Method for preparing a medicinal preparation and its use in the treatment of hypertensive diseases

Abstract

The application discloses a preparation method of a Chinese medicine preparation and application of the Chinese medicine preparation in treatment of hypertension, relates to the field of traditional Chinese medicine preparations, and comprises the following steps: determining core active ingredients, key action targets and signal pathways of the Chinese medicine in treatment of hypertension based on a network pharmacology method; preparing a Chinese medicine extract according to the determined core active ingredients; mixing the Chinese medicine extract with antihypertensive traditional Chinese medicine classical prescriptions and excipients to prepare the Chinese medicine preparation; and preparing the Chinese medicine preparation by compounding the Chinese medicine extract with antihypertensive traditional Chinese medicine classical prescriptions such as Banxia Baizhu Tianma Decoction and Shengma Gouteng Decoction and excipients. The Chinese medicine preparation solves the problems that the existing hypertension treatment only focuses on blood pressure value control, cannot comprehensively improve traditional Chinese medicine syndromes and internal pathological mechanisms, and lacks network pharmacology guidance and standardized application schemes for the Chinese medicine combined with classical prescriptions in treatment of various traditional Chinese medicine syndromes of hypertension, and finally realizes the effects of multi-target, multi-pathway synergistic antihypertension and overall conditioning.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparation technology, specifically to the preparation method of aromatic medicine preparations and their application in the treatment of hypertension. Background Technology

[0002] Hypertension, a common chronic non-communicable disease, is the leading risk factor for the incidence and mortality of cardiovascular and cerebrovascular diseases. Aromatic herbs, a unique category in traditional Chinese medicine, refer to drugs with aromatic properties, primarily affecting the spleen, stomach, and lung meridians, and possessing functions such as resolving dampness, regulating qi, opening orifices, and relieving pain. These include agarwood, sandalwood, costus root, patchouli, amomum villosum, tangerine peel, cyperus rotundus, sandalwood, and rose.

[0003] Although Traditional Chinese Medicine (TCM) does not have a specific disease name for "hypertension," its clinical manifestations highly overlap with categories such as "dizziness" and "headache." Common clinical syndromes include phlegm-dampness accumulation syndrome, liver yang hyperactivity syndrome, qi stagnation and blood stasis syndrome, yin deficiency and yang hyperactivity syndrome, yin and yang deficiency syndrome, and phlegm-blood stasis syndrome. Modern medicine treats hypertension primarily with drug intervention. Commonly used drugs include calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), and diuretics. These drugs play an important role in controlling blood pressure, but treatment often focuses on controlling blood pressure values ​​and is difficult to comprehensively improve accompanying symptoms such as dizziness, chest tightness, and fatigue, failing to fundamentally intervene in the underlying pathological mechanisms of hypertension's development.

[0004] Therefore, this invention provides a method for preparing aromatic herbal preparations and their application in the treatment of hypertension, a systematic study of combining aromatic herbs with traditional Chinese medicine formulas for the treatment of various types of hypertension, and a method for guiding the preparation of aromatic herbal preparations and their clinical application based on network pharmacology. Summary of the Invention

[0005] The purpose of this invention is to provide a method for preparing aromatic herbal preparations and their application in the treatment of hypertension, in order to solve the problem of the lack of network pharmacology guidance and standardized application schemes for the treatment of various TCM syndromes of hypertension by combining aromatic herbs with classic prescriptions in the prior art.

[0006] To achieve the above objectives, the present invention provides the following technical solution: a method for preparing aromatic preparations, comprising the following steps:

[0007] S1. Identify the core active ingredients of aromatic herbs for treating hypertension and their key targets and signaling pathways based on network pharmacology methods;

[0008] S2. Prepare aromatic extracts based on the identified core active ingredients;

[0009] S3. Mix the aromatic herb extract with traditional Chinese medicine formulas for lowering blood pressure and excipients to prepare aromatic herb preparations;

[0010] The aromatic herbs are selected from one or more of the following: agarwood, sandalwood, costus root, patchouli, amomum villosum, dried tangerine peel, cyperus rotundus, sandalwood, and rose.

[0011] Among them, the traditional Chinese medicine formulas for lowering blood pressure include Banxia Baizhu Tianma Decoction, Tianma Gouteng Drink, Xuefu Zhuyu Decoction, Zhengan Xifeng Decoction, Jinkui Shenqi Pill, Er Chen Decoction combined with Taohong Siwu Decoction.

[0012] Furthermore, the syndrome types of hypertension include phlegm-dampness accumulation syndrome, liver yang hyperactivity syndrome, qi stagnation and blood stasis syndrome, yin deficiency and yang hyperactivity syndrome, yin and yang deficiency syndrome, and phlegm-blood stasis syndrome.

