Traditional Chinese medicine composition for treating primary hypertension as well as effective components and application of traditional Chinese medicine composition

Abstract

The invention relates to a traditional Chinese medicine composition for treating primary hypertension. The traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 13-17 parts of prepared rehmannia root, 13-17 parts of gastrodia elata, 10-14 parts of glossy privet fruit, 7-11 parts of fried tribulus terrestris, 13-17 parts of nacre mother of pearl, 13-17 parts of oyster, 7-11 parts of mulberry and 8-12 parts of angelica sinensis. The invention further provides application of the traditional Chinese medicine composition. The nourishing and latent prescription disclosed by the invention comprises the following 17 effective active components: beta-sitosterol, beta-carotene, clove resinol diglucoside, stigmasterol, olivary glycoside, quercetin, dihydroquercetin and the like. 409 drug disease intersection targets are obtained, and 18 key targets are obtained through PPI analysis. GO enrichment results show that the number of enriched biological processes is 1001, and the enriched biological processes are mainly related to exogenous substance stimulation, protein phosphorylation, chromatin remodeling, positive regulation and control of cell mass proliferation, inflammatory response and the like. According to KEGG analysis, 169 signal channels are enriched, and analysis shows that a MAPK signal channel, a PI3K-Akt signal channel and an IL-17 signal channel are greatly associated with the treatment of the primary hypertension by the nourishing and latent prescription.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and specifically, to a traditional Chinese medicine composition for treating essential hypertension, its active ingredients and applications. Background Art

[0002] Essential hypertension, also known as hypertensive disease, refers to a condition where, without the use of antihypertensive drugs, the systolic blood pressure (high blood pressure) ≥ 140 mmHg and / or the diastolic blood pressure (low blood pressure) ≥ 90 mmHg. The cause has not been fully understood and is related to multiple factors such as genetics and environment, accounting for more than 95% of the hypertensive population. It is one of the most common cardiovascular diseases and an important risk factor for common diseases that cause human death (such as stroke, coronary heart disease, heart failure, etc.).

[0003] Chinese Patent CN: 104491237A discloses the use of a traditional Chinese medicine preparation in the preparation of a drug for treating essential hypertension. The main raw materials of this traditional Chinese medicine preparation include Chinese medicinal herbs such as alisma orientale, ligusticum wallichii, astragalus membranaceus, atractylodes macrocephala, cassia obtusifolia, honeysuckle flower, hawthorn fruit, taxillus chinensis, motherwort herb, pheretima, prunella vulgaris, apocynum venetum, salvia miltiorrhiza, mint, talc, liquorice, etc. These Chinese medicinal herbs are made into finished preparations required clinically by the method developed in the present invention. It not only has the treatment technical advantages of treating both the symptoms and root causes, being not prone to recurrence, having no drug dependence, and having no toxic and side effects for essential hypertension, but also has the promotion advantages of simple preparation process, stable efficacy of the preparation, good general adaptability, and being easy to promote and apply.

[0004] Chinese Patent CN: 106421564A discloses a traditional Chinese medicine for treating essential hypertension, which includes the following raw materials in parts by weight: 20 - 30 parts of ginseng, 15 - 25 parts of stir-fried astragalus membranaceus, 15 - 25 parts of salvia miltiorrhiza, 10 - 20 parts of notoginseng, 10 - 20 parts of costus root, 15 - 25 parts of immature bitter orange, 10 - 20 parts of scrophularia ningpoensis, 10 - 20 parts of moutan bark, 10 - 20 parts of stir-fried atractylodes macrocephala, 15 - 25 parts of lily, 25 - 35 parts of prepared rehmannia root, 15 - 25 parts of trichosanthes root, 10 - 20 parts of magnolia officinalis, 15 - 25 parts of stir-fried atractylodes lancea, 10 - 20 parts of succinum, 10 - 20 parts of sparganium, 5 - 15 parts of uncaria rhynchophylla, 10 - 20 parts of bombyx batryticatus, 10 - 20 parts of scolopendra, 15 - 25 parts of albizia bark, 15 - 25 parts of American ginseng. For hyperactivity of liver-yang, add hematite and abalone shell; for kidney deficiency, add cibotium barometz and eucommia ulmoides, and curculigo orchioides. The whole formula has the effects of promoting blood circulation to remove stasis, nourishing yin and tonifying the kidney, strengthening the spleen and replenishing qi, calming the mind and improving intelligence; it can regulate and tonify the qi, blood, yin and yang of the heart, increase the contractility of the heart, and make the blood supply to the heart and brain sufficient; relieve vasospasm, increase the blood flow of the heart and periphery, and make the blood pressure drop steadily. The total effective rate of blood pressure reduction is 95%, and the total effective rate of symptoms is 98%.

