Traditional Chinese medicine composition containing areca, extract and use thereof for preventing and treating pulmonary arterial hypertension

Abstract

The present application relates to the medical technical field, and relates to a traditional Chinese medicine formula containing Areca catechu and an extract, and purposes of preventing and treating pulmonary arterial hypertension. Specifically, the present application relates to the application of a traditional Chinese medicine formula containing Areca catechu and an extract in the preparation of a medicine for preventing and / or treating pulmonary arterial hypertension and its complications. The present application shows that the water extract of the formula and its components can be absorbed through the oral cavity and the gastrointestinal tract, can reduce pulmonary arterial pressure, inhibit right ventricular wall hypertrophy, alleviate pulmonary edema and the like, and can play a significant pharmacological role in preventing and treating pulmonary arterial hypertension and its complications. The present formula can be an ideal medicine for preventing and treating pulmonary arterial hypertension and its complications, and can be used for preparing products for preventing and / or treating pulmonary arterial hypertension and its complications, chronic pulmonary heart disease, high altitude disease, hypoxic injury and right heart failure.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medicine, in particular to a traditional Chinese medicine formula containing Areca catechu and an extract thereof, and application of the traditional Chinese medicine formula in preparation of a medicine for preventing and / or treating pulmonary arterial hypertension and complications thereof. BACKGROUND

[0002] Pulmonary arterial hypertension is a disease characterized by progressive increase in pulmonary arterial pressure, and its clinical diagnostic criterion is that the mean pulmonary arterial pressure (mPAP) is greater than or equal to 25 mmHg in a resting state as measured by right heart catheterization. In recent years, the incidence of pulmonary arterial hypertension has shown an upward trend, and it is a disease with high morbidity and mortality. Unlike cardiovascular diseases such as hypertension, the pathogenesis of pulmonary arterial hypertension is complex, and drugs commonly used for the treatment of hypertension cannot be used to reduce pulmonary arterial pressure. Moreover, existing therapeutic drugs cannot fully meet the clinical needs. Pulmonary arterial hypertension has a poor prognosis, and the 5-year survival rate is extremely low. It is a very serious disease involving the cardiovascular and respiratory systems.

[0003] When pulmonary arterial hypertension occurs, patients exhibit symptoms such as dyspnea, palpitations, chest pain, hemoptysis, syncope, and the like. In the late stage, symptoms such as hypoxia, right heart hypertrophy, and even right heart failure may occur, and in severe cases, death may occur. At present, the treatment methods and drugs for this disease are still very lacking, and the prognosis is very poor. Only 20% of patients can be effectively controlled, and most patients may die within 2-3 years after diagnosis. The first-line drug for treating pulmonary arterial hypertension in clinical practice is bosentan, but its therapeutic effect is not satisfactory. Developing new drugs that can effectively treat pulmonary arterial hypertension is a very important and urgent task.

[0004] The traditional Chinese medicine formula containing Areca catechu comprises Areca catechu, Radix Paeoniae Alba, Anemarrhena asphodeloides, Scutellaria baicalensis, Magnolia officinalis, Glycyrrhiza uralensis, and Amomum tsao-ko. The present application has prepared the traditional Chinese medicine formula containing Areca catechu, and can obtain stable quality Areca catechu formula and its extract, and analyze and identify the effective components thereof. Experiments have shown that the traditional Chinese medicine formula containing Areca catechu has a significant preventive and therapeutic effect on pulmonary arterial hypertension at the whole animal level, and this effect has not been reported in the literature. SUMMARY

[0005] The technical problem solved by the present application is to invent a traditional Chinese medicine formula containing Areca catechu and an extract thereof, and apply them to the prevention and / or treatment of pulmonary arterial hypertension and complications thereof.

[0006] To solve the technical problem of the present application, the present application provides the following technical solutions:

[0007] The first aspect of the technical solutions of the present application is to provide a traditional Chinese medicine formula containing Areca catechu, which contains Areca catechu and one or more of the following medicinal materials: Radix Paeoniae Alba, Glycyrrhiza uralensis, Anemarrhena asphodeloides, Scutellaria baicalensis, Magnolia officinalis, and Amomum tsao-ko.

[0008] The Chinese medicine formula containing Areca catechu is made of the following raw materials by weight: Areca catechu 10-40 parts by weight, Radix Paeoniae Alba 5-20 parts, Anemarrhena asphodeloides 5-20 parts, Scutellaria 5-20 parts, Magnolia officinalis 5-20 parts, Glycyrrhiza 5-10 parts, Amomum 5-10 parts.

