CN100356932C - Use of astragalus root in preparing medicine for dilating blood vessel - Google Patents

Abstract

The invention provides the application of astragalus in the preparation of vasodilators, and the application of the astragalus in the preparation of blood pressure-lowering, anti-angina pectoris and other vascular disease drugs. The astragalus can be combined with pharmacodynamically acceptable excipients to prepare a preparation. Forms of preparation mainly include liquid preparations and solid preparations. Solid preparations mainly include granules, tablets, capsules (including soft capsules), and drop pills. Liquid preparations mainly include oral liquid preparations and injection liquid preparations. Administration forms mainly include oral administration or parenteral administration, preferably oral administration. The invention carries out secondary development on the pharmacological action of the traditional Chinese medicine Astragalus membranaceus, and expands the medicinal scope of Astragalus membranaceus; the direct blood vessel expansion effect of Astragalus membranaceus can be used to treat various related vascular diseases.

Description

Application of Radix Astragali in Preparation of Vasodilators

technical field

The invention relates to the application of the traditional Chinese medicine astragalus, and mainly relates to the application of the traditional Chinese medicine astragalus in the preparation of vasodilator drugs, which is suitable for the preparation of blood pressure lowering drugs and also for the preparation of antiangina pectoris drugs.

Background technique

In my country, high blood pressure is a common cardiovascular disease with a high prevalence rate, and its heart, brain, kidney, limbs and other vascular complications and/or complications lead to mortality and disability among various diseases First of all, it is extremely harmful to human health. According to the results of the national census in 1991, the prevalence rate of hypertension in my country was 11.88%. The third sampling survey in Zhejiang Province in 2003 showed that the prevalence rate of hypertension in Zhejiang Province increased by 275% within 13 years. At present, the treatment of hypertension and its related vascular complications and/or comorbidities mainly relies on western medicine, but there has been no breakthrough in the treatment of hypertension with traditional Chinese medicine. Therefore, how to develop the traditional medicine of the motherland and utilize the unique resources of our country to develop traditional Chinese medicine for the treatment of cardiovascular and cerebrovascular diseases such as hypertension has become imperative.

Astragalus, a traditional Chinese medicine, was first recorded in "Shen Nong's Materia Medica", which has a history of more than 2,000 years. According to the records in "Compendium of Materia Medica", Astragalus is sweet and warm in nature, and enters the spleen and lung meridians. It belongs to the category of "qi invigorating" because it has the effects of nourishing qi and raising yang, diuresis and swelling, nourishing qi and strengthening the surface, nourishing blood and strengthening muscles to relieve poison. Medicine, listed as top grade. Previous clinical practice and experimental studies have confirmed that Astragalus has the following main functions: 1) As an immune tonic, it can improve the body's resistance to disease, and it can mainly treat colds, epidemic infectious diseases, viral myocarditis, hepatitis, fever and febrile diseases, and diseases caused by low immunity. In recent years, it has also been used for anti-tumor, adjuvant chemotherapy and other treatments; 2) as a qi-tonifying drug to enhance the yang qi of the spleen and other organs, it is mainly used to treat fatigue, weakness, poor appetite, anemia, Uterine blood loss; in addition, traditional Chinese medicine believes that astragalus has the effect of invigorating qi, promoting yang, diuresis and reducing swelling, and may have a certain effect on the treatment of hypertension in the elderly with spleen and kidney qi ^{deficiency[1]} , so compound preparations containing astragalus (blood pressure Ning, Fangji Astragalus capsules, etc.) ^[2,3,4] , or different formulations of Astragalus (decoction, water infusion, alcohol infusion, etc.) to assist in lowering blood pressure ^[5,6,7] . However, so far, it is not clear whether astragalus can be used alone as a vasomodulatory drug for the treatment of heart, brain, kidney, limbs and other vascular complications and/or comorbidities. Therefore, on the existing basis, the secondary development of the traditional Chinese medicine Astragalus is yet to be carried out.

Contents of the invention

The object of the present invention is to provide the application of astragalus in the preparation of medicines for treating vascular diseases.

In order to observe the regulating effect of single drug Astragalus membranaceus directly on blood vessels, the present invention adopts blood vessel in vitro perfusion technology to eliminate the influence of various nerve and body fluid factors on the vasodilating effect of Astragalus membranaceus in in vivo experiments. It was found that astragalus had a concentration-dependent relaxation effect on isolated blood vessels, and this effect was related to the activation of nitric oxide-guanylate cyclase pathway in vascular endothelial cells by astragalus, antagonism of α-adrenoceptor agonists, and blockade of vascular smooth muscle Inositol triphosphate-sensitive calcium channels on the endoplasmic reticulum.

According to the above research results, the pharmacological effects of Astragalus are similar to those of nitrates and α-adrenoceptor blockers currently used clinically, and have the pharmacological characteristics of some calcium antagonists. Therefore, it can relax smooth muscle, especially the smooth muscle of blood vessels, and is suitable for lowering blood pressure, anti-angina pectoris and other vascular diseases.

The Radix Astragali described in the present invention can be combined with pharmacodynamically acceptable excipients to prepare a preparation.

