Pharmaceutical composition for treating benign prostatic hyperplasia and preparation method thereof

Abstract

The invention relates to the technical field of traditional Chinese medicine preparations, in particular to a pharmaceutical composition for treating benign prostatic hyperplasia and a preparation method thereof. The composition is prepared from the following medicinal materials in parts by weight: 6 to 8 parts of radix aconiti lateralis preparata, 3 to 5 parts of cortex cinnamomi, 10 to 15 parts of fructus alpiniae oxyphyllae, 10 to 15 parts of fructus psoraleae, 5 to 10 parts of semen myristicae, 5 to 10 parts of ground beeltle, 8 to 12 parts of spina gleditsiae, 10 to 15 parts of radix angelicae sinensis, 8 to 12 parts of radix linderae, 15 to 20 parts of radix rehmanniae praeparata, 10 to 15 parts of fructus corni, 8 to 12 parts of rhizoma anemarrhenae, 15 to 20 parts of radix scrophulariae, 8 to 12 parts of rhizoma alismatis, 5 to 10 parts of radix stephaniae tetrandrae and 10 to 15 parts of radix cyathulae. The invention provides the self-prepared medicine composition for treating the prostatic hyperplasia, the diseases of patients with the prostatic hyperplasia are remarkably improved through the synergistic effect of all the medicines in the composition, and a new traditional Chinese medicine treatment thought is provided for clinical treatment of the BPH disease. According to the traditional Chinese medicine composition, medicine pairs are increased or decreased on the basis of referring to a traditional Chinese medicine classic treatment compound, the unique traditional Chinese medicine composition is finally formed, and all the medicine pairs in the formula cooperate with one another and are indispensable.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of traditional Chinese medicine preparation, and particularly relates to a pharmaceutical composition for treating prostatic hyperplasia and a preparation method thereof. BACKGROUND

[0002] Prostatic hyperplasia (BPH) is one of the most common diseases in middle-aged and elderly men, which refers to benign prostatic hyperplasia, and histologically, it is manifested as the hyperplasia of prostatic epithelium and interstitial components; anatomically, it is manifested as the increase in the volume of prostate; clinically, it is manifested as the appearance of lower urinary tract symptoms (LUTS); and urodynamically, it is manifested as bladder outlet obstruction (BOO). The incidence rate of BPH shows an upward trend with the increase in age, and the general onset age of BPH is after 35-45 years old, and the incidence rate gradually increases with the increase in age, among which, the incidence rate of BPH in the male population of 50-70 years old is as high as 50%, and the incidence rate of BPH in patients over 80 years old is as high as more than 90%. The symptoms and complications related to LUTS induced by BPH have a serious impact on the quality of life of patients, such as the increase in nocturia affecting the quality of sleep, leading to the decline in attention, and the frequent nocturia increasing the probability of falling of elderly patients. Therefore, the in-depth research on BPH urgently needs to be paid attention to. The pathogenesis of BPH is particularly complex and has not been fully elucidated at present, and some studies point out that estrogen can promote the occurrence of BPH through the two pathways of antagonizing or synergizing androgen, in addition, some studies also point out that high concentration of testosterone can also inhibit prostatic hyperplasia, and some studies also point out that immune inflammatory factors can induce BPH by intervening in the generation of prostatic blood vessels.

[0003] The core concept of current western medicine treatment of BPH is mainly aimed at the mechanism of prostate gland hyperplasia (androgen metabolism, cell proliferation, etc.), directly intervening pathological changes through drugs or surgery, for example, the bladder neck muscle can be relaxed by alpha receptor blockers to improve urination; for example, the prostate volume can be reduced by 5 alpha reductase inhibitors, and for severe patients, the hyperplastic tissue can also be removed by transurethral resection of the prostate. However, western medicine often has some side effects, such as alpha blockers may cause dizziness, orthostatic hypotension, 5 alpha reductase inhibitors can cause decreased libido, and surgical treatment also has certain surgical risks, and many patients are not willing to accept surgical treatment. Compared with western medicine treatment, traditional Chinese medicine treatment has the advantages of multi-target regulation, less side effects, low recurrence rate, etc. For some patients who do not need or are not willing to accept surgical treatment, it can be used as a selectable treatment scheme, and the core concept of traditional Chinese medicine treatment is mainly classified as "Lengbi" category, which is caused by kidney deficiency, dampness-heat and blood stasis, and emphasizes the overall regulation of kidney tonification and blood activation, heat clearing and urination. However, the actual application of traditional Chinese medicine compound for the clinical treatment of BPH is still limited, especially for the complex syndromes of kidney deficiency and blood stasis, dampness-heat and blood stasis, and the existing traditional Chinese medicine compound has certain limitations in treatment effect, so it is necessary to further explore new traditional Chinese medicine composition which can provide reference for the clinical treatment of BPH. SUMMARY

[0004] In view of the deficiencies in the prior art, the present application provides a self-prepared drug composition for treating prostate hyperplasia. The traditional Chinese medicine compound significantly improves the symptoms of patients with prostate hyperplasia through synergistic action of each drug, and provides a new traditional Chinese medicine treatment idea for the clinical treatment of BPH. In the research of the self-prepared traditional Chinese medicine compound, the causes of BPH disease are analyzed in depth, and the increase and decrease of drug pairs are carried out on the basis of the classical treatment compound of traditional Chinese medicine, and finally the unique traditional Chinese medicine composition of the present application is formed, and each drug in the prescription is indispensable to each other.

