Traditional Chinese medicine composition for treating hypertension and preparation method, traditional Chinese medicine preparation and application thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating hypertension and a preparation method, a traditional Chinese medicine preparation and application thereof. The traditional Chinese medicine composition is prepared from the following traditional Chinese medicine raw materials in parts by weight: 5-15 parts of centella asiatica, 10-20 parts of tribulus terrestris, 5-15 parts of scutellaria baicalensis, 15-25 parts of radix puerariae, 5-15 parts of radix stephaniae tetrandrae, 10-20 parts of angelica sinensis, 5-15 parts of eucommia ulmoides and 5-15 parts of liquorice. In-vivo and in-vitro tests show that the traditional Chinese medicine composition provided by the invention is scientific and reasonable in compatibility, has the effects of calming the liver, freeing orifices, clearing and activating the channels and collaterals, dispelling wind, relieving pain, clearing heat and promoting diuresis, can regulate and control hypertension targets and regulate abnormal systolic pressure and diastolic pressure caused by hypertension, and plays a role in treating hypertension.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and in particular relates to a traditional Chinese medicine composition for treating hypertension, a preparation method thereof, a traditional Chinese medicine preparation and application thereof. Background Art

[0002] Hypertension is a common chronic disease. Epidemiological surveys show that the prevalence of hypertension among Chinese adults is close to 33%, which means that about one in three adults suffers from hypertension. The diagnostic criteria for hypertension are usually systolic blood pressure greater than 140 mmHg and / or diastolic blood pressure greater than 90 mmHg. Hypertension is a potential risk factor that may lead to a variety of serious health problems, including heart disease, stroke, kidney disease, etc. The causes of hypertension are mostly genetic factors and unhealthy lifestyles, such as high-salt diet, excessive drinking, long-term mental stress and lack of physical activity.

[0003] At present, the etiology of hypertension is still a scientific problem. Hypertension is divided into primary hypertension and secondary hypertension. The current clinical treatment of hypertension includes taking some commonly used antihypertensive drugs such as angiotensin converting enzyme inhibitors, angiotensin receptor antagonists, diuretics and beta-blockers. However, antihypertensive drugs require patients to take them for a long time and will bring more side effects, such as fatigue, dizziness, nausea, chest tightness, taste loss and palpitations. Therefore, there is an urgent need to develop high-efficiency and low-toxic drugs that can effectively intervene and treat hypertension.

[0004] Traditional Chinese medicine has unique advantages in treating complex diseases. Natural plant medicines represented by traditional Chinese medicine have the characteristics of low toxicity and side effects and good tolerance. The theory of traditional Chinese medicine emphasizes dialectical treatment and regards people as a unified whole. On the one hand, it replenishes the body's deficiency and regulates the patient's immune function and yin and yang imbalance from the overall system; on the other hand, it detoxifies and disperses the knot to treat the disease, focusing on the unity of treatment and conditioning to improve the patient's overall condition. At present, the theory of traditional Chinese medicine believes that the occurrence of hypertension is caused by multiple reasons such as visceral yin and yang imbalance, poor circulation of qi, blood and body fluids, and deficiency of the liver, spleen and kidney.

[0005] The inventor team has discovered a new type of Chinese medicine composition in the study of hypertension and combined with clinical practice. The dosage is small and the ratio is scientific and reasonable. It can effectively treat hypertension, and can effectively regulate the systolic blood pressure (SBP, Systolic Blood Pressure) and diastolic blood pressure (DBP, Diastolic Blood Pressure) of the hypertensive animal model, and has less toxic and side effects and better safety. The Chinese medicine composition of the present invention is expected to regulate the imbalance of yin and yang in the internal organs of patients with hypertension, improve the deficiency of the patient's organs, and promote blood circulation, calm the liver and relieve depression, and is expected to provide a low-toxic and efficient treatment method for the clinical treatment of hypertension. Summary of the invention

[0006] The purpose of the present invention is to solve the deficiencies of the prior art and provide a Chinese medicine composition for treating hypertension and a preparation method, a Chinese medicine preparation and application thereof.

