A traditional Chinese medicine composition, a preparation method and application thereof

Abstract

The present application relates to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition and preparation and application thereof. The composition provided by the present application comprises Ramulus cinnamomi, Poria cocos, Cortex moutan, Semen persicae, Radix paeoniae alba, Radix rubiae, Cornus officinalis, and Rhizoma sparganii. The composition can obviously reduce the prostate index and prostate epithelial thickness of a benign prostatic hyperplasia model rat, and relieve interstitial edema. The experimental results show that the composition can obviously reduce the content of dihydrotestosterone, estradiol, testosterone, gonadotropin-releasing hormone, and rat luteinizing hormone in the prostate serum of a model mouse, and increase the content of follicle-stimulating hormone. The above results show that the traditional Chinese medicine composition can inhibit sex hormone disorder, and has the effect of treating prostatic hyperplasia.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition, its preparation and application. Background Art

[0002] Benign prostatic hyperplasia (BPH), as a common disease in middle-aged and elderly men, is a series of urinary obstruction symptoms caused by the hyperplasia of prostate tissue. The hyperplasia of prostate tissue leads to an increase in the volume of the prostate, which in turn compresses the urethra. This compression makes the urethra narrow, obstructing the discharge of urine, thus causing urinary obstruction. The symptoms can manifest as difficulty in urination, weak urine stream, prolonged urination time, and even urinary stream interruption. In addition, patients may also experience symptoms such as frequent urination, urgency of urination, and increased nocturia, which will seriously affect the patient's sleep quality and quality of life.

[0003] There is no record of prostatic hyperplasia in ancient Chinese medical books. According to clinical symptoms, BPH is considered to belong to the categories of "strangury syndrome", "retention of urine", and "prostatic obstruction". "Strangury syndrome" refers to frequent and short urination with stabbing pain, and "retention of urine" means difficult urination and complete obstruction of urine. "Strangury syndrome" and "retention of urine" only reflect a part of the specific symptoms of BPH and cannot fully cover them. Modern medicine refers to the prostate, testis, and epididymis as the "sperm chamber", and the lesion of the "sperm chamber" is "prostatic obstruction", which fully covers the characteristics of BPH. Traditional Chinese medicine believes that kidney deficiency is the main cause of BPH. BPH mostly occurs in middle-aged and elderly people. Due to old age or prolonged illness resulting in deficiency of qi in the kidney, the qi transformation is weak, leading to unfavorable qi transformation in the bladder; or damp-heat accumulates in the lower jiao, and the body fluid is consumed, resulting in deficiency of kidney yin, causing abnormal qi transformation in the bladder and leading to the disease. Zhao Jianye believes that weakness of kidney qi is the constitutional cause, blood stasis forming nodules is the common pathology, and the interaction between kidney deficiency and blood stasis is the basic pathogenesis. Traditional Chinese medicine believes that the main syndromes of BPH include syndrome of deficiency of kidney yang, syndrome of hyperactivity of fire due to yin deficiency, syndrome of obstruction of stasis and turbidity, syndrome of damp-heat in the bladder, syndrome of qi stagnation due to lung heat, and syndrome of weakness of spleen qi. Professor Zhang Chunhe collected the data of 540 BPH patients and found that the syndrome of deficiency of kidney yang was the most (256 cases), followed by the syndrome of obstruction of blood stasis in the water passage (238 cases), and the rest were in turn the syndrome of deficiency of kidney yin, syndrome of damp-heat pouring downward, syndrome of weakness of spleen qi, syndrome of phlegm turbidity stagnation, syndrome of qi stagnation due to liver depression, and syndrome of qi stagnation due to lung heat. It was also confirmed that there was rarely a single syndrome, and mostly two or three syndromes existed simultaneously. The pathogenesis of this disease is mainly kidney deficiency, accompanied by stasis, phlegm, mass, dampness, heat, etc. Therefore, the treatment principle should be mainly to tonify the kidney, and concurrently promote blood circulation to remove stasis, reduce masses, clear heat and resolve dampness, etc.

[0004] Currently, conservative and surgical treatments are the common options for treating benign prostatic hyperplasia (BPH) in Western medicine. Conservative treatment is recommended for patients with mild symptoms, while surgery is advised for those with more severe symptoms or those for whom conservative treatment is ineffective. Previously, open surgery was commonly used, but this procedure is highly invasive and has a higher probability of causing postoperative complications such as bleeding and urinary tract infections. With the continuous development of medical technology, minimally invasive surgery has been developed, offering advantages over open surgery, such as being less invasive and having fewer complications. For patients with moderate to severe symptoms, medication is recommended as the primary treatment method. Commonly used medications include 5α-reductase inhibitors, α1-receptor blockers, anticholinergic drugs, and phosphodiesterase type 5 inhibitors.

[0005] Traditional Chinese medicine (TCM) believes that the main causes and mechanisms of benign prostatic hyperplasia (BPH) are old age-related weakness, qi stagnation and blood stasis, and dysfunction of the triple burner (San Jiao). Therefore, treatment focuses on tonifying the kidneys and strengthening the body's foundation, promoting blood circulation and removing blood stasis, and clearing heat and dampness. Commonly used formulas include Guizhi Fuling Wan, Qianlie Shu Wan, Xiaoli Tang, and Qianlie Tongyu Capsules, which can improve symptoms such as urinary frequency, urgency, and difficulty urinating caused by BPH. However, the mechanisms of action of these existing drugs are not fully understood, and they are difficult to be effective for BPH caused by multiple etiologies. Summary of the Invention

[0006] In view of this, the technical problem to be solved by the present invention is to provide a traditional Chinese medicine composition and its preparation and application.