[0005] In traditional Chinese medicine, there is no specific disease name for BPH. Ancient Chinese medical texts often categorize it under "urinary retention," "spermatorrhea," or "dysuria." Its occurrence is closely related to factors such as aging-related kidney deficiency, impaired qi transformation, blood stasis, and damp-heat accumulation. BPH is located in the seminal vesicle, and its basic pathogenesis is dysfunction of the triple burner and impaired bladder qi transformation. It is closely related to the lungs, liver, spleen, and kidneys, with kidney deficiency as the root cause and qi stagnation, blood stasis, phlegm, and damp-heat as the manifestations. Pathologically, it is mostly a case of deficiency in the root and excess in the branch, with deficiency in the kidneys and spleen (qi and yang), and excess in qi stagnation, blood stasis, damp-heat, and phlegm. Common syndrome types include kidney qi deficiency syndrome, kidney yin deficiency syndrome, damp-heat accumulation syndrome, blood stasis syndrome, liver qi stagnation syndrome, middle qi sinking syndrome, and kidney deficiency with blood stasis syndrome, especially the complex syndromes of kidney deficiency with blood stasis and damp-heat with blood stasis syndrome, which are the most common clinically. For BPH with kidney deficiency and blood stasis syndrome, this invention, after considering the core treatment principles of warming the kidney and assisting yang, promoting blood circulation and removing blood stasis, and clearing the urinary tract and dispersing nodules, has obtained the self-formulated compound prescription by adding and subtracting from the classic Chinese medicine prescription - Jisheng Shenqi Prescription.

[0006] Specifically, the first aspect of this invention provides a pharmaceutical composition for treating benign prostatic hyperplasia, comprising the following medicinal materials: prepared aconite root, cinnamon, alpinia oxyphylla, psoralea corylifolia, nutmeg, ground beetle, gleditsia sinensis thorns, angelica sinensis tail, lindera root, prepared rehmannia root, cornus officinalis, anemarrhena asphodeloides, scrophularia ningpoensis, alisma plantago-aquatica, fangchi root, and achyranthes bidentata. In this formula, prepared aconite root and cinnamon are the principal herbs, working together to provide warming and invigorating effects, thus warming the kidneys and tonifying yang. Alpinia oxyphylla, psoralea corylifolia, nutmeg, ground beetle, gleditsia sinensis thorns, angelica sinensis tail, and lindera root are the assistant herbs. Alpinia oxyphylla, psoralea corylifolia, and nutmeg assist the principal herbs in warming and consolidating yang, while nutmeg also warms the kidneys and spleen, achieving a simultaneous treatment of the kidneys and spleen. The combination of ground beetle, gleditsia sinensis thorns, and angelica sinensis tail breaks up blood stasis, warms and disperses nodules, and is supplemented by lindera root to promote qi and blood circulation to eliminate stagnation, thereby eliminating blood stasis. Rehmannia glutinosa, Cornus officinalis, Anemarrhena asphodeloides, Scrophularia ningpoensis, Alisma plantago-aquatica, and Stephania tetrandra are used as adjuvant herbs. Rehmannia glutinosa and Cornus officinalis nourish yin, tonify the kidneys, and replenish essence, preventing Aconitum carmichaelii and Cinnamomum cassia from depleting yin essence. Anemarrhena asphodeloides and Scrophularia ningpoensis clear heat, nourish yin, and reduce fire; they counteract the dryness and heat of warming herbs and prevent prolonged stagnation from transforming into heat and damaging yin. Alisma plantago-aquatica promotes diuresis, eliminates dampness, and clears heat; combined with Stephania tetrandra, it assists Alisma plantago-aquatica in guiding dampness downwards, achieving the effect of purging turbidity and relieving strangury. Achyranthes bidentata is used as the guiding herb; while promoting blood circulation, removing blood stasis, and regulating menstruation, it guides the herbs downwards, allowing them to directly reach the liver, kidneys, and lower jiao. Among them: Prepared aconite root is a processed product of the root of Aconitum carmichaelii, a plant in the Ranunculaceae family (processed through steaming, boiling, and other techniques). Properties: Pungent, sweet, very hot; toxic. Channels entered: Heart, Kidney, Spleen. Functions: Restores Yang and rescues from collapse, tonifies fire and assists Yang, dispels cold and relieves pain.

[0007] Cinnamon is the dried bark of the cinnamon tree (Cinnamomum cassia), a plant in the Lauraceae family. Its properties are pungent, sweet, and very hot. It enters the kidney, spleen, heart, and liver meridians. Its functions include tonifying fire and assisting yang, dispelling cold and relieving pain, warming the meridians and promoting blood circulation, and guiding fire back to its source.

[0008] Alpinia oxyphylla is the dried, mature fruit of the plant Alpinia oxyphylla, belonging to the ginger family. Its properties are pungent and warm. It enters the spleen and kidney meridians. Its functions include warming the kidneys, consolidating essence, reducing urination, warming the spleen, stopping diarrhea, and reducing salivation.

[0009] Psoralea corylifolia is the dried, ripe fruit of the legume Psoralea corylifolia. Its properties are pungent, bitter, and warm. It enters the kidney and spleen meridians. Its functions include tonifying the kidneys and strengthening yang, consolidating essence and reducing urination, warming the spleen and stopping diarrhea, and relieving asthma.

[0010] Nutmeg is the dried seed kernel of the nutmeg plant (Myristica fragrans). Its properties are pungent and warm. It enters the spleen, stomach, and large intestine meridians. Its functions are to warm the middle jiao (spleen and stomach), promote qi circulation, astringe the intestines, and stop diarrhea.

[0011] Ground beetle is the dried body of the female ground beetle (Eupolyphaga sinensis) or the Chinese ground beetle (Eupolyphaga chinensis) of the Blattodea family. Properties: Salty, cold; slightly toxic. Meridian tropism: Liver meridian. Functions: Breaks up blood stasis, promotes blood circulation, and heals tendons and bones.

[0012] Gleditsia sinensis thorns are the dried thorns of the Fabaceae plant Gleditsia sinensis. Properties: pungent, warm. Channels entered: Liver, Stomach.

[0013] Efficacy: Reduces swelling and promotes detoxification, drains pus, and kills parasites.

[0014] Angelica sinensis root tail is the dried root tail of the Angelica sinensis plant (family Apiaceae) (the medicinal part). Properties: pungent, sweet, warm. Channels entered: liver, heart, spleen. Functions: invigorates blood and removes blood stasis (leaning towards invigorating blood and unblocking channels; it is one of the medicinal parts of Angelica sinensis).