[0005] There are many traditional Chinese medicine compositions for treating essential hypertension, but they all have more or less drawbacks. For example, they have too many medicinal flavors, are difficult to obtain raw materials, and are expensive; their medicinal effects are not obvious, and the treatment effect is poor. Therefore, there is an urgent need for a traditional Chinese medicine composition that has obvious effects in treating essential hypertension, has a small number of medicinal flavors, is practical, has high compliance, and is safe and effective. Summary of the Invention

[0006] The object of the present invention is to provide a traditional Chinese medicine composition for treating essential hypertension, its active ingredients and applications in view of the deficiencies in the prior art.

[0007] In a first aspect, the present invention provides a traditional Chinese medicine composition for treating essential hypertension, which is made from the following raw materials in parts by weight: 13 - 17 parts of Rehmannia glutinosa preparata, 13 - 17 parts of Gastrodia elata, 10 - 14 parts of Glossy Privet Fruit, 7 - 11 parts of stir-fried Tribulus terrestris, 13 - 17 parts of Concha Margaritifera Usta, 13 - 17 parts of Concha Ostreae, 7 - 11 parts of Mulberry Fruit, 8 - 12 parts of Angelica sinensis.

[0008] As a preferred example, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 14 - 16 parts of Rehmannia glutinosa preparata, 14 - 16 parts of Gastrodia elata, 11 - 13 parts of Glossy Privet Fruit, 8 - 10 parts of stir-fried Tribulus terrestris, 14 - 16 parts of Concha Margaritifera Usta, 14 - 16 parts of Concha Ostreae, 8 - 10 parts of Mulberry Fruit, 9 - 11 parts of Angelica sinensis.

[0009] As another preferred example, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 15 parts of Rehmannia glutinosa preparata, 15 parts of Gastrodia elata, 12 parts of Glossy Privet Fruit, 9 parts of stir-fried Tribulus terrestris, 15 parts of Concha Margaritifera Usta, 15 parts of Concha Ostreae, 9 parts of Mulberry Fruit, 10 parts of Angelica sinensis.

[0010] As another preferred example, the active ingredients of the traditional Chinese medicine composition are β-sitosterol, β-carotene, syringaresinol diglucoside, stigmasterol, oleuropein, quercetin, dihydroquercetin, tribulamide, ganoderic acid D, luteolin, moracin M, kaempferol, eriodictyol, cyanidin, deoxyinosine diphosphate, isorhamnetin, lucidusculin.

[0011] In a second aspect, the present invention provides a pharmaceutical composition for treating essential hypertension, which is composed of the traditional Chinese medicine composition and amlodipine besylate.

[0012] In a third aspect, the present invention provides the application of the traditional Chinese medicine composition in the preparation of a drug for treating essential hypertension.

[0013] As a preferred example, the essential hypertension is essential hypertension of the syndrome of yin deficiency and yang hyperactivity.

[0014] In a fourth aspect, the present invention provides the application of the pharmaceutical composition in the preparation of a drug for treating essential hypertension.

[0015] As a preferred example, the essential hypertension is essential hypertension of the syndrome of yin deficiency and yang hyperactivity.

[0016] The advantages of the present invention are as follows:

[0017] The present invention adheres to its core treatment principle of "calming the liver and extinguishing wind, tonifying the liver and kidney", and is optimized according to the characteristics of the syndrome of yin deficiency and yang hyperactivity. The whole formula takes "nourishing yin and suppressing yang" as the outline, and achieves the treatment of both the principal and secondary aspects of the disease through the coordination of the monarch, minister, assistant, and guide drugs. In the formula, Rehmannia glutinosa nourishes yin and replenishes blood, and Gastrodia elata calms the liver and extinguishes wind, and they are used as the monarch drugs together; Tribulus terrestris calms the liver and soothes the liver, and Oyster and Concha Margaritifera Usta suppress yang by calming the liver, and when combined with the monarch drugs, they enhance the power of calming the liver and extinguishing wind; Ligustrum lucidum nourishes and tonifies the liver and kidney, Morus alba nourishes yin and moistens dryness, and Angelica sinensis promotes blood circulation and nourishes blood, and they are used as the assistant drugs together. The whole formula takes both the principal and secondary aspects into consideration, nourishes yin and suppresses yang, and together achieves the effect of calming the liver and extinguishing wind, and tonifying the liver and kidney. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 Comparison of traditional Chinese medicine syndrome scores before and after treatment. Note: ns represents P>0.05, * indicates comparison with before treatment, * P < 0.05, ** P < 0.01, *** P < 0.001; # indicates comparison between groups, # P < 0.05, ## P < 0.01, ### P < 0.001.

[0019] Figure 2 Comparison of clinic blood pressure of two groups of patients before and after treatment. Note: * indicates comparison with before treatment, * P < 0.05, ** P < 0.01, *** P < 0.001; # indicates comparison between groups, # P < 0.05, ## P < 0.01, ### P < 0.001.

[0020] Figure 3 Effective rate of traditional Chinese medicine syndrome of two groups after treatment.

[0021] Figure 4 Antihypertensive effective rate of two groups after treatment.

[0022] Figure 5 Comparison of FMD of two groups after treatment. Note: * indicates comparison with before treatment, * P < 0.05, ** P < 0.01, *** P < 0.001; # indicates comparison between groups, # P < 0.05, ## P < 0.01, ### P < 0.001.