[0007] The traditional Chinese medicine composition provided by this invention includes cinnamon twig, poria cocos, peony bark, peach kernel, white peony root, dipsacus root, processed epimedium, and sparganium rhizome. Experiments have demonstrated that this traditional Chinese medicine composition can significantly reduce the prostate coefficient in model mice. Furthermore, this composition can significantly reduce the levels of DHT, ER, and T in the serum of model rats.

[0008] In this invention, the composition comprises the following raw materials in parts by weight:

[0009] Cinnamon twig 1-100 parts, Poria cocos 1-100 parts, Moutan bark 1-100 parts, Peach kernel 1-100 parts, White peony root 1-100 parts, Dipsacus root 1-100 parts, Prepared epimedium 1-100 parts, and Sparganium rhizome 1-100 parts.

[0010] This invention combines cinnamon twig, poria cocos, peony bark, peach kernel, white peony root, dipsacus root, processed epimedium, and sparganium rhizome, resulting in a more significant therapeutic effect on benign prostatic hyperplasia compared to existing drugs. Furthermore, experiments demonstrate a synergistic effect among the components of this composition. It exhibits significant advantages over existing cinnamon twig and poria cocos capsules or the combination of dipsacus root, processed epimedium, and sparganium rhizome.

[0011] Preferably, the composition comprises the following raw materials in parts by weight: 3-54 parts of cinnamon twig, 3-54 parts of poria cocos, 3-54 parts of peony bark, 3-54 parts of peach kernel, 3-54 parts of white peony root, 5-90 parts of Sichuan teasel root, 3-60 parts of processed epimedium, and 3-60 parts of sparganium rhizome.

[0012] Preferably, the composition comprises the following raw materials in parts by weight: 3-9 parts of cinnamon twig, 3-9 parts of poria cocos, 3-9 parts of peony bark, 3-9 parts of peach kernel, 3-9 parts of white peony root, 5-15 parts of dipsacus root, 3-10 parts of processed epimedium, and 3-10 parts of sparganium rhizome.

[0013] More preferably, the composition comprises the following raw materials in parts by weight: 9 parts cinnamon twig, 9 parts poria cocos, 9 parts peony bark, 9 parts peach kernel, 9 parts white peony root, 15 parts Sichuan teaspoon, 10 parts processed epimedium, and 10 parts sparganium.

[0014] Alternatively, the composition may consist of the following raw materials in parts by weight: 3 parts cinnamon twig, 3 parts poria cocos, 3 parts peony bark, 3 parts peach kernel, 3 parts white peony root, 5 parts Sichuan teaspoon, 3 parts processed epimedium, and 3 parts sparganium rhizome.

[0015] The composition described in this invention can be prepared by simply mixing the components, or by extracting a portion of it and then mixing it with other components, or by pulverizing the components and then mixing them. This invention does not limit the scope of the invention.

[0016] Furthermore, the present invention also provides a traditional Chinese medicine extract, which is obtained by extraction from the aforementioned composition.

[0017] This invention does not limit the preparation method of the extract, and the extraction methods of each component can be the same or different. For example, the extract in this invention can be prepared by water decoction extraction, water heating and reflux extraction, or other auxiliary extraction methods, and this invention does not limit the method.

[0018] In some embodiments, the extract is prepared by water heating and reflux extraction. In this embodiment, the preparation method of the extract includes: adding cinnamon twig, poria cocos, peony bark, peach kernel, white peony root, dipsacus root, processed epimedium, and sparganium rhizome to water, refluxing and extracting, then concentrating and drying the extract to obtain the traditional Chinese medicine extract.

[0019] As a preferred method, cinnamon twig, poria cocos, peony bark, peach kernel, white peony root, Sichuan teasel root, processed epimedium, and sparganium rhizome are added to 4 to 12 times the amount of water and refluxed for 1 to 3 times, each time for 0.5 to 3 hours. The extracts are combined and concentrated under reduced pressure to obtain a water extract.

[0020] In this embodiment, the mass of the water is 8 to 12 times the mass of the medicinal material, for example, 8, 9, 10, 11, or 12 times the mass of the medicinal material, preferably 10 times. The reflux extraction is performed twice, each time for 1 to 2 hours. The extract is concentrated to a density of 1.10 to 1.40.

[0021] Preferably, the method includes the following steps:

[0022] Add 4 to 12 times the amount of water to extract the following ingredients 1 to 3 times, for 0.5 to 3 hours each time: cinnamon twig, poria cocos, peony bark, peach kernel, white peony root, Sichuan teasel root, processed epimedium, and sparganium rhizome. Combine the extracts and concentrate to obtain an aqueous extract.

[0023] In this embodiment, during the water extraction step, the mass of water is 8 to 12 times the mass of the medicinal material, for example, 8, 9, 10, 11, or 12 times the mass of the medicinal material, preferably 10 times. The reflux extraction is performed twice, each time for 1 to 2 hours. The extract is then concentrated to a density of 1.00 to 1.30.