[0007] Specifically, the present invention is realized through the following technical solutions:

[0008] In the first aspect, the present invention provides a traditional Chinese medicine composition for treating hypertension, which is made of the following traditional Chinese medicine raw materials in parts by weight: 5-15 parts of Centella asiatica, 10-20 parts of Tribulus terrestris, 5-15 parts of Scutellaria baicalensis, 15-25 parts of Pueraria lobata, 5-15 parts of Stephania tetrandra, 10-20 parts of Angelica sinensis, 5-15 parts of Eucommia ulmoides, and 5-15 parts of Licorice.

[0009] As an optional manner, in the above-mentioned traditional Chinese medicine composition, the traditional Chinese medicine composition is made of the following traditional Chinese medicine raw materials in parts by weight: 8-12 parts of Centella asiatica, 12-18 parts of Tribulus terrestris, 6-10 parts of Scutellaria baicalensis, 18-22 parts of Pueraria lobata, 8-12 parts of Stephania tetrandra, 10-15 parts of Angelica sinensis, 6-10 parts of Eucommia ulmoides, and 6-10 parts of Licorice.

[0010] As an optional manner, in the above-mentioned traditional Chinese medicine composition, the traditional Chinese medicine composition is made of the following traditional Chinese medicine raw materials in parts by weight: 10 parts of Centella asiatica, 15 parts of Tribulus terrestris, 8 parts of Scutellaria baicalensis, 20 parts of Pueraria lobata, 10 parts of Stephania tetrandra, 15 parts of Angelica sinensis, 12 parts of Eucommia ulmoides, and 8 parts of Licorice.

[0011] In a second aspect, the present invention provides a method for preparing the Chinese medicine composition for treating hypertension described in the first aspect, wherein the preparation method is selected from any one of the following:

[0012] A: Add 5-12 times the amount of water to the Chinese medicinal raw materials in the prescription, decoct together, filter, and concentrate the filtrate;

[0013] B: Add 50-90% ethanol aqueous solution to the Chinese medicinal raw materials in the prescription amount for reflux extraction, filter, and concentrate the filtrate;

[0014] C: Add 5-12 times the amount of water to the Chinese medicinal raw materials in the prescription and decoct them, then filter; add 50-90% ethanol aqueous solution to the medicinal residues for reflux extraction, filter, and combine the filtrates for concentration.

[0015] As an optional manner, in the above-mentioned preparation method, in the above-mentioned method A, method B or method C, water is added and decocted for 1-3 times, and each extraction is 1-12 hours, preferably 2-4 hours; the amount of ethanol aqueous solution used in the ethanol aqueous solution reflux extraction operation is 8-10 times the weight of the medicinal material, and each extraction is 1-12 hours, preferably 2-4 hours.

[0016] In the third aspect, the present invention provides a traditional Chinese medicine preparation for treating hypertension, which comprises the traditional Chinese medicine composition described in the first aspect or the traditional Chinese medicine composition prepared by the preparation method described in the second aspect, and a pharmaceutically acceptable carrier and / or excipient.

[0017] As an optional method, in the above-mentioned traditional Chinese medicine preparation, the pharmaceutically acceptable carrier and / or excipient is selected from one or more of liposomes, microcrystalline cellulose, sodium carboxymethyl starch, sodium carboxymethyl cellulose, polyethylene glycol, polyvinyl alcohol, acrylic polymers, glycerol, propylene glycol, sorbitol, β-cyclodextrin, Tween-80, lactose, starch, Euqite S-100, Euqite L-100, sodium alginate, pectin, and dextrin.

[0018] As an optional mode, in the above-mentioned traditional Chinese medicine preparation, the traditional Chinese medicine preparation is granules, capsules, oral liquids, tablets, pills, pellets, ointments, decoctions, injections or microcapsules.

[0019] In the fourth aspect, the present invention provides the use of the Chinese medicine composition described in the first aspect, or the Chinese medicine composition prepared by the preparation method described in the second aspect, or the Chinese medicine preparation described in the third aspect in the preparation of drugs for treating hypertension.

[0020] The Chinese medicine composition for treating hypertension provided by the present invention comprises:

[0021] Centella asiatica is cold and bitter in nature, and enters the liver, spleen, and kidney meridians. It has the effects of clearing away heat and dampness, detoxifying and reducing swelling.