[0023] Figure 6 Comparison of FMD between the two groups after treatment. Note: * indicates comparison with before treatment, * P < 0.05, ** P < 0.01, *** P < 0.001; # indicates comparison between groups, # P < 0.05, ## P < 0.01, ### P < 0.001.

[0024] Figure 7 Venn diagram of the intersection targets of Ziqian Recipe and essential hypertension.

[0025] Figure 8 Target protein interaction diagram.

[0026] Figure 9 Core targets.

[0027] Figure 10 Traditional Chinese medicine - ingredient - target - pathway diagram.

[0028] Figure 11 Results of GO enrichment analysis.

[0029] Figure 12 KEGG pathway enrichment analysis. Specific implementation manners

[0030] The present invention will be further described below in conjunction with specific implementation manners. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. In addition, it should be understood that after reading the content recorded in the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of this application.

[0031] Example 1 Traditional Chinese medicine composition for treating essential hypertension (one)

[0032] 15 parts of Rehmannia glutinosa, 15 parts of Gastrodia elata, 12 parts of Glossy privet fruit, 9 parts of stir-fried Tribulus terrestris, 15 parts of Concha margaritifera usta, 15 parts of Concha ostreae, 9 parts of Mulberry fruit, 10 parts of Angelica sinensis.

[0033] Example 2 Traditional Chinese medicine composition for treating essential hypertension (two)

[0034] 15 parts of Rehmannia glutinosa, 14 parts of Gastrodia elata, 13 parts of Glossy privet fruit, 7 parts of stir-fried Tribulus terrestris, 17 parts of Concha margaritifera usta, 15 parts of Concha ostreae, 8 parts of Mulberry fruit, 11 parts of Angelica sinensis.

[0035] Example 3 Traditional Chinese medicine composition for treating essential hypertension (three)

[0036] 14 parts of Rehmannia glutinosa, 16 parts of Gastrodia elata, 10 parts of Glossy Privet Fruit, 11 parts of Stir-fried Tribulus terrestris, 15 parts of Concha Margaritifera, 14 parts of Concha Ostreae, 10 parts of Mulberry Fruit, 8 parts of Angelica sinensis.

[0037] Example 4 Traditional Chinese Medicine Composition for Treating Essential Hypertension (IV)

[0038] 16 parts of Rehmannia glutinosa, 13 parts of Gastrodia elata, 14 parts of Glossy Privet Fruit, 9 parts of Stir-fried Tribulus terrestris, 14 parts of Concha Margaritifera, 16 parts of Concha Ostreae, 7 parts of Mulberry Fruit, 12 parts of Angelica sinensis.

[0039] Example 5 Traditional Chinese Medicine Composition for Treating Essential Hypertension (V)

[0040] 13 parts of Rehmannia glutinosa, 17 parts of Gastrodia elata, 12 parts of Glossy Privet Fruit, 8 parts of Stir-fried Tribulus terrestris, 16 parts of Concha Margaritifera, 13 parts of Concha Ostreae, 11 parts of Mulberry Fruit, 10 parts of Angelica sinensis.

[0041] Example 6 Traditional Chinese Medicine Composition for Treating Essential Hypertension (VI)

[0042] 17 parts of Rehmannia glutinosa, 15 parts of Gastrodia elata, 11 parts of Glossy Privet Fruit, 10 parts of Stir-fried Tribulus terrestris, 13 parts of Concha Margaritifera, 17 parts of Concha Ostreae, 9 parts of Mulberry Fruit, 9 parts of Angelica sinensis.

[0043] Example 7 Traditional Chinese Medicine Composition for Treating Essential Hypertension (VII)

[0044] 15 parts of Rehmannia glutinosa, 16 parts of Gastrodia elata, 10 parts of Glossy Privet Fruit, 11 parts of Stir-fried Tribulus terrestris, 15 parts of Concha Margaritifera, 14 parts of Concha Ostreae, 10 parts of Mulberry Fruit, 8 parts of Angelica sinensis.

[0045] Example 8 Traditional Chinese Medicine Composition for Treating Essential Hypertension (VIII)

[0046] 14 parts of Rehmannia glutinosa, 13 parts of Gastrodia elata, 14 parts of Glossy Privet Fruit, 9 parts of Stir-fried Tribulus terrestris, 14 parts of Concha Margaritifera, 16 parts of Concha Ostreae, 7 parts of Mulberry Fruit, 12 parts of Angelica sinensis.

[0047] Example 9 Traditional Chinese Medicine Composition for Treating Essential Hypertension (IX)

[0048] 16 parts of Rehmannia glutinosa, 17 parts of Gastrodia elata, 12 parts of Glossy Privet Fruit, 8 parts of Stir-fried Tribulus terrestris, 16 parts of Concha Margaritifera, 13 parts of Concha Ostreae, 11 parts of Mulberry Fruit, 10 parts of Angelica sinensis.

