CN1304039C - Chinese medicine composition with functions of reducing blood-pressure, reducing-fat, anti-dizzy and calming wind, its preparing method and use - Google Patents

Abstract

The invention relates to a traditional Chinese medicine composition which has the functions of lowering blood pressure, lowering fat, regulating dizziness and regulating wind. The traditional Chinese medicine composition is prepared from the following components in parts by weight: Tianma 1365-4095, Eucommia 1365-4095, Wild Chrysanthemum 3350-10050, Eucommia Leaf 4195-12585 and Chuanxiong 1675-5025. The composition has the unique functions of lowering blood pressure, lowering fat, dizziness, and wind, and has a significant curative effect on treating hypertension, arteriosclerosis, hyperlipidemia or headache, dizziness, dizziness, tinnitus, insomnia and other diseases caused by them, and No toxic side effects. The invention also relates to a preparation method and application of the traditional Chinese medicine composition.

Description

A traditional Chinese medicine composition with the functions of lowering blood pressure, lowering fat, dizziness and wind, its preparation method and its application

technical field

The invention relates to a traditional Chinese medicine composition with the functions of lowering blood pressure, lowering fat, dizziness and wind, in particular to a composition for treating hypertension, arteriosclerosis, hyperlipidemia or headache, dizziness, dizziness and tinnitus caused by them. , insomnia and other diseases of the traditional Chinese medicine composition and its preparation method and use.

Background technique

Cardiovascular and cerebrovascular diseases are a class of diseases that seriously endanger human health. In recent years, with the progress of society, the improvement of people's living standards and the continuous acceleration of the pace of work, the morbidity and mortality of cardiovascular and cerebrovascular diseases have shown an obvious upward trend, and have gradually become the number one killer of human health. With the continuous development of medical science, people realize that cholesterol, fat, etc. are the basic causes of cardiovascular and cerebrovascular diseases. It is a major risk factor for coronary heart disease and hypertension. Therefore, drugs with antihypertensive and lipid-lowering effects have become the first-selected drugs for the treatment of cardiovascular and cerebrovascular diseases.

A variety of Chinese and Western medicines have been used to treat hyperlipidemia at home and abroad. Although these medicines have certain effects on lowering blood pressure and lipids, there are still many defects. , curative effect is not significant enough, and disadvantages such as carrying, inconvenient to use.

Contents of the invention

The object of the present invention is to provide a traditional Chinese medicine composition with functions of lowering blood fat, lowering blood pressure, dizziness and wind, and is characterized in that the composition of raw materials of medicinal ingredients used in the preparation of the composition is as follows in parts by weight: Gastrodia elata 1365-4095 parts , Eucommia 1365-4095 parts, wild chrysanthemum 3350-10050 parts, Eucommia leaves 4195-12585 parts and Chuanxiong 1675-5025 parts.

The composition of the preferred composition is: 2048-3412 parts of Gastrodia elata, 2048-3412 parts of Eucommia ulmoides, 5025-8385 parts of wild chrysanthemum, 6293-10487 parts of Eucommia ulmoides leaves and 2513-4187 parts of Chuanxiong.

More preferably, the composition is as follows: 2730 parts of Gastrodia elata, 2730 parts of Eucommia ulmoides, 6700 parts of wild chrysanthemum, 8390 parts of Eucommia ulmoides leaves and 3350 parts of Chuanxiong.

The composition of the present invention has the unique functions of lowering blood pressure, lowering fat, dizziness, and wind, and has the effects of clearing away heat and calming the liver, cooling blood and lowering blood pressure, and is used for treating hypertension, arteriosclerosis, cardiovascular disease, hyperlipidemia, and the above diseases Symptoms such as headache, dizziness, dizziness, tinnitus, insomnia, and nocturia caused by it have a significant effect.

The diseases treated by this prescription belong to the vertigo syndrome of traditional Chinese medicine, which is mostly caused by excessive liver yang heat, and can appear in diseases such as hypertension, arteriosclerosis, and hyperlipidemia in Western medicine. In the prescription, Gastrodia elata, Ganping, entering the liver meridian, calming the wind and calming the liver, and stopping dizziness are the monarch drugs; wild chrysanthemum, slightly cold in nature, bitter in taste, clears heat and detoxifies, cools blood and lowers blood pressure, and is compatible with Gastrodia elata to enhance the effect of clearing away heat and calming the liver , is a ministerial drug; Chuanxiong activates blood and promotes qi, dispels wind and relieves pain, and is combined with Gastrodia elata, that is, Xiongma Yin in the book "Su Shen Liang Fang", which is a famous prescription for treating liver yang, dizziness and headache, and is an adjuvant drug; Eucommia ulmoides leaves are the same as Eucommia, It has the functions of nourishing liver and kidney, strengthening bones and bones, and lowering blood pressure. It is a commonly used antihypertensive drug in Chinese medicine clinics. The combination of various medicines has the functions of clearing away heat, calming the liver, cooling blood and lowering blood pressure, and the combination of all prescriptions targets the pathogenesis of liver yang and brain dizziness. And the properties and effects of the medicine are specific, and the monarch, minister, assistant, and envoy are complete, which is the basis for the prescription to achieve good effects in treating the aforementioned diseases.

Another pharmacological test proves that Eucommia ulmoides, leaves of Eucommia ulmoides, and wild chrysanthemum have strong antihypertensive and lipid-lowering effects; Gastrodia elata and Chuanxiong have the effects of analgesic and vertigo-relieving, improving blood supply to the brain, and can obviously relieve the symptoms of high blood pressure. And the composition of the present invention is its mutually coordinated prescription, which can receive better curative effects of lowering blood pressure, lowering fat, and improving symptoms of cardiovascular and cerebrovascular diseases.