[0022] Tribulus terrestris is warm and slightly bitter in nature, and it enters the liver meridian. It has the effects of calming the liver, relieving depression, promoting blood circulation and dispelling wind.

[0023] Scutellaria baicalensis is mild in nature and bitter in taste. It enters the heart, lung, and gallbladder meridians and has the effects of removing excess fire and dampness and heat.

[0024] Pueraria root is cool in nature and sweet in taste. It enters the stomach, lung and spleen meridians and has the effects of relieving muscle and fever, promoting blood circulation and activating collaterals.

[0025] Fangji is cold in nature and sweet in taste. It enters the bladder and lung meridians and has the effects of dispelling wind and relieving pain, promoting diuresis and reducing swelling.

[0026] Angelica sinensis is warm in nature and sweet and spicy in flavor. It enters the liver, heart, and spleen meridians and has the effects of nourishing blood, activating blood circulation, regulating menstruation and relieving pain, and enhancing immunity.

[0027] Eucommia ulmoides is warm in nature and sweet in taste. It enters the liver and kidney meridians and has the effects of nourishing yin and kidney, nourishing the liver and improving eyesight.

[0028] Licorice is warm in nature and sweet in taste. It enters the heart, lung, stomach and spleen meridians. It has the effects of tonifying the spleen and stomach, replenishing qi and restoring the pulse.

[0029] The above drugs are used together based on the theory of "monarch, minister, assistant and messenger" in traditional Chinese medicine, and are reasonably configured and compatible with each other. In the present invention, Pueraria root is used as the monarch drug to promote blood circulation and activate collaterals, relieve muscle and promote body fluid; Eucommia ulmoides, Angelica sinensis, Tribulus terrestris, Stephania tetrandra are used as ministers to dispel wind and relieve pain, soothe the liver and relieve depression, promote diuresis and reduce swelling, and nourish yin and tonify the kidney; Scutellaria baicalensis and Centella asiatica are used as adjuvants to detoxify and reduce swelling, and remove dampness and heat; Licorice is used as a messenger to clear heat and detoxify, and harmonize the drugs. The eight drugs are used together to play the effects of soothing the liver, promoting blood circulation, activating collaterals, and dispelling wind and relieving pain.

[0030] The compound Chinese medicine composition for treating hypertension provided by the present invention has the following advantages compared with the prior art:

[0031] 1. The present invention is based on the theory of traditional Chinese medicine and combines the most cutting-edge research results on hypertension. It adopts the principle of dialectical treatment and systemic regulation to screen Chinese medicine prescriptions. The compound Chinese medicine composition preparation provided can regulate multiple hypertension targets and has a good therapeutic effect on hypertension.

[0032] 2. The experimental results show that the Chinese medicine composition for treating hypertension provided by the present invention has the effects of calming the liver, opening the orifices, promoting blood circulation, dispelling wind and relieving pain, and at the same time plays a multi-target systemic role in treating hypertension. Clinical practice shows that the Chinese medicine composition for treating hypertension provided by the present invention is highly safe and has very low toxic and side effects.

[0033] 3. The Chinese medicine composition for treating hypertension provided by the present invention can be prepared into various dosage forms using pharmaceutical carriers / excipients, etc., which is convenient for patients to take. In addition, the Chinese medicine composition for treating hypertension provided by the present invention has a scientific and reasonable ratio, a small dosage, can quickly exert its efficacy, has a stable preparation process, and is suitable for industrial large-scale production. DETAILED DESCRIPTION

[0034] Example 1

[0035] Take Chinese medicine raw materials by weight, specifically, take 15 grams of Centella asiatica, 20 grams of Tribulus terrestris, 15 grams of Scutellaria baicalensis, 25 grams of Pueraria root, 15 grams of Stephania tetrandra, 20 grams of Angelica sinensis, 15 grams of Eucommia ulmoides, and 15 grams of Licorice. Add 12 times (i.e. 1680 mL) of water according to the weight of the prescription amount, decoct together, extract 3 times, each time for 2 hours, filter naturally through a 120-mesh stainless steel mesh, and apply a macroporous adsorption resin column to the concentrate. After elution, further reduce pressure and concentrate to an extract with a relative density of 1.20-1.30, vacuum dry, and ultrafinely grind at low temperature to obtain fine powder, add diluent lactose and corn starch to mix evenly, put into enteric-coated capsules and prepare capsules of the Chinese medicine composition of the present invention (batch number: T001).