[0049] Example 10 Traditional Chinese Medicine Composition for Treating Essential Hypertension (X)

[0050] 13 parts of Rehmannia glutinosa, 15 parts of Gastrodia elata, 11 parts of Glossy Privet Fruit, 10 parts of Stir-fried Tribulus terrestris, 13 parts of Concha Margaritifera, 17 parts of Concha Ostreae, 9 parts of Mulberry Fruit, 9 parts of Angelica sinensis.

[0051] Example 11 Traditional Chinese Medicine Composition for Treating Essential Hypertension (XI)

[0052] 17 parts of Rehmannia glutinosa Libosch. preparata, 14 parts of Gastrodia elata Blume, 13 parts of Glossy privet fruit, 7 parts of stir-fried Tribulus terrestris L., 17 parts of Concha Margaritifera Usta, 15 parts of Concha Ostreae, 8 parts of Mulberry fruit, 11 parts of Angelica sinensis (Oliv.) Diels.

[0053] Example 12

[0054] Clinical study on the treatment of essential hypertension (yin deficiency and yang hyperactivity syndrome) with the Ziyin Qianyang formula of the present invention 1. Clinical data

[0055] 1.1 Research subjects

[0056] Patients who visited the cardiovascular department ward and outpatient clinic during the period from September 2023 to November 2024 were selected. They were diagnosed with essential hypertension by Western medicine and differentiated into the syndrome of yin deficiency and yang hyperactivity. This research project has been approved by the ethics committee (approval number: 2020 - 806 - 13).

[0057] 1.2 Research design

[0058] This study is a prospective, randomized, controlled clinical trial. For patients meeting the inclusion criteria, they were randomly divided into an experimental group and a control group. By evaluating the changes in traditional Chinese medicine syndrome scores, traditional Chinese medicine syndrome efficacy, hypertension efficacy, clinic blood pressure, brachial - ankle pulse wave velocity (baPWV), flow - mediated dilation (FMD), nitric oxide (NO), homocysteine (Hcy), interleukin - 6 (IL - 6), and free fatty acids before and after treatment, the efficacy and safety of the Ziyin Qianyang formula in treating EH patients were evaluated.

[0059] 2. Research methods

[0060] 2.2 Randomization method

[0061] This study adopted the method of blocked randomization grouping. The specific implementation process: Professional statisticians used SPSS software to complete the generation of the random allocation sequence. The specific steps included setting appropriate block lengths and initial seed values; generating random allocation codes for the experimental group and the control group in a 1:1 ratio; all randomization parameter settings followed the requirements of clinical trial specifications, covering key information such as block size, random seed, and SPSS execution code, and were completely recorded in the randomization process document to ensure the reproducibility of this random grouping.

[0062] 2.3 Treatment plan

[0063] All enrolled patients were instructed to adopt the lifestyle intervention methods recommended in the Guidelines for the Prevention and Treatment of Hypertension in China

[21] (2018 Revised Edition). The main measures included: reducing sodium intake, increasing potassium intake, having a reasonable diet, a balanced diet, controlling body weight, not smoking, not drinking or restricting alcohol consumption, increasing exercise (moderate intensity), reducing mental stress, and maintaining psychological balance.

[0064] (1) Control group: The subjects took amlodipine besylate for basic treatment. Drug specification: 5 mg; Administration method: once a day, one tablet each time, orally taken at 6:00. The above drug was produced by Huizhi Pharmaceutical (Dalian) Co., Ltd.

[0065] (2) Experimental group: On the basis of amlodipine besylate treatment, the subjects were additionally administered the Ziyin Qianyang formula granules of the present invention (composed of 15 parts of Rehmannia glutinosa, 15 parts of Gastrodia elata, 12 parts of Ligustrum lucidum, 9 parts of stir-fried Tribulus terrestris, 15 parts of Concha Margaritifera Usta, 15 parts of Concha Ostreae, 9 parts of Morus alba fruit, and 10 parts of Angelica sinensis), twice a day, one bag each time, taken orally with warm water after meals. The above drug was produced by Jiangyin Tianjiang Pharmaceutical Co., Ltd.

[0066] Course of treatment: 4 weeks was taken as one course of treatment, and a total of 3 courses of treatment were observed with the drug. Telephone follow-up was conducted 12 weeks after the end of the course of treatment.

[0067] 2.4 Observation indicators

[0068] 2.4.1 General information

[0069] Age, height, weight, smoking history, drinking history, disease course, combined diseases and medication history, drug allergy history, etc.

[0070] 2.4.2 Main efficacy indicators

[0071] Refer to the "Clinical Guidelines for New Chinese Medicines"

[22] The syndrome scoring scale formulated was used for scoring. Main symptoms (vertigo, headache, soreness of the waist, weakness of the knees, feverish sensation in the five centers): no symptom was scored 0, mild was scored 2, moderate was scored 4, and severe was scored 6; secondary symptoms (palpitation, insomnia, amnesia, tinnitus): no symptom was scored 0, mild was scored 1, moderate was scored 2, and severe was scored 3.