[0024] Furthermore, the present invention also provides the use of the composition as described above, the traditional Chinese medicine extract as described above, or the traditional Chinese medicine extract prepared by the method as described above in the preparation of a medicament for treating benign prostatic hyperplasia.

[0025] In this invention, the prostatic hyperplasia is benign prostatic hyperplasia, including castration-induced prostatic hyperplasia or androgen-induced prostatic hyperplasia.

[0026] In this invention, the anti-prostate hyperplasia includes inhibiting benign prostatic hyperplasia, improving bladder outlet obstruction, and / or improving prostatic hypertrophy.

[0027] Furthermore, the present invention also provides a medicament for treating benign prostatic hyperplasia, comprising the composition as described above, the traditional Chinese medicine extract as described above, or the traditional Chinese medicine extract prepared by the method described above.

[0028] The drug described in this invention also includes pharmaceutically acceptable excipients or additives.

[0029] In the drug of the present invention, the excipients include at least one of the following: filler, lubricant, disintegrant, binder, suspending agent, emulsifier, preservative, flavoring agent, colorant, transdermal penetration enhancer, antioxidant, solubilizer, cosolvent, sustained-release agent, controlled-release agent, enteric material, coating material, osmotic pressure regulator, pH regulator, stabilizer, and adsorbent.

[0030] In this embodiment of the invention, the dosage form of the drug is a decoction, granules, capsules, tablets, oral liquid, pills, soft capsules, drop pills, tinctures, syrups, suppositories, gels, sprays, or injections.

[0031] The present invention also provides a method for treating benign prostatic hyperplasia, comprising administering the composition as described above, the traditional Chinese medicine extract as described above, or the traditional Chinese medicine extract prepared by the method described above.

[0032] The administration methods of the drug include, but are not limited to, oral administration or gavage.

[0033] In this invention, the object of the gift is a human or a mammal, including bovines, equines, sheep, pigs, canines, felines, rodents, and primates.

[0034] The composition provided by this invention includes cinnamon twig, poria cocos, peony bark, peach kernel, white peony root, dipsacus root, processed epimedium, and sparganium rhizome. This composition significantly reduces the prostate index and prostate epithelial thickness in rats with benign prostatic hyperplasia (BPH), alleviates interstitial edema, and experimental results show that administration of this composition significantly reduces the levels of dihydrotestosterone, estradiol, testosterone, gonadotropin-releasing hormone, and luteinizing hormone in the prostate serum of model mice, while increasing the level of follicle-stimulating hormone (FSH). These results indicate that the traditional Chinese medicine composition of this invention can inhibit sex hormone imbalance and has a therapeutic effect on benign prostatic hyperplasia. Attached Figure Description

[0035] Figure 1 The effect of the composition on prostate pathological damage in rats with benign prostatic hyperplasia was shown. Detailed Implementation

[0036] This invention provides a traditional Chinese medicine composition, its preparation method, and its application in the preparation of drugs for treating benign prostatic hyperplasia. Those skilled in the art can refer to the content of this document and appropriately modify the process parameters to achieve the desired results. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included in this invention. The methods and applications of this invention have been described through preferred embodiments. Those skilled in the art can clearly modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit, and scope of this invention to realize and apply the technology of this invention.

[0037] Unless otherwise defined in this invention, the scientific and technical terms associated with this invention shall have the meanings understood by one of ordinary skill in the art.

[0038] In this application, the term "and / or" describes the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent: A existing alone, A and B existing simultaneously, or B existing alone. A and B can be singular or plural.

[0039] In this application, "at least one" means one or more, and "more than one" means two or more. "At least one of the following" or similar expressions refer to any combination of these items, including any combination of single or multiple items.

[0040] The terms “comprising,” “including,” and “having” are used interchangeably in this document to indicate the inclusiveness of a scheme, meaning that the scheme may contain elements other than those listed. It should also be understood that the use of “comprising,” “including,” and “having” in this document also provides for schemes “consisting of…”.

[0041] The test materials used in this invention are all common commercial products and can be purchased on the market.

[0042] Cinnamon twigs are the dried tender branches of *Cinnamomum cassia* Presl., a plant in the Lauraceae family. They are harvested in spring and summer, the leaves are removed, and they are sun-dried, or sliced ​​and sun-dried. [Properties and Flavors] Pungent, sweet, warm. [Meridians Entered] Heart, Lung, Bladder. [Functions and Indications] Induces sweating and relieves muscle tension, warms and unblocks the meridians, assists Yang and transforms Qi, and calms and descends Qi. Used for common cold due to wind-cold, abdominal pain due to cold, amenorrhea due to blood stasis, joint pain, phlegm retention, edema, palpitations, and sudden abdominal pain.

[0043] Poria cocos is the dried sclerotium of the fungus Poria cocos (family Polyporaceae).

Properties and Flavors

Meridians Entered

Functions and Indications

[0044] Peony bark is the dried root bark of Paeonia suffruticosa Andr., a plant in the Ranunculaceae family. The roots are harvested in autumn, the fine roots are removed, the root bark is peeled off, and then dried in the sun. [Properties and Flavors] Bitter, pungent, slightly cold. [Meridians Entered] Heart, Liver, Kidney. [Functions and Indications] Clears heat and cools blood, invigorates blood and removes blood stasis. Used for febrile diseases with rashes, hematemesis, epistaxis, night fever with morning chills, steaming bone fever without sweating, amenorrhea, dysmenorrhea, carbuncles, boils, and traumatic injuries.