[0015] Lindera root is the dried tuberous root of Lindera root, a plant in the Lauraceae family. Properties: pungent, warm. Channels entered: Lung, Spleen, Kidney, Bladder. Functions: Promotes qi circulation and relieves pain, warms the kidneys and dispels cold.

[0016] Prepared Rehmannia root is the dried tuberous root of Rehmannia glutinosa, a plant in the Scrophulariaceae family, processed through a special method. Properties: Sweet, slightly warm. Channels entered: Liver and Kidney. Functions: Nourishes blood and yin, replenishes essence and marrow.

[0017] Cornus officinalis is the dried, ripe fruit pulp of the Cornus officinalis plant (family Cornaceae). Its properties are: sour, astringent, and slightly warm. It enters the liver and kidney meridians. Its functions are: tonifying the liver and kidneys, and astringing and consolidating.

[0018] Anemarrhena asphodeloides is the dried rhizome of the plant Anemarrhena asphodeloides, belonging to the Liliaceae family. Its properties are bitter, sweet, and cold. It enters the lung, stomach, and kidney meridians. Its functions are to clear heat and purge fire, nourish yin and moisten dryness.

[0019] Scrophularia is the dried root of the plant Scrophularia ningpoensis, belonging to the Scrophulariaceae family. Its properties are: sweet, bitter, and salty, slightly cold. It enters the lung, stomach, and kidney meridians. Its functions are: clearing heat and cooling the blood, nourishing yin and reducing fire, detoxifying and dissipating nodules.

[0020] Alisma plantago-aquatica is the dried tuber of the plant Alisma plantago-aquatica, belonging to the Alismataceae family. Its properties are sweet, bland, and cold. It enters the kidney and bladder meridians. Its functions include promoting diuresis and eliminating dampness, clearing heat, resolving turbidity, and lowering lipids.

[0021] Han Fangji is the dried root of *Stephania tetrandra*, a plant in the Menispermaceae family (commonly known as "Han Fangji"). Properties: Bitter, pungent, cold. Channels entered: Bladder, Lung. Functions: Dispels wind and relieves pain, promotes diuresis and reduces swelling.

[0022] Achyranthes bidentata is the dried root of the plant Achyranthes bidentata (family Amaranthaceae). Its properties are: sweet, slightly bitter, and neutral. It enters the liver and kidney meridians. Its functions include: removing blood stasis and promoting menstruation, facilitating joint movement, and promoting urination.

[0023] As a further explanation of the present invention, the composition comprises the following medicinal materials in parts by weight: 6-8 parts of processed aconite root, 3-5 parts of cinnamon bark, 10-15 parts of Alpinia oxyphylla, 10-15 parts of Psoralea corylifolia, 5-10 parts of nutmeg, 5-10 parts of Eupolyphaga sinensis, 8-12 parts of Gleditsia sinensis thorns, 10-15 parts of Angelica sinensis tail, 8-12 parts of Lindera strychnifolia, 15-20 parts of Rehmannia glutinosa, 10-15 parts of Cornus officinalis, 8-12 parts of Anemarrhena asphodeloides, 15-20 parts of Scrophularia ningpoensis, 8-12 parts of Alisma plantago-aquatica, 5-10 parts of Stephania tetrandra, and 10-15 parts of Achyranthes bidentata.

[0024] As a further explanation of the present invention, the composition consists of the following medicinal materials in parts by weight: 7 parts prepared aconite root, 4 parts cinnamon, 12 parts Alpinia oxyphylla, 12 parts Psoralea corylifolia, 8 parts nutmeg, 8 parts Eupolyphaga sinensis, 10 parts Gleditsia sinensis thorns, 12 parts Angelica sinensis tail, 10 parts Lindera strychnifolia, 18 parts Rehmannia glutinosa, 12 parts Cornus officinalis, 10 parts Anemarrhena asphodeloides, 18 parts Scrophularia ningpoensis, 10 parts Alisma plantago-aquatica, 12 parts Stephania tetrandra, and 12 parts Achyranthes bidentata.

[0025] A second aspect of this invention provides a method for preparing a traditional Chinese medicine preparation for treating benign prostatic hyperplasia, comprising the following steps: S1: Prepare a traditional Chinese medicine fluid extract from the traditional Chinese medicine composition described in any one of the above-mentioned methods for later use; S2: Add clinically acceptable excipients to the fluid extract of traditional Chinese medicine obtained in step S1, and prepare it using conventional formulation methods to produce a clinically acceptable oral traditional Chinese medicine preparation.

[0026] As a further explanation of the present invention, the traditional Chinese medicine preparation is any one of decoction, powder, pill, granule, capsule, tablet, drop pill, syrup, or oral liquid.

[0027] As a further explanation of the present invention, in S1, the traditional Chinese medicine fluid extract is prepared by any one of the following methods: decoction concentration method, percolation method, maceration concentration method, and reflux extraction concentration method.

[0028] As a further explanation of the present invention, in S1, when using the decoction and concentration method, the prepared aconite is decocted separately for 1-1.5 hours before the other medicinal materials are added, and the cinnamon is added 5-10 minutes before the end of the decoction.

[0029] A third aspect of the present invention provides a traditional Chinese medicine preparation for treating benign prostatic hyperplasia, wherein the traditional Chinese medicine preparation is made by conventional preparation methods using the traditional Chinese medicine composition described in any one of the above-mentioned methods and clinically acceptable excipients.

[0030] The fourth aspect of the present invention provides the use of the traditional Chinese medicine composition described in any one of the above-mentioned methods, or the traditional Chinese medicine preparation made by any one of the above-mentioned methods, or the traditional Chinese medicine preparation described in any one of the above-mentioned methods, in the preparation of a medicament for treating benign prostatic hyperplasia.

[0031] Compared with the prior art, the present invention has the following beneficial technical effects: This invention provides a self-formulated pharmaceutical composition for treating benign prostatic hyperplasia (BPH). The individual herbs in this composition work synergistically to significantly improve the symptoms of BPH patients, offering a new TCM treatment approach for the clinical treatment of BPH. In the research of this self-formulated TCM compound, the pathogenesis of BPH was analyzed in depth. Based on classic TCM treatment formulas, the herb pairs were added or subtracted, ultimately forming the unique TCM composition of this invention. Each herb pair in the formula works synergistically and is indispensable. Attached Figure Description

[0032] Figure 1 The results show the prostate index and volume of rats in each group.