[0072] 2.4.3 Secondary efficacy indicators

[0073] (1) Clinic blood pressure

[0074] Refer to the "Chinese Guidelines for the Prevention and Treatment of Hypertension" (2018 Revised Edition)

[21] The standardized operation process formulated was used to measure blood pressure. Clinic blood pressure values were collected at week 0 and week 12 respectively. Before each measurement, the subject needed to rest for 10 minutes, and the average value of 3 readings was taken as the final result.

[0075] (2) Flow-mediated vasodilation function

[0076] The flow-mediated vasodilation function (FMD) was measured using a general ultrasonic image diagnostic device (manufacturer: Omron Medical Devices Co., Ltd., model: UNEXEF18VG). The vascular function detection of all subjects was completed by the same cardiovascular specialist physician who had received professional training, and the FMD of the patients was evaluated at week 0 and week 12.

[0077] (3) Arterial vessel stiffness

[0078] The brachial-ankle pulse wave velocity (baPWV) was measured using a Japanese Omron arteriosclerosis detection device (model: BP-203RPEⅢ). The baPWV measurements of all subjects were completed by the same cardiovascular specialist who had received professional training, and the bilateral baPWV of the patients was measured at week 0 and week 12.

[0079] 3. Results

[0080] 3.1 Case collection

[0081] A total of 80 subjects were included in this study and randomly divided into two groups, including an experimental group and a control group, with 40 people in each group. During the 12-week treatment process, no cases were lost.

[0082] 3.2 Comparison of efficacy indexes between the two groups of patients

[0083] 3.2.1 Comparison of traditional Chinese medicine syndrome scores between the two groups of patients after treatment

[0084] Intra-group comparison showed that the total traditional Chinese medicine syndrome scores of both the experimental group and the control group were lower than before, and the difference was statistically significant (P < 0.05); compared with the control group, the syndrome score level of the experimental group was significantly lower than that of the control group after treatment (P < 0.05), as shown in Table 1. Figure 1 .

[0085] Table 1 Comparison of syndrome scores between the two groups of patients [M(P25, P75)]

[0086]

[0087]

[0088] 3.2.2 Comparison of blood pressure between the two groups of patients after treatment

[0089] Intra-group comparison showed that the systolic blood pressure and diastolic blood pressure of both groups were lower after treatment than before, and the difference was statistically significant (P < 0.05). Compared with the control group, the systolic blood pressure and diastolic blood pressure of the experimental group were significantly lower after treatment (P < 0.05), as shown in Table 2. Figure 2 .

[0090] Table 2 Comparison of blood pressure between the two groups of patients

[0091]

[0092] 3.2.3 Comparison of the efficacy of traditional Chinese medicine syndromes between the two groups after treatment

[0093] After 12 weeks of intervention, there was a significant difference between the experimental group and the control group in the improvement of TCM syndrome (P<0.05). The effective rate of TCM syndrome score in the experimental group was 80%, while that in the control group was 20%. The effective rate in the experimental group was higher than that in the control group (see Table 3). Figure 3 .

[0094] Table 3 The efficacy of TCM syndromes in the two groups of patients after treatment

[0095]

[0096] 3.2.4 Comparison of blood pressure efficacy between the two groups after treatment

[0097] After 12 weeks of intervention, the blood pressure control effect evaluation showed that the blood pressure reduction rate in the experimental group was 57.5%, and the blood pressure reduction rate in the control group was 40%. There was no statistically significant difference between the two groups (P>0.05). See Table 4. Figure 4 .

[0098] Table 4 Blood pressure efficacy of the two groups of patients after treatment

[0099]

[0100] 3.2.5 Comparison of FMD between the two groups after treatment

[0101] Before treatment, there was no significant difference in FMD between the two groups (P>0.05). After treatment, the intra-group comparison showed that the FMD of the experimental group after treatment was higher than that before treatment, and the difference was statistically significant (P<0.05). The FMD of the control group after treatment was lower than that before treatment, and the difference was not statistically significant (P>0.05). Compared with the control group, the FMD of the experimental group was higher than that of the control group, and the difference between the two groups was statistically significant (P<0.05). See Table 5. Figure 5 .

[0102] Table 5 Comparison of FMD between the two groups of patients [M (P25, P75)]

[0103]

[0104] 3.2.6 Comparison of BaPWV between the two groups after treatment

[0105] Before treatment, there was no significant difference in bilateral BaPWV between the two groups (P>0.05). After treatment, intra-group comparison showed that the bilateral BaPWV of the experimental group was lower than that before treatment, and the difference was statistically significant (P<0.05). The left BaPWV of the control group was lower than that before treatment, and the difference was statistically significant (P<0.05). Inter-group comparison showed that the left BaPWV and right BaPWV of the experimental group were lower than those of the control group, and the difference between the two groups was statistically significant (P<0.05). See Table 6. Figure 6 .

