collateral diseases in traditional Chinese medicine. From October to December 1999, the author used Qinggan Jiangya Capsules to treat 60 patients with diabetes and hypertension, and received good results. The report is as follows:

Objects and methods

Clinical data: The selected patients were all diabetic patients in our hospital's specialized outpatient clinic, who met the WHO's criteria for the diagnosis and staging of hypertension①.

Randomly select 60 hypertensive patients with diabetes and stop antihypertensive drugs for at least 2 weeks. If the mean systolic blood pressure (MSBP) ≥ 21.3Kpa (160mHg) or mean diastolic blood pressure (SDBP) ≥ 12.6Kpa (95mmHg) or all meet the standard, then enter the treatment period ②.

Exclusion criteria: (1) Patients with myocarditis, angina pectoris, cerebrovascular accident, orthostatic hypotension, active ulcer, severe liver and kidney dysfunction, acute complications of diabetes and severe chronic vascular complications in the past 6 months are not eligible. included in this study group.

The selected subjects were randomly divided into Qinggan Jiangya capsule group (30 cases in the treatment group) and Yufeng Ningxin tablet group (30 cases in the control group). There was no significant difference between the two groups in age, gender, average course of disease, cardiac function class, blood lipid, blood sugar, and blood pressure.

Observation method: four weeks as a course of treatment

1. Serum, liver and kidney function, blood sugar, blood lipids, electrolytes, fundus, alkaline phosphatase, blood, urine, stool routine, and electrocardiogram were measured before and after treatment.

2. Measure blood pressure in sitting position once a week, and record heart rate, medication and side effects.

3. Medication method: Qinggan Jiangya Capsules three times a day, three capsules each time; (produced by Beijing Hongtianli Pharmaceutical Co., Ltd., batch number (1999) 2-94) Yufeng Ningxin Tablets three times a day, three tablets each time, with hands Afterwards, take with warm water.

Judgment of curative effect: The average value of the last two SBP and DBP is used as the evaluation index, and other selection criteria refer to the epidemiological research of common cardiovascular diseases and the 1979-1985 plan of population prevention and control, which are divided into three levels: markedly effective, effective, and ineffective.

Statistics: Calculate MSBP and MDBP mean ± standard deviation before and after treatment ( x+S), for significant difference t test.

result

1. The comparison of blood pressure lowering efficacy between the treatment group and the control group is shown in Table 1:

Table 1 Comparison of blood pressure between Qinggan Jiangya Capsules and Yufeng Ningxin Tablets in the treatment of diabetes and hypertension

^* P<0.05 ^** P<0.001

2. The total effective rate is shown in Table 2

Table 2 Comparison of antihypertensive effects between the two groups P＜0.05

3. Before and after treatment, there were no abnormal changes in liver and kidney function, hematuria and stool routine, blood sugar, blood lipid, alkaline phosphatase, heart rate, and electrocardiogram in the two groups.

4. No adverse reactions or side effects were observed during the observation.

discuss

Hypertension is the most common cardiovascular disease and a major public health issue worldwide. In 1991, the standardized prevalence rate of hypertension in my country was 11.26%. By 2020, non-communicable diseases will account for 79% of the mortality rate in my country, among which cardiovascular diseases will take the first place①.

The purpose of treating hypertension ① is not only to lower blood pressure itself, but also to reduce the incidence and mortality of cardiovascular diseases in the future.

Qinggan Jiangya Capsules main medicinal flavors Prunella vulgaris and Radix Polygoni Multiflori, etc. have the functions of clearing away heat, calming the liver, and nourishing the liver and kidney. They are used for high blood pressure, migraine, palpitations, tinnitus, upset, and irritability. The antihypertensive effect of pharmacodynamic studies is that the antihypertensive effect can expand peripheral blood vessels, reduce the total peripheral resistance, and have no effect on heart rate and cardiac pumping function. This observation proves that it has no effect on heart rate, and the antihypertensive effect is significant and stable. A considerable part of the hypertensive patients receiving treatment can prevent stroke by controlling high blood pressure③, which has a good effect on improving the heart and brain function of diabetic patients.