[0033] Figure 2 The results of prostate tissue pathological scoring for each group of rats are shown. Detailed Implementation

[0034] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0035] Example 1 This embodiment provides a pharmaceutical composition for treating benign prostatic hyperplasia, which consists of the following medicinal materials in parts by weight: 7 parts prepared aconite root, 4 parts cinnamon bark, 12 parts Alpinia oxyphylla, 12 parts Psoralea corylifolia, 8 parts nutmeg, 8 parts Eupolyphaga sinensis, 10 parts Gleditsia sinensis thorns, 12 parts Angelica sinensis tail, 10 parts Lindera strychnifolia, 18 parts Rehmannia glutinosa, 12 parts Cornus officinalis, 10 parts Anemarrhena asphodeloides, 18 parts Scrophularia ningpoensis, 10 parts Alisma plantago-aquatica, 12 parts Stephania tetrandra, and 12 parts Achyranthes bidentata.

[0036] Example 2 This embodiment provides a pharmaceutical composition for treating benign prostatic hyperplasia, which consists of the following medicinal materials in parts by weight: 6 parts prepared aconite root, 3 parts cinnamon bark, 10 parts Alpinia oxyphylla, 10 parts Psoralea corylifolia, 5 parts nutmeg, 5 parts Eupolyphaga sinensis, 8 parts Gleditsia sinensis thorns, 10 parts Angelica sinensis tail, 8 parts Lindera strychnifolia, 15 parts Rehmannia glutinosa, 10 parts Cornus officinalis, 8 parts Anemarrhena asphodeloides, 15 parts Scrophularia ningpoensis, 8 parts Alisma plantago-aquatica, 5 parts Stephania tetrandra, and 10 parts Achyranthes bidentata.

[0037] Example 3 This embodiment provides a pharmaceutical composition for treating benign prostatic hyperplasia, which consists of the following medicinal materials in parts by weight: 8 parts of processed aconite root, 5 parts of cinnamon bark, 15 parts of Alpinia oxyphylla, 15 parts of Psoralea corylifolia, 10 parts of nutmeg, 10 parts of Eupolyphaga sinensis, 12 parts of Gleditsia sinensis thorns, 15 parts of Angelica sinensis tail, 12 parts of Lindera strychnifolia, 20 parts of Rehmannia glutinosa, 15 parts of Cornus officinalis, 12 parts of Anemarrhena asphodeloides, 20 parts of Scrophularia ningpoensis, 12 parts of Alisma plantago-aquatica, 10 parts of Stephania tetrandra, and 15 parts of Achyranthes bidentata.

[0038] Comparative Example 1: This comparative example provides a pharmaceutical composition for treating benign prostatic hyperplasia, which differs from Example 1 in that it removes Alpinia oxyphylla, Psoralea corylifolia, and Myristica fragrans.

[0039] Comparative Example 2: This comparative example provides a pharmaceutical composition for treating benign prostatic hyperplasia, which differs from Example 1 in that it removes the ground beetle and soapberry thorns from the composition.

[0040] Comparative Example 3: This comparative example provides a pharmaceutical composition for treating benign prostatic hyperplasia, which differs from Example 1 in that the tail of Angelica sinensis and Lindera strychnifolia are removed from the composition.

[0041] Comparative Example 4: This comparative example provides a pharmaceutical composition for treating benign prostatic hyperplasia, which differs from Example 1 in that it omits Rehmannia glutinosa and Cornus officinalis.

[0042] Comparative Example 5: This comparative example provides a pharmaceutical composition for treating benign prostatic hyperplasia, which differs from Example 1 in that it removes Anemarrhena asphodeloides and Scrophularia ningpoensis.

[0043] Comparative Example 6: This comparative example provides a pharmaceutical composition for treating benign prostatic hyperplasia, which differs from Example 1 in that it removes Alisma plantago-aquatica and Stephania tetrandra from the formula.

[0044] The traditional Chinese medicine compositions provided in the above examples and comparative examples are prepared into traditional Chinese medicine fluid extracts using concentration methods such as decoction concentration, percolation, maceration concentration, and reflux extraction concentration. Then, clinically acceptable excipients are added, and conventional formulation methods are used to prepare them into clinically acceptable oral traditional Chinese medicine preparations, such as decoctions, powders, pills, granules, capsules, tablets, drop pills, syrups, and oral liquids.

[0045] I. The efficacy of the traditional Chinese medicine composition provided in the embodiments and comparative examples of this invention on benign prostatic hyperplasia was verified through animal experiments.

[0046] 1. Experimental materials: 1.1 Laboratory Animals Male SD rats, 6-8 weeks old, with an average weight of (200g±20g), were purchased from the Animal Experiment Center of the Hainan Hospital of Guangdong Provincial Hospital of Traditional Chinese Medicine. After purchase, they were acclimatized under standard laboratory conditions for 1 week before subsequent experiments were conducted.

[0047] 1.2 Experimental drugs: The traditional Chinese medicine dry extract powder prepared from the above-described embodiments and comparative examples is prepared as follows: Each herb in the traditional Chinese medicine composition provided in the above embodiments and comparative examples is weighed according to the proportions, added to purified water, and soaked for 40-60 minutes. Then, it is decocted for 40 minutes, filtered, and the remaining dregs are added to water (approximately two-thirds of the first decoction volume) and decocted a second time for 20 minutes. The two filtrates are combined, impurities are filtered out, and the mixture is concentrated to a viscous paste (relative density 1.20). The concentrated paste is then vacuum-dried and ground into a fine powder to obtain the traditional Chinese medicine dry extract powder. It should be noted that prepared aconite root needs to be decocted separately for about 1 hour beforehand, and tasted until there is no numbing sensation on the tongue to remove its toxicity; to prevent the loss of volatile oils from cinnamon, it should be added 5 minutes before turning off the heat; and because the thorns of soapberry are hard, they need to be crushed before decocting.