[0106] Comparison of baPWV between two groups of patients [M(P25, P75)]

[0107]

[0108]

[0109] 3.2.7 Comparison of laboratory test indexes between two groups after treatment

[0110] Before treatment, there was no significant difference in laboratory indexes between the two groups of patients (P > 0.05). After treatment, there were significant differences in MAU, IL-6, and NO within and between the experimental group and the control group (P < 0.05), while there were no significant differences in Hcy and FFA indexes within and between the experimental group and the control group (P > 0.05), as shown in Table 7

[0111] Table 7 Comparison of laboratory test indexes between two groups of patients

[0112]

[0113] Note: * indicates comparison with before treatment, * P < 0.05, ** P < 0.01, *** P < 0.001; # indicates comparison between groups, # P < 0.05, ## P < 0.01, ### P < 0.001

[0114] 4. Summary

[0115] (1) A total of 80 subjects were included in this study, with 40 in the experimental group and 40 in the control group. There were no case dropouts during the 12-week treatment process

[0116] (2) TCM syndrome scores and syndrome efficacy: After treatment, the TCM syndrome scores of both groups of patients decreased significantly compared with the baseline level (P < 0.001); compared with the control group, the experimental group showed a more significant advantage in improving TCM syndrome scores, with a statistically significant difference (P < 0.001); in terms of treatment effectiveness, the total effective rate of the experimental group reached 87.50%, while that of the control group was only 20%, and there was a significant statistical difference between the two groups (P < 0.05).

[0117] (3) Blood pressure evaluation: After treatment, the clinic blood pressure of the experimental group decreased compared with that before treatment, with a statistically significant difference (P < 0.05); the clinic blood pressure of the control group also decreased compared with that before treatment, with a statistically significant difference (P < 0.05); after comparison between groups, the clinic blood pressure of the experimental group was lower than that of the control group, with a statistically significant difference (P < 0.05).

[0118] (4) Vascular function: In terms of BaPWV, the bilateral BaPWV in the experimental group showed a statistically significant decrease compared with the baseline value (P < 0.05), while only the left BaPWV in the control group was significantly lower than that before treatment (P < 0.05); the comparison between groups showed that the bilateral BaPWV levels in the experimental group were lower than those in the control group, with a statistically significant difference (P < 0.05). In terms of FMD, the FMD in the experimental group increased after treatment compared with that before treatment, with a statistically significant difference (P < 0.05), while the FMD in the control group showed a non-statistically significant decrease after treatment (P > 0.05). After between-group analysis, the improvement of FMD in the experimental group was better than that in the control group, and the difference between the two groups was statistically significant (P < 0.05). In terms of NO: After treatment, the NO levels in both groups showed a statistically significant increase (P < 0.05). After between-group comparison, the NO level in the experimental group was higher than that in the control group, and the difference between the two groups was statistically significant (P < 0.05).

[0119] (5) Target organ damage: After treatment, the MAU levels in both the experimental group and the control group showed a statistically significant decrease (P < 0.05). After between-group analysis, the MAU level in the experimental group was significantly lower than that in the control group, with a statistically significant difference (P < 0.05).

[0120] (6) Inflammatory level: After treatment, the IL-6 levels in both the experimental group and the control group were significantly decreased (P < 0.05). After between-group analysis, the IL-6 level in the experimental group was lower than that in the control group, and the difference was statistically significant (P < 0.05).

[0121] Example 13

[0122] Exploring the Mechanism of Ziqian Prescription in the Treatment of Essential Hypertension Based on Network Pharmacology

[0123] 1. Research Objectives

[0124] Based on the analysis results of clinical research, Ziqian Prescription has shown significant antihypertensive efficacy in the treatment of essential hypertension, but its mechanism of action needs to be further systematically elucidated. The mechanism of action of traditional Chinese medicine compound has the characteristics of multiple components and multiple targets. As an emerging interdisciplinary subject integrating systems biology, bioinformatics and computational science, network pharmacology constructs a multi-dimensional network model of "traditional Chinese medicine active ingredients - key targets - signaling pathways", which highly fits with the overall concept of traditional Chinese medicine, providing an innovative technical path for analyzing the complex action network of compound traditional Chinese medicine. This study uses network pharmacology methods to explore the multi-component and multi-target synergistic mechanism of Ziqian Prescription in the treatment of essential hypertension. Through the integration of bioinformatics analysis, it can not only provide a scientific explanation for the previous clinical efficacy, but also provide a theoretical basis for subsequent molecular biology experiments and research on the material basis of drug efficacy.

[0125] 2. Research Methods

[0126] 2.1 Collection of Chemical Constituents and Related Targets of Ziqian Prescription

[0127] Retrieve the chemical constituent information of Ziqian Prescription (Rehmannia glutinosa, Gastrodia elata, Ligustrum lucidum, Tribulus terrestris, Concha Margaritifera Usta, Concha Ostreae, Morus alba, Angelica sinensis) in the TCMSP database and the BATMAN-TCM database. Screen the active ingredients of Ziqian Prescription in the TCMSP database, and set the screening thresholds of OB≥30% and DL≥0.18; import the screened active ingredients into the PubChem database for retrieval, and download the two-dimensional structure files (Sdf format) of the active ingredients. Use the SwissTargetPrediction platform to predict the targets of the compound structure in SDF format, and download and save them. At the same time, retrieve the active ingredients of each medicinal material through the BATMAN-TCM database, and include the targets with a "score not less than 20". After merging all the targets, delete the duplicates.

