A pharmaceutical composition, preparation and preparation method and application for treating hypertension

Abstract

The application discloses a medicine composition, preparation and preparation method and application for treating hypertension, and belongs to the technical field of traditional Chinese medicine compositions. The technical problem to be solved is to simplify a prescription, make the action relationship of medicine flavors more definite, and improve the effect of the medicine in treating hypertension and related diseases. The technical solution is that a medicine composition for treating hypertension is prepared from the following raw materials in parts by weight: 8-10 parts of pinellia ternate, 5-7 parts of poria cocos, 5-7 parts of orange red and 5-7 parts of jujube.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine composition technology, specifically to a pharmaceutical composition, preparation, preparation method, and application for treating hypertension. Background Technology

[0002] Hypertension is a common cardiovascular disease worldwide and a major risk factor for damage to target organs such as the heart, brain, and kidneys, as well as cardiovascular events. While first-line antihypertensive drugs are effective in controlling blood pressure, individual efficacy variations, side effects, and long-term tolerability issues exist. Traditional Chinese medicine (TCM) has unique advantages in holistic regulation and syndrome differentiation-based treatment of hypertension. Therefore, finding safe and effective antihypertensive drugs or complementary treatment options from traditional Chinese medicine is of significant clinical importance.

[0003] Banxia Baizhu Tianma Decoction is a classic formula for treating dizziness and headache caused by phlegm-dampness. Its composition is as follows: Pinellia ternata 9g, Gastrodia elata 6g, Poria cocos 6g, Citrus reticulata peel 6g, Atractylodes macrocephala 18g, Glycyrrhiza uralensis 3g, Zingiber officinale 5g, and Ziziphus jujuba 6g. Preliminary modern research suggests it may be beneficial for hypertension, but its target of action remains unclear. In the research of traditional Chinese medicine compound formulas, "simplification and modification" based on classic formulas—reducing the number of herbs and clarifying the core drug groups while retaining or enhancing the core efficacy—is a key step in achieving the modernization, standardization, and in-depth study of the mechanisms of traditional Chinese medicine. This helps reduce the complexity of preparations, improve quality control, reduce potential drug interactions, and more clearly elucidate the pharmacodynamic material basis.

[0004] Spontaneously hypertensive rats (SHRs) are currently the internationally recognized animal model for studying essential hypertension. Their blood pressure rises continuously with age, closely resembling the pathophysiological process of essential hypertension in humans, making them one of the "gold standard" models for evaluating the efficacy of antihypertensive drugs. Therefore, combining traditional Chinese medicine (TCM) formulas with the SHR model in research on hypertension can more scientifically evaluate the efficacy of TCM formulas.

[0005] Relevant patent documents retrieved: The document, published in China (CN104645279A) on May 27, 2015, discloses a traditional Chinese medicine formula for treating hypertension. The dosage per dose is as follows: 9g of Pinellia ternata, 6g each of Gastrodia elata, Poria cocos, and Citrus reticulata peel, 15g of Atractylodes macrocephala, 4g of Glycyrrhiza uralensis, 10g of Zingiber officinale, and 2 jujubes. It is said to be very effective for hypertension patients with phlegm-dampness retention or spleen deficiency with liver hyperactivity. Related non-patent literature found includes: The journal or book title is "China Health Standards Management", the document title is "Study on the Effect of Banxia Baizhu Tianma Decoction on Primary Hypertension", volume number is 13, and the publication date is 2022. This document discloses that the use of Banxia Baizhu Tianma Decoction to treat primary hypertension has significant effects and can effectively improve patients' blood pressure and TCM syndrome scores.

[0006] The prior art represented by the aforementioned documents has at least the following unresolved technical problems or defects: The prescription contains many components and the relationships between substances are relatively complex. Relevant evidence is that Chinese Patent Publication No. CN104645279A contains eight herbs, and their relationships are unclear.

[0007] In solving the above problems or overcoming the above defects, the present invention encountered the following difficulties and obstacles: Existing technologies mainly involve combining Banxia Baizhu Tianma Decoction with other prescriptions for the treatment of hypertension, or modifying the classic Banxia Baizhu Tianma Decoction formula with additional or modified ingredients, resulting in prescriptions with more ingredients and more complex interactions.

[0008] Other content that is useful for understanding, searching, and examining this invention: Currently, no research has been found on reducing the formula of the classic Banxia Baizhu Tianma Decoction. Summary of the Invention

[0009] The purpose of this invention is to provide: A pharmaceutical composition for treating hypertension, and related technologies thereof, to address technical issues such as simplifying prescriptions, clarifying the relationship between drug components, and improving the efficacy of drugs in treating hypertension and related diseases, or combinations thereof.

[0010] Terminology Explanation: Unless otherwise defined, all technical terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this subject matter pertains. Unless otherwise stated, all patents, patent inventions, and disclosures cited throughout this document are incorporated herein by reference in their entirety. Where multiple definitions exist for terms herein, the definitions provided in this chapter shall prevail.

[0011] It should be understood that the above brief description and the following detailed description are exemplary and for illustrative purposes only, and do not limit the subject matter of the invention in any way. In this invention, the singular is used in conjunction with the plural unless otherwise specifically stated. It should also be noted that, unless otherwise stated, the use of “or” or “or” means “and / or”. Furthermore, the use of the term “comprising” and other forms such as “including,” “containing,” and “contains” are not limiting.

[0012] The definition of standard chemical terms can be found in the reference "Pharmacopoeia of the People's Republic of China (2025 Edition): China Medical Science and Technology Press: March 2025: 1st Edition".

[0013] Unless otherwise stated, conventional methods within the scope of the art, such as methods for testing blood pressure, shall be used.

[0014] Unless specifically defined herein, the use of all commercially available products herein employs standard techniques. For example, it may be carried out using the manufacturer's instructions for use with the kit, or in accordance with methods known in the art or the description of this invention. The techniques and methods described herein can generally be implemented according to conventional methods well known in the art, based on the descriptions in the various summary and more specific documents cited and discussed in this specification.

[0015] The medicinal materials mentioned in this article can be substituted with legally processed products.

[0016] The term "Pinellia" as used in this article refers to the dried tuber of *Pinellia ternata* (Thunb.) Breit., a plant belonging to the Araceae family. It is harvested in summer and autumn, washed, the outer skin and fibrous roots removed, and then sun-dried. Unprocessed medicinal material is called "raw Pinellia." Besides raw Pinellia, it can also be replaced by any legally processed product such as processed Pinellia (processed with ginger), prepared Pinellia (processed with ginger), or processed Pinellia (processed with real ginger).

[0017] Raw Pinellia ternata is pungent and warm in nature; it is also toxic. It enters the spleen, stomach, and lung meridians. It dries dampness and resolves phlegm, relieves nausea and vomiting, and dissipates lumps and nodules. It is used for damp phlegm, cold phlegm, cough with excessive phlegm, phlegm-fluid retention causing dizziness and palpitations, wind-phlegm causing dizziness, phlegm-induced headache, vomiting and nausea, chest and epigastric fullness, and globus hystericus; externally, it is used to treat carbuncles and phlegm nodules.

[0018] "Prepared Pinellia" is a processed product of Pinellia ternata. Take Pinellia ternata, separate the large and small pieces, soak them in water until there is no dry core inside, and take them out. Take an appropriate amount of licorice, add water and decoct twice, combine the decoctions, pour them into lime solution made with an appropriate amount of water, stir well, add the soaked Pinellia ternata, soak, stir 1 to 2 times a day, and keep the pH value of the soaking solution above 12, until the cross-section is uniformly yellow and there is a slight numbing sensation on the tongue when tasted, take it out, wash it, and air-dry or bake it to obtain the product.