[0048] Finasteride tablets, 1mg strength 60 tablets, National Drug Approval Number H20233730, Wuhan Renfu Pharmaceutical Co., Ltd.

[0049] Testosterone propionate injection, 25 mg / 1 mL 10 vials, approval number veterinary drug number 120031054, Hefei Qianfang Animal Health Technology Co., Ltd.

[0050] 2. Experimental methods: 2.1 Animal model establishment, grouping, and drug administration A rat model of benign prostatic hyperplasia (BPH) was established by subcutaneous injection of testosterone propionate. Rats other than the control group were subcutaneously injected with testosterone propionate, while rats in the control group were subcutaneously injected with an equal dose of physiological saline. The injection dose was 5 mg / kg / time, once daily. After four weeks, three rats from the control group and three rats from the model group were randomly selected. The ventral lobe of the prostate was harvested and weighed, and the prostate index (PI = prostate wet weight (mg) / rat body weight (g)) was calculated. The prostate tissue of the model group was stained with hematoxylin and eosin (HE) and observed under a light microscope for pathological examination. A PI increase of more than 50% in the model group compared to the control group, along with HE-stained pathological tissue showing: glandular dilation, enlarged glandular lumen, increased number of glandular epithelial cell layers; tall columnar epithelial cells arranged disorderedly, with papillary processes protruding into the glandular lumen; stromal fibrosis, increased smooth muscle cells, and inflammatory cell infiltration. Meeting both of these indicators was considered a successful modeling indicator.

[0051] Grouping: The successfully modeled rats were randomly divided into 9 groups of 10 each: model group, positive control group, Example 1 group, comparative example 1 group, comparative example 2 group, comparative example 3 group, comparative example 4 group, comparative example 5 group, and comparative example 6 group. Ten rats that were injected with saline alone were used as a control.

[0052] Administration: 24 hours after successful model establishment, rats in Example 1 were administered the herbal extract powder prepared from the herbal composition provided in Example 1, and rats in Comparative Examples 1-6 were administered the same herbal extract powder. The herbal extract powder was administered to all groups at a dose of 5 g / kg via gavage once daily. Rats in the positive control group were given finasteride tablets at a dose of 0.5 mg / kg via gavage once daily. The model group and the blank control group were administered an equal volume of physiological saline via gavage at corresponding time points. All rats in all groups underwent continuous administration for four weeks before their indicators were measured.

[0053] 2.2 Detection Indicators and Methods 2.2.1 Detection of serum biochemical markers ELISA method for detecting dihydrotestosterone (DHT), testosterone (T), and interleukin in rat serum Interleukin The content of.

[0054] 2.2.2 Prostate index and volume detection The rats were weighed using an electronic balance, and the wet weight of the ventral lobe of the prostate was measured using a precision balance. The prostate index (PI = prostate wet weight (mg) / rat body weight (g)) was calculated. The prostatic volume (PV (mL)) of the ventral lobe of the prostate was measured using a graduated cylinder. 2.2.3 Histopathological scoring Tissue from the ventral lobe of the prostate was fixed in 4% paraformaldehyde for 24 hours, then subjected to graded ethanol dehydration, paraffin embedding, 4μm sectioning, HE staining, and neutral resin mounting. The prepared slides were then examined under a light microscope to observe glandular structure, number of epithelial cell layers, and degree of stromal hyperplasia, and the following pathological scoring was performed: The scoring criteria include four dimensions: glandular structure, glandular epithelial cell hyperplasia, stromal hyperplasia, and inflammatory cell infiltration. Each dimension is scored from 0 to 3 points according to its severity, and the total score is the sum of all dimensions (0-12 points). The specific scoring criteria are as follows: ① Glandular structure disorder: 0 points: Acini are uniform in size, regular in shape, and neatly arranged, without dilation or fusion. 1 point: A few acini are slightly dilated, slightly disordered in arrangement, and have clear boundaries. 2 points: Some acini are moderately dilated, significantly disordered in arrangement, and branching or slight fusion can be seen. 3 points: A large number of acini are significantly dilated, severely disordered in arrangement, and acini fusion presents as cord-like or cystic changes with blurred boundaries.

[0055] ② Glandular epithelial cell hyperplasia: 0 points: Simple columnar or cuboidal epithelium, regular in shape, nucleus located at the base, no protrusions. 1 point: Mild epithelial cell hyperplasia in some areas, basically normal in shape, no papillary protrusions. 2 points: Obvious epithelial cell hyperplasia, a few papillary protrusions are visible. 3 points: Severe epithelial cell hyperplasia, prominent papillary protrusions, irregular cell shape.

[0056] ③ Interstitial hyperplasia: 0 points: Normal interstitial ratio, smooth muscle and fibrous tissue evenly distributed, no obvious hyperplasia. 1 point: Mild increase in interstitial mass, with a small amount of fibrous tissue or smooth muscle bundles visible locally, not affecting glandular structure. 2 points: Moderate interstitial hyperplasia, significantly increased fibrous tissue / smooth muscle, septating acini, widening of interglandular distance. 3 points: Severe interstitial hyperplasia, with a large amount of fibrous tissue or smooth muscle hyperplasia, forming dense cords, causing glandular compression and deformation.

[0057] ④ Inflammatory cell infiltration: 0 points: No obvious inflammatory cells. 1 point: A small number of inflammatory cells, without obvious aggregation. 2 points: Moderate inflammation, with small inflammatory foci visible. 3 points: Severe inflammation, with multiple inflammatory foci visible or fused into patches.

[0058] Note: Scoring must be completed independently by two pathologists in a double-blind manner, and the average value should be taken; if the difference is greater than 1 point, joint review is required.

[0059] 3. Statistical Analysis Statistical analysis was performed using SPSS 25.0 software. Quantitative data were expressed as mean ± standard deviation (x ± s) to ensure normality and homogeneity of variance. t-tests were used, with P < 0.05 or P < 0.01 considered statistically significant.