[0045] Peach kernel is the dried, mature seed of *Prunus persica* (L.) Batsch or *Prunus davidiana* (Carr.) Franch., both belonging to the Rosaceae family. The fruit is harvested after ripening, the pulp and shell are removed, and the seeds are extracted and dried. [Properties and Flavors] Bitter, sweet, neutral. [Meridians Entered] Heart, Liver, Large Intestine. [Functions and Indications] Activates blood circulation and removes blood stasis, moistens the intestines and promotes bowel movement. Used for amenorrhea, dysmenorrhea, abdominal masses, traumatic injuries, and constipation due to intestinal dryness.

[0046] White peony root is the dried root of Paeonia lactiflora Pall., a plant in the Ranunculaceae family.

Properties and Flavors

Meridians Entered

Functions and Indications

[0047] Dipsaci is the root of the perennial herb Radix Dipsaci Asperoidis. It has the effects of tonifying the liver and kidneys, strengthening tendons and bones, healing fractures, and stopping metrorrhagia.

[0048] Processed Epimedium, also known as horned goat's foot or leaf, is the stem and leaves of Epimedium brevicornu, Epimedium velutipes, or Epimedium sagittatum, all belonging to the Berberidaceae family. Processed Epimedium is a prepared form of Epimedium with added mutton fat, and its efficacy is stronger than that of natural Epimedium, with effects such as regulating endocrine function, enhancing immunity, and maintaining blood health.

[0049] The tuber of *Sparganium stoloniferum*, *Sparganium stenophyllum*, and *Sparganium simplex* is a plant belonging to the family Sparganaceae. Latin botanical names: 1. *Sparganium stoloniferum* Buch.-Ham; 2. *Sparganium stenophyllum* Maxim; 3. *Sparganium simplex* Huds. [Taste and Properties] Pungent; astringent; cool. [Meridians Entered] Liver; Spleen. [Functions and Indications] Promotes blood circulation and qi flow; eliminates stagnation and relieves pain. Mainly used for abdominal masses; amenorrhea due to blood stasis; dysmenorrhea; abdominal distension and pain due to food stagnation; and pain from falls and injuries.

[0050] The numerical ranges and parameters involved in this invention have been presented as precisely as possible in the specific embodiments. However, any numerical value inevitably contains standard deviations due to individual test methods. Therefore, unless otherwise explicitly stated, it should be understood that all numerical ranges or specific data used in this disclosure may have a reasonable deviation within a certain range, such as ±10%, ±5%, ±1%, or ±0.5%.

[0051] It should be understood that in the various embodiments of this application, the order of the above processes does not imply the order of execution. Some or all steps may be executed in parallel or sequentially. The execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of this application.

[0052] The present invention will be further illustrated below with reference to the embodiments:

[0053] Example 1: Traditional Chinese Medicine Composition

[0054] Formula: Cinnamon twig 9 parts, Poria cocos 9 parts, Moutan bark 9 parts, Peach kernel 9 parts, White peony root 9 parts, Dipsacus asper 15 parts, Prepared Epimedium 10 parts, Sparganium 10 parts.

[0055] The preparation method of this traditional Chinese medicine composition granules is as follows:

[0056] Take cinnamon twig, poria cocos, peony bark, peach kernel, white peony root, Sichuan teasel root, prepared epimedium, and sparganium rhizome, add 10 times the amount of water and reflux extract twice, each time for 1 to 2 hours, combine the extracts, concentrate under reduced pressure to an extract with a relative density of 1.10 to 1.40, dry under reduced pressure and pulverize to obtain the traditional Chinese medicine composition.

[0057] Example 2 Traditional Chinese Medicine Composition

[0058] Formula: Cinnamon twig 3 parts, Poria cocos 3 parts, Moutan bark 3 parts, Peach kernel 3 parts, White peony root 3 parts, Dipsacus root 5 parts, Prepared epimedium 3 parts, Sparganium rhizome 3 parts.

[0059] The preparation method of this traditional Chinese medicine composition granules is as follows:

[0060] Take cinnamon twig, poria cocos, peony bark, peach kernel, white peony root, Sichuan teasel root, prepared epimedium, and sparganium rhizome, add 10 times the amount of water and reflux extract twice, each time for 1 to 2 hours, combine the extracts, concentrate under reduced pressure to an extract with a relative density of 1.10 to 1.40, dry under reduced pressure and pulverize to obtain the traditional Chinese medicine composition.

[0061] Comparative Example

[0062] Formula: 15 parts of Dipsacus asperoides, 10 parts of processed Epimedium, and 10 parts of Sparganium stoloniferum.

[0063] The preparation method for this comparative example is as follows:

[0064] Take 15 parts of Dipsacus asperoides, 10 parts of processed Epimedium, and 10 parts of Sparganium stoloniferum, add 10 times the amount of water and extract twice, each time for 1 to 2 hours. Combine the extracts and concentrate under reduced pressure to an extract with a relative density of 1.10 to 1.40. Dry under reduced pressure and pulverize to obtain Comparative Example 1.