[0036] Example 2

[0037] Take Chinese medicinal raw materials by weight, specifically, take 5 grams of Centella asiatica, 10 grams of Tribulus terrestris, 5 grams of Scutellaria baicalensis, 15 grams of Pueraria lobata, 5 grams of Stephania tetrandra, 10 grams of Angelica sinensis, 5 grams of Eucommia ulmoides, and 5 grams of Licorice. Add 8 times (i.e. 480 mL) of water according to the weight of the prescription and decoct together, filter naturally through a 120-mesh stainless steel mesh, add 10 times by weight of 50% ethanol 600 mL of reflux extraction to the residue, filter naturally through a 120-mesh stainless steel mesh, combine the filtrate, apply the concentrate to a macroporous adsorption resin column, further reduce pressure and concentrate after elution to an extract with a relative density of 1.20-1.30, and after vacuum drying, ultrafinely grind at low temperature to obtain fine powder, add glycerol and sorbitol excipients to prepare an ointment (batch number: T002) of the Chinese medicine composition of the present invention for oral administration.

[0038] Example 3

[0039] Take Chinese medicinal raw materials by weight, specifically, take 10 grams of Centella asiatica, 15 grams of Tribulus terrestris, 8 grams of Scutellaria baicalensis, 20 grams of Pueraria root, 10 grams of Stephania tetrandra, 15 grams of Angelica sinensis, 12 grams of Eucommia ulmoides, and 8 grams of Licorice. Add 10 times (i.e. 980 mL) of water according to the weight of the prescription and decoct together, filter naturally through a 120-mesh stainless steel mesh, add 10 times by weight of 70% ethanol 980 mL of reflux extraction to the residue, extract 3 times, each time for 2 hours, filter naturally through a 120-mesh stainless steel mesh, combine the filtrate, apply the concentrate to a macroporous adsorption resin column, and further reduce the pressure and concentrate after elution to obtain an extract with a relative density of 1.20-1.30, vacuum dry, ultrafinely grind at low temperature to obtain fine powder, add dextrin, and spray to obtain the granules of the Chinese medicine composition of the present invention (batch number: T003).

[0040] Example 4

[0041] Take Chinese medicinal raw materials by weight, take 10 grams of Centella asiatica, 20 grams of Tribulus terrestris, 10 grams of Scutellaria baicalensis, 10 grams of Pueraria root, 10 grams of Stephania tetrandra, 10 grams of Angelica sinensis, 10 grams of Eucommia ulmoides, and 10 grams of Licorice. Add 10 times (i.e. 900 mL) of water according to the weight of the prescription amount and decoct together, extract 3 times, each time for 2 hours, filter naturally through a 120-mesh stainless steel mesh, and apply a macroporous adsorption resin column to the concentrate. After elution, further reduce pressure and concentrate to an extract with a relative density of 1.20-1.30, vacuum dry, and ultrafinely grind at low temperature to obtain fine powder, add microcrystalline cellulose, sodium carboxymethyl starch, and lubricant magnesium stearate, mix evenly, and compress the tablets to prepare tablets (batch number: T004) of the Chinese medicine composition of the present invention.

[0042] Example 5

[0043] Take Chinese medicinal raw materials by weight, take 5 grams of Centella asiatica, 15 grams of Tribulus terrestris, 5 grams of Scutellaria baicalensis, 5 grams of Pueraria root, 5 grams of Stephania tetrandra, 5 grams of Angelica sinensis, 5 grams of Eucommia ulmoides, and 5 grams of Licorice. Add 8 times of 70% ethanol solution according to the weight of the prescription, that is, 400 mL of ethanol solution for reflux extraction, extract 3 times, each time for 2 hours, filter naturally through a 120-mesh stainless steel mesh, and add the concentrate to a macroporous adsorption resin column. After elution, further reduce pressure and concentrate to an extract with a relative density of 1.20-1.30, vacuum dry and then ultrafinely grind at low temperature to obtain fine powder, add acrylic polymer, polyethylene glycol excipient and binder, and adopt a melting method to prepare the Chinese medicine composition drip pill dosage form of the present invention (batch number: T005).