It can prevent and reduce the occurrence and development of cardiovascular and cerebrovascular complications in diabetic patients, has no toxic and side effects, and is safe to use.

Suitable for diabetic patients with mild to moderate hypertension.

literature

1. Chinese guidelines for prevention and treatment of hypertension 1999.10

2. Liu Guoyi, Wang Shuyun, Liu Lisheng, et al. Observation on curative effect of Jiangyaning in treating hypertension

3. Prospects for the latest research on heart disease and hypertension, volume 1. issue 9 44-45

Treatment of 30 cases of hypertension with Qinggan Jiangya Capsules

                 Clinical observation

Department of Traditional Medicine, Beijing Tiantan Hospital

From May 30, 1999 to September 1, 1999, our department treated Qinggan Jiangya Capsules (approval number: Guoyao Zhunzi (1999) Z-94) produced by Beijing Hongtianli Pharmaceutical Co., Ltd. to treat hyperactivity of liver-fire, liver-kidney The clinical curative effect of yin-deficiency hypertension has been preliminarily observed, and the clinical curative effect of the observed 30 patients is now summarized.

clinical information

1. The source of general information and cases. The 30 patients were all outpatients in our department from May to September 1999. They all had a clear history of essential hypertension and could follow the observation requirements designed by the observation table. 15 patients who did not meet the requirements Patients were excluded. Among the 30 cases, there were 15 males and 15 females, the oldest was 83 years old, the youngest was 28 years old, and the average age was 53.7 years old. The course of the disease ranges from 1 to 45 years. Those with secondary hypertension or essential hypertension belonging to other syndromes of TCM syndrome differentiation were not included in the scope of observation of this group. There were 30 cases in the control group, and there was no significant difference between the two groups in terms of age, gender, disease course and stage of hypertension.

2. Treatment and Observation Methods Observation Patients were randomly divided into two groups after TCM syndrome differentiation. The treatment group was given Qinggan Jiangya Capsules, 3 capsules each time, orally 3 times a day. The control group was given Naoliqing, 10 capsules each time, daily. 3 times orally. The other medications were basically the same in the two groups. The medication continued for 3 weeks, and the blood pressure was monitored with a desktop mercury column sphygmomanometer before and at the 1st, 2nd, and 3rd weeks after the medication, and the unit was expressed in mmHg.

3. Observation indicators Observe clinical symptoms, blood pressure, ECG changes before and after taking the medicine, and toxic and side effects during taking the medicine 1, 2, and 3 weeks after taking the medicine. Specific symptoms include dizziness, headache, red face, red eyes, irritability, dry mouth and bitter taste, soreness of the waist and knees, palpitations, insomnia, tinnitus, forgetfulness, dry stool, and tongue and pulse conditions.

result

1. Efficacy standards refer to the "Guiding Principles for Clinical Research of New Chinese Medicines" formulated and promulgated by the Ministry of Health in 1993, and evaluate the efficacy in combination with clinical practice, mainly based on clinical symptoms and blood pressure reduction. Significantly effective: the systolic blood pressure drops by more than 20mmHg, the diastolic blood pressure drops by more than 10mmHg or falls to normal, the clinical symptoms are significantly improved, and half of the symptoms are eliminated; effective: the systolic blood pressure drops by more than 10mmHg, the diastolic blood pressure drops by more than 5mmHg, and the clinical symptoms also improve.

2. Treatment results (1) Antihypertensive effect: Qinggan Jiangya Capsule has moderate and stable antihypertensive effect. Both the systolic and diastolic blood pressure decreased significantly in the first week, and the systolic blood pressure decreased significantly again in the second week, and continued to decline on the basis of the second week in the third week, and there was also a significant difference. The systolic blood pressure in the control group decreased significantly in the first week (p <0.05), until the third week, although the systolic blood pressure still decreased but slowly, the range was small. Diastolic blood pressure also decreased significantly compared with before treatment (p<0.05). see table 1