[0013] Furthermore, the network pharmacology method described in S1 includes:

[0014] S11. Using "fragrant medicine name" as keywords, such as agarwood, sandalwood, costus root, patchouli, amomum villosum, dried tangerine peel, cyperus rotundus, sandalwood, and rose, search for bioactive ingredients from the TCMSP database. Use oral bioavailability ≥30% and drug-likeness ≥0.18 as screening criteria to obtain potential active ingredients of fragrant medicines.

[0015] S12. The SMILES structure of the active ingredient is imported into the SwissTargetPrediction database and the CTD database for target prediction to obtain the potential targets of the active ingredient of the aromatic medicine.

[0016] S13. Using "Hypertension" as the keyword, screen for targets related to hypertension from the Genecards database and the OMIM database;

[0017] S14. By performing an intersection analysis between the potential targets of the active ingredients of aromatic herbs and the targets of hypertension, the potential targets of aromatic herbs in treating hypertension can be obtained.

[0018] S15. Import the intersection target points into the STRING database to construct a PPI network, perform topology analysis using Cytoscape software, and select the core target points based on the degree values.

[0019] S16. Import the intersection target points into the MetaScape database for GO function enrichment analysis and KEGG pathway enrichment analysis to determine the main signaling pathways.

[0020] Furthermore, the core active ingredient described in S1 includes at least one of 6,7-dimethoxy-2-(2-phenylethyl)chromone, DMPEC, norboridine, C09495, nubigenol, boridine, β-sitosterol, stigmasterol, and quercetin.

[0021] Furthermore, the core target mentioned in S15 includes at least one of SRC, TP53, AKT1, EGFR, ESR1, CTNNB1, HIF1A, STAT3, SMAD3, and MDM2.

[0022] Furthermore, the main signaling pathways mentioned in S16 include at least one of the following signaling pathways: PI3K-Akt, cGMP-PKG, AGE-RAGE, HIF-1, MAPK, FoxO, and Apelin.

[0023] Furthermore, the aromatic extract described in S2 is extracted using alcohol extraction, water extraction, or a combination of alcohol and water extraction processes.

[0024] Application of aromatic medicinal preparations prepared according to the preparation method in the treatment of hypertension.

[0025] Furthermore, in the daily dosage of the aromatic medicine preparation, the amount of raw herbs in the traditional Chinese medicine formula is calculated according to the original formula ratio, and the aromatic herbs are 1-4g based on the amount of raw herbs.

[0026] Furthermore, the applications include at least one of the following: lowering systolic blood pressure, lowering diastolic blood pressure, improving TCM syndromes, improving insulin resistance, reducing inflammatory factor levels, improving vascular endothelial function, and regulating gut microbiota.

[0027] Compared with existing technologies, the method for preparing aromatic medicinal preparations and their application in the treatment of hypertension provided by this invention elucidates the core active ingredients, key targets, and main signaling pathways of aromatic medicinals such as agarwood, sandalwood, and costus root in the treatment of hypertension based on network pharmacology. The aromatic medicinal extracts are combined with antihypertensive traditional Chinese medicine formulas such as Banxia Baizhu Tianma Decoction and Tianma Gouteng Decoction, as well as excipients, to prepare aromatic medicinal preparations. This solves the problems of existing hypertension treatments that only focus on blood pressure numerical control and are difficult to comprehensively improve TCM syndromes and internal pathological mechanisms, as well as the lack of network pharmacology guidance and standardized application schemes for the combined use of aromatic medicinals and classic formulas to treat various TCM syndromes of hypertension. Ultimately, it achieves synergistic antihypertensive and overall conditioning effects across multiple targets and pathways. Attached Figure Description

[0028] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in this invention. For those skilled in the art, other drawings can be obtained based on these drawings.

[0029] Figure 1 Venn diagram showing the intersection of potential targets of aromatic active ingredients and targets of hypertension provided in this embodiment of the invention;

[0030] Figure 2The drug-component-target-disease network diagram provided in the embodiments of the present invention;

[0031] Figure 3 A network diagram of PPI interactions in the treatment of hypertension with aromatic herbs provided in this embodiment of the invention;

[0032] Figure 4 This is a GO functional enrichment analysis diagram of the intersection target of aromatic herbs in treating hypertension provided in an embodiment of the present invention;

[0033] Figure 5 This is a bubble diagram showing the KEGG pathway enrichment of overlapping targets for aromatic medicines in treating hypertension, provided in an embodiment of the present invention. Detailed Implementation

[0034] To enable those skilled in the art to better understand the technical solution of the present invention, the present invention will be further described in detail below with reference to the accompanying drawings.