The compositions of the present invention can be in various dosage forms well known in the art. The dosage forms suitable for the present invention can be oral preparations, external preparations and injections. Oral preparations can be selected from tablets, capsules, granules, pills, powders, dripping pills, syrups, mixtures, dews or teas, etc.; external preparations can be selected from gels, plasters, plasters, ointments, liniments , lotion, smear or coagulant, etc.; injection can be selected from injection, infusion and freeze-dried powder. The preparation of the composition of the present invention can be accomplished by means of formulation techniques well known in the art.

The pharmaceutically acceptable carrier is well known in the art and is a commonly used excipient or auxiliary material for the preparation of the above preparations. Excipients or adjuvants commonly used in oral or external preparations include but are not limited to fillers or diluents, lubricants or glidants or anti-adhesives, dispersants, wetting agents, binders, regulators, solubilizers, anti-adhesives, Oxygen, bacteriostat, emulsifier, etc. Binders such as syrup, gum arabic, gelatin, sorbitol, tragacanth, cellulose and its derivatives, gelatin syrup, sugar syrup, starch slurry or polyvinylpyrrolidone, preferred cellulose derivatives are microcrystalline cellulose, carboxylated Sodium methylcellulose, ethylcellulose, hydroxypropylmethylcellulose; fillers such as lactose, powdered sugar, dextrin, starch and its derivatives, cellulose and its derivatives, inorganic calcium salts, sorbitol or Glycine, preferably inorganic calcium salts are calcium sulfate, calcium phosphate, calcium hydrogen phosphate, precipitated calcium carbonate; lubricants, such as micronized silica gel, magnesium stearate, talcum powder, aluminum hydroxide, boric acid, hydrogenated vegetable oil, polyethylene glycol; Disintegrants such as starch and its derivatives, polyvinylpyrrolidone or microcrystalline cellulose, preferred starch derivatives are sodium carboxymethyl starch, sodium starch glycolate, pregelatinized starch, modified starch, hydroxypropyl starch, cornstarch; wetting agents such as sodium lauryl sulfate, water or alcohol; preferably the pharmaceutically acceptable carrier for oral preparations is microcrystalline cellulose, magnesium stearate or ethanol and the like.

The commonly used excipients or auxiliary materials for the injection include but are not limited to: antioxidants, such as sodium sulfite, sodium bisulfite and sodium metabisulfite; bacteriostatic agents, such as 0.5% phenol, 0.3% cresol, 0.5% trichlorobutyl Alcohols; regulators such as hydrochloric acid, citric acid, potassium hydroxide (sodium), sodium citrate and buffers sodium dioxyphosphate and disodium hydrogenphosphate; emulsifiers such as polysorbate-80, sorbitan dichloride , Pluronic F-68, lecithin, soybean lecithin; antioxidants, such as sodium sulfite, sodium metabisulfite, dibutyl benzoic acid, etc.; solubilizers, such as Tween-80, bile, glycerin, etc.

In addition, the active ingredient can also be mixed with a pharmaceutically acceptable sustained and controlled release carrier according to its preparation requirements, and then follow the well-known preparation methods of sustained and controlled release preparations in the art, such as adding a blocking agent coating or microsurfacing the active ingredient. After encapsulation, it is made into pellets, such as sustained release pellets or controlled release pellets; the slow and controlled release carriers include but not limited to oily doping agents, hydrophilic colloids or coating retarders, etc., the The oily blending agent is glyceryl monostearate, hydrogenated castor oil, mineral oil, polysiloxane, dimethylsiloxane; the hydrophilic colloid is sodium carboxymethylcellulose, hydroxypropyl Cellulose derivatives such as cellulose, hydroxypropyl methylcellulose, or PVP, gum arabic, tragacanth gum or carbopol, etc.; the coating retarder is ethyl cellulose (EC), hydroxyl Propylmethylcellulose (HMPC), polyvinylpyrrolidone (PVP), cellulose acetate phthalate (CAP), acrylic resin, etc.

Another object of the present invention is to provide a method for preparing the composition of the present invention, comprising the following steps: taking half of the Gastrodia elata and pulverizing into fine powder to obtain Gastrodia elata fine powder; taking the remaining half of Gastrodia elata and pulverizing into coarse powder, and refluxing with alcohol solvent Extract, combine and filter the extracts, recover ethanol and concentrate into Gastrodia elata extract; mix the gastrodia elata residue after alcohol extraction with Eucommia ulmoides, Eucommia leaves, wild chrysanthemum, and Chuanxiong, add water to boil for extraction, combine and filter the boiled extract, and concentrate the filtrate to The relative density is 1.15-1.5 (40-80°C), preferably 1.25-1.45 (40-80°C), more preferably 1.35-1.40 (40-80°C), to obtain a mixed thick paste; then add Gastrodia elata fine powder to Gastrodia elata extract and mixed thick paste, mix well, add appropriate amount of pharmaceutically acceptable carrier, and prepare required preparation according to conventional preparation method.

Preferably said alcoholic solvent is ethanol, methanol, propylene glycol or solvents known in the art with properties similar to it; the volume of the preferred alcoholic solvent is 5-30 times, more preferably 5-15 times, most preferably 10 times the weight of Gastrodia elata meal The concentration of the preferred alcohol solvent is 40-90v/v%, more preferably 50-80v/v%, most preferably 60-70v/v%; the number of times of preferred reflux extraction is 1-5 times, more preferably 2-4 times , most preferably 2-3 times; the preferred reflux extraction time is 0.5-3 hours, more preferably 1-2 hours, most preferably 1 hour; the concentration method is selected from vacuum concentration or film concentration.

Another aspect of the present invention is to provide the application of the composition of the present invention in the preparation of drugs for the treatment of lipid-lowering, blood pressure-lowering, dizziness-fixing and wind-fixing. The composition of the present invention has the unique functions of lowering blood pressure, lowering fat, dizziness, and wind, and has the effects of clearing away heat and calming the liver, cooling blood and lowering blood pressure, and is used for treating hypertension, arteriosclerosis, cardiovascular disease, hyperlipidemia, and hypertension Combined with arteriosclerosis, high blood pressure with hyperlipidemia or headache, dizziness, dizziness, tinnitus, insomnia, nocturia and other symptoms caused by it, and the curative effect is significant. The hypertension is selected from hypertensive liver-fire hypertensive hypertension, yin-deficiency and yang-excessive hypertension, yin-yang both-deficiency hypertension, stage 1 hypertension, stage 2 hypertension or stage 3 hypertension.