[0060] 4. Experimental Results 4.1 Results of detection of biochemical markers in the serum of rats in each group Table 1 shows the serum levels of DHT, T, IL-6, and IL-8 in each group of rats.

[0061] Note: ## P < 0.01 compared with the control group; Compared with the model group, P<0.01; n=10.

[0062] The occurrence of benign prostatic hyperplasia (BPH) is directly related to excessive stimulation by androgens (especially dihydrotestosterone, DHT). Testosterone (T) is converted into the more potent DHT by 5α-reductase, which can promote the proliferation of prostatic epithelial cells. The pathological process of BPH is often accompanied by a chronic inflammatory response. Inflammatory cell infiltration in prostatic tissue can release a large number of pro-inflammatory factors, thereby promoting cell proliferation and tissue fibrosis. The level of inflammatory factors in serum can reflect the systemic and local inflammatory state. Therefore, serum androgen levels and inflammatory factors are key indicators for evaluating the treatment effect of BPH. This invention detects the levels of androgens (dihydrotestosterone (DHT) and testosterone (T)) and inflammatory factors (interleukins) in rat serum. Interleukin The levels of DHT, T, and [other substances] were measured in the serum of rats in the model group to verify the therapeutic effect of the drug on BPH. Specifically, as shown in Table 1, the levels of DHT, T, and [other substances] in the serum of rats in the model group were [high / low]. and The levels in the rats were significantly higher than those in the control group, and the inter-group comparison P < 0.01, indicating statistical significance. This suggests that the serum DHT, T, and... levels in rats with benign prostatic hyperplasia were significantly higher than those in healthy rats. and The levels of these indicators were significantly elevated. Compared to the model group rats, the serum levels of DHT, T, and... in the positive control group and the Example 1 group rats were significantly higher. and The levels were significantly reduced, and the inter-group comparison P<0.01, indicating a statistically significant difference. This suggests that the traditional Chinese medicine composition provided by this invention has a significant effect on improving the symptoms of benign prostatic hyperplasia in rats, and the improvement effect is basically equivalent to that of Western medicine.

[0063] 4.2 Results of prostate index and volume detection in each group of rats Table 2 shows the results of prostate index and volume detection in each group of rats.

[0064] Note: ## P < 0.01 compared with the control group; Compared with the model group, P < 0.01; Compared with Example 1 group, P<0.05. Compared with Example 1, P<0.01, n=10.

[0065] The core pathological feature of BPH lies primarily in the excessive growth and enlargement of prostate tissue. Increased volume is one of the most direct manifestations of hyperplasia. The prostate index, which standardizes the ratio of prostate weight to body weight, accurately reflects the degree of abnormal prostate hyperplasia relative to the overall size of the rat. An elevated index indicates a disproportionate enlargement of the prostate. Therefore, this invention reflects the degree of prostate hyperplasia before and after treatment in each group of rats by detecting the prostate index and volume. Specifically, from Table 2 and... Figure 1 As can be seen, the PI and PV values ​​of the model group rats were significantly higher than those of the blank group, indicating that the prostate of the model group rats underwent significant hyperplasia. The PI and PV values ​​of the positive control group and the Example 1 group rats were significantly lower than those of the model group (P<0.01), indicating a statistically significant difference. This demonstrates that the traditional Chinese medicine composition provided by this invention has a significant ameliorative effect on the degree of prostate hyperplasia in rats with benign prostatic hyperplasia. The PI and PV values ​​of the comparative examples 1-6 rats were all higher than those of the Example 1 group (P<0.05), indicating a statistically significant difference. This shows that the absence of certain traditional Chinese medicine pairs in the traditional Chinese medicine composition of this invention significantly affects the therapeutic effect of the composition on benign prostatic hyperplasia, and also indicates that there is a significant synergistic effect among the drug pairs in the traditional Chinese medicine composition provided by this invention; each drug pair is indispensable.

[0066] 4.3 Pathological scoring results of prostate tissue in each group of rats Table 3 shows the histopathological scores of prostate tissue in each group of rats.

[0067] Note: ## P < 0.01 compared with the control group; Compared with the model group, P < 0.01; Compared with Example 1 group, P<0.05. Compared with Example 1, P<0.01, n=10.

[0068] The prostate tissue of BPH rats exhibits certain degrees of pathological changes, primarily manifested as prostate gland hyperplasia, glandular epithelial cell proliferation, stromal fibrosis, and inflammatory cell infiltration. These pathological structures can be observed through HE staining. By observing multidimensional pathological features and using quantitative scoring, the differences in the degree of lesions among different groups of rats can be better distinguished. Therefore, this invention performed pathological scoring of prostate tissue from different groups of rats. Specifically, see Table 3 and... Figure 2As can be seen, the pathological scores of the model group rats were significantly higher than those of the blank group, indicating that the prostate tissue of the model group rats had obvious lesions. The pathological scores of the positive control group and the rats in Example 1 group were significantly lower than those of the model group (P<0.01), indicating a statistically significant difference. This suggests that the traditional Chinese medicine composition provided by this invention has a significant ameliorative effect on the degree of prostate tissue lesions in rats with benign prostatic hyperplasia. The pathological scores of rats in Comparative Examples 1-6 were all higher than those in Example 1 group (P<0.05), indicating a statistically significant difference. This shows that the absence of certain traditional Chinese medicine pairs in the traditional Chinese medicine composition of this invention significantly affects the therapeutic effect of the composition on benign prostatic hyperplasia, and also demonstrates that there is a significant synergistic effect among the drug pairs in the traditional Chinese medicine composition provided by this invention; each drug pair is indispensable.

[0069] In summary, the above animal experiments demonstrate that the traditional Chinese medicine composition provided by this invention has a significant therapeutic effect on rats with benign prostatic hyperplasia. Furthermore, there is a clear synergistic effect among the various herbs in the traditional Chinese medicine composition provided by this invention, and each herb pair is indispensable, thus showcasing the unique compatibility advantages of the traditional Chinese medicine composition provided by this invention.