[0035] Example 1:

[0036] Please see Figure 1-5 In this embodiment, we will conduct a network pharmacological screening of aromatic herbs for the treatment of hypertension with phlegm and dampness accumulation. The method used in this embodiment is the same for the network pharmacological screening of sandalwood, costus root, patchouli, amomum villosum, tangerine peel, cyperus rotundus, sandalwood, and rose.

[0037] 1. Screening of chemical components and their potential targets

[0038] Using "agarwood" as the search keyword, a total of 128 agarwood-related bioactive components were retrieved from the TCMSP database. Based on the screening criteria of oral bioavailability (OB) ≥30% and drug-likeness (DL) ≥0.18, nine core active components were finally selected, namely 6,7-dimethoxy-2-(2-phenylethyl)chromone, DMPEC, norboridine, C09495, nubigenol, boridine, β-sitosterol, stigmasterol, and quercetin. Detailed information on each component is shown in Table 1.

[0039] Table 1. Core active ingredients of agarwood and their screening parameters

[0040] MolID Ingredient name OB DL OB / DL MOL010495 6,7-Dimethoxy-2-(2-phenylethyl)chromone 31.93 0.3 106.43 MOL010496 DMPEC 32.38 0.39 83.02 MOL010907 Norboldine 40.92 0.46 88.95 MOL010913 C09495 77.09 0.25 308.36 MOL010916 Nubigenol 42.55 0.19 223.94 MOL010917 Boldine 31.18 0.51 61.13 MOL000358 β-sitosterol 36.91 0.75 49.21 MOL000359 sitosterol 36.91 0.75 49.21 MOL000098 Quercetin 46.43 0.28 165.82

[0041] Target prediction was performed using a combination of CTD, PubChem, and SwissTargetPrediction databases. A total of 4,999 potential targets related to the active ingredients of agarwood were obtained, and after deduplication, 4,658 potential targets were obtained.

[0042] 2. Acquisition of targets for hypertension-related diseases

[0043] Using "Hypertension" as the search keyword, 14,235 hypertension-related targets were obtained, and the top 500 targets were selected. A search of the OMIM database yielded 200 hypertension-related targets. The search results from the two databases were merged and deduplicated, ultimately resulting in 631 core disease targets for hypertension.

[0044] 3. Construction of a drug-active ingredient-target-disease network diagram

[0045] Potential targets of agarwood active ingredients (4658) and targets of hypertension (631) were imported into Venny 2.1.0 online software for intersection analysis, and Venn diagrams were plotted (see...). Figure 1 A total of 296 overlapping targets were obtained, which are the potential targets for the treatment of hypertension by agarwood.

[0046] The 296 intersecting targets were imported into Cytoscape 3.9.1 software to construct an interaction network diagram of "drug-active ingredient-target-disease" (see...). Figure 2 In this topological analysis, swallowtail nodes represent diseases, triangular nodes represent drugs, circular nodes represent active ingredients, and rhomboid nodes represent intersection targets. Based on degree ranking, the core active ingredients of agarwood for treating hypertension were identified as quercetin, β-sitosterol, DMPEC, norboridine, and 6,7-dimethoxy-2-(2-phenylethyl)chromone, suggesting that these components may be the key material basis for agarwood's intervention in hypertension.

[0047] 4. Protein-protein interaction (PPI) network analysis

[0048] The 296 intersection target points were imported into the STRING database to construct a PPI network, resulting in 292 nodes and 245 edges. The average node degree was 1.68, the local clustering coefficient was 0.331, and the p-value was <1×10⁻⁶. -6 This indicates that the PPI network is statistically significant. The PPI network data was imported into Cytoscape 3.9.1 software for visualization analysis (see...). Figure 3 In a network, the darker the color, the larger the shape, and the larger the font of a node, the higher its degree value and the more critical its role in network regulation.

[0049] Based on degree ranking, the core targets in the PPI network were selected, in descending order: proto-oncogene tyrosine protein kinase Src (SRC), cell tumor antigen p53 (TP53), RAC-α serine / threonine protein kinase (AKT1), epidermal growth factor receptor (EGFR), and estrogen receptor (ESR1). Detailed topological parameters for each core target are shown in Table 2. These core targets are largely involved in vascular function regulation, inflammatory responses, and cell proliferation and apoptosis, suggesting they may be key targets for agarwood's therapeutic effect on hypertension.