The composition of the present invention is composed of Eucommia ulmoides, leaves of Eucommia ulmoides, wild chrysanthemum, gastrodia elata and chuanxiong. Among them, pinoresinol ~ β ~ diglucoside is the antihypertensive active ingredient of Eucommia ulmoides, and it has been proved by experiments that using 5 ml of eucommia extract (containing 1 ~ 2 grams of crude drug) to anesthetized dogs for acute antihypertensive test can produce obvious antihypertensive effects. The antihypertensive effect lasts for 2 to 3 hours; Eucommia leaves contain the same antihypertensive chemical components as Eucommia bark, and it has been proved by experiments that Eucommia leaves replace Eucommia bark, the clinical antihypertensive effect of the two is the same, and the antihypertensive mechanism may be It is related to the inhibition of the central nervous system and the direct expansion of peripheral blood vessels. In addition, Eucommia bark and Eucommia leaves also contain hydroxyflavonoids, which can inhibit the absorption of cholesterol and have a lipid-lowering effect. The main components of wild chrysanthemum are inulin, adenine, choline, flavonoids, etc., which have the functions of clearing heat and detoxifying, cooling blood and lowering blood pressure. Its in vitro test can reduce peripheral vascular resistance and inhibit sympathetic nerve center and vasomotor center. Effect, and produce antihypertensive effect, and also contain flavonoids, thus have antihypertensive, lipid-lowering effect. Gastrodia elata has a long history of medicinal use. Pharmacological studies have shown that Gastrodia elata has obvious anticonvulsant properties and can effectively stop epileptic seizures. In addition, it also has a certain analgesic effect. Chuanxiong contains alkaloids, lactones and other components, which mainly lower blood pressure by expanding peripheral blood vessels, and also have anti-platelet aggregation, improve microcirculation and anti-vitamin E deficiency.

According to clinical observation, the composition of the present invention can obviously improve the cerebral blood flow diagram of patients with hypertension complicated with cerebral arteriosclerosis and cerebral blood supply insufficiency.

It can be seen that Eucommia ulmoides, leaves of Eucommia ulmoides, and wild chrysanthemums in the composition of the present invention have stronger blood pressure-lowering and lipid-lowering effects, while Gastrodia elata and Chuanxiong have good analgesic and vertigo-reducing effects, and can improve the blood supply to the brain, so they can Significantly alleviate the symptoms of patients with hypertension, hyperlipidemia, atherosclerosis or their complications or sequelae.

The usual dose range of the composition of the present invention is (containing crude drug amount or drug amount 2390g/1000 unit dose, every g is equivalent to crude drug 6.8g) every day 4-6 unit dose, every day 2-4 times; More preferably administration The dosage range is 5 unit doses per day, 3 times a day. The composition of the invention has the characteristics of unique curative effect, high bioavailability, good stability, beautiful appearance, convenient carrying and taking, and the like.

Detailed ways

The present invention will be described in detail below in conjunction with the examples. The examples of the present invention are only used to illustrate the technical solutions of the present invention, and do not limit the essence of the present invention.

The preparation of embodiment 1 tablet

The composition of the tablet is: Tianma 2730, Eucommia 2730, Wild Chrysanthemum 6700, Eucommia Leaf 8390 and Chuanxiong 3350.

Preparation method: take half of Gastrodia elata and grind it into fine powder, pass through a 100-mesh sieve to get Gastrodia elata fine powder; take the remaining half of Gastrodia elata, grind it into coarse powder, reflux extract twice with 60v/v% alcohol solvent, combine and filter the extracts, and recover ethanol and concentrated into Gastrodia elata extract; mix the gastrodia elata residue after alcohol extraction with Eucommia ulmoides, Eucommia leaves, wild chrysanthemum, and Chuanxiong, boil and extract three times, combine and filter the boiled extract, and concentrate the filtrate to a relative density of 1.35-1.40 to obtain a mixture Thick paste; then add Gastrodia elata fine powder to Gastrodia elata extract and mix the thick paste, mix well, granulate, compress into tablets, and coat with sugar to obtain.

The preparation of embodiment 2 capsules

The composition of the capsule is: Gastrodia elata 1365g, Eucommia ulmoides 1365g, wild chrysanthemum 3350g, Eucommia ulmoides leaves 4195g and Chuanxiong 1675g.

The preparation method is the same as in Example 1, and the required capsules are prepared.

The preparation of embodiment 3 pills

The composition of the pill is: Gastrodia elata 4095g, Eucommia ulmoides 4095g, wild chrysanthemum 10050g, Eucommia ulmoides leaves 12585g and Chuanxiong 5025g.

The preparation method is the same as in Example 1, and the required pills are prepared.

The preparation of embodiment 4 powder

The composition of the powder is: Gastrodia elata 2048g, Eucommia ulmoides 2048g, wild chrysanthemum 5025g, Eucommia ulmoides leaves 6293g and Chuanxiong 2513g.

The preparation method is the same as in Example 1, and the required powder is prepared.

The preparation of embodiment 5 granules

The composition of the granule is: Tianma 3412g, Eucommia 3412g, wild chrysanthemum 8385g, Eucommia leaves 10487g and Chuanxiong 4187g.

The preparation method is the same as in Example 1, and the required granules are prepared.

The therapeutic effect of the pharmaceutical composition of the present invention on biliary system diseases will be verified by the following drug efficacy test examples or toxicity test examples. The medicine used in the test example is the dry powder of the composition of the present invention. During the test, the dry powder of the composition is made into the required concentration for testing with physiological liquid medicine, wherein 1 g of the dry powder is equivalent to 6.8 g of the crude drug. Unless otherwise specified, the dosage standards of the test examples of the present invention are based on crude drug.