[0070] II. The efficacy of the traditional Chinese medicine composition provided in Example 1 of this invention on benign prostatic hyperplasia was verified through clinical trials.

[0071] 1. Materials and Methods 1.1 General Information One hundred patients with benign prostatic hyperplasia (BPH) treated at the Hainan Hospital of Guangdong Provincial Hospital of Traditional Chinese Medicine from June 2024 to August 2025 were included in this study and randomly divided into a control group and a treatment group, with 50 patients in each group. There were no statistically significant differences in age, disease duration, and other general characteristics between the two groups (P>0.05).

[0072] 1.2 Diagnostic criteria 1.2.1 Western Medicine Diagnostic Criteria Relevant diagnostic criteria were developed with reference to the "Guidelines for the Diagnosis and Treatment of Urological and Andrological Diseases in China".

[0073] Symptoms: Storage phase symptoms: urinary frequency (≥7 times during the day), urgency, increased nocturia (≥2 times / night), urinary incontinence; Voiding phase symptoms: urinary hesitancy, weak urine stream, thin urine stream, difficulty urinating, interrupted urine stream, split urine stream; Post-voiding symptoms: incomplete emptying of the bladder, feeling of residual urine in the bladder.

[0074] Symptom scores: ① International Prostate Symptom Score (IPSS): Mild symptoms: 0-7 points; Moderate symptoms: 8-19 points; Severe symptoms: 20-35 points. ② Quality of Life (QOL) score ≥ 4 points.

[0075] Examination: ① Ultrasound: Transabdominal or transrectal ultrasound shows prostate volume (PV) > 20 ml. ② Urinary flow rate: Maximum urinary flow rate (Qmax) < 12 ml / s.

[0076] Exclude: organic lesions such as prostate cancer, neurogenic bladder, urinary tract infection, bladder stones, and urethral stricture.

[0077] 1.2.2 Traditional Chinese Medicine Diagnostic Criteria The following diagnostic criteria for kidney deficiency and blood stasis type BPH were formulated with reference to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine" and the "Standards for Diagnosis and Efficacy of Diseases and Syndromes in Traditional Chinese Medicine".

[0078] Main symptoms: frequent urination, nocturia; difficulty urinating; dribbling or incomplete urination.

[0079] Secondary symptoms: soreness and weakness in the lower back and knees; stabbing pain in the lower abdomen / perineum; sallow complexion; dampness in the scrotum and perineum; aversion to cold, cold limbs, or hot flashes in the palms, soles, and chest.

[0080] Tongue and pulse: The tongue is dark red; there are petechiae and ecchymoses on the tongue; the coating is white or yellow and greasy; the pulse is wiry, thready, rapid and hesitant.

[0081] Both primary and secondary symptoms are categorized into four degrees: none, mild, moderate, and severe, based on clinical presentation. Primary symptoms are scored from 0 to 6 points, with a total score of 0-18 points. Secondary symptoms are scored from 0 to 1 to 2 to 3 points, with a total score of 0-15 points. The sum of primary and secondary symptoms constitutes the total TCM syndrome score. Tongue and pulse are assessed as normal, abnormal, or severe based on the physician's judgment. When the total score of primary and secondary symptoms is ≥8 points, the syndrome is diagnosed as kidney deficiency and blood stasis.

[0082] 1.3 Inclusion Criteria ① After diagnosis, the clinical manifestations meet the diagnostic criteria of Western medicine and traditional Chinese medicine; ② Male, aged 50 to 80 years; ③ IPSS score of 8-35 points, QOL score ≥3 points; ④ Can receive treatment with the traditional Chinese medicine and control drug provided by this invention; ⑤ Informed about the research, following the principle of voluntariness, and signing an informed consent form.

[0083] 1.4 Exclusion Criteria ① History of prostate cancer, bladder cancer, urethral stricture, or acute urinary retention. ② Severe heart, liver, or kidney disease (Cr > 1.5 times the upper limit of normal, ALT / AST > 2 times the upper limit of normal, NYHA functional class III-IV). ③ Neurogenic bladder or diabetic bladder disease. ④ History of prostate surgery / minimally invasive treatment. ⑤ Currently using related medications (within 2 weeks). ⑥ Allergic constitution or allergy to any component of the herbal medicine in this test.

[0084] 1.5 Rejection and Shedding Criteria ① Patients who experience severe adverse reactions during treatment and are unable to complete the entire treatment cycle. ② Patients who abandon or interrupt treatment midway. ③ Errors in results caused by other reasons.

[0085] 1.6 Treatment Methods Control group: Tamsulosin hydrochloride sustained-release capsules, 1 capsule / day / time, taken orally before bedtime. (Specification: 0.2mg / capsule).

[0086] Experimental group: The herbal decoction was prepared according to the formula in Example 1 (7g of prepared aconite root, 4g of cinnamon, 12g of Alpinia oxyphylla, 12g of Psoralea corylifolia, 8g of nutmeg, 8g of Eupolyphaga sinensis, 10g of Gleditsia sinensis thorns, 12g of Angelica sinensis tail, 10g of Lindera strychnifolia, 18g of Rehmannia glutinosa, 12g of Cornus officinalis, 10g of Anemarrhena asphodeloides, 18g of Scrophularia ningpoensis, 10g of Alisma plantago-aquatica, 12g of Stephania tetrandra, and 12g of Achyranthes bidentata). 200mL was taken orally twice a day.

[0087] The treatment course for both groups of patients was 4 weeks.

[0088] 1.7 Observation of therapeutic effect 1.7.1 Traditional Chinese Medicine Symptom Score Assessment The total TCM syndrome score (the sum of the scores of the primary and secondary symptoms) of patients in the control group and the experimental group before and after treatment was quantified and compared.

[0089] 1.7.2 Clinical efficacy evaluation The following assessment criteria were developed with reference to the International Prostate Symptom Score: Effectiveness: IPSS reduced to 7 points or below, QOL score reduced to 1 point or below, Qmax ≥ 18 ml / s, at least two of these conditions must be met; Effective: IPSS score reduced to 13 or below, QOL score reduced by 2 or more points for those with a score of 4 or above, Qmax ≥ 12 ml / s, meeting any one of these criteria is sufficient; Invalid: No significant changes in any of the scores; the criteria for validity have not been met.