[0044] Example 6

[0045] The regulating effect of the Chinese medicine composition prepared in the embodiment of the present invention on the symptoms of hypertension was evaluated by the spontaneously hypertensive rats (SHR) model. Spontaneously hypertensive rats are a common animal model for screening antihypertensive drugs. Benaricept hydrochloride tablets are a common drug used clinically to treat hypertension and are used as positive control drugs in the experiment. The following experiment was commissioned by Shanghai Medicilon Biopharmaceutical Co., Ltd., and the project number is DLG2401P.

[0046] After one week of feeding the SHR hypertensive rats (purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd., experimental animal production license number: SCXK (Beijing) 2021-0006) model during the adaptation period, the systolic and diastolic blood pressure of all animals were measured. After the systolic blood pressure of SHR rats was >140 mmHg, they were divided into 3 groups on average, 6 in each group, plus 6 normal control rats (WYK rats), a total of 4 groups, specifically: normal control group, model group, Benaripi Hydrochloride Tablets Treatment Group (dose: 1 mg / kg), Chinese medicine composition preparation treatment group (batch number: T003, dose: 6 g / kg). After the animals were grouped, they were given solvent control, positive control drug or Chinese medicine composition preparation (T003) by oral gavage once a day for two consecutive weeks. Body weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured once a week for all animals.

[0047] The experimental data were expressed as Mean±SD and statistically analyzed using Excel-TTEST. P<0.05 was considered to be a significant difference.

[0048] As shown in Table 1, from Day 0 to Day 14, the SDP and DBP of rats in the Model group continued to be significantly higher than those in the blank group, proving that the hypertensive rat model was successful (P<0.01, P<0.001). From Day 0 to Day 14, the SDP and DBP of rats in the Benazepril Hydrochloride Tablets 1 mg / kg group decreased first and then increased, and were significantly lower than those in the Model group from Day 7 (P<0.05, P<0.001); the SDP and DBP of rats in the Chinese medicine composition preparation treatment group maintained a downward trend, and the SDP was significantly lower than that in the Model group from Day 7 (P<0.05), and the DBP was significantly lower than that in the Model group from Day 14 (P<0.05).

[0049] Table 1: Effects of oral administration of the test substances twice a day for two consecutive weeks on SBP and DBP in SHR hypertensive rats

[0050]

[0051] ## P<0.01, ### P<0.001vs. normal control group; * P<0.05, *** P<0.001vs. model group.

[0052] This experiment shows that the Chinese medicine composition preparation of the present invention has a good regulatory effect on the systolic and diastolic blood pressure of the spontaneously hypertensive SHR rat model after treatment. In particular, the regulatory effect of the Chinese medicine composition preparation of the present invention on systolic blood pressure is close to that of the positive control drug Benaripi Hydrochloride Tablets, proving that the Chinese medicine composition preparation of the present invention has a potential therapeutic effect on abnormal systolic and diastolic blood pressure caused by hypertension.

[0053] Example 7

[0054] By examining the acute toxicity data of the Chinese medicine composition preparations of the present invention (batch numbers: T001, T002, T003, T004 and T005), the oral safety of the Chinese medicine composition preparations of the present invention can be understood. 50 healthy ICR mice (SPF level, purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd., Experimental Animal Production License Number: SCXK (Beijing) 2021-0006) were randomly divided into 5 experimental groups, with 10 mice in each group. The five batches of compound composition preparations were formulated into concentrated solutions. After measuring the weight of the mice, the dosage was calculated according to 50g / kg body weight, and the solution was administered orally by gavage. The adverse reaction symptoms of the animals were observed every hour after administration. After 24 hours, the mortality rate of each group of animals was calculated and the adverse reactions were recorded. The experimental results are shown in Table 2. The results show that the acute toxicity values ​​of the five batches of Chinese medicine composition preparations were all LD 50 >50g / kg, no adverse reactions were observed in animals during the experiment, it is non-toxic and has a high oral safety.