[0050] Table 2. Topology parameters of PPI network core targets in agarwood therapy for hypertension

[0051] Serial Number Target Name Degree value Medium Tightness 1 Proto-oncogene tyrosine protein kinase Src (SRC) 32 1467.25097 44.48333 2 Cellular tumor antigen p53 (TP53) 30 862.19996 41.82619 3 RAC-α serine / threonine protein kinase (AKT1) 30 1262.78675 43.05952 4 Epidermal growth factor receptor (EGFR) 28 978.53224 43.06667 5 Estrogen receptor (ESR1) 26 1046.68715 43.4 6 Chain protein β-1 (CTNNB1) 26 763.40573 42.48333 7 Hypoxia-inducible factor 1-αHIF1A 24 805.39453 41.67619 8 Signal transducers and transcription activator 3 (STAT3) 22 335.08201 39.77619 9 SMAD Family Member 3 (SMAD3) 22 649.59954 39.90952 10 E3 ubiquitin ligase Mdm2 (MDM2) 22 670.66699 39.04286

[0052] 5. GO functional enrichment analysis and KEGG pathway enrichment analysis

[0053] 296 intersection target points were imported into the MetaScape database for GO function enrichment analysis, and then visualized using the MicroBioinformatics platform (see...). Figure 4 The results showed that 208 items were enriched in the Biological Process (BP) category, mainly involving blood circulation, response to decreased oxygen levels, and tube morphogenesis; 106 items were enriched in the Cellular Component (CC) category, mainly including receptor complex, membrane raft, and apical part of cell; and 114 items were enriched in the Molecular Function (MF) category, mainly involving signaling receptor regulator activity, protein homodimerization activity, tetrapyrrole binding, and steroid binding. The top 10 GO items in each category were summarized, and detailed information is shown in Table 3.

[0054] Table 3. GO Functional Enrichment Table of Intersecting Targets in Agarwood Treatment of Hypertension

[0055]

[0056]

[0057] 296 overlapping targets were imported into the MetaScape database for KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis, yielding 132 relevant signaling pathways. The top 15 pathways were selected, and a KEGG pathway enrichment bubble chart was generated using the MicroBio platform (see [link to data]). Figure 5 The results showed that the potential targets of agarwood in treating hypertension were mainly enriched in 10 significantly different signaling pathways, and detailed enrichment information for each pathway is shown in Table 4. These pathways are mostly involved in processes such as vasomotor regulation, inflammatory response, energy metabolism, and cell proliferation and apoptosis, suggesting that agarwood may exert a multi-target synergistic antihypertensive effect by regulating these signaling pathways.

[0058] Table 4. KEGG pathway enrichment table of intersection targets for agarwood in the treatment of hypertension

[0059] Term Enrichment (%) P-value Count Pathways in cancer development 21.28 4.17062E-49 63 Age-Rage Signaling Pathway in Diabetic Complications 11.15 1.95577E-41 33 Hormone signaling 11.15 2.55045E-29 33 PI3K-Akt signaling pathway 11.15 3.37746E-22 33 Diabetic cardiomyopathy 10.81 5.82422E-29 32 HIF-1 signaling pathway 8.78 1.08385E-28 26 cGMP-PKG signaling path 8.78 9.3116E-24 26 FoxO signaling pathway 7.43 8.12132E-21 22 Apelin signaling pathway 7.09 5.23146E-19 21 Malaria 6.76 1.24197E-27 20 Rheumatoid arthritis 6.76 3.04295E-21 20 Non-alcoholic fatty liver disease 6.42 1.55586E-15 19 Adipocytokine signaling pathway 5.07 2.2738E-16 15 Aldosterone-regulated sodium reabsorption 4.05 1.34054E-15 12 Bladder cancer 4.05 3.80999E-15 12

[0060] Example 2:

[0061] This embodiment provides a combination of aromatic herbs (agarwood) and Banxia Baizhu Tianma Decoction for the treatment of hypertension with phlegm-dampness accumulation.

[0062] In this embodiment, after screening using the method provided in Example 1, 100g of agarwood was taken, pulverized into coarse powder, and the core active ingredient was selected as the target for extraction. Ten times the volume (v / w) of 70% ethanol was added, and the mixture was heated under reflux twice, 1.5 hours each time. The extracts were combined, filtered, and the ethanol was recovered from the filtrate under reduced pressure. The extract was then concentrated to a clear paste with a relative density of 1.25 (60°C) to obtain the agarwood extract. HPLC fingerprinting technology was used for quality control of the core active ingredient. The chromatographic conditions were: C18 column, gradient elution with methanol-0.1% phosphoric acid aqueous solution as the mobile phase, and a detection wavelength of 254nm. The fingerprint of the test sample was required to be consistent with the standard fingerprint, and the quercetin content was not less than 0.1%.