The hypolipidemic effect of test example 1 composition of the present invention

The tested product is the medicated powder of the composition of the present invention, which is dark brown powder, and every gram is equivalent to 6.8 grams of the original drug, and it is prepared into a suitable concentration of distilled water suspension for subsequent use.

Take 32 SD white mice (provided by the animal farm of Xi'an Medical College), half male and half male, weighing 224-241 grams, and randomly divide them into 4 groups, 8 rats in each group, that is, set up normal saline control group, hyperlipidemia model group, high-dose Dosing group and small dose dosing group. The normal saline control group was supplied with normal pill feed, and the hyperlipidemia model group was supplied with self-prepared high-lipid feed. Raised in groups, with free access to food and water. The high-dose administration group is given 0.4ml/100g concentration by intragastric administration simultaneously when giving hyperlipidemia diet and is 20% medicinal powder aqueous suspension of the composition of the present invention (equivalent to the former drug dose being 5.44g/kg) for treatment, small dose Administration group is when giving hyperlipidemia diet, and simultaneously gavages and administers 0.2ml/100g concentration and is 20% medicinal powder aqueous suspension of the composition of the present invention (being equivalent to former medicine amount is 2.72g/kg); Physiological saline control group gives etc. Once a day, for 21 consecutive days, on the next day after the last administration, blood was collected on an empty stomach to measure serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein ( LDL) level. The results are shown in Table 1.

Table 1 The influence of the composition of the present invention on the blood lipid level of hyperlipidemic rats group number of animals Dose (g/kg) TC(mg/dl) TG (mg/dl) LDL (mg/dl) HDL (mg/dl) normal control group 8 - 76.23±12.87 58.4±23.80 236.0±41.4 46.2±8.5 Model control group 8 - 216.61±17.23 207.8±16.2 503.2±31.8 54.7±16.9 high dose group 8 5.4 187.30±21.02 ^* 189.3±13.3 ^* 327.7±18.3 ^** 68.4±17.0 low dose group 8 2.7 195.27±12.26 ^* 190.2±12.4 ^* 364.4±22.0 ^** 56.0±12.1

X±SD compared with normal control group, ^* P<0.05, ^** P<0.01

Table 1 result shows, in hyperlipidemia model group, each index of model control group animal is obviously higher than normal control group, and the large and small dosage administration group of composition of the present invention can obviously reduce the serum TG, TC, LDL level of animal, And its HDL has a rising trend, but the difference is not significant. The composition of the invention has a certain effect of lowering blood fat.

The antihypertensive effect of test example 2 compositions of the present invention

1. Effect on dog blood pressure

Take 12 mixed-breed dogs (provided by the animal farm of Xi'an Medical College) weighing 8-12Kg, both male and female, and randomly divide them into 3 groups with 4 dogs in each group. During the experiment, the animals were anesthetized intravenously with 3% pentobarbital sodium, fixed in the supine position, separated the common carotid artery (on one side), inserted an arterial cannula, connected a mercury manometer, traced blood pressure, inserted a tracheal cannula, and A Ricci drum was connected, respiration was recorded, and heart rate was recorded with a lead II ECG. After the operation is completed and the blood pressure is stabilized, the duodenum is administered, and the animals of each dosage group are given 20% of the composition powder water suspension of the present invention 4ml/kg, 8ml/kg, 12ml/kg respectively by three doses of large, medium and small. kg (the equivalent amount of crude drug is 5.4g/kg, 10.9g/kg, 16.3g/kg respectively), the results are shown in Table 2.

Table 2 duodenum gives the composition of the present invention the impact X ± SD on dog blood pressure group number of animals Dose (g/kg) Blood pressure before administration (mmHg) Blood pressure after administration (mmHg) 5min 15min 30min 45min low dose group 4 5.4 149.6±16.7 144.3±12.6 136.7+13.1 131.3±13.1 147.8±15.3 Middle dose group 4 10.9 136.2±10.6 131.6±14.2 127.0±11.2 120.3±10.4 133.6±13.2 high dose group 4 16.3 144.7±12.2 137.7±10.0 132.3±12.2 126.6±14.5 141.2±11.0

The results showed that 5 minutes after the administration, the dog's blood pressure began to drop slowly, and the blood pressure dropped to the peak at about 30 minutes, but compared with before the administration, the difference was not significant. About 45 minutes, the blood pressure basically returned to normal, the animal's breathing was stable, and the heart rate was not obvious. changes, indicating that the composition of the present invention has a short-term and slow hypotensive tendency.

2. Rapid tolerance test of antihypertensive effect

4 hybrid dogs, recorded blood pressure as before method, intravenously injected 10% of the composition powder filtrate of the present invention 2.5ml/kg (equivalent crude drug amount 1.7g/kg), caused blood pressure to obviously drop, after blood pressure returns to normal and stable, then with The same dose was administered three times repeatedly within 30 minutes, and the degree of blood pressure drop each time was the same as that of the first administration. It shows that the antihypertensive effect of the composition of the present invention has no rapid tolerance phenomenon. The results are shown in Table 3.

Table 3 Rapid tolerance test of the antihypertensive effect of the composition of the present invention animal number gender Weight (Kg) Dose (g/kg) blood pressure (mmHg) before/after administration before/after administration before/after administration before/after administration 1 ♂ 12 1.7 132/100 132/100 136/90 136/90 2 ♂ 13 1.7 122/72 120/74 118/68 148/70 3 ♀ 10 1.7 149/96 149/100 146/92 146/88 4 ♀ 10.5 1.7 150/100 150/60 150/100 146/88 average 138.25/92.00 137.50/87.50 137.50/87.50 136.75/83.00

Conclusion: the composition of the present invention can not only reduce serum TC, TG and LDL levels of rats with hyperlipidemia, but also make their HDL tend to increase; Receptivity.