[0009] The Chinese medicine formula containing Areca catechu is made of the following raw materials by weight: Areca catechu 10-40 parts by weight, Radix Paeoniae Alba 5-20 parts, Anemarrhena asphodeloides 5-20 parts, Scutellaria 5-20 parts, Magnolia officinalis 5-20 parts, Glycyrrhiza 5-10 parts, Amomum 5-10 parts.

[0010] The second aspect of the technical solution of the present application provides a Chinese medicine formula extract containing Areca catechu, characterized in that the extract is prepared by water extraction of the Chinese medicine formula described in the first aspect of the technical solution.

[0011] The preparation method of the extract prepared from the Chinese medicine formula containing Areca catechu includes water extraction: adding 4-10 times the amount of water or ethanol based on the total weight of the raw materials of the Chinese medicine formula, soaking for 1-12 hours, and then boiling for 30 minutes to 2 hours to obtain a medicinal liquid; adding 4 times the amount of water to the remaining dregs, boiling for 30 minutes to 2 hours to obtain a medicinal liquid; adding 3 times the amount of water to the remaining dregs, boiling for 30 minutes to 2 hours to obtain a medicinal liquid; combining all the medicinal liquids, concentrating under reduced pressure, and then passing through a 20-mesh sieve to obtain a concentrated medicinal liquid; drying at 70°C to obtain an extract infusion.

[0012] The preparation method of the extract prepared from the Chinese medicine formula containing Areca catechu includes water extraction: adding 4-10 times the amount of water or ethanol based on the total weight of the raw materials of the Chinese medicine formula, soaking for 1-12 hours, and then boiling for 30 minutes to 2 hours to obtain a medicinal liquid; adding 4 times the amount of water to the remaining dregs, boiling for 30 minutes to 2 hours to obtain a medicinal liquid; adding 3 times the amount of water to the remaining dregs, boiling for 30 minutes to 2 hours to obtain a medicinal liquid; combining all the medicinal liquids, concentrating under reduced pressure, and then passing through a 20-mesh sieve to obtain a concentrated medicinal liquid; drying at 70°C to obtain an extract infusion.

[0013] The third aspect of the technical solution of the present application is to provide a pharmaceutical composition, which contains the Chinese medicine formula containing Areca catechu described in the first aspect of the technical solution or the Chinese medicine formula extract containing Areca catechu described in the second aspect of the technical solution or a pharmaceutically acceptable carrier or excipient.

[0014] In the present application, the pharmaceutical composition of the extract of the Chinese medicine formula containing Areca catechu can be in a dosage form selected from the following: granules, drop pills, solutions, suspensions, freeze-dried powder needles, emulsions, pills, capsules, powders, controlled release or sustained release preparations, depending on the administration route.

[0015] The pharmaceutical composition of the extract of the Chinese medicine formula containing Areca catechu of the present application can be prepared by known methods and administered to subjects using several routes, including but not limited to parenteral, oral, topical, intradermal, intramuscular, intraperitoneal, subcutaneous, intravenous, intranasal routes.

[0016] The TCM formula extract containing Areca catechu in the present application can be prepared by known methods.

[0017] The TCM formula extract containing Areca catechu in the present application can be optionally formulated with one or more pharmaceutically acceptable carriers and / or excipients by any conventional method. Therefore, the Areca catechu formula and its pharmaceutically acceptable derivatives can be particularly formulated, for example, for inhalation or insufflation (through the mouth or nose) or oral, buccal, parenteral or rectal administration.

[0018] The TCM formula extract containing Areca catechu can also adopt granules, dripping pills, solutions, suspensions, emulsions, pills, capsules, powders, controlled release or sustained release preparations. These preparations will contain a therapeutically effective amount of the TCM formula extract containing Areca catechu, and an appropriate amount of carriers to provide a suitable administration form for patients.

[0019] The fourth aspect of the technical solution of the present application is to provide the use of the TCM formula containing Areca catechu in the first aspect and the TCM formula extract containing Areca catechu in the second aspect and the pharmaceutical composition in the third aspect in the preparation of a medicine for preventing and / or treating pulmonary arterial hypertension and its complications. The pulmonary arterial hypertension and its complications are selected from hypoxic pulmonary arterial hypertension, arterial pulmonary arterial hypertension, chronic pulmonary heart disease, high altitude disease, hypoxic injury, right heart failure.

[0020] The effect of preventing and / or treating pulmonary arterial hypertension and its complications is achieved by reducing the pulmonary arterial pressure, inhibiting the occurrence of right heart hypertrophy, and reducing pulmonary edema of the TCM formula extract containing Areca catechu.