[0019] "Ginger-processed Pinellia" is a processed product of Pinellia ternata. Take clean Pinellia ternata, separate them by size, soak them in water until the inside is no longer dry, then remove them. Separately, slice fresh ginger and decoct it in water, add alum and boil the Pinellia ternata together until thoroughly cooked, remove, and air dry, or air dry until semi-dry, then dry completely; or slice thinly and dry. For every 100kg of clean Pinellia ternata, use 25kg of fresh ginger and 12.5kg of alum.

[0020] "Qing Banxia" refers to the processed form of Pinellia ternata. Clean Pinellia ternata is taken, separated by size, and soaked or boiled in an 8% alum solution until the inside is no longer dry and a slightly numbing sensation is felt on the tongue. It is then removed, washed, cut into thick slices, and dried. For every 100kg of clean Pinellia ternata, 12.5kg of alum is used for the boiling method, and 20kg for the soaking method.

[0021] The term "Poria" used in this article refers to the dried sclerotium of the fungus *Poria cocos* (Schw.) Wolf, belonging to the Polyporaceae family. It is mostly harvested from July to September. After being dug up, the soil and sand are removed, and the fungus is piled up to "sweat," then spread out to dry until the surface is dry. This process of "sweating" is repeated several times until wrinkles appear and most of the internal moisture is lost. It is then air-dried, and this is called "Poria cocos pieces." Alternatively, fresh Poria cocos can be cut into different parts and air-dried, respectively called "Poria cocos chunks" and "Poria cocos slices." It is sweet, bland, and neutral in nature. It enters the heart, lung, spleen, and kidney meridians. It promotes diuresis and eliminates dampness, strengthens the spleen, and calms the mind. It is used for edema with scanty urine, phlegm retention with dizziness and palpitations, spleen deficiency with poor appetite, loose stools and diarrhea, restlessness, palpitations, and insomnia. In this article, "Poria cocos" can be extended to refer to Poria cocos or its specific medicinal parts. In addition, "Poria cocos" can be replaced with *Poria cocos sclerotium*, or a mixture of Poria cocos and *Poria cocos sclerotium*.

[0022] "Fu Shen" refers to the white part of the dried sclerotium of the fungus Poria cocos (Schw.) Wolf, which contains pine branches or roots.

[0023] The term "juhong" as used in this article refers to the dried outer peel of the citrus fruit (Citrus reticulata Blanco) and its cultivated varieties, belonging to the Rutaceae family. It is harvested in late autumn and early winter after the fruit matures, and the outer peel is peeled off with a knife and then sun-dried or shade-dried. The main cultivated varieties are Citrus reticulata 'Dahongpao' and Citrus reticulata 'Tangerina'. It is pungent, bitter, and warm in nature. It enters the lung and spleen meridians. It regulates qi, relieves chest congestion, dries dampness, and resolves phlegm. It is used for cough with excessive phlegm, food stagnation, alcohol poisoning, nausea, and epigastric fullness. In addition, juhong can be replaced with dried tangerine peel (chenpi) or a mixture of dried tangerine peel and juhong.

[0024] "Chenpi" refers to the dried, mature peel of the citrus fruit, Citrus reticulata Blanco, and its cultivated varieties, belonging to the Rutaceae family. The medicinal material is divided into "Chenpi" and "Guangchenpi". Mature fruits are harvested, the peel is removed, and then sun-dried or dried at low temperatures.

[0025] The term "jujube" as used in this article refers to the dried, ripe fruit of the jujube plant (Ziziphus jujuba Mill.), belonging to the Rhamnaceae family. The fruit is harvested in autumn when ripe and then dried.

[0026] The term "SHR rat" used in this article refers to the spontaneously hypertensive rat, a strain developed by Japanese scholar Okamoto in 1963 from Wistar-Kyoto rats through 20 generations of selective inbreeding. SHR rats develop elevated blood pressure at 4-6 weeks of age, and their systolic blood pressure stabilizes at 160-200 mmHg in adulthood. They may also experience cardiovascular complications such as left ventricular hypertrophy and stroke.

[0027] As used herein, the term "therapeuticly effective amount" is an amount sufficient to provide therapeutic benefit in the treatment of a condition or sufficient to delay or minimize one or more symptoms associated with that condition. A therapeutically effective amount of an active ingredient means an amount by which the therapeutic agent, alone or in combination with other therapies, provides therapeutic benefit in the treatment of a condition. The term "therapeuticly effective amount" may encompass amounts that improve overall therapy, reduce or prevent symptoms, signs, or causes of a condition, and / or enhance the therapeutic efficacy of another therapeutic agent. In some embodiments, a therapeutically effective amount is an amount sufficient to treat any of the diseases or conditions described.

[0028] In a first aspect, the present invention provides: a pharmaceutical composition for treating hypertension, which is made from the following raw materials in parts by weight: 8-10 parts of Pinellia ternata, 5-7 parts of Poria cocos, 5-7 parts of Citrus reticulata peel and 5-7 parts of jujube.

[0029] This includes technical features such as the dosage and ratio of Pinellia ternata, Poria cocos, Citrus reticulata peel, and other components.

[0030] Among them, the technical feature of Pinellia ternata is selected from at least one of raw Pinellia ternata, processed Pinellia ternata, ginger-processed Pinellia ternata, and prepared Pinellia ternata.

[0031] Among them, the technical feature of Poria cocos is selected from at least one of Poria cocos and Poria cocos sclerotium.

[0032] The technical feature of orange peel is selected from at least one of orange peel and dried tangerine peel.

[0033] The preferred ratio of the technical characteristic components is: 9 parts Pinellia ternata, 6 parts Poria cocos, 6 parts Citrus reticulata peel, and 6 parts Jujube.

[0034] Based on further solutions to the technical problems of the present invention, or simultaneous solutions to multiple technical problems, the preferred solution in the technical solution provided in the first aspect of the present invention includes: A pharmaceutical composition for treating hypertension, comprising, by weight, the following raw materials: 9 parts Pinellia ternata, 6 parts Poria cocos, 6 parts Citrus reticulata peel, and 6 parts Ziziphus jujuba. This technical solution, having already addressed the technical issues of "simplifying prescriptions, clarifying the relationship between the medicinal components, and improving the efficacy of the drug in treating hypertension and related diseases," further addresses the technical issue of "improving the efficacy of the drug in treating hypertension and related diseases."

[0035] Secondly, the present invention provides a method for preparing the pharmaceutical composition, comprising the following steps: mixing the raw materials, adding water and decocting, filtering, and obtaining the final product.

[0036] This includes technical features such as the number of times to decoct, the decoction time, the decoction process steps, and the amount of water used.

[0037] The technical feature of the number of times to boil is selected from 1 to 3 times.

[0038] The preferred number of times for decocting is 2.

[0039] The cooking time is selected from 1-2.5h, preferably 80-120 minutes, and more preferably 100 minutes.

[0040] The preferred step in the decocting process is to soak the food before decocting.

[0041] This includes a technical feature: soaking time.

[0042] The soaking time for the technical feature is selected from 0.5-1.5h.

[0043] The amount of water used in the technical feature is selected from 3 to 7 times the total mass of each raw material.

[0044] When the decoction is performed twice, the preferred decoction process is as follows: for the first time, soak the ingredients in 5-7 times the amount of water for 0.5-1.5 hours and decoct for 0.5-1.5 hours; for the second time, add 3-5 times the amount of water and decoct for 0.5-1 hours.