The acute toxicity test of test example 3 compositions of the present invention

The test product is the composition powder of the present invention (dark brown powder, every gram is equivalent to 6.8 grams of crude drug), and it is made into 30% water suspension when used.

20 mice of Kunming species, weighing 18-22 grams, half male and half male, were provided by the animal farm of Xi'an Medical College. Under experimental conditions (room temperature maintained at 20±4°C, humidity about 57%, conventional ventilation, tap water and solid feed. Cages in groups, free intake of food and water) after seven days of adaptive feeding, the dosage of 0.2ml/10g Intragastric administration of the composition powder suspension of the present invention is administered three times a day, so that its cumulative dose reaches 0.6ml/10g (60ml/kg, equivalent to the original drug dose of 122.4g/kg), and then observe the activities and behaviors of animals in seven days , Mental condition, diet, urine and hair, etc. are there any abnormalities. If any animal died, a necropsy was performed immediately, and a pathological examination was performed. It was found that within seven days after the administration, no animal died, and its hair was shiny, its activity behavior was normal, its mental state, diet, and stool and other general conditions also showed abnormal performance. It shows that the composition medicament powder of the present invention has no obvious toxic effect under the dosage of 122.4g/kg, administered by intragastric administration.

The subchronic toxicity test of test example 4 compositions of the present invention

The tested product is the composition medicated powder of the present invention, which is dark brown powder, and every gram is equivalent to 6.8 grams of the original drug, and is made into a 20% aqueous suspension when used.

42 SD rats, half male and half male, weighing 216-232 grams, were provided by the animal farm of Xi'an Medical College. At a room temperature of 20±4°C with a relative humidity of 64%, conventional ventilation, tap water and solid feed, rearing in groups and cages, free access to food and water.

42 SD rats were randomly divided into three groups, set normal control group (14), high-dose group (14), and low-dose group animals (14). Medicine, large and small dosage group animals are given 20% composition medicine powder aqueous suspension 4ml/100g of the present invention respectively, 2ml/100g (equivalent to former drug dose 54.4g/kg and 27.2g/kg), once a day, continuous 6 week. At the same time, observe the general situation of animals such as food intake, body weight, activity, hair, and mental behavior. At the end of the experiment period, the animals were sacrificed, blood was collected to measure hematological parameters: liver and kidney function, autopsy was performed at the same time, major organs were removed and weighed, the organ/body ratio was calculated, and gross pathology and microscopic examination were performed. The results are as follows:

1. General condition

The body weight of the animals was weighed before the administration and in the second week and the sixth week after the administration, and the general conditions of the animals were observed at the same time, such as diet, feces, hair, activity and mental state, and the number of dead animals. The results are shown in Table 4.

The influence of table 4 composition medicated powder administration of the present invention on the body weight of rats for 6 weeks group Dose g/kg Before administration the second week sixth week number of animals weight(g) number of animals weight(g) number of animals weight(g) Saline group 14 218.4±21.0 14 232.6±41.4 14 365.9±46.3 low dose group 27.2 14 224.4±22.2 14 234.8±38.8 12 349.4±53.0 high dose group 54.4 14 220.3±20.6 14 238.7±24.1 14 375.7±27.9

The results showed that the growth values of the animals were all within the normal range, and the autopsy results of the dead animals showed obvious pathological changes. The animal's hair is glossy, it moves freely, and its mental state is normal, suggesting that the continuous gavage of the composition powder of the present invention for six weeks has no obvious influence on the general condition of the animal.

2. Hematological parameters

At the end of the experiment, blood was collected by decapitation, and the hemoglobin (Hb) content, red blood cell (RBC) and white blood cell (WBC) counts and white blood cell classification in the animal blood were measured. The results are shown in Table 5.

The influence of table 5 composition medicated powder administration of the present invention on rat hematological parameters for 6 weeks group number of animals Hb(g%) RBC (10,000/mm ³ ) WBC(thousand/mm ³ ) WBC classification (%) neutral lymph Saline group 14 15.8±9.6 556.8±69.2 7.3±0.41 49.3±2.3 51.2±2.7 low dose group 12 16.2±5.6 621.4±41.5 7.6+0.85 49.5±3.7 50.2±2.6 high dose group 14 15.8±7.3 549.0±51.9 7.9±0.82 49.0±3.2 51.0±2.9

Conclusion: The composition of the present invention has no significant difference on various parameters of rat hematology, indicating that there is no significant impact on rat hematology parameters.

3. Determination of liver and kidney function

At the end of the experiment period, the blood was collected by decapitation, and the serum was collected after static centrifugation. The activities of serum alanine aminotransferase (sGPT) and aspartate aminotransferase (sGOT) were determined by Rei's method, and the content of serum urea nitrogen (BUN) was determined by diacetyl oxime method. The results are shown in Table 6.

The influence of table 6 composition administration of the present invention on rat liver and kidney function for 6 weeks group number of animals sGPT(U) sGOT(U) BUN(mg%) Saline group 14 21.5±8.2 22.3±6.1 22.3±8.6 low dose group 12 19.2±8.9 17.3±6.9 17.5±7.7 high dose group 14 21.1±6.5 19.0±4.7 19.8±10.1

Conclusion: Compared with the control group, the levels of sGPT, sGOT and BUN in the serum of the animals in the administration group are all within the normal range, indicating that the medicinal powder of the composition of the present invention has no obvious effect on the liver and kidney functions of the animals.

4. Organ/body weight ratio

At the end of the experiment period, the animals were sacrificed, the heart, liver, kidney, lung, spleen and other major organs were removed and weighed, and the organ/body ratio was calculated. The results are shown in Table 7.