The preparation forms prepared by the Radix Astragali and pharmaceutical excipients in the present invention mainly include liquid preparations and solid preparations. Solid preparations mainly include granules, tablets, capsules (including soft capsules), and drop pills. Liquid preparations mainly include oral liquid preparations and injection liquid preparations.

The administration form of the preparation mainly includes oral administration or parenteral administration, preferably oral administration.

The beneficial effects of the present invention are: (1) carry out secondary development on the pharmacological action of traditional Chinese medicine Astragalus membranaceus, and expand the medicinal scope of Astragalus membranaceus; disease treatment.

Description of drawings

Figure 1 shows the effect of Astragalus membranaceus on aortic ring tension in the basal state of endothelial integrity.

Figure 2 is the effect of Astragalus membranaceus on aortic ring tension in the basal state of endothelial removal.

Figure 3 is the effect of astragalus on the tension of endothelial intact aortic rings precontracted with potassium chloride.

Figure 4 is the effect of astragalus on KCl-precontracted endothelial-removed aortic ring tension.

Figure 5 shows the effect of Astragalus membranaceus on the tension of intact aortic rings in phenoxyephrine-precontracted endothelium compared with the corresponding control group.

Figure 6 is the effect of astragalus on the tension of phenoxyephrine-precontracted endothelial-removed aortic rings compared to the corresponding control group.

Figure 7 shows the effect of L-NAME and methylene blue pretreatment on the relaxation effect of astragalus on the relaxation effect of phenoxyephrine pre-shrinking endothelial intact aortic ring.

Figure 8 shows the effect of calcium-free solution, calcium-free solution plus heparin on the relaxation effect of Astragalus membranaceus making phenoxyephrine pre-shrink the endothelium to remove the aortic ring.

Detailed ways

The present invention is described further in conjunction with embodiment.

Example 1 Preparation of Rat Isolated Aortic Ring

1. Experimental drug

Astragalus injection is produced by Chengdu Di'ao Pharmaceutical Co., Ltd., containing 2g of Astragalus raw material per milliliter, and containing astragaloside ≥ 0.03mg.

2. Experimental steps:

Clean grade male Sprague-Dawley (SD) rats, weighing 240-260g.

Quickly dissociate the thoracic aorta of SD rats, place it in KH solution pre-saturated with 95% O ₂ and 5% CO ₂ mixed gas at 4°C, remove the surrounding connective tissue, and cut into vascular rings of 3-4 mm, and pay attention to protecting the blood vessels during the process The inner membrane of the ring is not damaged. According to the needs of the experiment, the method of rubbing the inner surface of the vascular ring with a cotton swab was used to prepare a part of the vascular ring as a model in which the endothelium was removed. Then the vascular ring was suspended in a bath pre-prepared with 10mL KH solution, one end was fixed, and the other end was connected to the Medlab biological signal acquisition system through a tension transducer. In the state of continuously passing the mixed gas of 95% O ₂ and 5% CO ₂ , adjust the base tension to 2.0 g, and keep it stable at 37°C for 60 min, during which the liquid is changed every 15 min. The stimulation was repeated three times with KCl (60mmol·L ^-1 ) to induce the maximum contraction range of blood vessels. After the vascular ring was re-stabilized, phenylephrine (PE) (1 μmol·L ^-1 ) was used to constrict the vascular ring to reach the peak value, and acetylcholine (ACh) (10 μmol·L ^-1 ) was added to check the integrity of the vascular endothelium sex. If the PE pre-contracted vascular ring is relaxed by more than 80% after adding ACh, the endothelium can be considered intact; otherwise, the endothelium can be considered to be removed. The maximum contraction amplitude induced by PE (1μmol·L ^-1 ) or KCl (60mmol·L ^-1 ) was taken as 100%, and the ratio of the vascular tension amplitude after adding the drug to the maximum contraction amplitude induced by PE or KCl was used to reflect the vascular tension. Variety.

Example 2 Effect of Radix Astragali on the Relaxation and Contraction Function of the Isolated Aortic Ring

(1) Observing the effect of Astragalus membranaceus on the tension of the vascular ring in the basic state

The source of Radix Astragali is the same as in Example 1. Accumulative dosing method was used to add Astragalus membranaceus once every 10 minutes to observe the effect of accumulatively administering 0.01-3.0 g·L ^-1 of Astragalus membranaceus on endothelial integrity and endothelial removal of vascular rings; in the control group, KH solution was added in equal volume instead of Astragalus membranaceus.

(2) Effect of astragalus on tension of PE or KCl pre-contracted vascular ring

60mmol·L ^-1 KCl or 0.3μmol·L ^-1 PE were used to pre-shrink the vascular ring with complete endothelium, add astragalus 0.01-3.0g·L ^-1 cumulatively every 10min, and observe its effect on pre-shrinking endothelial integrity and endothelial removal of vascular ring The effect of tension; the control group was added with KH solution instead of astragalus.