[0063] The traditional Chinese medicine formula uses the original Banxia Baizhu Tianma Decoction. The herbs are weighed, soaked in 8 times their volume of water for 30 minutes, and then decocted twice: the first time for 2 hours, and the second time for 1.5 hours. The decoctions are combined, filtered, and the filtrate is concentrated under reduced pressure to a clear extract with a relative density of 1.25 (60℃). One dose is taken daily, decocted in water and taken warm in two divided doses.

[0064] Agarwood extract and classical extract are mixed, and appropriate amounts of dextrin and lactose are added. The mixture is stirred until smooth, formed into a soft mass, and granulated using a 14-mesh sieve. The wet granules are dried at 60°C and sized to obtain the aromatic herbal preparation granules. Each sachet of granules contains 1g of raw agarwood.

[0065] Patients meeting the Western medicine diagnostic criteria for grade 1-2 essential hypertension, the TCM diagnostic criteria for phlegm-dampness excess syndrome, aged 18-70 years (regardless of gender), who had not taken any medications related to this study (including agarwood and other aromatic preparations) within the past two weeks, were willing to participate in this clinical study, signed written informed consent forms, and were able to cooperate in completing the entire treatment and follow-up process, were selected. Forty patients meeting the above criteria were included. The aromatic preparation granules (equivalent to 1g of raw agarwood per day) prepared above were administered once daily, divided into two doses, for an 8-week treatment period.

[0066] Table 5 Comparison of clinical data before and after treatment

[0067] Clinical data Before treatment After treatment Systolic blood pressure (mmHg) 149.8±9.7 132.6±7.8 Diastolic blood pressure (mmHg) 95.7±5.9 82.7±5.0 Total score of TCM syndrome 339.6±26.0 272.1±21.8 Headache and dizziness score 4.2±0.7 3.1±0.6 Score for greasy taste 3.8±0.9 3.0±0.7 Limb sluggishness score 4.3±0.6 3.2±0.6 Sticky and uncomfortable stool scores points 3.9±0.8 3.1±0.7 Fasting insulin (μU / mL) 18.7±3.3 12.5±2.5 HOMA-IR 5.73±1.3 3.44±0.9 TNF-α (pg / mL) 12.6±2.2 6.8±1.6 IL-6 (pg / mL) 8.4±1.8 6.3±1.5 FMD / (%) 4.9±1.0 6.4±1.3 Shannon Index 2.4±0.5 3.3±0.5 Total SCFA / (μmol / g) 44.8±9.5 61.3±9.8

[0068] As shown in Table 5, the patients' systolic and diastolic blood pressures were significantly reduced, and the symptoms of phlegm-dampness excess, such as heaviness in the head, dizziness, greasy mouth and limbs, and sticky stools, were significantly improved. Insulin resistance, inflammatory factor levels, vascular endothelial function, and intestinal flora diversity were also effectively improved.

[0069] Example 3:

[0070] This embodiment provides a treatment for hypertension with liver yang hyperactivity syndrome using aromatic herbs (Cyperus rotundus and rose) combined with Gastrodia elata and Uncaria rhynchophylla decoction.

[0071] Bioactive components were retrieved from the TCMSP database using "Cyperus rotundus" and "rose" as keywords. Based on oral bioavailability ≥30% and drug-likeness ≥0.18, core active components such as 6,7-dimethoxy-2-(2-phenylethyl)chromone, β-sitosterol, stigmasterol, and quercetin were identified. Through target prediction, disease target intersection, PPI network analysis, and KEGG pathway enrichment, core targets such as SRC, TP53, and AKT1, as well as key signaling pathways such as PI3K-Akt and HIF-1, were determined.

[0072] Weigh out 100g of mixed aromatic herbs (Cyperus rotundus and Rosa rugosa) in a 1:1 ratio. Grind the herbs into a coarse powder. Targeting the core active ingredients, add 10 times (v / w) of 70% ethanol and extract twice under reflux, 1.5 hours each time. Combine the extracts, filter, recover the ethanol from the filtrate under reduced pressure, and further concentrate to a clear extract with a relative density of 1.25 (60℃) to obtain the Cyperus rotundus and Rosa rugosa mixed extract. HPLC fingerprinting technology was used for quality control of the core active ingredients.