The influence of table 7 composition of the present invention administration on rat viscera/body ratio for 6 weeks group number of animals Liver/body ratio (%) heart liver spleen lung kidney (double) Saline group 14 0.345±0.04 3.61±0.42 0.337±0.15 0.806±0.17 0.621±0.19 low dose group 12 0.395±0.08 4.14±0.88 0.488±0.16 0.822±0.17 0.775±0.186 high dose group 14 0.375±0.04 4.13±0.89 0.427±0.098 0.762±0.14 0.711±0.12

Conclusion: Compared with the saline group, the viscera ratio of the animals in the composition of the present invention and the administration group is not significantly different, indicating that the drug has no effect on the viscera/body ratio of animals.

5. Pathological examination

At the end of the experiment, the animals were sacrificed, and gross pathological and microscopic pathological examinations were performed on each major organ and tissue. The results showed that there were no obvious pathological changes in the cells of the heart, liver, spleen, lung, kidney, stomach, small intestine, adrenal gland, thymus and other important organs and tissues of the animals in the administration group and the control group. It shows that continuous administration of the composition of the present invention has no obvious histological toxicity to animals.

Experimental example 4 The curative effect observation of composition treatment of the present invention 374 cases hypertension

The composition of the present invention treats 374 cases of hypertensive patients. Through clinical observation, it is found that the medicine has good curative effects in reducing blood pressure, improving symptoms, and lowering fat, and no adverse reactions and side effects are found.

1. Case selection

From among the hypertensive patients in rural areas, mainly in the 2nd stage of hypertension, random cluster sampling was divided into three groups, and they took the composition of the present invention (abbreviated as the dizzy group), reserpine (abbreviated as the benefit group) and compound antihypertensive drug respectively. (referred to as complex group). In addition to detailed medical history records, all cases underwent physical examination, electrocardiogram, fundus examination, chest X-ray and blood lipid measurement, and some patients had blood and urine routine and blood sugar measurement. There were 374 cases in the vertigo group, including 154 males and 220 females. The youngest was 20 years old, the oldest was 80 years old, the average was 60 years old, and most of them were 40-70 years old. There were 42 cases in the benefit group, including 15 males and 27 females. The youngest was 22 years old, the oldest was 80 years old, and the average was 61 years old. The shortest course of disease was 1 year, and the longest was 25 years, with an average of 4.6 years. A total of 57 cases were regrouped, including 26 males and 31 females. The youngest was 38 years old, the oldest was 78 years old, and the average was 59 years old. The shortest course of disease was 1 year, the longest was 20 years, and the average was 3.7 years. The distribution of gender, age, and course of disease in each group is shown in Table 8.

Table 8 The distribution of gender, age and course of disease of patients in each group

In the dizzy group, there were 76 patients with stage 1 hypertension, accounting for 20.32%, 293 cases in stage 2, accounting for 78.34%, and 5 cases in stage 3, accounting for 1.34%. , accounting for 54.76%, 1 case of stage 3, accounting for 2.38%, 3 cases of hypertensive stage 1 patients in the regroup, accounting for 5%, and 54 cases of stage 2, accounting for 95%. The blood pressure staging of each group is shown in Table 9.

Table 9 Hypertension staging of patients in each group

According to the understanding and classification of hypertension in traditional Chinese medicine, the above cases are divided into three types:

Hyperactivity of Liver Fire: The main symptoms are headache, dizziness, irritability, light red tongue or red tip, thin white or yellow fur, and strong pulse. There were 48 cases in this type of vertigo group, 9 cases in the sharp group, and 11 cases in the complex group.

Yin deficiency and yang hyperactivity: tinnitus, numbness of limbs, soreness of waist and knees. Red tongue, thin white fur, thready or rapid pulse, 242 cases of this type of vertigo group, 22 cases of benefit group, 31 cases of complex group.

Deficiency of both yin and yang: palpitations, shortness of breath, cold extremities, frequent urination at night, pale or dark purple tongue, white fur, deep pulse, weak pulse, or knots. There were 84 cases in this type of vertigo group, 11 cases in the benefit group, and 15 cases in the complex group.

All patients had not received systemic treatment before taking the medicine.

2. Medication method and course observation

Three groups of patients were treated for three months. Wherein the composition of the present invention takes 6 unit doses (each g is equivalent to 6.8 grams of crude drug), three times a day. Reserpine 0.25 mg once, three times a day. The compound antihypertensive medicine is taken one tablet at a time, three times a day. All patients stopped taking all antihypertensive and lipid-lowering drugs within one week before and during the medication. Before the medication, the blood pressure was measured three times in a row on different days (if the blood pressure was normal once, it was eliminated), and the average value was taken as the blood pressure before treatment. Blood pressure was measured regularly once a week during the treatment period for three consecutive months, and the last blood pressure was taken as the blood pressure after treatment. Three months after the end of the course of treatment, the blood pressure was measured three times on the same day, and the average value was used as the blood pressure at the time of the re-examination.

3. Evaluation methods and standards for curative effect

1. Antihypertensive curative effect: According to the standards established by the National Conference on Epidemiology and Population Prevention of Cardiovascular Diseases in 1979.

Significant effect: ①Diastolic blood pressure decreased by 10 mm Hg or above and reached the normal range.

②Although the diastolic blood pressure has not dropped to normal, it has dropped by 20 mm Hg or above.

Effective: ① Diastolic blood pressure drops less than 10 mm Hg but has reached the normal range.

②Diastolic blood pressure decreased by 10-19 mm Hg compared with before treatment, but did not reach the normal range.

③Systolic blood pressure decreased by 30 mm Hg or more than before treatment.

Invalid, did not meet the above criteria.

2. Symptom curative effect:

Choose the five main symptoms of high blood pressure: headache, dizziness, vertigo, palpitations, and limb numbness. Each symptom is scored 3 points, 2 points, 1 point, and 0 points according to severity (30), moderate (20), light (10), and none (1). The sum of each symptom score is the total score of the symptoms before treatment, and the scores are scored in the same way according to the improvement of the symptoms every week after taking the medicine, and the last score sum is taken as the total score of the symptoms after treatment.

Significantly effective: after treatment, all the symptoms disappear or the total score drops by 75% or more than before treatment.

Effective, the total score decreased by 50% and above after treatment, but not 75%.