[0045] Thirdly, the present invention provides: a formulation comprising the pharmaceutical composition and pharmaceutically acceptable excipients.

[0046] This includes technical features: dosage form of the formulation and pharmaceutically acceptable excipients.

[0047] The dosage form of the technically characteristic preparation is selected from: granules, ointments, tablets, capsules or liquid preparations.

[0048] When the formulation is in the form of granules, the pharmaceutically acceptable excipients include binders and flavoring agents.

[0049] This includes technical features such as the mass ratio of each component in the adhesive, flavoring agent, and auxiliary materials.

[0050] The technical feature adhesive is selected from at least one of dextrin, starch, and sodium carboxymethyl starch.

[0051] The flavoring agent used in this process is selected from glucose.

[0052] The mass ratio of each component in the technical feature excipients is selected from the following: the mass ratio of binder and flavoring agent is 4-5:5.

[0053] Wherein, when the pharmaceutically acceptable excipients are glucose, starch and sodium carboxymethyl starch, the mass ratio of the three is 10:7:1.

[0054] Fourthly, the present invention provides a method for preparing a formulation, wherein the formulation is a granule, comprising the following steps: mixing the raw materials, adding water and boiling, filtering, concentrating the filtrate to obtain a thick paste, adding pharmaceutically acceptable excipients for granulation, and drying to obtain the final product.

[0055] This includes technical features such as the number of times to decoct, the decoction time, the decoction process steps, the amount of water used, and the relative density of the thick paste.

[0056] The technical feature of the number of times to boil is selected from 1 to 3 times.

[0057] The preferred number of times for decocting is 2.

[0058] The cooking time is selected from 1-2.5h, preferably 80-120 minutes, and more preferably 100 minutes.

[0059] The preferred step in the decocting process is to soak the food before decocting.

[0060] This includes a technical feature: soaking time.

[0061] The soaking time for the technical feature is selected from 0.5-1.5h.

[0062] The amount of water used in the technical feature is selected from 3 to 7 times the total mass of each raw material.

[0063] When the decoction is performed twice, the preferred decoction process is as follows: for the first time, soak the ingredients in 5-7 times the amount of water for 0.5-1.5 hours and decoct for 0.5-1.5 hours; for the second time, add 3-5 times the amount of water and decoct for 0.5-1 hours.

[0064] The relative density of the technical characteristic paste is selected from: a relative density of 1.18-1.25 at 60℃.

[0065] The volume ratio of the thick paste to the mass ratio of the excipients is 1 mL: 1 g.

[0066] Fifthly, the present invention provides the use of the pharmaceutical composition or the formulation in the preparation of a medicament for treating hypertension and / or related diseases.

[0067] Among them, the technical feature is: hypertension-related diseases.

[0068] Among them, the technical characteristic of hypertension-related diseases is selected from at least one of the following: kidney disease, vascular disease, and heart disease.

[0069] These include technical features such as kidney disease, vascular disease, and heart disease.

[0070] Among them, the technical characteristic of kidney lesions is selected from: glomerular atrophy.

[0071] Among them, the technical characteristic vascular lesions are selected from: increased abdominal aortic pulsatility index, increased abdominal aortic resistance index, thickening of abdominal aortic vessel wall, increased renal artery pulsatility index, increased renal artery resistance index, thickening of renal artery vessel wall, increased superior mesenteric artery pulsatility index, increased superior mesenteric artery resistance index, and thickening of superior mesenteric artery vessel wall.

[0072] Among them, the technical characteristic cardiac lesions are selected from: reduced ejection fraction, reduced shortening fraction, and disordered arrangement of myocardial cells.

[0073] The present invention has at least the following beneficial effects: This invention provides a simplified and optimized formula derived from the original Banxia Baizhu Tianma Decoction through scientific modification. The optimization primarily involves removing Tianma, Baizhu, Gancao, and Shengjiang from the original formula, while retaining Banxia (for drying dampness and resolving phlegm), Fuling (for strengthening the spleen and eliminating dampness), Juhong (for regulating qi and resolving phlegm), and Dazao (for protecting stomach qi and harmonizing the other herbs). The sweet and moistening nature of Dazao helps to mitigate the drying and harshness of Banxia and synergistically enhances its spleen-strengthening effect with Fuling, making the formula more focused and refined.

[0074] The optimized formula of this invention is not an arbitrary deletion, but a study based on a deep understanding of the original formula's treatment principles (strengthening the spleen and removing dampness, resolving phlegm and extinguishing wind) and the pathogenesis of hypertension. Traditional Chinese medicine believes that the spleen and stomach are the source of qi and blood production. When the spleen and stomach are dysfunctional, qi flow is obstructed, and water metabolism is disrupted, leading to phlegm and dampness. Therefore, the spleen is the source of phlegm. When phlegm disturbs the sensory orifices, it causes dizziness, headaches, and many other symptoms of qi and blood disharmony. In the optimized formula: Pinellia ternata (chief herb) dries dampness, resolves phlegm, and harmonizes the stomach; Poria cocos (assistant herb) strengthens the spleen and removes dampness, working synergistically with Pinellia ternata to resolve phlegm and eliminate its source; Citrus reticulata peel (adjuvant herb) regulates qi and removes stagnation, ensuring smooth qi flow and thus eliminating phlegm, while also strengthening the spleen. Jujube (guide herb) is used for its sweet and mild properties to counteract the drying and harshness of Pinellia ternata, protecting stomach qi and conforming to the principle of "eliminating pathogens without harming the body's vital energy." Furthermore, jujube itself has the function of tonifying the spleen and harmonizing the stomach, synergistically strengthening the fundamental principle of "strengthening the spleen to eliminate the source of phlegm" with Poria cocos. The optimized formula completely removes the original formula's drugs targeting "wind" (Gastrodia elata) and conventional qi-tonifying and spleen-strengthening drugs (Atractylodes macrocephala and Glycyrrhiza uralensis), so that the firepower is completely focused on "phlegm" and "dampness", especially the "spleen deficiency generates dampness" aspect. The formula's meaning is purer and its target is more concentrated.

[0075] The optimized formulation of this invention, while maintaining or even improving the core efficacy against hypertension, contains fewer medicinal ingredients, giving it a greater development advantage. Fewer medicinal ingredients mean lower raw material costs, a simpler production process, more easily controlled quality standards, and a clearer pathway for in vivo metabolic research.

[0076] This invention, through standardized animal experiments, has demonstrated that the optimized formula has a significant antihypertensive effect, which is significantly superior to the original classic formula. It also exhibits more significant efficacy against hypertension-related diseases, achieving unexpected technical results. This discovery is surprising, breaking the conventional understanding that "the more ingredients, the better the effect," and clearly defining the core drug components of the classic formula for treating hypertension. The composition is simplified, and the efficacy is definite.

[0077] Considering the possibility of this invention entering other countries, this invention also provides the following technical solutions: A method of treating hypertension includes administering a therapeutically effective amount of the above-mentioned pharmaceutical composition to a patient requiring treatment.

[0078] The dosage of the pharmaceutical composition, calculated based on the amount of raw medicinal material, is 0.19-0.77 g / kg / d, which translates to 13.3-53.9 grams per day, administered 1-2 times daily.

[0079] The pharmaceutical composition is provided in the form of granules, ointments, tablets, capsules or liquid formulations.

[0080] The pharmaceutical composition is provided orally.

[0081] The treatment period is 10 weeks or more, preferably 10-14 weeks, and more preferably 12 weeks.