[0065] Experimental Example 1: Effect of the composition of the present invention on benign prostatic hyperplasia in rats

[0066] 1. Experimental Materials

[0067] 1.1 Drugs and Reagents

[0068] Test drug:

[0069] The traditional Chinese medicine composition prepared in Example 1, Jiangsu Kangyuan Pharmaceutical Co., Ltd., batch number 18501;

[0070] Finasteride Enteric-coated Tablets, Tianjin Tasly Shengte Pharmaceutical Co., Ltd., Batch No. 24230108, Specification: 10 tablets / box;

[0071] Testosterone propionate injection, Ningbo No. 2 Hormone Factory, batch number 110251054, specification 10 vials / box;

[0072] Estradiol Benzoate Injection, Ningbo Second Hormone Factory, Batch No. 110252511, Specification 10 vials / box;

[0073] Corn oil, Beijing Solarbio Technology Co., Ltd., batch number C7030, 500ml;

[0074] Dihydrotestosterone (DHT) ELISA kit, Sangon Biotech (Shanghai) Co., Ltd., batch number D751011, specification 96T;

[0075] Rat / Porcine Estradiol (Estradiol) ELISA Kit, Sangon Biotech (Shanghai) Co., Ltd., Batch No. D751045, Specification 96T;

[0076] Testosterone ELISA kit, Sangon Biotech (Shanghai) Co., Ltd., batch number D751045, specification 96T;

[0077] Chloral hydrate, Sinopharm Chemical Reagent Co., Ltd., batch number 20171222, specification 250g;

[0078] 0.9% Sodium Chloride, Jiangsu Huai'an Shuanghe Pharmaceutical Co., Ltd., Batch No. 1703132C, Specification 100ml.

[0079] 1.2 Animals

[0080] SD rats, SPF grade, male, weighing 180–220g, were provided by Spiford (Beijing) Biotechnology Co., Ltd., certificate number: SYXK(Su)2023-0035. Hull conditions: room temperature 20–26℃, humidity 50–70%, free access to food and water, bedding changed twice weekly, and drinking water disinfected.

[0081] 1.3 Instruments

[0082] ME104E electronic balance, Mettler Toledo, Switzerland; ACS-DII electronic weighing scale, Shanghai Sanfeng; FlexStation 3 multi-mode microwell detection system, Molecular Devices, USA; XMTD-8222 electric thermostatic water bath, Shanghai Jinghong Experimental Equipment Co., Ltd.; Centrifuge 5804R high-speed refrigerated centrifuge, Eppendorf; Flex Station 3 microplate reader, Molecular Devices, USA.

[0083] 2. Experimental Methods

[0084] Modeling and Drug Administration: Rats were fed a normal diet with free access to food. Their feces were formed and their condition was good. Rats were weighed and randomly divided into 6 groups of 10 each: normal control group, model group, positive control finasteride group, Guizhi Fuling capsule, traditional Chinese medicine combination, and comparative example 1 drug (Dipsacus asper + processed Epimedium + Sparganium). Modeling: 0.125 mL of estradiol benzoate injection, 1.6 mL of testosterone propionate injection, and 8.225 mL of corn oil were mixed evenly to form a mixed injection solution containing 0.05 mg / mL estradiol benzoate injection and 4 mg / mL testosterone propionate injection. Rats were subcutaneously injected with 1 mL / kg. The blank group was given corn oil, and the other groups were given the modeling drugs. The model group and normal control group were given purified water. Rats in each drug group were given the corresponding drug solution. The finasteride group was given 2 mg / kg, and each combination group was given 8.03 g crude drug / kg. The drug volume was 10 ml / kg body weight, once a day for 4 consecutive weeks. By the end of the fourth week, rats were fasted for 18 hours before the last administration of medication, but water was allowed. After anesthesia, blood was collected from the abdominal aorta of each group of rats, serum was separated, and relevant serum indicators were tested. Prostate tissue was collected, weighed, and organ prostate index was calculated.

[0085] Indicator observation: Serum samples from rats in each group were collected for dihydrotestosterone (DHT), estradiol, and testosterone, and serum sex hormone levels were measured by ELISA.

[0086] This study used SPSS 13.0 statistical software for data processing and analysis. Quantitative data were expressed as mean ± standard deviation (x±s), and t-tests were used. A p-value < 0.05 was considered statistically significant.

[0087] 3. Experimental Results:

[0088] Compared with the normal control group, the prostate index and serum levels of dihydrotestosterone, estradiol, and testosterone were significantly increased in the model group rats (P<0.01). Compared with the model group, the serum levels of dihydrotestosterone, estradiol, and testosterone were significantly decreased in rats treated with finasteride, Guizhi Fuling capsules, and the traditional Chinese medicine combination, and the prostate index was also decreased in all groups (P<0.05, P<0.01). Compared with the Guizhi Fuling capsule group, the prostate index and serum levels of dihydrotestosterone, estradiol, and testosterone were decreased in rats treated with the traditional Chinese medicine combination, indicating that the efficacy of the traditional Chinese medicine combination was superior to that of Guizhi Fuling capsules (P<0.05). Compared with the traditional Chinese medicine combination group, the prostate index and serum levels of dihydrotestosterone, estradiol, and testosterone were significantly increased in rats treated with the drug in Comparative Example 1 (P<0.01), but there was no significant difference compared with the model group, indicating that the drug in Comparative Example 1 had no significant efficacy. The results are shown in Tables 1 and 2.