Invalid: Does not meet the above criteria.

3. Blood lipid curative effect:

Significantly effective: After treatment, cholesterol drops by 20 mg% and above, triglycerides drop by 20 mg% and above; beta lipoprotein drops by 50 mg% and above.

Effective: Cholesterol decreased by 10-19 mg% after treatment; triglyceride decreased by 10-19 mg%; β-lipoprotein decreased by 30-50 mg%.

Invalid: The following criteria are not met.

4. Treatment results

1. Antihypertensive efficacy;

Dazzle group: 205 cases were markedly effective, accounting for 54.81%, 98 cases were effective, accounting for 26.20%, 71 cases were ineffective, accounting for 18.98%, and the total effective rate was 81.02%. cases, accounted for 35.53%, 13 cases were ineffective, accounting for 17.10%, and the effective rate was 82.90%. In the second phase, 158 cases were markedly effective, accounting for 53.93%, 79 cases were effective, accounting for 26.96%, 56 cases were ineffective, accounting for 19.11%, and the effective rate was 80.89%. In the 3rd phase, 2 cases were effective and 3 cases were ineffective. See Table 10 for the step-down range.

The range of blood pressure reduction (mm Hg) of the composition of the present invention in table 10 Mean Buck standard error X±S X systolic blood pressure 35 0.92 35±0.92 diastolic pressure 19 0.60 19±0.60

Conclusion: The composition of the present invention has a definite curative effect on patients with hypertension stage 1 and stage 2, and the number of patients with stage 3 is small, so it is still difficult to conclude. The antihypertensive effect has no significant difference with age, gender and course of disease (P>0.05).

2. Symptom curative effect:

Dazzle group: Among the 374 patients, 214 cases were markedly effective, accounting for 57.22%; 75 cases were effective, accounting for 20.05%, 85 cases were ineffective, accounting for 22.73%, and the total effective rate was 77.27%. %, 15 cases were effective, accounting for 19.74%; 8 cases were ineffective, accounting for 10.52%, and the effective rate was 89.48%. 115 cases were markedly effective in the second phase, accounting for 19.27%, 62 cases were effective, accounting for 21.16%, 72 cases were ineffective, accounting for 24.57%, and the effective rate was 75.43%. 1 case was markedly effective in the third phase, and 1 case was effective. 3 cases were ineffective, it can be seen that the effect of improving the symptoms of patients with hypertension stage 1 and 2 is better.

3. See Table 11 for the curative effect comparison of the dizzy group, the benefit group and the complex group.

The curative effect comparison of table 11 dizzy group, benefit group, compound group

Antihypertensive curative effect: Compared with the dizzy group and the benefit group, P>0.05, there is no significant difference in antihypertensive effect; compared with the dizzy group and the complex group, P<0.05, there is a significant difference, indicating that the complex group is better than the dizzy group.

Symptom curative effect; compared with dizzy group and benefit group, P＜0.05, there is significant difference, illustrates that dizzy group is better than benefit group, especially to headache, palpitation curative effect is very significant (P＜0.01), dizzy group compares with benefit group, P >0.05, no significant difference, see Table 12 for the curative effect observation of individual symptoms in each group.

Table 12 Curative Effect Observation of Individual Symptoms in Each Group

4. The curative effect of TCM classification:

Hyperactivity of Liver Fire: 27 cases in the dizzy group were markedly effective, accounting for 56.25%, 7 cases were effective, accounting for 14.58%, and 14 cases were ineffective, accounting for 29.17%; the total effective rate was 70.83%. In the beneficial group, 8 cases were markedly effective, accounting for 88.89%, and 1 case was effective, accounting for 11.11%, and the effective rate was 100%. In the compound group, 7 cases were markedly effective, accounting for 63.64%, 2 cases were effective, accounting for 18.18%; 2 cases were ineffective, accounting for 18.18%, and the effective rate was 81.82%.

Yin deficiency and yang hyperactivity: 142 cases in dizzy group were markedly effective, accounting for 58.68%, 46 cases were effective, accounting for 19.01%, 54 cases were ineffective, accounting for 2.31%; the total effective rate was 77.59%; 17 cases of benefit group were markedly effective, accounting for 77.27%; 3 cases were effective , accounting for 13.64%, 2 cases were ineffective, accounting for 9.19%, and the effective rate was 90.91%. 16 cases in the compound group were markedly effective, accounting for 51.61%: 5 cases were effective, accounting for 16.13%, 10 cases were ineffective, accounting for 32.26%, and the effective rate was 67.74%.

Deficiency of both yin and yang: 47 cases in dizzy group were markedly effective, accounting for 55.95%, and 20 cases were effective, accounting for 23.81%. 17 cases were invalid, accounting for 20.24%. The total effective rate was 79.76%. In the benefit group, 9 cases were markedly effective, accounting for 81.82%, and 2 cases were effective, accounting for 18.18%, and the effective rate was 100%. In the compound group, 8 cases were markedly effective, accounting for 53.33%, 5 cases were effective, accounting for 33.33%, and 2 cases were ineffective, accounting for 13.34%, and the effective rate was 86.66%.

As can be seen from the above, the composition of the present invention has obvious curative effects on the three types, and there is no significant difference through statistical processing (P>0.05).

5. Lipid-lowering curative effect of dizzy group:

There were 91 cases of hyperlipidemia in this group (in this area, cholesterol > 200 mg%, β-lipid protein > 600 mg%, triglyceride 100 mg% as the standard), and blood lipids all decreased to varying degrees after treatment. See Table 13 for details.

Table 13 The fat-lowering difference of the composition of the present invention

Among them, cholesterol decreased by an average of 61 mg%, β-lipoprotein decreased by 153 mg%, and triglyceride decreased by 56 mg%. The contrast difference before and after treatment was very significant (P<0.01), and the total effective rate of cholesterol decreased was 92%. See the table for details 14.