Table 1. Antihypertensive effect of Qinggan Jiangya Capsules (x±s, mmHg) group no Before treatment 1 week after treatment 2 weeks after treatment 3 weeks after treatment systolic blood pressure diastolic pressure systolic blood pressure diastolic pressure systolic blood pressure diastolic pressure systolic blood pressure diastolic pressure treat 30 189.3±32.4 105.7±15.8 177.6± ^29.5Δ 99.9± ^14.3Δ 170.5±24.4yΔ ^* 96.4± ^13.4y 160.3±16.7y ^Δ* 92.3±10.3 ^y*Δ control 30 192.8±35.7 106.9±19.4 182.7± ^30.7Δ 103.2±19.9 180.9± ^27.7Δ 102.1±17.5 172.3 ^Δ ±22.7 ^Δ 100.8± ^19.4Δ

ΔCompared with before treatment, *compared with the first week, yCompared with two groups, p<0.05

(2) The marked rate and total effective rate of Qinggan Jiangya Capsules after treatment (before) and after (the third week) were significantly higher than those of the control group. see table 2

Table 2. Comparison of antihypertensive efficacy between the two groups group no Significant efficiency% Total effective rate% therapy group 30 43.3 ^Δ 83.3 ^ΔΔ control group 30 36.7 66.7

      Δp < 0.05, Δ Δp < 0.01

(3) Improvement effect of Qinggan Jiangya Capsules on clinical symptoms

Qinggan Jiangya Capsules improved clinical symptoms steadily and significantly. With the increase of taking time, the effective rate and total effective rate gradually increased. After 3 weeks, the effective rate and total effective rate of headache, flushed eyes, and palpitations were both obvious. The total effective rate for insomnia and tinnitus is also significantly higher than that of the control group (p<0.01). There was no significant difference in the improvement of other symptoms, tongue condition and pulse condition compared with the control group. see table 3

Table 3 The improvement effect of Qinggan Jiangya Capsules on hypertension symptoms group symptom no week 1 week 2 week 3 Significantly effective (%) efficient(%) Total effective rate (%) Significantly effective (%) efficient(%) Total effective rate (%) Significantly effective (%) efficient(%) Total effective rate (%) treat dizziness 28 8(28) 9(32.1) 60.1 