[0089] Table 1. Effects of the composition on the prostate index in rats with benign prostatic hyperplasia (X+SD)

[0090] Group n dose Prostate index (g / kg) Normal control 10 —— 2.425±0.255 Model 10 —— <![CDATA[6.802±0.684 △△ ]]> Fina Xiong'an 10 2mg / kg 5.058±0.850** Guizhi Fuling Capsules 10 8.03g crude drug / kg 5.841±0.485* Traditional Chinese medicine composition 10 8.03g crude drug / kg 5.095±0.765**& Comparative Example 1 Drug 10 8.03g crude drug / kg 6.363±0.332^^

[0091] △△P<0.01 compared with the normal control group, *P<0.05, **P<0.01 compared with the model group, &P<0.05 compared with the Guizhi Fuling capsule group, ^^P<0.01 compared with the traditional Chinese medicine combination group.

[0092] Table 2. Effects of the composition on sex hormones in rats with benign prostatic hyperplasia (X+SD)

[0093] Group n dose ER (mmol / L) T(mmol / L) DHT (ng / mL) Normal control 10 —— 112.26±22.82 24.72±3.91 1.43±0.39 Model 10 —— <![CDATA[170.80±11.07 △△ ]]> <![CDATA[116.32±8.98 △△ ]]> <![CDATA[11.16±2.15 △△ ]]> Fina Xiong'an 10 2mg / kg 119.90±19.51** 52.11±2.79** 7.27±1.25** Guizhi Fuling Capsules 10 8.03g crude drug / kg 143.96±20.27* 77.89±6.26* 7.45±1.37* Traditional Chinese medicine composition 10 8.03g crude drug / kg 117.52±19.63**& 56.44±4.25**& 4.91±1.15**& Comparative Example 1 Drug 10 8.03g crude drug / kg 150.80±10.11^^ 96.32±3.73^^ 9.76±0.92^^

[0094] △△P<0.01 compared with the normal control group, *P<0.05, **P<0.01 compared with the model group, &P<0.05 compared with the Guizhi Fuling capsule group, ^^P<0.01 compared with the traditional Chinese medicine combination group.

[0095] Benign prostatic hyperplasia (BPH) is a complex disease involving multiple factors. Current research on its etiology mainly focuses on sex hormone induction. BPH leads to a significant increase in serum T and DHT levels, as well as in prostate DHT, T, E2, AR, and ERα levels. In this experiment, a rat model of BPH was established using estrogen and androgen induction. After 4 weeks of modeling, the model group showed elevated serum T, DHT, and ER levels, and an increased prostate coefficient, consistent with reported BPH rat models. Therefore, the data in Tables 1 and 2 indicate that the traditional Chinese medicine composition has a therapeutic effect on benign prostatic hyperplasia.

[0096] The effects of the traditional Chinese medicine composition in Example 2 are similar to those of the traditional Chinese medicine composition in Example 1.

[0097] Experimental Example 2: Effects of the composition of the present invention on an androgen-induced rat model of benign prostatic hyperplasia

[0098] 1. Experimental Materials

[0099] 1.1 Drugs and Reagents

[0100] Test drug:

[0101] The traditional Chinese medicine composition prepared in Example 1, Jiangsu Kangyuan Pharmaceutical Co., Ltd., batch number 18501;

[0102] Finasteride Enteric-coated Tablets, Tianjin Tasly Shengte Pharmaceutical Co., Ltd., Batch No. 24230108, Specification: 10 tablets / box;

[0103] Testosterone propionate injection, Ningbo No. 2 Hormone Factory, batch number 110251054, specification 10 vials / box;

[0104] Chloral hydrate, Sinopharm Chemical Reagent Co., Ltd., batch number 20171222, specification 250g;

[0105] 0.9% Sodium Chloride, Jiangsu Huai'an Shuanghe Pharmaceutical Co., Ltd., Batch No. 1703132C, Specification 100ml;

[0106] Hematoxylin-eosin (HE) staining kit, batch number C0105S, specification 200 tests, Shanghai Beyotime Biotechnology Co., Ltd.

[0107] Xylene, batch number X112051, specification 500ml, Shanghai Aladdin Biochemical Technology Co., Ltd.;

[0108] Liquid paraffin, batch number YA0012, 500ml, Beijing Solarbio Technology Co., Ltd.

[0109] Neutral resin, batch number Abs9177, 50ml, manufactured by Aibisin Biotechnology Co., Ltd.

[0110] 1.2 Animals

[0111] 1.2 Animals

[0112] SD rats, SPF grade, male, weighing 180–220g, were provided by Spiford (Beijing) Biotechnology Co., Ltd., certificate number: SYXK(Su)2023-0035. Hull conditions: room temperature 20–26℃, humidity 50–70%, free access to food and water, bedding changed twice weekly, and drinking water disinfected.