[0090] 2. Results 2.1 Statistical Analysis Statistical analysis was performed using SPSS 25.0 software. Quantitative data were expressed as mean ± standard deviation (x ± s) and analyzed using t-tests. Categorical data were analyzed using R×C chi-square tests. The test method considered P < 0.05 or P < 0.01 as statistically significant.

[0091] 2.2 Statistical Results 2.2.1 Comparison of TCM syndrome scores before and after treatment in the two groups of patients Table 4. Results of TCM syndrome scores before and after treatment in the two groups of patients.

[0092] Note: Compared with the control group before treatment, P<0.01; ## Compared with the experimental group before treatment, P<0.01; n=50.

[0093] As can be seen from Table 4, the total TCM symptom scores of both the experimental group and the control group after treatment were significantly lower than before treatment, and the inter-group comparison P<0.01, indicating a statistically significant difference. This shows that the TCM composition provided by the present invention can significantly improve the TCM symptoms of patients.

[0094] 2.2.2 Comparison of clinical efficacy between the two groups of patients Table 5 Comparison of clinical efficacy between the two groups of patients

[0095] Table 5 shows a comparison of the clinical efficacy between the two groups of patients. As can be seen from Table 5, the total effective rate of treatment in both the experimental group and the control group reached more than 70%, indicating that the traditional Chinese medicine composition provided by the present invention has a significant effect on patients with benign prostatic hyperplasia, and the total effective rate reached more than 80%.

[0096] It should be noted that, in this document, terms such as “comprising,” “including,” or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0097] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A pharmaceutical composition for treating benign prostatic hyperplasia, characterized in that, The composition consists of the following medicinal materials: prepared aconite root, cinnamon, alpinia oxyphylla, psoralea corylifolia, nutmeg, ground beetle, soapberry thorn, angelica sinensis tail, lindera root, prepared rehmannia root, cornus officinalis, anemarrhena asphodeloides, scrophularia ningpoensis, alisma plantago-aquatica, fangchi chinensis, and achyranthes bidentata.

2. The pharmaceutical composition for treating benign prostatic hyperplasia as described in claim 1, characterized in that, The composition consists of the following medicinal materials in parts by weight: 6-8 parts of processed aconite root, 3-5 parts of cinnamon bark, 10-15 parts of Alpinia oxyphylla, 10-15 parts of Psoralea corylifolia, 5-10 parts of nutmeg, 5-10 parts of Eupolyphaga sinensis, 8-12 parts of Gleditsia sinensis thorns, 10-15 parts of Angelica sinensis tail, 8-12 parts of Lindera strychnifolia, 15-20 parts of Rehmannia glutinosa, 10-15 parts of Cornus officinalis, 8-12 parts of Anemarrhena asphodeloides, 15-20 parts of Scrophularia ningpoensis, 8-12 parts of Alisma plantago-aquatica, 5-10 parts of Stephania tetrandra, and 10-15 parts of Achyranthes bidentata.

3. The pharmaceutical composition for treating benign prostatic hyperplasia as described in claim 1, characterized in that, The composition consists of the following medicinal materials in parts by weight: 7 parts prepared aconite root, 4 parts cinnamon, 12 parts Alpinia oxyphylla, 12 parts Psoralea corylifolia, 8 parts nutmeg, 8 parts Eupolyphaga sinensis, 10 parts Gleditsia sinensis thorns, 12 parts Angelica sinensis tail, 10 parts Lindera strychnifolia, 18 parts Rehmannia glutinosa, 12 parts Cornus officinalis, 10 parts Anemarrhena asphodeloides, 18 parts Scrophularia ningpoensis, 10 parts Alisma plantago-aquatica, 12 parts Stephania tetrandra, and 12 parts Achyranthes bidentata.

4. A method for preparing a traditional Chinese medicine preparation for treating benign prostatic hyperplasia, characterized in that, Includes the following steps: S1: Prepare a traditional Chinese medicine fluid extract from the traditional Chinese medicine composition according to any one of claims 1-3 for later use; S2: Add clinically acceptable excipients to the fluid extract of traditional Chinese medicine obtained in step S1, and prepare it using conventional formulation methods to produce a clinically acceptable oral traditional Chinese medicine preparation.

5. The method for preparing the traditional Chinese medicine preparation for treating benign prostatic hyperplasia as described in claim 4, characterized in that, The traditional Chinese medicine preparation is any one of the following: decoction, powder, pill, granule, capsule, tablet, drop pill, syrup, or oral liquid.

6. The method for preparing the traditional Chinese medicine preparation for treating benign prostatic hyperplasia as described in claim 4, characterized in that, S1 is prepared into a traditional Chinese medicine fluid extract using any one of the following methods: decoction concentration, percolation, maceration concentration, or reflux extraction concentration.

7. The method for preparing the traditional Chinese medicine preparation for treating benign prostatic hyperplasia as described in claim 6, characterized in that, In S1, when using the decoction and concentration method, the prepared aconite should be decocted separately for 1-1.5 hours before adding the other medicinal materials, and the cinnamon should be added 5-10 minutes before the end of the decoction.

8. A traditional Chinese medicine preparation for treating benign prostatic hyperplasia, characterized in that, The traditional Chinese medicine preparation is made using any one of the traditional Chinese medicine compositions according to claims 1-3 and clinically acceptable excipients in a conventional formulation manner.

9. The traditional Chinese medicine preparation for treating benign prostatic hyperplasia as described in claim 8, characterized in that, The traditional Chinese medicine preparation is any one of the following: decoction, powder, pill, granule, capsule, tablet, drop pill, syrup, or oral liquid.

10. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3, or the traditional Chinese medicine preparation prepared by any one of claims 4 to 7, or the traditional Chinese medicine preparation according to any one of claims 8 to 9, in the preparation of a medicament for treating benign prostatic hyperplasia.

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