[0073] The traditional Chinese medicine formula Tianma Gouteng Decoction was used, extracted and concentrated using the conventional water decoction method according to the original formula. A mixed extract of Cyperus rotundus and rose was mixed with the extract of Tianma Gouteng Decoction and granulated. The total raw amount of Cyperus rotundus and rose in the daily dosage was 2g. Patients meeting the Western medicine diagnostic criteria for grade 1-2 essential hypertension, the TCM diagnostic criteria for liver yang hyperactivity, aged 18-70 years, regardless of gender, who had not taken any medications related to this study within the past two weeks, were willing to participate in this clinical study, signed written informed consent, and were able to cooperate in completing the entire treatment and follow-up process were selected. Forty patients meeting the above criteria were included. The prepared aromatic herbal granules were administered once daily, divided into two doses, for an 8-week treatment period.

[0074] Eight weeks after administration, the patient's blood pressure was effectively reduced, and symptoms of liver yang hyperactivity, such as dizziness, headache, flushed face and red eyes, and irritability, were significantly improved. At the same time, it inhibited inflammation and repaired vascular endothelial function.

[0075] Example 4:

[0076] This embodiment provides a combination of aromatic herbs (sandalwood, costus root, and sandalwood) and Xuefu Zhuyu Decoction for the treatment of hypertension with qi stagnation and blood stasis syndrome.

[0077] Bioactive components were retrieved from the TCMSP database using keywords such as "sandalwood," "costus root," and "fragrant sandalwood." Based on oral bioavailability ≥30% and drug-likeness ≥0.18, core active components such as β-sitosterol, stigmasterol, and quercetin were identified. Through target prediction, disease target intersection, PPI network analysis, and KEGG pathway enrichment, core targets and key signaling pathways such as AGE-RAGE and MAPK were determined.

[0078] A mixture of sandalwood, costus root, and sandalwood was weighed in a 1:1:1 ratio, totaling 100g. The mixture was coarsely powdered and extracted using 70% ethanol under reflux, targeting the core active ingredients. The extract was concentrated to a relative density of 1.25 (60℃) to obtain a clear extract. The extract was then quality controlled by HPLC fingerprinting to obtain the sandalwood, costus root, and sandalwood mixed extract. The traditional Chinese medicine formula Xuefu Zhuyu Decoction was used for water decoction extraction, which was then concentrated to obtain a clear extract. The clear extract of the mixed extract and the clear extract of the traditional Chinese medicine formula were mixed and granulated to obtain the aromatic medicine preparation granules. In the daily dosage, the traditional Chinese medicine formula uses the original proportions of raw herbs, and the total raw herb content of the mixed aromatic herbs is 1g.

[0079] Patients meeting the Western medicine diagnostic criteria for grade 1-2 essential hypertension, the TCM diagnostic criteria for Qi stagnation and blood stasis, aged 18-70 years (regardless of gender), who had not taken any medications related to this study within the past two weeks, were willing to participate in this clinical study, signed written informed consent forms, and were able to cooperate in completing the entire treatment and follow-up process were selected. Forty patients meeting these criteria were included. The prepared aromatic herbal granules were administered once daily, divided into two doses, for an 8-week treatment period.

[0080] Eight weeks after administration, the patient's blood pressure decreased significantly, and symptoms of qi stagnation and blood stasis, such as stabbing headache, chest tightness and rib pain, and purplish tongue, improved, as well as vascular function and metabolic status.

[0081] Example 5:

[0082] This embodiment provides a treatment for hypertension with yin deficiency and yang hyperactivity syndrome using aromatic herbs (dried tangerine peel, rose) combined with Zhengan Xifeng Decoction.

[0083] Bioactive components were retrieved from the TCMSP database using "dried tangerine peel" and "rose" as keywords. Based on oral bioavailability ≥30% and drug-likeness ≥0.18, core active components such as quercetin and β-sitosterol were identified. Through target prediction, disease target intersection, PPI network analysis, and KEGG pathway enrichment, core targets and key signaling pathways such as FoxO and Apelin were determined.

[0084] Tangerine peel and rose petals were used as raw materials. The core active ingredients were extracted using a water extraction process and concentrated to a clear extract with a relative density of 1.25 (60℃). HPLC fingerprinting was used for quality control. The traditional Chinese medicine formula Zhengan Xifeng Decoction was used, extracted by decoction and concentrated to obtain a clear extract. The mixed extract of tangerine peel and rose petals was combined with the extract of Zhengan Xifeng Decoction. The total raw material weight of tangerine peel and rose petals in the daily dosage was 2g.

[0085] Patients meeting the Western medicine diagnostic criteria for grade 1-2 essential hypertension, the TCM diagnostic criteria for Yin deficiency and Yang hyperactivity, aged 18-70 years, regardless of gender, who had not taken any medications related to this study within the past two weeks, were willing to participate in this clinical study, signed written informed consent forms, and were able to cooperate in completing the entire treatment and follow-up process were selected. Forty patients meeting the above criteria were included. The prepared aromatic medicine preparation was administered once daily, divided into two doses, for a treatment period of 8 weeks.