[0113] 1.3 Instruments

[0114] BS224S electronic analytical balance, Arctic Sartorius Instrument Systems Co., Ltd.; ACS-DII electronic weighing scale, Shanghai Sanfeng; LEICAHI1210 tissue slicer, Leica GmbH, Germany; KD-BM biological tissue embedding machine, Jinhua Kedi Instrument Equipment Co., Ltd., Zhejiang Province; immunohistochemistry pen, Abisin Biotechnology Co., Ltd.; upright fluorescence microscope, Leica GmbH, Germany.

[0115] Experimental methods

[0116] Modeling and Drug Administration: Rats were fed a normal diet with free access to food, resulting in formed feces and good condition. Rats were weighed and randomly divided into 6 groups of 10 each: normal control group, model group, positive control finasteride group, Guizhi Fuling capsule, traditional Chinese medicine combination, and comparative example 1 drug (Dipsacus asper + processed Epimedium + Sparganium). Modeling: The blank group was subcutaneously injected with corn oil, while the other groups were subcutaneously injected with testosterone propionate 25 mg / ml. The model group and normal control group were given purified water, while the drug-treated groups were given the corresponding drug solutions. The finasteride group received 2 mg / kg, and the combination groups received 8.03 g crude drug / kg. The administration volume was 10 ml / kg body weight, once daily for 4 weeks. After anesthesia, the prostate was removed, weighed, and half of the prostate was placed in 10% formaldehyde overnight. The fixed brain tissue blocks were removed and sequentially placed in ethanol of different concentrations for dehydration. After dehydration, they were embedded in paraffin and then stained with hematoxylin and eosin (HE).

[0117] Indicator observation: HE staining analysis of pathological damage in rat prostate tissue.

[0118] Experimental results

[0119] In the control group, the prostate glands were of uniform size and clearly arranged, with single-layer columnar epithelial cells, smooth surfaces, and minimal secretions. Compared to the control group, the prostate gland area in the model group was larger, the thickness of the glandular epithelial cells was significantly increased, and there was mild interstitial congestion and edema. Compared to the model group, the thickness of the prostate epithelium and the interstitial edema were significantly reduced in the herbal composition group, and the efficacy was superior to that of Guizhi Fuling capsules. Compared to the herbal composition group, the prostate gland area in the control group (Example 1) was larger, the thickness of the glandular epithelial cells was significantly increased, and there was mild interstitial congestion and edema, but there was no significant difference compared to the model group. These results suggest that the herbal composition has a certain therapeutic effect on androgen-induced benign prostatic hyperplasia. (See attached results) Figure 1 The effects of the traditional Chinese medicine compositions in Examples 1 and 2 are similar.

[0120] The prostate is a sex accessory organ highly dependent on sex hormones, and the occurrence and development of benign prostatic hyperplasia (BPH) are inextricably linked to sex hormones. An imbalance in the estrogen / androgen ratio is considered key to the pathogenesis of BPH. This experiment established a rat model of benign prostatic hyperplasia using androgen-induced prostate hyperplasia, revealing an increased prostate gland area, significantly increased glandular epithelial cell thickness, and mild interstitial congestion and edema. The traditional Chinese medicine composition significantly reduced prostate pathological damage in the model rats and demonstrated a good protective effect against androgen-induced benign prostatic hyperplasia.

[0121] Experimental Example 3: Effects of the composition of the present invention on castration-induced benign prostatic hyperplasia model rats

[0122] 1. Experimental Materials

[0123] 1.1 Drugs and Reagents

[0124] Test drugs: The traditional Chinese medicine composition prepared in Example 1, Jiangsu Kangyuan Pharmaceutical Co., Ltd., batch number 18501; Finasteride enteric-coated tablets, Tianjin Tasly Shengte Pharmaceutical Co., Ltd., batch number 24230108, specification 10 tablets / box; Gonadotropin-releasing hormone (GnRH) ELISA kit, Sangon Biotech (Shanghai) Co., Ltd., batch number D751032, specification 96T; Rat luteinizing hormone (LH) ELISA kit, Sangon Biotech (Shanghai) Co., Ltd., batch number D731015, specification 96T; Rat follicle-stimulating hormone (FSH) ELISA kit, Sangon Biotech (Shanghai) Co., Ltd., batch number D731057, specification 96T; Chloral hydrate, Sinopharm Chemical Reagent Co., Ltd., batch number 20171222, specification 250g; 0.9% sodium chloride, Jiangsu Huaian Shuanghe Pharmaceutical Co., Ltd., batch number 1703132C, specification 100ml;

[0125] 1.2 Animals

[0126] SD rats, SPF grade, male, weighing 180–220g, were provided by Spiford (Beijing) Biotechnology Co., Ltd., certificate number: SYXK(Su)2023-0035. Hull conditions: room temperature 20–26℃, humidity 50–70%, free access to food and water, bedding changed twice weekly, and drinking water disinfected.

[0127] 1.3 Instruments

[0128] BS224S electronic analytical balance, Sartorius Instrument Systems, Inc.; ACS-DII electronic weighing scale, Shanghai Sanfeng; XMTD-8222 electric thermostatic water bath, Shanghai Jinghong Experimental Equipment Co., Ltd.; Centrifuge 5804R high-speed refrigerated centrifuge, Eppendorf; FlexStation 3 calcium flow workstation, Molecular Devices, Inc., USA.