10(35.7) 9(32.1) 67.8 13 (46.4) 10(35.7) 82.1 control 29 7(24.1) 7(24.1) 48.2 9(33.3) 10(36.6) 69.9 12 (41.4) 10(34.5) 75.9 treat Headache 27 8(30) 10(37.1) 67.1 10(37.1) 11(40.1) 77.1 14(51.9) ^Δ 11(40.1) 92.0 ^Δ control 27 6(22.2) 8(30) 52.2 8(30) 10(37.1) 67.1 9(33.3) 12(44.4) 77.7 treat red face 13 1(8) 3(23.1) 31.1 2(15.4) 5(38.5) 43.9 5(38.5) ^Δ 7(53.8) 92.3 ^Δ control 14 2(12.3) 2(12.3) 24.6 3(21.4) 4(24.6) 46.0 4(24.6) 6(42.8) 77.4 treat irritable twenty two 5(23) 7(31.8) 54.8 7(31.8) 7(31.8) 63.6 9(40.9) 10(45.5) 86.4 control 25 5(20) 8(32) 52 8(32) 8(32) 64 8(32) 10(40) 72 treat dry mouth 25 4(16) 5(20) 36 5(20) 7(28) 48 8(32) 10(40) 72 control twenty four 4(16.7) 4(16.7) 33.4 6(25) 7(29.2) 54.2 8(33.4) 9(37.5) 70.9 treat Soreness of the waist and knees 11 1(9) 2(18) 27 3 (27.3) 3 (27.3) 54.6 4(36) 5(45.6) 81.6 control 12 3(25) 25 2(16.7) 4(33.3) 50.0 4(33.3) 6(50) 83.3 treat heart palpitations 16 2(13) 2(13) 26 4(26) 4(26) 52 6(37.5) 7(43.8) 81.3 ^Δ control 13 1(8) 2(16) twenty four 2(16) 3(23.1) 39.1 3(23.1) 5(38.5) 61.4 treat insomnia twenty two 2(9) 2(9) 18 5(24.7) 6(27) 51.7 7(31.8) 10(45.5) 77.3 ^Δ control twenty four 3(12.5) 2(9) 21.5 4(16.7) 5(20.9) 37.6 6(25) 7(29.2) 54.2 treat tinnitus twenty two 3(14) 2(9.1) 23.1 5(23) 5(23) 46 8(36.7) 8(36.7) 73.4 ^Δ control twenty four 3(12.5) 3(12.5) 25 4(16.7) 5(20.9) 37.6 7(29.2) 7(29.2) 58.4 treat forgetful 11 2(18) 1(9.1) 27.1 3 (27.3) 3 (27.3) 54.6 4(36) 4(36) 72 control 10 1(10) 1(10) 20 3(30) 3(30) 60 3(30) 4(40) 70 treat dry 20 5(25) 6(30) 55 7(35) 7(35) 70 8(40) 9(45) 85 control 18 3(16.7) 6(33.3) 50 5(27.8) 9(50) 77.8 7(27.8) 9(50) 77.8 treat red tongue 27 1(3.7) 5(19) 22.7 3(11.1) 7(25.6) 36.7 5(19) 8(29.9) 48.9 control 26 1(3.8) 5(19.2) twenty three 4(16) 6(23.1) 39.1 6(23) 8(30.8) 54.1 treat Tongue coating yellow 27 2(7.5) 4(15) 22.5 5(18.5) 8(30) 48.5 10(37.1) 12(44.4) 81.5 control 27 2(7.5) 4(15) 22.5 4(15) 6(22.2) 37.2 10(37.1) 11 (40.7) 77.8 treat pulse string 30 1(3.3) 5(17) 20.3 4(13.3) 8(26.7) 41 7(23.3) 13 (43.3) 66.9 control 28 2(7.1) 4(14.3) 21.4 4(14.3) 8(28.9) 43.2 6(21.2) 14(50) 71.2