[0086] Eight weeks after administration, the patient's blood pressure was effectively controlled, and symptoms of yin deficiency and yang excess, such as dizziness, tinnitus, soreness of the lower back and knees, and hot flashes in the palms, soles, and chest, were all improved, as was the level of inflammation.

[0087] Example 6:

[0088] This embodiment provides a treatment for hypertension with yin and yang deficiency syndrome using a combination of aromatic herbs (Amomum villosum) and Jin Kui Shen Qi Wan (a traditional Chinese medicine formula).

[0089] Bioactive components were retrieved from the TCMSP database using "Amomum villosum" as the keyword. Based on oral bioavailability ≥30% and drug-likeness ≥0.18, core active components such as β-sitosterol, stigmasterol, and quercetin were obtained. Through target prediction, disease target intersection, PPI network analysis, and KEGG pathway enrichment, core targets and key signaling pathways such as PI3K-Akt and cGMP-PKG were identified.

[0090] The core active ingredient of Amomum villosum was extracted using an alcohol extraction process and concentrated to a clear extract with a relative density of 1.25 (60℃). HPLC fingerprinting was used for quality control. The traditional Chinese medicine formula Jin Kui Shen Qi Wan was used, and the extract was prepared by decocting with water and concentrating to obtain a clear extract. The Amomum villosum extract was mixed with the Jin Kui Shen Qi Wan extract, and the daily dosage of raw Amomum villosum was 4g.

[0091] Patients meeting the Western medicine diagnostic criteria for grade 1-2 essential hypertension, the TCM diagnostic criteria for Yin-Yang deficiency, aged 18-70 years, regardless of gender, who had not taken any medications related to this study (including Amomum villosum and other aromatic herbal preparations) within the past two weeks, were willing to participate in this clinical study, signed written informed consent forms, and were able to cooperate in completing the entire treatment and follow-up process were selected. Forty patients meeting the above criteria were included. The aromatic herbal preparations prepared above were administered once daily, divided into two doses, for a treatment period of 8 weeks.

[0092] After 8 weeks of treatment, the aromatic herbal preparation provided in this embodiment steadily reduced blood pressure, improved symptoms of Yin and Yang deficiency such as aversion to cold, cold limbs, dizziness, fatigue, and frequent urination at night, and improved insulin resistance and vascular endothelial function.

[0093] Example 7:

[0094] This embodiment provides a treatment for hypertension with phlegm and blood stasis syndrome using aromatic herbs (dried tangerine peel) combined with Er Chen Tang and Tao Hong Si Wu Tang.

[0095] Bioactive components were retrieved from the TCMSP database using "dried tangerine peel" as the keyword. Based on oral bioavailability ≥30% and drug-likeness ≥0.18, common core active components such as β-sitosterol, stigmasterol, and quercetin were identified. Through target prediction, disease target intersection, PPI network analysis, and KEGG pathway enrichment, core targets such as SRC, AKT1, and STAT3, as well as key signaling pathways such as PI3K-Akt and AGE-RAGE, were determined.

[0096] 100g of dried tangerine peel was weighed, pulverized into coarse powder, and extracted using a dual alcohol-water extraction process targeting the core active ingredients. The powder was concentrated to a clear extract with a relative density of 1.25 (60℃). HPLC fingerprinting was used for quality control of the core active ingredients to obtain the dried tangerine peel extract. A traditional Chinese medicine formula, Er Chen Tang combined with Tao Hong Si Wu Tang, was used for decoction extraction and concentration to obtain a clear extract. The mixed aromatic herb extract and the formula extract were then granulated. The daily dosage of raw dried tangerine peel was 2g.

[0097] Patients meeting the Western medicine diagnostic criteria for grade 1-2 essential hypertension, the TCM diagnostic criteria for phlegm-blood stasis syndrome, aged 18-70 years, regardless of gender, who had not taken any medications related to this study within the past two weeks, were willing to participate in this clinical study, signed written informed consent forms, and were able to cooperate in completing the entire treatment and follow-up process were selected. Forty patients meeting the above criteria were included. The prepared aromatic herbal preparation was administered once daily, divided into two doses, for a treatment period of 8 weeks.

[0098] After eight weeks of treatment, blood pressure was significantly reduced, symptoms of phlegm and blood stasis such as chest tightness, excessive phlegm, numbness and fixed tingling in the limbs were improved, and metabolism, inflammation and intestinal microecology were regulated.