(3) Results

Referring to Figure 1 and Figure 2, cumulative administration of 0.01-3.0 g·L ^-1 of Astragalus had no significant effect on the basal tension of vascular rings with intact or removed endothelium. Similarly, referring to Fig. 3 and Fig. 4, each concentration of Astragalus membranaceus could not significantly relax the intact endothelium or the removed vascular ring induced by KCl. However, for PE pre-contracted endothelium intact and removed vascular rings, (0.1～3g·L ^-1 ) Astragalus showed a concentration-dependent relaxation effect, see Figure 5 and Figure 6, where ^* P<0.05, ^** P<0.01 , and the relaxation effect on the endothelium-removed vascular ring is weaker than that of the endothelium intact (see Figure 5, Figure 6).

Example 3 Effects of Radix Astragali on the diastolic function of different pretreatment aortic rings

According to the above experimental results, it was found that when the Astragalus concentration accumulated to 3.0g/L, its effect had reached the maximum degree of stability, so the concentration of 3.0g/L was selected for the next experiment, and the source of Astragalus was the same as in Example 1.

(1) The effect of astragalus on the intact vascular ring of endothelium

Take nitric oxide synthase (NOS) inhibitor L-nitroarginine methyl ester (N(ω)-nitro-L-arginine-methyl-ester, L-NAME) (0.1mmol·L ^-1 ) or guanosine The acid cyclase inhibitor methylene blue (10μmol·L ^-1 ) pretreated the ^vascular ring with intact endothelium for 15min, and then preconstricted the blood vessels with 0.3μmol·L ^-1 PE. The effect of vascular ring tension; in the control group, KH solution was added instead of Astragalus at equal volume.

(2) The effect of astragalus on endothelial removal of vascular rings

The endothelium-removed vascular rings were pretreated with calcium-free solution and calcium-free solution plus (5×10 ^-2 g/L) heparin for 20 min, and then 3×10 ^-7 mol/L PE was added to make the blood vessels shrink. Astragalus (3.0 g • Effect of L ^-1 ) on contraction of vascular ring tension. In the control group (n=8), KH solution was used instead of astragalus to incubate the vascular rings removed from the endothelium.

(3) Effects of different pretreatment vascular rings on the effect of Astragalus membranaceus

The above experimental results showed that when the concentration of Astragalus membranaceus reached 3 g·L ^-1 , its relaxation effect on PE pre-contracted vascular rings reached the maximum. Therefore, take it as the best relaxation concentration to further explore the mechanism of Astragalus dilating blood vessels.

It was found that pretreatment of intact endothelial vascular rings with the nitric oxide synthase inhibitor L-NAME or the guanylate cyclase inhibitor methylene blue could significantly inhibit the relaxation induced by 3g·L ^-1 astragalus, See Figure 7, which shows that compared with the corresponding control group, ^* P<0.05, ^** P<0.01; compared with the non-pretreated Astragalus group, ⁺ P<0.05, ⁺⁺ P<0.01.

After pretreatment with calcium-free solution, the relaxation effect of astragalus on vascular rings was not blocked; but after pretreatment with calcium-free solution plus heparin, the effect was significantly inhibited. See Figure 8, which shows that compared with the corresponding control group, ^* P<0.05, ^** P<0.01; compared with the non-pretreated Astragalus group, ⁺ P<0.05, ⁺⁺ P<0.01.

Without further elaboration, it is believed that one skilled in the art can, using the preceding disclosure, utilize it to its fullest extent. Accordingly, the foregoing preferred specific embodiments should be understood as illustrative only and not limiting the scope of the invention in any way.

Part of the references involved in the present invention

1. Non-author. Astragalus membranaceus. Alternative Medicine Review 2003, 8(1): 72-27.

2. Xiao Yan, Wen Wangxiu, Cheng Kanglin, Zhang Zhong. Clinical observation of 34 cases of essential hypertension of the phlegm-turbidity obstruction type treated by traditional Chinese medicine Fangji Huangqi Capsules combined with western medicine. Chinese Journal of Traditional Chinese Medicine 2002, 43(4): 271-272.

3. Xiong Shangzhong, Xu Xiaozhou. Syndrome Differentiation Treatment of 120 Cases of Elderly Hypertension. Sichuan Traditional Chinese Medicine 2001, 19(8): 38.

4. Song Wenhua, Huang Jingwen. 58 Cases of Elderly Hypertension Treated by Integrated Traditional Chinese and Western Medicine. Shaanxi Traditional Chinese Medicine 1998, 19(1): 9.

5. Shanghai Journal of Traditional Chinese Medicine 1956, (1): 8.

6. Fujian Traditional Chinese Medicine 1963, 8(3): 27.

7. Journal of Beijing University of Traditional Chinese Medicine 1960, (2): 128.

Claims (2)

1. the application of Radix Astragali in the preparation of vasodilators, characterized in that it is used in the preparation of blood pressure lowering or antiangina pectoris drugs. 2. the application of Radix Astragali according to claim 1 in the preparation of vasodilators is characterized in that: said Radix Astragali is a single component containing astragaloside IV, and the preparation forms prepared with pharmaceutical excipients include liquid preparations and solid preparations.

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