[0082] A method for treating hypertension-related diseases includes administering a therapeutically effective amount of the above-mentioned pharmaceutical composition to a patient requiring treatment.

[0083] The dosage of the pharmaceutical composition, calculated based on the amount of raw medicinal material, is 0.19-0.77 g / kg / d, which translates to 13.3-53.9 grams per day, administered 1-2 times daily.

[0084] The pharmaceutical composition is provided in the form of granules, ointments, tablets, capsules or liquid formulations.

[0085] The pharmaceutical composition is provided orally.

[0086] The treatment period is 10 weeks or more, preferably 10-14 weeks, and more preferably 12 weeks.

[0087] Hypertension-related diseases are selected from at least one of the following: kidney disease, vascular disease, and heart disease.

[0088] Among them, kidney lesions are selected from: glomerular atrophy.

[0089] Among them, vascular lesions are selected from: elevated abdominal aortic pulsatility index, elevated abdominal aortic resistance index, thickened abdominal aortic vessel wall, elevated renal artery pulsatility index, elevated renal artery resistance index, thickened renal artery vessel wall, elevated superior mesenteric artery pulsatility index, elevated superior mesenteric artery resistance index, and thickened superior mesenteric artery vessel wall.

[0090] Among them, cardiac lesions are selected from: decreased ejection fraction, decreased shortening fraction, and disordered arrangement of myocardial cells. Attached Figure Description

[0091] Figure 1 The image shows a comparison of the effects of different doses of the optimized formula and Banxia Baizhu Tianma Decoction on systolic blood pressure in SHR rats; among them, compared with the WKY group, the SHR group showed #p<0.05; compared with the SHR group, the SHR + Banxia Baizhu Tianma Decoction group, the SHR + low-dose optimized formula group, the SHR + medium-dose optimized formula group, the SHR + high-dose optimized formula group, and the SHR + valsartan group showed significant differences. p<0.05; Compared with the SHR+Banxia Baizhu Tianma Decoction group, the SHR+Optimized Formula low dose group %p<0.05, the SHR+Optimized Formula medium dose group @p<0.05, the SHR+Optimized Formula high dose group &p<0.05, and the SHR+Valsartan group ¥p<0.05.

[0092] Figure 2 The image shows a comparison of the effects of different doses of the optimized formula and Banxia Baizhu Tianma Decoction on diastolic blood pressure in SHR rats; among them, compared with the WKY group, the SHR group showed #p<0.05; compared with the SHR group, the SHR + Banxia Baizhu Tianma Decoction group, the SHR + low-dose optimized formula group, the SHR + medium-dose optimized formula group, the SHR + high-dose optimized formula group, and the SHR + valsartan group showed significant differences. p<0.05; Compared with the SHR+Banxia Baizhu Tianma Decoction group, the SHR+Optimized Formula Medium Dose Group @p<0.05, the SHR+Optimized Formula High Dose Group &p<0.05, and the SHR+Valsartan Group ¥p<0.05.

[0093] Figure 3 The image shows a comparison of the effects of different doses of the optimized formula and Banxia Baizhu Tianma Decoction on the mean arterial pressure of SHR rats; among them, compared with the WKY group, the SHR group showed #p<0.05; compared with the SHR group, the SHR + Banxia Baizhu Tianma Decoction group, the SHR + low-dose optimized formula group, the SHR + medium-dose optimized formula group, the SHR + high-dose optimized formula group, and the SHR + valsartan group showed significant differences. p<0.05; Compared with the SHR+Banxia Baizhu Tianma Decoction group, the SHR+Optimized Formula low dose group %p<0.05, the SHR+Optimized Formula medium dose group @p<0.05, the SHR+Optimized Formula high dose group &p<0.05, and the SHR+Valsartan group ¥p<0.05.

[0094] Figure 4 A comparative graph showing the effects of different dosages of the optimized formula and Banxia Baizhu Tianma Decoction on the body weight of SHR rats.

[0095] Figure 5 A comparative graph showing the effects of different dosages of the optimized formula and Banxia Baizhu Tianma Decoction on the abdominal aortic pulsatility index in SHR rats; among them, compared with the WKY group, p<0.05; compared with the SHR group, #p<0.05; compared with the SHR+Banxia Baizhu Tianma Decoction group, &p<0.05.

[0096] Figure 6 A comparative graph showing the effects of different dosages of the optimized formula and Banxia Baizhu Tianma Decoction on the abdominal aortic resistance index in SHR rats; among them, compared with the WKY group, p<0.05; compared with the SHR group, #p<0.05.

[0097] Figure 7 A comparative diagram showing the effects of different dosages of the optimized formula and Banxia Baizhu Tianma Decoction on the thickness of the abdominal aortic vessel wall in SHR rats; among them, compared with the WKY group, p<0.05; compared with the SHR group, #p<0.05; compared with the SHR+Banxia Baizhu Tianma Decoction group, &p<0.05.

[0098] Figure 8 Comparison of HE staining effects of different dosages of the optimized formula and Banxia Baizhu Tianma Decoction on the morphology of the abdominal aorta in SHR rats.

[0099] Figure 9 A comparative graph showing the effects of different dosages of the optimized formula and Banxia Baizhu Tianma Decoction on the renal artery pulsatility index in SHR rats; among them, compared with the WKY group, p<0.05; compared with the SHR group, #p<0.05; compared with the SHR+Banxia Baizhu Tianma Decoction group, &p<0.05.

[0100] Figure 10 A comparative graph showing the effects of different dosages of the optimized formula and Banxia Baizhu Tianma Decoction on the renal artery resistance index in SHR rats; among them, compared with the WKY group, p<0.05; compared with the SHR group, #p<0.05; compared with the SHR+Banxia Baizhu Tianma Decoction group, &p<0.05.

[0101] Figure 11Comparative image of HE staining effects of different dosages of the optimized formula and Banxia Baizhu Tianma Decoction on the renal artery morphology of SHR rats.

[0102] Figure 12 A comparative diagram showing the effects of different dosages of the optimized formula and Banxia Baizhu Tianma Decoction on the superior mesenteric artery pulsatility index in SHR rats; among them, compared with the WKY group, p<0.05; compared with the SHR group, #p<0.05; compared with the SHR+Banxia Baizhu Tianma Decoction group, &p<0.05.

[0103] Figure 13 A comparative diagram showing the effects of different dosages of the optimized formula and Banxia Baizhu Tianma Decoction on the superior mesenteric artery resistance index in SHR rats; among them, compared with the WKY group, p<0.05; compared with the SHR group, #p<0.05; compared with the SHR+Banxia Baizhu Tianma Decoction group, &p<0.05.

[0104] Figure 14 Comparative HE staining effects of different dosages of the optimized formula and Banxia Baizhu Tianma Decoction on the morphology of the superior mesenteric artery in SHR rats.

[0105] Figure 15 A comparative graph showing the effects of different dosages of the optimized formula and Banxia Baizhu Tianma Decoction on left ventricular ejection fraction in SHR rats; among them, compared with the WKY group, p<0.05; compared with the SHR group, #p<0.05; compared with the SHR+Banxia Baizhu Tianma Decoction group, &p<0.05.

[0106] Figure 16 A comparative graph showing the effects of different dosages of the optimized formula and Banxia Baizhu Tianma Decoction on the fractional shortening of the left ventricle in SHR rats; among them, compared with the WKY group, p<0.05; compared with the SHR group, #p<0.05; compared with the SHR+Banxia Baizhu Tianma Decoction group, &p<0.05.

[0107] Figure 17 Comparison of HE staining effects of different dosages of the optimized formula and Banxia Baizhu Tianma Decoction on the pathological morphology of heart tissue in SHR rats.