Δp<0.05

(4) Effect on ECG

In the treatment group, 11 patients had abnormal electrocardiograms. After 3 weeks of treatment, 3 cases were markedly effective, with a marked rate of 27.3%, and 3 cases were improved, with a total effective rate of 54.5%. In the control group, 13 patients had abnormal electrocardiograms. In one case, the effective rate was 7.7%, 3 cases were improved, and the total effective rate was 30.8%. Compared with the obvious rate and total effective rate of the two groups, p<0.05.

Summary

1. Qinggan Jiangya Capsules has a better antihypertensive effect, the antihypertensive effect is stable, there is no phenomenon of rebound and hypotension, and the antihypertensive effect is better than that of Naoliqing in the second and third weeks of taking the medicine.

2. Qinggan Jiangya Capsules can significantly improve the headache, flushed eyes, and palpitations caused by high blood pressure. Yu Naoliqing (p<0.05) has the same improvement effect on other symptoms, tongue condition and pulse condition as Naoliqing.

3. Qinggan Jiangya Capsules can also improve the abnormal ECG of hypertensive patients. Due to the small number of cases, further observation is required.

4. Qinggan Jiangya Capsules have no obvious toxic and side effects in the course of taking.

October 26, 1999

Description of drawings

Fig. 1 preparation process of Qinggan Jiangya Capsules

Detailed ways

Example 1 According to the formula Prunella vulgaris 250g, Polygonum multiflorum 250g, Sophora japonica 150g, Sangji 290g, Pueraria lobata 150g, Salvia miltiorrhiza 220g, Alisma 290g, Small thistle 80g, Polygala 200g, and Achyranthes bidentata 100g for scale-up production of Qinggan Jiangya capsules The drug property is stable, and the drug effect can meet the requirements of clinical administration. The preparation process is as follows: Polygonum multiflorum, Pueraria lobata, Alisma, and Achyranthes bidentata are reflux extracted with 8 times the amount of 60% ethanol for 3 times, each time for 2 hours, the filtrates are combined, ethanol is recovered, concentrated under reduced pressure to a relative density of 1.20-1.35 ( 60 DEG C) thick ointment for subsequent use; Prunella vulgaris and Salvia miltiorrhiza were extracted twice with 10 times the amount of 80% ethanol under reflux, each time for 2 hours, the filtrate was combined, ethanol was reclaimed, concentrated under reduced pressure into the thick ointment required above for subsequent use; Prunella vulgaris, Salvia miltiorrhiza, Danshen herb dregs, Sophora japonica, Sangji, Xiaoji, Polygala are decocted twice with 12 times of water, 1.5 hours each time, the filtrates are combined, concentrated under reduced pressure to form a thick paste as required above for later use. Combine all the above-mentioned thick pastes, mix evenly, dry under reduced pressure, pulverize, add appropriate amount of dextrin, granulate, and fill into 1000 capsules.

Example 2 According to the formula Prunella vulgaris 200g, Polygonum multiflorum 150g, Sophora japonica 300g, Sangji 300g, Pueraria lobata 150g, Salvia miltiorrhiza 220g, Alisma 290g, Thistle 100g, Polygala 150g, and Achyranthes bidentata 120g, the liver-clearing and hypotensive capsules were scaled up and produced The drug property is stable, and the drug effect can also meet the requirements of clinical use. Its preparation process is: Radix Polygoni Multiflori, Radix Puerariae, Alisma, and Achyranthes bidentata are reflux extracted with 10 times the amount of 50% ethanol for 3 times, each time for 2 hours, the filtrates are combined, ethanol is recovered, concentrated under reduced pressure to a relative density of 1.20-1.35 ( 60 DEG C) thick ointment for subsequent use; Prunella vulgaris and Salvia miltiorrhiza were extracted twice with 12 times the amount of 70% ethanol under reflux, each time for 2 hours, the filtrate was combined, ethanol was reclaimed, concentrated under reduced pressure into the thick ointment required above for subsequent use; Prunella vulgaris, Salvia miltiorrhiza, The dregs of Salvia miltiorrhiza, sophora japonica, chrysanthemum, and polygala are decocted with 10 times the water for 3 times, each time for 1.5 hours, and the filtrates are combined and concentrated under reduced pressure to form a thick paste as required above for later use. Combine all the above-mentioned thick pastes, mix evenly, dry under reduced pressure, pulverize, add appropriate amount of dextrin, granulate, and fill into 1000 capsules.

Claims (2)

1. capsule for clearing liver and reducing blood pressure, it is as follows to it is characterized in that making capsule for clearing liver and reducing blood pressure raw materials of effective components medicine and consumption thereof: Spica Prunellae 150～350g, Radix Polygoni Multiflori 120～400g, Flos Sophorae 100～300g, Herba Taxilli 150～350g, Radix Puerariae 100～250g, Radix Salviae Miltiorrhizae 150～350g, Rhizoma Alismatis 100～350g, Herba Cirsii 80～200g, Radix Polygalae 100～200g, Radix Cyathulae 100～250g; 1000 preparations, the 0.5g/ grain.

2. capsule for clearing liver and reducing blood pressure, the preparation method that it is characterized in that capsule for clearing liver and reducing blood pressure: 120～400g Radix Polygoni Multiflori, 100～250g Radix Puerariae, 100～350g Rhizoma Alismatis, 100～250g Radix Cyathulae are with 50～70% alcohol reflux of 6～10 times of amounts 2～3 times, 150～350g Spica Prunellae, 150～350g Radix Salviae Miltiorrhizae are with 60～95% alcohol reflux of 8～12 times of amounts 1～3 time, and Spica Prunellae, Radix Salviae Miltiorrhizae decoction dregs and 100～300g Flos Sophorae, 150～350g Herba Taxilli, 80～200g Herba Cirsii, 100～200g Radix Polygalae are boiled 2～3 times with 10～14 times decocting; Extract filtrate with above-mentioned three kinds and be condensed into thick paste respectively, merge three kinds of thick pastes and mixing; Through drying under reduced pressure, pulverizing, granulation, load into capsule for clearing liver and reducing blood pressure.