[0128] 2.2 Collection of Disease Targets Related to Essential Hypertension

[0129] Use "Essential Hypertension" as the keyword to retrieve the disease targets related to essential hypertension in the GeneCards database and the OMIM database, and remove the duplicates to obtain the disease targets of essential hypertension.

[0130] 2.3 Obtaining the Intersection Targets of Disease and Drug

[0131] Use the Venn diagram drawing software to extract the data of the overlapping part of the drug targets of Ziqian Prescription and the disease targets of essential hypertension, and draw the Venn diagram of the intersection targets.

[0132] 2.4 Constructing a Protein-Protein Interaction (PPI) Network to Screen Key Targets

[0133] Import the intersection targets of the drug and the disease into the STRING database, select the target species as "Homo sapiens", and the threshold of the PPI relationship is minimum required interaction score>0.400, construct the PPI network of Ziqian Prescription in the treatment of essential hypertension, and export the node data. Use Cytoscape 3.10.2 software to analyze the PPI relationship.

[0134] 2.5 Constructing a Traditional Chinese Medicine-Active Ingredient-Target Network

[0135] Import the active ingredients and the intersection targets of the drug and the disease into the Cytoscape 3.10.2 software to construct a traditional Chinese medicine-active ingredient-target network.

[0136] 2.6 GO Functional Analysis and KEGG Pathway Analysis

[0137] KEGG pathway enrichment analysis and GO function analysis were carried out using the Metascapes online analysis platform. The species was set to Homo sapiens, the P-value threshold was set to 0.05, and the enrichment results were downloaded in standard format. The above enrichment data was visualized in the form of bubble charts and bar charts using the Weishengxin online analysis platform.

[0138] 3. Results

[0139] 3.1 Active ingredients and drug targets of the Ziyin Qianyang Prescription

[0140] After screening through the TCMSP database with OB≥30% and DL≥0.18, the obtained active ingredients were: 2 for Rehmanniae Radix Praeparata, 4 for Tribuli Fructus, 1 for Angelicae Sinensis Radix, 12 for Ligustri Lucidi Fructus, and 6 for Mori Fructus. The predicted targets in the Swiss TargetPrediction database were exported, including 86 for Rehmanniae Radix Praeparata, 179 for Ligustri Lucidi Fructus, 344 for Tribuli Fructus, 100 for Angelicae Sinensis Radix, and 212 for Mori Fructus. Gastrodiae Rhizoma, Concha Ostreae, and Concha Margaritiferae Usta in the prescription were not included in the TCMSP, so the active ingredients and targets could not be obtained. Therefore, after searching through the BATMAN-TCM database, the ingredients that met the condition of a predicted target score of not less than 20 were obtained, including 30 for Concha Ostreae, 28 for Concha Margaritiferae Usta, and 220 for Gastrodiae Rhizoma. After merging and removing duplicate targets, 463 drug targets were obtained. The results of some active ingredients of the Ziyin Qianyang Prescription are as follows:

[0141] Table 8 Some chemical components of the Ziyin Qianyang Prescription

[0142]

[0143]

[0144] 3.2 Disease targets related to essential hypertension

[0145] A total of 13,737 disease-related targets were obtained. After summarizing and removing duplicates, 13,721 disease-related targets were obtained. After taking the intersection of the drug targets and the disease targets, a Venn diagram was drawn, and 409 intersection targets were extracted and obtained (see Figure 7 )

[0146] 3.3 PPI network construction and key target screening

[0147] The 409 intersection target points obtained were imported into the STRING database to construct the PPI network of the Ziqian formula for treating essential hypertension. There were 407 nodes, 5424 edges, and an average node degree of 26.7. The data obtained from STRING was imported into Cytoscape 3.10.2 to construct a visual analysis of the target protein interaction network. The brighter the color and the larger the size of the node indicate a higher degree value, which reflects the core position of the node in the network.( Figure 8 )

[0148] Eighteen core genes were screened out according to the descending order of connectivity (Degree), which were AKT1, TNF, INS, SRC, EGFR, IL1B, ESR1, BCL2, HIF1A, PTGS2, HSP90AA1, PPARG, NFKB1, MMP9, HSP90AB1, IFNG, GSK3B, and MTOR in turn.( Figure 9 )

[0149] 3.4 Traditional Chinese Medicine - Active Ingredient - Target Network

[0150] The traditional Chinese medicine - active ingredient - target network of the Ziqian formula for treating essential hypertension was constructed using Cytoscape 3.10.2 software (see Figure 10 ). The top 8 chemical components were selected as potential active ingredients of the Ziqian formula for treating essential hypertension according to the degree value, which were Luteolin, Kaempferol, Morin, Isorhamnetin, Quercetin, Eriodictyol, Sitosterol, and Beta - Sitosterol respectively.