[0108] Figure 18 Comparison of HE staining effects of different dosages of the optimized formula and Banxia Baizhu Tianma Decoction on the pathological morphology of kidney tissue in SHR rats. Detailed Implementation

[0109] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection claimed by the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, and such changes should also fall within the scope of protection claimed by the present invention.

[0110] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all instruments, devices, equipment, reagents, products, etc., used in the embodiments of the present invention are obtained through conventional commercial means.

[0111] Example 1 1. Materials 1.1 Laboratory Animals Seven healthy male WKY rats (weighing 87±1 g) aged four weeks were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. They were housed in the SPF-grade laboratory of the Laboratory Animal Center of Fujian University of Traditional Chinese Medicine. Sufficient food and water were provided, and a 12-hour light / dark cycle was maintained. The temperature was 23±1 ℃, and the humidity was controlled at 50%, all within acceptable ranges for laboratory animals. The rats were used in experiments after one week of acclimatization feeding.

[0112] All animal experiments were conducted in accordance with the regulations of laboratory animal ethics and the Fujian University of Traditional Chinese Medicine Animal Management Association, and the laboratory animal ethics review form has been approved, with approval number FJTCM IACUC 2025306.

[0113] 2. Experimental Methods 2.1 Drug Preparation The optimized formula of Banxia Baizhu Tianma Decoction (hereinafter referred to as the optimized formula): Weigh out 450g of Pinellia ternata, 300g of Poria cocos, 300g of Citrus reticulata peel, and 300g of Ziziphus jujuba (total raw herb amount 1350g). Decoct twice with water. For the first decoction, add 6 times the amount of water, soak for 1 hour, and decoct for 60 minutes. For the second decoction, add 4 times the amount of water and decoct for 40 minutes. Combine the two decoctions, filter, and concentrate the filtrate to a thick paste with a relative density of 1.18 (60℃). Add 1g of excipients (based on the total amount of excipients) to every 1mL of the thick paste. Finally, add 225g of anhydrous glucose, 157.5g of medicinal starch, and 22.5g of sodium carboxymethyl starch. Granulate in a fluidized bed, dry, and package into 100 bags to obtain granules. Each bag is equivalent to 13.5g of raw herbs.

[0114] Banxia Baizhu Tianma Decoction: Weigh out 450g of Pinellia ternata, 900g of Atractylodes macrocephala, 300g of Gastrodia elata, 300g of Poria cocos, 300g of Citrus reticulata peel, 150g of prepared licorice root, 250g of fresh ginger, and 300g of jujube, totaling 2950g. Add water and decoct twice. For the first decoction, add 6 times the amount of water, soak for 1 hour, and decoct for 60 minutes. For the second decoction, add 4 times the amount of water and decoct for 40 minutes. Combine the two decoctions, filter, and concentrate the filtrate to a thick paste with a relative density of 1.21 (60℃). Add 1g of excipients (based on the total amount of excipients) to every 1mL of the thick paste. Finally, add 450g of anhydrous glucose, 315g of medicinal starch, and 45g of sodium carboxymethyl starch. Granulate in a fluidized bed, dry, and package into 100 bags to obtain granules. Each bag is equivalent to 29.5g of raw herbs.

[0115] 2.2 Animal grouping and administration Animal grouping: Seven male WKY rats were used as the control group (WKY group). Forty-two male SHR rats were randomly divided into six groups according to their baseline blood pressure and body weight: SHR group, SHR + low-dose optimized formula group (1.215 g / kg / d, also known as low-dose optimized formula group), SHR + medium-dose optimized formula group (2.43 g / kg / d, also known as medium-dose optimized formula group), SHR + high-dose optimized formula group (4.86 g / kg / d, also known as high-dose optimized formula group), SHR + Banxia Baizhu Tianma Decoction group (also known as Banxia Baizhu Tianma Decoction group), and SHR + valsartan group, with seven rats in each group.

[0116] Animal drug administration: The WKY and SHR groups were administered drinking water by gavage. The remaining groups were administered 1.215 g / kg / day, 2.43 g / kg / day, and 4.86 g / kg / day (based on total raw drug content) of the optimized Banxia Baizhu Tianma Decoction, 2.43 g / kg / day (based on total raw drug content) of Banxia Baizhu Tianma Decoction, and 7.2 mg / kg / day of valsartan by gavage, respectively. Gavage was performed daily at 9:00 AM, with each rat receiving 1 ml of the decoction. The WKY and SHR groups received an equal volume of sterile ultrapure water via parallel gavage. The dosages in the optimized Banxia Baizhu Tianma Decoction and Banxia Tianma Decoction correspond to the human clinical dosages (for 200g rats, the conversion factor is 0.018). Drug administration was discontinued after 12 weeks.

[0117] 2.3 Blood Pressure Measurement During the experiment, CODA model was used. ™Non-invasive precision blood pressure monitors were used to measure the mean arterial pressure (MAP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) of each group of rats. Measurements were taken weekly, and the data were statistically analyzed. Changes in the body weight of each rat were also recorded weekly. The specific procedures are as follows: (1) Assemble the rat heating plate, sensor and computer, etc. (2) Place the rat in the restraint device and place it stably on the rat heating plate. Turn on the rat heating plate to maintain the rat's body temperature and ensure smooth blood flow in the tail artery. (3) Place both the blocking kit and the volumetric pressure sensor on the rat's tail; (4) Open Coda 4.1 software, set the software conditions, and perform 15 cycles per period. Before measurement, place the rat stably on the heating plate and let it rest for 10 minutes. During the measurement period, keep the surrounding environment quiet. After the measurement, the volumetric pressure sensor will transmit the values ​​of each measurement to the computer. (5) Record the systolic blood pressure, diastolic blood pressure, and mean arterial pressure of each rat in each week and weigh the rat. Calculate the mean and standard deviation.

[0118] The formula for calculating mean arterial pressure is: mean arterial pressure = (systolic pressure + (2 × diastolic pressure)) ÷ 3.

[0119] 2.4 Measurement of abdominal aortic resistance index, pulsatility index, and thickness. (1) Echocardiography detection time: After the experiment, the abdominal aortic vascular function of rats in each group was detected using the Vevo F2 small animal ultrasound instrument.

[0120] (2) Abdominal hair removal and animal anesthesia: The hair on the abdomen of the rats was removed with hair removal cream. Each rat was anesthetized by inhalation with 1.5% isoflurane and fixed in a supine position on a 37°C constant temperature heating plate.

[0121] (3) Obtaining the abdominal aorta section: Apply coupling agent to the anterior chest and abdomen of the rat to expose the abdominal aorta and obtain the abdominal aorta section. The probe is UHF29× and the frequency is 15~29MHz.

[0122] (4) Ultrasound results analysis and calculation method: After the operation, the Abdominal Aortic Resistance Index (RI) and Abdominal Aortic Pulsatility Index (PI) of each group of rats were calculated using Vevo Strain Software (VevoLAB 1.7.1), and the average value was calculated for each of the three calculations; at the same time, the vascular thickness was analyzed by ultrasound results, and the average value was calculated for each of the three calculations.

[0123] 2.5. Echocardiography to assess cardiac function The procedures for chest hair removal and rat anesthesia were the same as described in 2.4. The ultrasound probe was then placed vertically on the left chest of the rat, and the probe was adjusted so that its notch faced the rat's head. In B-Mode, the probe was slowly adjusted until a clear cardiac image was obtained. The mode was then switched to M-Mode to acquire the rat's cycle time. At least three cardiac cycles were measured for each rat, and the average value was taken after the ultrasound scan for subsequent statistical analysis. The measured cardiac function parameters were left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS).