Table 14 lipid-lowering situation of the composition of the present invention

6. Comparison of electrocardiogram, fundus and chest X-ray before and after treatment: all groups of patients had their electrocardiogram, fundus and chest X-ray checked before and after taking the medicine, and there was no significant difference through statistical processing (P>0.05).

7. Review status:

In order to observe the maintenance curative effect of the dizzy group, the patients in each group were re-examined after stopping the drug for three months, and the results are shown in Table 15.

Table 15 Re-examination of each group

Conclusion: The blood pressure maintenance effect of dazzle group is longer than that of benefit group and compound group. And during the observation period of the whole course of treatment, no adverse reactions and side effects of the drug have been found, which is well received by patients.

The composition of the present invention has the following advantages:

(1) The antihypertensive effect is slow, mild and lasting. Clinical symptoms will not be aggravated by a sudden drop in blood pressure. Patients are willing to accept it, and it is suitable for long-term use by hypertensive patients. It is also suitable for those with high blood pressure and cerebral arteriosclerosis.

(2) No toxic side effects and contraindications have been found, and the application range is wide.

(3) It has obvious lipid-lowering effect, so it is suitable for patients with hypertension and hyperlipidemia.

(4) All the medicines used are widely distributed, large in output, easy to collect, convenient to produce on the spot, and have higher economic value.

Claims (25)

1. A traditional Chinese medicine composition with lipid-lowering, blood pressure-lowering, dizziness-fixing and wind-fixing effects, characterized in that the raw materials of the active ingredients used to prepare the composition consist of: 1365-4095 parts of Gastrodia elata, 1365-4095 parts of Eucommia ulmoides 4095 parts, 3350-10050 parts of wild chrysanthemum, 4195-12585 parts of Eucommia leaves and 1675-5025 parts of Chuanxiong. 2. The traditional Chinese medicine composition according to claim 1, characterized in that the raw materials of the active ingredients used in the preparation of the composition are composed by weight: 2048-3412 parts of Gastrodia elata, 2048-3412 parts of Eucommia ulmoides, 5025-8385 parts of wild chrysanthemum, Eucommia leaves 6293-10487 parts and Chuanxiong 2513-4187 parts. 3. The traditional Chinese medicine composition according to claim 2, characterized in that the raw materials of the active ingredients used in the preparation of the composition are composed by weight: 2730 parts of Gastrodia elata, 2730 parts of Eucommia ulmoides, 6700 parts of wild chrysanthemum, 8390 parts of Eucommia ulmoides leaves and Ligusticum chuanxiong 3350 copies. 4. The Chinese medicine composition according to any one of claims 1-3, which is an oral preparation. 5. Chinese medicine composition according to claim 4, described oral preparation is selected from tablet, capsule, granule, pill, powder, dripping pill, syrup, mixture, dew, tea or its sustained and controlled release preparation . 6. A method for preparing the Chinese medicine composition described in any one of claims 1-5, comprising the steps of: taking half of Gastrodia elata and pulverizing into fine powder to obtain Gastrodia elata fine powder; getting remaining half of Gastrodia elata and pulverizing into coarse powder, using Alcohol solvent reflux extraction, combined and filtered extracts, recovered ethanol and concentrated into Gastrodia elata extract; mixed evenly the residue of Gastrodia elata after alcohol extraction with Eucommia ulmoides, Eucommia leaves, wild chrysanthemum, and Chuanxiong, boiled with water, combined, filtered and boiled extracts, concentrated Filtrate to prepare a mixed thick paste with a relative density of 1.15-1.5 at 40-80°C; then add Gastrodia elata fine powder to Gastrodia elata extract and mixed thick paste, mix well, add an appropriate amount of pharmaceutically acceptable carrier, and follow the routine Formulation Methods The desired formulations were prepared. 7. The method according to claim 6, wherein the alcohol solvent is selected from ethanol, methanol or propylene glycol. 8. The method according to claim 6, the volume of the alcohol solvent is 10-30 times of the weight of Gastrodia elata meal. 9. The method according to claim 8, the volume of the alcohol solvent is 5-25 times of the weight of Gastrodia elata meal. 10. the method described in claim 9, the volume of described alcohol solvent is 20 times of Gastrodia elata meal weight. 11. The method according to claim 6, the concentration of the alcohol solvent is 40-90 v/v%. 12. The method according to claim 11, the concentration of the alcohol solvent is 50-80 v/v%. 13. The method according to claim 12, the concentration of the alcohol solvent is 60-70 v/v%. 14. The method according to claim 6, the number of times of said reflux extraction is 1-5 times. 15. The method according to claim 14, the number of times of said reflux extraction is 2-4 times. 16. The method according to claim 15, the number of times of said reflux extraction is 2-3 times. 17. The method according to claim 6, the reflux extraction time is 0.5-3 hours. 18. The method according to claim 17, the reflux extraction time is 1-2 hours. 19. The method according to claim 18, the reflux extraction time is 1 hour. 20. The method according to claim 6, said concentration method being selected from vacuum concentration or thin film concentration. 21. The method according to claim 6, the relative density of the mixed thick paste is 1.25-1.45. 22. The method according to claim 21, the relative density of the mixed thick paste is 1.35-1.40. 23. The application of the composition according to any one of claims 1-5 in the preparation of lipid-lowering, blood pressure-lowering, vertigo-fixing and wind-fixing medicines. 24. The composition of any one of claims 1-5 is used in the preparation of headaches caused by hypertension, arteriosclerosis, cardiovascular disease, hyperlipidemia, hypertension combined with arteriosclerosis, hypertension with hyperlipidemia and the above-mentioned diseases , dizziness, dizziness, tinnitus, insomnia or nocturia symptom drug application. 25. The application according to claim 24, wherein the hypertension is selected from the group consisting of liver-fire hypertensive hypertension, yin-deficiency and yang-excessive hypertension, yin-yang-deficiency hypertension, stage 1 hypertension, stage 2 hypertension, or stage 3 hypertension. Period hypertension.