[0151] 3.5 GO Functional Analysis, KEGG Pathway Analysis

[0152] GO enrichment analysis was carried out using the Metascape database. The results showed that there were 1001 biological processes (BP) enriched, mainly related to the stimulation of foreign substances, protein phosphorylation, chromatin remodeling, positive regulation of cell population proliferation, inflammatory response, etc. There were 292 molecular functions (MF) enriched, mainly related to protein kinase binding, protein kinase activity, cytokine receptor activity, nuclear receptor activity, ATP binding, etc.; there were 124 cellular components (CC) enriched, mainly participating in components such as the plasma membrane, neuronal synapses, extracellular exosomes, receptor complexes, cytoplasm, extracellular space, etc. The top 10 of each enrichment analysis result were taken for visual analysis, and the results are shown in the figure.( Figure 11 )

[0153] Pathway enrichment analysis was performed on the intersection targets through Metascape, and a total of 169 significant pathways with a P-value less than 0.01 were enriched. The top 25 were selected as key pathways, and a bubble chart was made for visual presentation. The results showed that the enriched pathways were mainly involved in the MAPK signaling pathway, PI3K-Akt signaling pathway, and IL-17 signaling pathway.( Figure 12 )

[0154] 4. Summary

[0155] (1) A total of 17 effective active ingredients of the Ziqian formula were screened out in the analysis: β-sitosterol, β-carotene, syringaresinol diglucoside, stigmasterol, oleuropein, quercetin, dihydroquercetin, tribulosamide, ganoderic acid D, luteolin, morin, kaempferol, eriodictyol, cyanidin, deoxyinosine diphosphate, isorhamnetin, glaucine may be the key components for the treatment of essential hypertension

[0156] (2) There were 409 drug-disease intersection targets, and 18 key targets were obtained through PPI analysis. The key targets mainly included AKT1, TNF, INS, SRC, EGFR, IL1B, ESR1, BCL2, HIF1A, PTGS2, HSP90AA1, PPARG, NFKB1, MMP9, HSP90AB1, IFNG, GSK3B, MTOR, etc.

[0157] (3) The GO enrichment results showed that there were 1001 biological processes (BP) enriched, mainly related to the stimulation of exogenous substances, protein phosphorylation, chromatin remodeling, positive regulation of cell population proliferation, inflammatory response, etc. There were 292 molecular functions (MF) enriched, mainly related to protein kinase binding, protein kinase activity, cytokine receptor activity, nuclear receptor activity, ATP binding, etc.; there were 124 cell components (CC) enriched, mainly participating in components such as plasma membrane, neuronal synapse, extracellular exosome, receptor complex, cytoplasm, extracellular space, etc.

[0158] (4) KEGG analysis enriched 169 signaling pathways. The analysis showed that the Ziqian formula had a relatively large association with the MAPK signaling pathway, PI3K-Akt signaling pathway, and IL-17 signaling pathway in the treatment of essential hypertension.

[0159] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the method of the present invention, several improvements and supplements can be made, and these improvements and supplements should also be regarded as the protection scope of the present invention.

Claims

1. A Chinese medicine composition for treating essential hypertension, characterized in that: The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 13-17 parts of Rehmannia root, 13-17 parts of Gastrodia elata, 10-14 parts of Ligustrum lucidum fruit, 7-11 parts of stir-fried Tribulus terrestris, 13-17 parts of mother of pearl, 13-17 parts of oyster, 7-11 parts of mulberry and 8-12 parts of angelica.

2. The Chinese medicine composition according to claim 1, characterized in that: The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 14-16 parts of Rehmannia root, 14-16 parts of Gastrodia elata, 11-13 parts of Ligustrum lucidum fruit, 8-10 parts of stir-fried Tribulus terrestris, 14-16 parts of mother of pearl, 14-16 parts of oyster, 8-10 parts of mulberry and 9-11 parts of angelica.

3. The Chinese medicine composition according to claim 1, characterized in that The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 15 parts of Rehmannia root, 15 parts of Gastrodia elata, 12 parts of Ligustrum lucidum fruit, 9 parts of stir-fried Tribulus terrestris, 15 parts of mother-of-pearl, 15 parts of oyster, 9 parts of mulberry and 10 parts of angelica.

4. The Chinese medicine composition according to any one of claims 1 to 3, characterized in that: The active ingredients of the traditional Chinese medicine composition are: β-sitosterol, β-carotene, syringaresinol diglucoside, stigmasterol, olive glycoside, quercetin, dihydroquercetin, tribulamide, ganoderin D, luteolin, mulberry yellow, kaempferol, eriodictyol, cyanidin, deoxyinosine diphosphate, isorhamnetin, and glossaconitine.

5. A pharmaceutical composition for treating essential hypertension, characterized in that: The pharmaceutical composition is composed of the traditional Chinese medicine composition according to any one of claims 1 to 3 and amlodipine besylate.

6. Use of the Chinese medicine composition according to any one of claims 1 to 4 or the pharmaceutical composition according to claim 5 in the preparation of a drug for treating essential hypertension.

7. The use according to claim 6, characterized in that: The essential hypertension described is essential hypertension of Yin deficiency and Yang hyperactivity syndrome.

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