[0124] 2.6 HE staining (1) Fixed Rat abdominal aorta, renal artery, superior mesenteric artery, heart and kidney tissue samples were fixed in 4% paraformaldehyde for 48 h, placed in tissue embedding cassettes and labeled.

[0125] (2) Dehydration and wax impregnation Heart tissue and kidney samples were sequentially immersed in the following reagents for dehydration and paraffin removal: 70% anhydrous ethanol (60 min) → 80% anhydrous ethanol (60 min) → 90% anhydrous ethanol (60 min) → 95% anhydrous ethanol (60 min) → 100% anhydrous ethanol I (20 min) → 100% anhydrous ethanol II (20 min) → 100% anhydrous ethanol III (50 min) → xylene I (5 min) → xylene II (20 min) → paraffin I (10 min) → paraffin II (20 min) → paraffin III (30 min).

[0126] Samples from the abdominal aorta, renal artery, and superior mesenteric artery were sequentially immersed in the following reagents for dehydration and paraffin removal: 70% anhydrous ethanol (30 min) → 80% anhydrous ethanol (30 min) → 90% anhydrous ethanol (30 min) → 95% anhydrous ethanol (30 min) → 100% anhydrous ethanol I (10 min) → 100% anhydrous ethanol II (10 min) → 100% anhydrous ethanol III (30 min) → xylene I (5 min) → xylene II (15 min) → paraffin I (10 min) → paraffin II (10 min) → paraffin III (25 min).

[0127] (3) Embedding Preheat the embedding mold and paraffin block, and place the tissue upright in the center of the bottom of the embedding mold. Gently place the embedding cassette on top of the mold and fill it with paraffin wax from above. Transfer the mold to a cooling table and wait for the paraffin wax to solidify. Place the paraffin block in a -20 °C freezer for 30 min. Carefully separate the paraffin block from the mold and store it at room temperature.

[0128] (4) Slicing Pre-cooled paraffin tissue blocks were fixed on a microtome, initially set to a coarse trimming thickness of 10 µm until the tissue structure was fully visible. The section thickness was then adjusted to 4 µm for fine trimming. Complete tissue sections were flattened in 39 °C warm water, gently removed, and placed sequentially on adhesive slides. The sections were baked at 60 °C for 1 h, then dried for 3 h, and stored at room temperature for subsequent experiments.

[0129] (5) Dewaxing Dewaxing was performed by immersing the reagents in the following order: Xylene I (25 min) → Xylene II (25 min) → Xylene III (15 min) → 100% anhydrous ethanol I (5 min) → 100% anhydrous ethanol II (5 min) → 95% anhydrous ethanol (5 min) → 80% anhydrous ethanol (5 min) → 70% anhydrous ethanol (5 min) → ultrapure water I (5 min) → ultrapure water II (5 min).

[0130] (6) Hematoxylin staining Immerse the heart slide in hematoxylin solution for 30 seconds to stain, then rinse with pure water.

[0131] (7) Eosin staining The glass slides were immersed in eosin solution for 15 seconds and then washed with pure water.

[0132] (8) Sealing After staining, immediately dry the sections and mount them with an appropriate amount of neutral resin.

[0133] (9) Microscopic observation Using an intelligent tissue section analysis system, a full-sample image of each sample was taken at 10× field of view, and six regions were randomly selected at 400× field of view for further imaging to observe the pathological changes in each group of samples.

[0134] 2.7 Statistical Analysis Statistical analysis of the data was performed using IBM SPSS Statistics (version 29.0.1.0) software.

[0135] The Shapiro-Wilk test was used to test the normality of the data. Data are expressed as mean ± standard deviation. When comparing differences among the three groups, assuming the data follow a normal distribution, ANOVA one-way ANOVA was used (LSD post-hoc test was used when the variances were homogeneous; otherwise, Dunnett's T3 post-hoc test was used). When the data did not follow a normal distribution, the nonparametric Kruskal-Wallis test was used to compare differences between groups. A p-value < 0.05 was considered statistically significant.

[0136] 3. Experimental Results 3.1 Effects of the optimized Banxia Baizhu Tianma Decoction on blood pressure and body weight in rats The results of the effect of the optimized formula on blood pressure are shown in Figures 1-3 As shown.

[0137] like Figure 1 As shown, compared with the WKY group, the systolic blood pressure (SBP) of rats in the SHR group was significantly higher (p<0.05). Compared with the SHR group, the SBP of rats in the SHR group after low, medium, and high doses of the optimized formula was significantly lower (p<0.05). Compared with the Banxia Baizhu Tianma Decoction group, the SBP of the low, medium, and high dose groups of the optimized formula was even lower (p<0.05), indicating that the optimized formula can significantly inhibit the increase of SBP and its effect is better than that of Banxia Baizhu Tianma Decoction.

[0138] like Figure 2 As shown, compared with the WKY group, the diastolic blood pressure (DBP) of rats in the SHR group was significantly increased (p<0.05). Compared with the SHR group, the DBP of rats in the SHR group after low, medium, and high doses of the optimized formula was significantly decreased (p<0.05). Compared with the Banxia Baizhu Tianma Decoction group, the DBP of the medium and high dose groups of the optimized formula was even lower (p<0.05), indicating that the optimized formula can significantly inhibit the increase of DBP and its effect is better than that of Banxia Baizhu Tianma Decoction.

[0139] like Figure 3As shown, compared with the WKY group, the mean arterial pressure (MAP) of rats in the SHR group was significantly increased (p<0.05). Compared with the SHR group, the MAP of rats in the SHR group after low, medium, and high doses of the optimized formula was significantly decreased (p<0.05). Compared with the Banxia Baizhu Tianma Decoction group, the MAP of the low, medium, and high dose groups of the optimized formula was even lower (p<0.05), indicating that the optimized formula can significantly inhibit the increase of MAP and its effect is better than that of Banxia Baizhu Tianma Decoction.

[0140] Simultaneously, body weight measurements revealed that the drug intervention had no significant effect on the rats' body weight. Figure 4 (P > 0.05).

[0141] Figures 1-4 The mean values ​​were statistically significant for blood pressure and body weight in rats at week 13 (i.e., week 12 of drug intervention).

[0142] 3.2. Investigation on the effect of the optimized Banxia Baizhu Tianma Decoction on the resistance index, pulsatility index, and thickness of the abdominal aorta in rats. After 12 weeks of drug intervention, rats were analyzed using small animal ultrasound to detect and measure the abdominal aortic resistance index, pulsatility index, and vascular thickness in each group. The results are shown in the table below. Figures 5-7 .

[0143] from Figure 5 It can be seen that, compared with the WKY group, the abdominal aortic pulsatility index of rats in the SHR group was significantly increased. After intervention with medium and high doses of the optimized formula, the abdominal aortic pulsatility index of rats in the SHR group was significantly reduced (p<0.05). However, there was no significant difference in the abdominal aortic pulsatility index between the Banxia Baizhu Tianma Decoction group and the SHR group.

[0144] from Figure 6 It was found that the abdominal aortic resistance index of rats in the SHR group was significantly higher than that in the WKY group. Compared with the SHR group, the abdominal aortic resistance index of rats in the SHR group after low, medium, and high doses of the optimized formula was significantly lower (p<0.05). Compared with the Banxia Baizhu Tianma Decoction group, the abdominal aortic resistance index was significantly lower after high-dose intervention with the optimized formula (p<0.05).