[0055] Table 2: Acute toxicity experimental data of the Chinese medicine composition preparation of the present invention

[0056] Group / Batch No. Animals (only) Dead animals (unit) mortality rate(%) T001 10 0 0 T002 10 0 0 T003 10 0 0 T004 10 0 0 T005 10 0 0

[0057] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A Chinese medicine composition for treating hypertension, characterized in that: The Chinese medicine composition is prepared from the following Chinese medicine raw materials in parts by weight: 5-15 parts of Centella asiatica, 10-20 parts of Tribulus terrestris, 5-15 parts of Scutellaria baicalensis, 15-25 parts of Pueraria root, 5-15 parts of Stephania tetrandra, 10-20 parts of Angelica sinensis, 5-15 parts of Eucommia ulmoides and 5-15 parts of Licorice.

2. The Chinese medicine composition for treating hypertension according to claim 1, characterized in that: The Chinese medicine composition is prepared from the following Chinese medicine raw materials in parts by weight: 8-12 parts of Centella asiatica, 12-18 parts of Tribulus terrestris, 6-10 parts of Scutellaria baicalensis, 18-22 parts of Pueraria root, 8-12 parts of Stephania tetrandra, 10-15 parts of Angelica sinensis, 6-10 parts of Eucommia ulmoides and 6-10 parts of Licorice.

3. The Chinese medicine composition for treating hypertension according to claim 2, characterized in that: The Chinese medicine composition is prepared from the following Chinese medicine raw materials in parts by weight: 10 parts of Centella asiatica, 15 parts of Tribulus terrestris, 8 parts of Scutellaria baicalensis, 20 parts of Pueraria root, 10 parts of Stephania tetrandra, 15 parts of Angelica sinensis, 12 parts of Eucommia ulmoides and 8 parts of Licorice.

4. The method for preparing the Chinese medicine composition for treating hypertension according to any one of claims 1 to 3, characterized in that: The preparation method is selected from any one of the following: A: Add 5-12 times the amount of water to the Chinese medicinal raw materials in the prescription, decoct together, filter, and concentrate the filtrate; B: Add 50-90% ethanol aqueous solution to the Chinese medicinal raw materials in the prescription amount for reflux extraction, filter, and concentrate the filtrate; C: Add 5-12 times the amount of water to the Chinese medicinal materials in the prescription, decoct and filter; The residues are added with 50-90% ethanol aqueous solution for reflux extraction, filtered, and the filtrates are combined and concentrated.

5. The method for preparing the Chinese medicine composition for treating hypertension according to claim 4, characterized in that: In the above method A, method B or method C, water is added and decocted for 1-3 times, and each extraction takes 1-12 hours, preferably 2-4 hours; in the ethanol-water reflux extraction operation, the amount of ethanol-water solution is 8-10 times the weight of the medicinal material, and each extraction takes 1-12 hours, preferably 2-4 hours.

6. A Chinese medicine preparation for treating hypertension, characterized in that: The Chinese medicine preparation comprises the Chinese medicine composition according to any one of claims 1 to 3 or the Chinese medicine composition prepared by the preparation method according to claim 4 or claim 5, and a pharmaceutically acceptable carrier and / or excipient.

7. The Chinese medicine preparation according to claim 6, characterized in that: The pharmaceutically acceptable carrier and / or excipient is selected from one or more of liposomes, microcrystalline cellulose, sodium carboxymethyl starch, sodium carboxymethyl cellulose, polyethylene glycol, polyvinyl alcohol, acrylic polymers, glycerol, propylene glycol, sorbitol, β-cyclodextrin, Tween-80, lactose, starch, Euqite S-100, Euqite L-100, sodium alginate, pectin, and dextrin.

8. The Chinese medicine preparation according to claim 6, characterized in that: The Chinese medicine preparation is granules, capsules, oral liquids, tablets, pills, dripping pills, ointments, decoctions, injections or microcapsules.

9. Use of the Chinese medicine composition according to any one of claims 1 to 3, or the Chinese medicine composition prepared by the preparation method according to claim 4 or claim 5, or the Chinese medicine preparation according to any one of claims 6 to 8 in the preparation of a medicament for treating hypertension.

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