[0021] The present application can be realized by the following technical solutions. A hypoxic chamber is used to establish a hypoxic pulmonary arterial hypertension mouse model. Three days before modeling, the treatment group animals are given 800 mg / kg / day of TCM formula extract containing Areca catechu extract. The model group and the treatment group animals are placed in a hypoxic chamber with an oxygen concentration of 10% for 2 weeks, and the treatment group is given TCM formula extract containing Areca catechu extract by gavage, with a dose of 800 mg / kg / day. On the 15th day, the indicators of the animals are detected, including body weight, right ventricular systolic pressure, right ventricular hypertrophy index, and organ index, to judge the preventive and therapeutic effects of the TCM formula containing Areca catechu on pulmonary arterial hypertension.

[0022] Beneficial technical effects: The characteristics and advantages of the present application are that the TCM formula containing Areca catechu is a TCM compound, which is safe, has reliable component sources, and has low production cost, and has good market development prospects. Oral administration of the TCM formula containing Areca catechu can improve the cardiopulmonary function of animals, reduce the pulmonary arterial pressure and right ventricular remodeling phenomenon, and can be applied to the preparation of products for preventing and / or treating pulmonary arterial hypertension and its complications, chronic pulmonary heart disease, high altitude disease, hypoxic injury, and right heart failure. BRIEF DESCRIPTION OF DRAWINGS

[0023] Figure 1 Effect of the extract of traditional Chinese medicine formula containing Areca catechu on the right ventricular systolic pressure of hypoxic pulmonary hypertension mice.

[0024] Figure 2 Effect of the extract of traditional Chinese medicine formula containing Areca catechu on the right ventricular remodeling of hypoxic pulmonary hypertension mice.

[0025] Figure 3 Pulmonary protection effect of the extract of traditional Chinese medicine formula containing Areca catechu on hypoxic pulmonary hypertension mice.

[0026] Figure 4 Effect of the extract of traditional Chinese medicine formula containing Areca catechu on the pulmonary vascular remodeling of hypoxic pulmonary hypertension mice. DETAILED DESCRIPTION

[0027] The pharmacological effect and drug use of the extract of traditional Chinese medicine formula containing Areca catechu in preventing and / or treating pulmonary arterial hypertension and its complications in vivo are further illustrated in the present application.

[0028] The following examples illustrate the present application in more detail, but are not intended to be limiting in any way.

[0029] Example 1

[0030] The extract of traditional Chinese medicine formula containing Areca catechu is prepared by water extraction, and the formula is prepared according to the weight ratio of Areca catechu: Radix Paeoniae Alba: Magnolia officinalis: Anemarrhena asphodeloides: Radix Scutellariae: Radix Glycyrrhizae: Amomum tsao-ko = 4:2:2:2:2:1:1. The preparation method is as follows:

[0031] ① The medicinal materials are mixed according to the above-mentioned ratio, 5 times the amount of water is added, and after soaking overnight, it is transferred to an extraction tank;

[0032] ② Boil (slightly boil) for 1.5 h, vacuum filter, and then pump the medicinal liquid into a concentration tank;

[0033] ③ Add 4 times the amount of water to the remaining medicinal residues in the extraction tank, boil (slightly boil) for 1.5 h, vacuum filter, and then pump the medicinal liquid into the concentration tank;

[0034] ④ Add 3 times the amount of water to the remaining medicinal residues in the extraction tank, boil (slightly boil) for 1.5 h, vacuum filter, and then pump the medicinal liquid into the concentration tank;

[0035] ⑤ Combine all the medicinal liquids, reduce pressure and concentrate, pass through a 20-mesh sieve, and obtain the medicinal liquid.

[0036] ⑥ Dry at 70℃ for 48 h to obtain the extract infusion.

[0037] Example 2

[0038] Efficacy evaluation of the extract of the Chinese medicine formula containing Areca catechu on a mouse model of hypoxic pulmonary arterial hypertension: 30 male C57 mice, weighing about 25 g, were divided into three groups, 10 in each group: normal group, model group, and Areca catechu formula group. After adaptive feeding for 3 days, the mice in the model group and the Areca catechu formula group were given the extract of the Chinese medicine formula containing Areca catechu at 800 mg / kg by gavage, and the mice in the normal group were given the same amount of saline by gavage. After 3 days of continuous administration, the mice in the model group and the Areca catechu formula group were placed in a hypoxic chamber with 10% oxygen content and continuously administered for 14 days. The food, water, bedding, and drug were replaced daily by briefly opening the chamber door.