[0145] from Figure 7 It was found that, compared with the WKY group, the abdominal aortic wall thickness of rats in the SHR group was significantly increased. After intervention with low, medium, and high doses of the optimized formula, the abdominal aortic wall thickness of rats in the SHR group was significantly increased and decreased (p<0.05). Compared with the Banxia Baizhu Tianma Decoction group, the abdominal aortic wall thickness was significantly decreased after intervention with high doses of the optimized formula (p<0.05).

[0146] In summary, as blood pressure increases in SHR rats, the resistance to blood flow within the blood vessels increases, leading to increased pulsatility under the influence of resistance. The optimized intervention can improve the increase in abdominal aortic resistance index and abdominal aortic pulsatility index caused by hypertension.

[0147] 3.3. Optimization of the treatment for pathological morphology of the rat abdominal aorta After 12 weeks of drug intervention in rats, the changes in the morphology of the abdominal aorta caused by the optimized formula were observed using HE staining. The results are shown in [Figure 1]. Figure 8 .

[0148] from Figure 8 It was found that, compared with the WKY group, the abdominal aortic vessel wall of rats in the SHR group was thickened. After intervention with low, medium, and high doses of the optimized formula, the thickening of the abdominal aortic vessel wall in rats was reduced. This indicates that the optimized formula can reduce the thickness of the abdominal aortic vessel wall and can be used to improve the phenomenon of abdominal aortic vessel wall thickening caused by hypertension.

[0149] 3.4. Effects of the optimized Banxia Baizhu Tianma Decoction on renal artery resistance index and pulsatility index in rats. After 12 weeks of drug intervention, the renal artery resistance index and pulsatility index of rats in each group were detected and analyzed using small animal ultrasound. The results are shown in the figure. Figures 9-10 .

[0150] from Figure 9 It can be seen that, compared with the WKY group, the renal artery pulsatility index of rats in the SHR group was significantly increased. After intervention with low, medium and high doses of the optimized formula, the renal artery pulsatility index of rats in the SHR group was significantly reduced (p<0.05), while there was no significant difference in renal artery pulsatility index between the Banxia Baizhu Tianma Decoction group and the SHR group.

[0151] from Figure 10 It can be seen that, compared with the WKY group, the renal artery resistance index of rats in the SHR group was significantly increased. After intervention with medium and high doses of the optimized formula, the renal artery resistance index of rats in the SHR group was significantly reduced (p<0.05). However, there was no significant difference in renal artery resistance index between the Banxia Baizhu Tianma Decoction group and the SHR group.

[0152] In summary, as blood pressure increases in SHR rats, the resistance to blood flow within the blood vessels increases, leading to increased pulsatility under the influence of resistance. The optimized intervention can improve the increase in renal artery resistance index and renal artery pulsatility index caused by hypertension.

[0153] 3.5. Observation of the pathological morphology of the renal artery in rats by the optimized formula After 12 weeks of drug intervention in rats, the changes in renal artery morphology caused by the optimized formula were observed using HE staining. The results are shown in [Figure 1]. Figure 11 .

[0154] from Figure 11It was found that, compared with the WKY group, the renal artery wall of rats in the SHR group was thickened. After intervention with low, medium, and high doses of the optimized formula, the thickening of the renal artery wall in rats was reduced. This indicates that the optimized formula can reduce the thickness of the renal artery wall and can be used to improve the thickening of the renal artery wall caused by hypertension.

[0155] 3.6. Investigation on the effect of the optimized Banxia Baizhu Tianma Decoction on the resistance index and pulsatility index of the superior mesenteric artery in rats. After 12 weeks of drug intervention, rats were examined and analyzed using small animal ultrasound to detect and analyze the resistance index and pulsatility index of the superior mesenteric artery in each group. The results are shown in the figure. Figures 12-13 .

[0156] from Figure 12 It can be seen that, compared with the WKY group, the superior mesenteric artery pulsatility index of rats in the SHR group was significantly increased. After intervention with medium and high doses of the optimized formula, the superior mesenteric artery pulsatility index of rats in the SHR group was significantly reduced (p<0.05), while there was no significant difference in the superior mesenteric artery pulsatility index between the Banxia Baizhu Tianma Decoction group and the SHR group.

[0157] from Figure 13 It can be seen that, compared with the WKY group, the superior mesenteric artery resistance index of rats in the SHR group was significantly increased. After intervention with medium and high doses of the optimized formula, the superior mesenteric artery resistance index of rats in the SHR group was significantly reduced (p<0.05), while there was no significant difference in the superior mesenteric artery resistance index between the Banxia Baizhu Tianma Decoction group and the SHR group.

[0158] In summary, as blood pressure increases in SHR rats, the resistance to blood flow within the blood vessels increases, leading to increased pulsatility under the influence of resistance. The optimized intervention can improve the elevated resistance index and pulsatility index of the superior mesenteric artery caused by hypertension.

[0159] 3.7. Optimized formula's effect on the pathological morphology of the superior mesenteric artery in rats. After 12 weeks of drug intervention in rats, the morphological changes of the optimized formula on the superior mesenteric artery were observed using HE staining. The results are shown in [Figure 1]. Figure 14 .

[0160] from Figure 14 It was found that, compared with the WKY group, the superior mesenteric artery wall of rats in the SHR group was thickened. After intervention with low, medium, and high doses of the optimized formula, the thickening of the superior mesenteric artery wall in rats was alleviated. This indicates that the optimized formula can reduce the thickness of the superior mesenteric artery wall and can be used to improve the phenomenon of superior mesenteric artery wall thickening caused by hypertension.

[0161] 3.8. Investigation on the effect of the optimized formula of Banxia Baizhu Tianma Decoction on cardiac function in rats. After 12 weeks of drug intervention, changes in cardiac function in rats were assessed by small animal ultrasound. The results are shown below. Figures 15-16 .

[0162] from Figures 15-16 It was found that, compared with the WKY group, the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) of rats in the SHR group were significantly reduced (p<0.05). Compared with the SHR group, the LVEF and LVFS of rats in the low, medium, and high dose groups of the optimized formula after intervention were significantly increased (p<0.05). This indicates that the optimized formula can improve ejection fraction and LVFS and can be used to improve the phenomenon of reduced ejection fraction and LVFS caused by hypertension.

[0163] 3.9. Investigation on the effect of the optimized formula of Banxia Baizhu Tianma Decoction on the pathological morphology of rat heart. After 12 weeks of drug intervention in rats, the effect of the optimized formula on the pathological morphology of rat heart tissue was assessed by HE staining. The results are shown in [Figure number missing]. Figure 17 The arrows indicate the disordered arrangement of myocardial cells.

[0164] from Figure 17 It was found that the nuclei of cardiomyocytes in the WKY group rats were clear, the cytoplasm was uniformly stained, and the cells were tightly and neatly arranged without degeneration or necrosis. Compared with the WKY group, the cardiac tissue morphology of the SHR group rats showed significant changes: the neatness of the cardiomyocyte arrangement was significantly reduced. In contrast, the cardiomyocytes in the medium and high dose groups of the optimized formula after intervention were neatly arranged. The arrangement of cardiomyocytes in the Banxia Baizhu Tianma Decoction group rats showed no significant improvement. This indicates that the optimized formula can significantly improve the pathological morphology of cardiac tissue caused by hypertension.

[0165] 3.10 Investigation on the pathological morphology of rat kidneys using the optimized formula of Banxia Baizhu Tianma Decoction After 12 weeks of drug intervention in rats, the effect of the optimized formula on the histopathological morphology of rat kidney tissue was evaluated by HE staining. The results are shown in [Figure 1]. Figure 18 The arrows indicate the direction of glomerular atrophy.