[0099] The foregoing has only described certain exemplary embodiments of the present invention by way of illustration. Undoubtedly, those skilled in the art can modify the described embodiments in various ways without departing from the spirit and scope of the present invention. Therefore, the foregoing drawings and descriptions are illustrative in nature and should not be construed as limiting the scope of protection of the claims of the present invention.

Claims

1. A method for preparing a spice preparation, characterized in that, Includes the following steps: S1. Identify the core active ingredients of aromatic herbs for treating hypertension and their key targets and signaling pathways based on network pharmacology methods; S2. Prepare aromatic extracts based on the identified core active ingredients; S3. Mix the aromatic herb extract with traditional Chinese medicine formulas for lowering blood pressure and excipients to prepare aromatic herb preparations; The aromatic herbs are selected from one or more of the following: agarwood, sandalwood, costus root, patchouli, amomum villosum, dried tangerine peel, cyperus rotundus, sandalwood, and rose. Among them, the traditional Chinese medicine formulas for lowering blood pressure include Banxia Baizhu Tianma Decoction, Tianma Gouteng Drink, Xuefu Zhuyu Decoction, Zhengan Xifeng Decoction, Jinkui Shenqi Pill, Er Chen Decoction combined with Taohong Siwu Decoction.

2. The method for preparing the aromatic preparation according to claim 1, characterized in that, The syndromes for treating hypertension with aromatic herbs include phlegm-dampness excess syndrome, liver yang hyperactivity syndrome, qi stagnation and blood stasis syndrome, yin deficiency and yang hyperactivity syndrome, yin and yang deficiency syndrome, and phlegm-blood stasis syndrome.

3. The method for preparing the aromatic preparation according to claim 1, characterized in that, The network pharmacology approach described in S1 includes: S11. Using "fragrant medicine name" as keywords, such as agarwood, sandalwood, costus root, patchouli, amomum villosum, dried tangerine peel, cyperus rotundus, sandalwood, and rose, search for bioactive ingredients from the TCMSP database. Use oral bioavailability ≥30% and drug-likeness ≥0.18 as screening criteria to obtain potential active ingredients of fragrant medicines. S12. The SMILES structure of the active ingredient is imported into the SwissTargetPrediction database and the CTD database for target prediction to obtain the potential targets of the active ingredient of the aromatic medicine. S13. Using "Hypertension" as the keyword, screen for targets related to hypertension from the Genecards database and the OMIM database; S14. By performing an intersection analysis between the potential targets of the active ingredients of aromatic herbs and the targets of hypertension, the potential targets of aromatic herbs in treating hypertension can be obtained. S15. Import the intersection target points into the STRING database to construct a PPI network, perform topology analysis using Cytoscape software, and select the core target points based on the degree values. S16. Import the intersection target points into the MetaScape database for GO function enrichment analysis and KEGG pathway enrichment analysis to determine the main signaling pathways.

4. The method for preparing the aromatic preparation according to claim 1, characterized in that, The core active ingredient of S1 includes at least one of 6,7-dimethoxy-2-(2-phenylethyl)chromone, DMPEC, norboridine, C09495, nubigenol, boridine, β-sitosterol, stigmasterol, and quercetin.

5. The method for preparing the aromatic preparation according to claim 3, characterized in that, The core targets mentioned in S15 include at least one of SRC, TP53, AKT1, EGFR, ESR1, CTNNB1, HIF1A, STAT3, SMAD3, and MDM2.

6. The method for preparing the aromatic preparation according to claim 3, characterized in that, The main signaling pathways mentioned in S16 include at least one of the following signaling pathways: PI3K-Akt, cGMP-PKG, AGE-RAGE, HIF-1, MAPK, FoxO, and Apelin.

7. The method for preparing the aromatic preparation according to claim 1, characterized in that, The aromatic extract described in S2 is extracted using alcohol extraction, water extraction, or a combination of alcohol and water extraction processes.

8. The application of the aromatic medicine preparation prepared according to any one of claims 1-7 in the treatment of hypertension.

9. The application of the aromatic medicine preparation according to claim 8 in the treatment of hypertension, characterized in that, In the daily dosage of the aromatic medicine preparation, the amount of raw herbs in the traditional Chinese medicine formula is based on the original formula ratio, and the aromatic herbs are 1-4g based on the amount of raw herbs.

10. The application of the aromatic medicine preparation according to claim 7 in the treatment of hypertension, characterized in that, The applications include at least one of the following: lowering systolic blood pressure, lowering diastolic blood pressure, improving TCM syndromes, improving insulin resistance, reducing inflammatory factor levels, improving vascular endothelial function, and regulating gut microbiota.

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