[0039] 1. Effect of the Areca catechu formula on the right ventricular systolic pressure of animals:

[0040] On the 15th day of hypoxic feeding of the mice, the physiological indicators of the animals were detected. After the mice were anesthetized and fixed, the right jugular vein of the mice was bluntly separated, a Miller catheter was used, and the right ventricular systolic pressure of the animals was measured by the classic right heart catheterization method. The average right ventricular systolic pressure of each group was calculated to represent the pulmonary arterial pressure. As shown in FIG. 1, after 2 weeks of hypoxia, the right ventricular systolic pressure of the animals was significantly increased, and the increase in the right ventricular systolic pressure of the animals given the Areca catechu formula was controlled, indicating that the Areca catechu formula can effectively prevent and treat the increase in pulmonary arterial pressure caused by hypoxia. The right ventricular systolic pressures of the animals in each group are shown in Table 1. Figure 1

[0041] Table 1. Effect of the Areca catechu formula on the right ventricular systolic pressure of mice with hypoxic pulmonary arterial hypertension.

[0042]

[0043]

[0044] 2. Effect of the Areca catechu formula on the right ventricular hypertrophy of animals:

[0045] When the hypoxic pulmonary arterial hypertension develops to a certain stage, the right ventricle of the diseased animals gradually remodels due to the increased pressure load, resulting in hypertrophy. The right ventricular index is the ratio of the right ventricular wall weight (RV) to the sum of the left ventricular wall weight (LV) and the interventricular septal mass (S), i.e., RV / (LV+S). As shown in FIG. 2, at the end of the experiment, an increase in the right ventricular index of the animals was observed, and the Areca catechu formula had a certain inhibitory effect on the right ventricular remodeling. The specific data of the right ventricular index of each group are shown in Table 2. Figure 2

[0046] Table 2. Effect of the Areca catechu formula on the right ventricular index of mice with hypoxic pulmonary arterial hypertension.

[0047]

[0048] ​​3. Protective effect of Areca nut formula on lung of animals:

[0049] As shown in Figure 3 , pulmonary edema occurred in pulmonary hypertension mice at the end of the experiment, and the lung index (lung wet weight / body weight*100%) increased significantly. After the intervention of Areca nut formula, the lung index showed a downward trend, and Areca nut formula may have a protective effect on the lung of pulmonary hypertension rats. The specific data of lung index of each group is shown in Table 3.

[0050] Table 3. Effect of Areca nut formula on lung index of hypoxic pulmonary hypertension mice.

[0051]

Claims

1. Use of a traditional Chinese medicine composition comprising Areca catechu in the preparation of a medicament for preventing and / or treating hypoxic pulmonary arterial hypertension, wherein the traditional Chinese medicine composition is prepared from the following raw materials: Areca catechu 10-40 parts by weight, Radix Paeoniae Alba 5-20 parts, Anemarrhena asphodeloides 5-20 parts, Scutellaria baicalensis 5-20 parts, Magnolia officinalis 5-20 parts, Glycyrrhiza 5-10 parts, Amomum tsao-ko 5-10 parts.

2. Use of an extract of a traditional Chinese medicine composition comprising Areca catechu in the preparation of a medicament for preventing and / or treating hypoxic pulmonary arterial hypertension, wherein the extract is prepared by extracting the traditional Chinese medicine composition with water, and the traditional Chinese medicine composition is prepared from the following raw materials: Areca catechu 10-40 parts by weight, Radix Paeoniae Alba 5-20 parts, Anemarrhena asphodeloides 5-20 parts, Scutellaria baicalensis 5-20 parts, Magnolia officinalis 5-20 parts, Glycyrrhiza 5-10 parts, Amomum tsao-ko 5-10 parts.

3. The use according to claim 2, wherein the preparation method of the traditional Chinese medicine formula extract comprises: 4-10 times the total weight of the raw materials of the traditional Chinese medicine composition is added to water, and the mixture is soaked for 1-12 hours, then boiled for 30 minutes-2 hours to obtain a medicinal liquid; The remaining residue is added to 4 times the amount of water, boiled for 30 minutes-2 hours to obtain a medicinal liquid; the remaining residue is added to 3 times the amount of water, boiled for 30 minutes-2 hours to obtain a medicinal liquid; all the medicinal liquids are combined, concentrated under reduced pressure, and then passed through a 20-mesh sieve to obtain a concentrated medicinal liquid; the concentrated medicinal liquid is dried at 70°C to obtain the extract.

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