[0166] from Figure 18 It was found that the kidney tissue morphology of the WKY group rats was normal, without degeneration, atrophy, or necrosis. Compared with the WKY group, the kidney tissue morphology of the SHR group rats showed significant changes, with obvious glomerular atrophy. The glomerular atrophy in the medium and high dose groups of the optimized formula after intervention was significantly improved. The glomerular atrophy in the Banxia Baizhu Tianma Decoction group rats showed no significant improvement. This indicates that the optimized formula can significantly improve the pathological morphology of kidney tissue caused by hypertension.

[0167] In summary, the optimized formula significantly reduces blood pressure, improves vascular function, and alleviates vascular pathological changes. It also improves the decreased cardiac function, myocardial cell hypertrophy, and thickening of blood vessel walls caused by hypertension, and its effect is better than that of Banxia Baizhu Tianma Decoction.

[0168] Example 2 A pharmaceutical composition for treating hypertension, comprising, by weight, the following ingredients: 8 parts Pinellia ternata, 7 parts Poria cocos, 7 parts Citrus reticulata peel, and 7 parts Jujube.

[0169] The preparation method is as follows: Boil twice with water. For the first decoction, add 6 times the amount of water, soak for 1 hour, and boil for 60 minutes. For the second decoction, add 4 times the amount of water and boil for 40 minutes. Combine the two decoctions, filter, and concentrate the filtrate to a thick paste with a relative density of 1.25 (60℃). Add 1g of excipients (anhydrous glucose, pharmaceutical starch, and sodium carboxymethyl starch in a mass ratio of 10:7:1) to every 1mL of the thick paste. Granulate in a fluidized bed, dry, and package into 100 bags to obtain the granules.

[0170] Example 3 A pharmaceutical composition for treating hypertension, comprising, by weight, the following ingredients: 10 parts Pinellia ternata, 5 parts Poria cocos, 5 parts Citrus reticulata peel, and 5 parts Jujube.

[0171] The preparation method is as follows: Boil twice with water. For the first decoction, add 6 times the amount of water, soak for 1 hour, and boil for 60 minutes. For the second decoction, add 4 times the amount of water and boil for 40 minutes. Combine the two decoctions, filter, and concentrate the filtrate to a thick paste with a relative density of 1.21 (60℃). Add 1g of excipients (anhydrous glucose, pharmaceutical starch, and sodium carboxymethyl starch in a mass ratio of 10:7:1) to every 1mL of the thick paste. Granulate in a fluidized bed, dry, and package into 100 bags to obtain the granules.

[0172] The granules prepared in Examples 2 and 3 were tested using the same experimental methods as in Example 1, with the dosage remaining consistent with the medium-dose group in Example 1, calculated at 2.43 g / kg / d based on the amount of raw drug. The results showed that the granules prepared in Examples 2 and 3 significantly reduced the systolic blood pressure, diastolic blood pressure, and mean arterial pressure in SHR rats (p<0.05), and the effect was significantly better than that of Banxia Baizhu Tianma Decoction at the same dosage (p<0.05), indicating that the drug compositions of Examples 2-3 also have excellent antihypertensive effects.

[0173] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A pharmaceutical composition for treating hypertension, characterized in that, It is made from the following ingredients by weight: 8-10 parts Pinellia ternata, 5-7 parts Poria cocos, 5-7 parts Citrus reticulata peel, and 5-7 parts Jujube.

2. The pharmaceutical composition according to claim 1, characterized in that, It is made from the following ingredients by weight: 9 parts Pinellia ternata, 6 parts Poria cocos, 6 parts Citrus reticulata peel, and 6 parts Jujube.

3. The pharmaceutical composition according to claim 1, characterized in that, The Pinellia ternata includes at least one of raw Pinellia ternata, processed Pinellia ternata, ginger-processed Pinellia ternata, and prepared Pinellia ternata; and / or the Poria cocos is replaced with Poria cocos sclerotium, or a mixture of Poria cocos and Poria cocos sclerotium; and / or the Citrus reticulata peel is replaced with Citrus reticulata peel, or a mixture of Citrus reticulata peel and Citrus reticulata peel.

4. A method for preparing the pharmaceutical composition according to any one of claims 1-3, characterized in that, The process includes the following steps: mix all the ingredients, add water and boil, then filter to obtain the final product.

5. The preparation method according to claim 4, characterized in that, The decoction is performed 1-3 times, preferably 2 times; And / or the simmering time is 1-2.5 hours, preferably 80-120 minutes, more preferably 100 minutes; The amount of water used is 3-7 times the total mass of all raw materials, preferably 4-6 times; Soak the food before frying or boiling. The soaking time is preferably 0.5-1.5 hours, more preferably 1 hour.

6. A formulation, characterized in that, It includes a pharmaceutical composition and pharmaceutically acceptable excipients, wherein the pharmaceutical composition is the pharmaceutical composition according to any one of claims 1-3 or the pharmaceutical composition prepared by any one of claims 4-5.

7. The formulation according to claim 6, characterized in that, The dosage form of the preparation is granules, ointment, tablets, capsules or liquid preparation.

8. The formulation according to claim 7, characterized in that, The formulation is in the form of granules, and the pharmaceutically acceptable excipients include binders and flavoring agents; Preferably, the binder comprises at least one of dextrin, starch, and sodium carboxymethyl starch; Preferably, the flavoring agent comprises glucose; Preferably, the mass ratio of the adhesive to the flavoring agent is 4-5:5; More preferably, the pharmaceutically acceptable excipients are glucose, starch and sodium carboxymethyl starch in a mass ratio of 10:7:

1.

9. A method for preparing the formulation according to claim 8, characterized in that, The process includes the following steps: mixing all the raw materials, adding water and boiling, filtering, concentrating the filtrate to obtain a thick paste, adding pharmaceutically acceptable excipients for granulation, and drying to obtain the final product; Preferably, the relative density of the paste at 60°C is 1.18-1.25; Preferably, the volume ratio of the thick paste to the mass ratio of the excipients is 1 mL: 1 g; Preferably, the decoction is performed 1-3 times, more preferably 2 times; the decoction time is 1-2.5 hours, more preferably 80-120 minutes, and even more preferably 100 minutes. Preferably, the amount of water used is 3-7 times the total mass of all raw materials, more preferably 4-6 times; Preferably, the ingredients are soaked before decocting, and the soaking time is preferably 0.5-1.5 hours, more preferably 1 hour.

10. The use of a pharmaceutical composition or formulation in the preparation of a medicament for treating hypertension and / or related diseases; The pharmaceutical composition is the pharmaceutical composition according to any one of claims 1-3 or the pharmaceutical composition prepared by the preparation method according to any one of claims 4-5; The formulation is the formulation according to any one of claims 6-8 or the formulation prepared by the preparation method according to claim 9; Preferably, hypertension-related diseases include at least one of kidney disease, vascular disease, and heart disease; More preferably, the kidney lesion includes glomerular atrophy; More preferably, the vascular lesions include at least one of the following: elevated abdominal aortic pulsatility index, elevated abdominal aortic resistance index, thickening of the abdominal aortic wall, elevated renal artery pulsatility index, elevated renal artery resistance index, thickening of the renal artery wall, elevated superior mesenteric artery pulsatility index, elevated superior mesenteric artery resistance index, and thickening of the superior mesenteric artery wall. More preferably, the cardiac lesion includes at least one of reduced ejection fraction, reduced shortening fraction, and disordered cardiomyocyte arrangement.

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