[0129] Experimental methods

[0130] Modeling and Drug Administration: Rats were fed a normal diet with free access to food. Their feces were formed and their condition was good. Rats were weighed and randomly divided into 6 groups of 10 each: normal control group, model group, positive control finasteride group, Guizhi Fuling capsule, traditional Chinese medicine combination, and comparative example 1 drug (Dipsacus asper + processed Epimedium + Sparganium). Modeling: After anesthetizing the rats, they were fixed in a supine position on the operating table. The scrotal area was disinfected, and a longitudinal incision of about 1.0 cm was made in the center of the scrotum. The skin, fascia, and muscles were separated layer by layer to expose the location of the testis. The abdominal cavity was lowered into the scrotum. The right testis was gently pulled to free the testis and spermatic cord, which was then severed at the external inguinal ring and double-ligated with silk sutures. The right testis and epididymis were completely removed. The left testis and epididymis were removed in the same way. After checking that there was no obvious active bleeding from the wound, the wound was closed and the incision was sutured layer by layer with absorbable sutures. The model group and the normal control group were given purified water, and the rats in each drug group were given the corresponding drug solution. The finasteride group was given 2 mg / kg, and the combination groups were given 8.03 g crude drug / kg. The administration volume was 10 ml / kg body weight, once a day for 4 consecutive weeks.

[0131] Indicator observation: Serum samples from rats in each group were collected to detect gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH).

[0132] This study used SPSS 13.0 statistical software for data processing and analysis. Quantitative data were expressed as mean ± standard deviation (x±s), and t-tests were used. A p-value < 0.05 was considered statistically significant.

[0133] 3. Experimental Results

[0134] Compared with the normal control group, the prostate index, serum gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) levels in the model group rats were significantly increased, while the follicle-stimulating hormone (FSH) level was significantly decreased (P<0.01). Compared with the model group, the serum GnRH and LH levels in finasteride, Guizhi Fuling capsules, and the traditional Chinese medicine composition were significantly decreased, while the FSH level was significantly increased (P<0.05, P<0.01). Compared with the Guizhi Fuling capsule group, the FSH level in rats treated with the traditional Chinese medicine composition was increased, while the serum GnRH and LH levels were decreased, indicating that the efficacy of the traditional Chinese medicine composition was superior to that of Guizhi Fuling capsules (P<0.05). Compared with the traditional Chinese medicine composition group, the FSH level in rats treated with the drug in Comparative Example 1 was decreased, while the serum GnRH and LH levels were increased (P<0.05), with no significant difference compared with the model group. The effect of the traditional Chinese medicine composition in Example 2 was similar to that in Example 1. The results are shown in Table 3.

[0135] Table 3. Effects of the composition on castration-induced benign prostatic hyperplasia model rats (X+SD)

[0136]

[0137] △△P<0.01 compared with the normal control group, **P<0.01 compared with the model group, &P<0.05, &&P<0.01, compared with the Guizhi Fuling capsule group, ^^P<0.01 compared with the traditional Chinese medicine combination group.

[0138] The HPG axis regulates reproductive function and fertility by producing various hormones, including GnRH, FSH, LH, and sex steroids. The hypothalamus, through binding to GnRH receptors on pituitary gonadotropin cells, pulses and releases GnRH to stimulate the biosynthesis and secretion of gonadotropins LH and FSH. LH and FSH then act on the gonads, triggering a series of synthesis and releases of sex steroids, steroids (T), and steroids (E2). Steroids (T) exert a negative feedback effect on hypothalamic GnRH secretion. FSH binds to receptors on the membranes of testicular supporting cells, generating androgen-binding protein. Normal binding of androgens to androgens ensures sufficient androgen levels in the seminiferous tubules, thereby activating sperm and providing the impetus for sperm production, enabling germ cells to complete normal differentiation and development. In this experiment, a rat model of benign prostatic hyperplasia (BPH) induced by castration was established. The results showed elevated follicle-stimulating hormone (FSH) levels and decreased serum gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) levels in the rats. The traditional Chinese medicine composition exhibited a good protective effect against castration-induced BPH in rats.

[0139] The above are merely preferred embodiments of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition comprising the following raw materials in parts by weight: Cinnamon twig 1-100 parts, Poria cocos 1-100 parts, Moutan bark 1-100 parts, Peach kernel 1-100 parts, White peony root 1-100 parts, Dipsacus root 1-100 parts, Prepared epimedium 1-100 parts, and Sparganium rhizome 1-100 parts.

2. The composition according to claim 1, characterized in that, The raw materials include the following parts by weight: Cinnamon twig 3-54 parts, Poria cocos 3-54 parts, Moutan bark 3-54 parts, Peach kernel 3-54 parts, White peony root 3-54 parts, Dipsacus root 5-90 parts, Prepared Epimedium 3-60 parts, and Sparganium rhizome 3-60 parts.

3. The composition according to claim 1, characterized in that, It is composed of the following raw materials in parts by weight: Cinnamon twig 3-9 parts, Poria cocos 3-9 parts, Moutan bark 3-9 parts, Peach kernel 3-9 parts, White peony root 3-9 parts, Dipsacus asper 5-15 parts, Prepared Epimedium 3-10 parts, and Sparganium stoloniferum 3-10 parts.

4. The composition according to claim 1, characterized in that, It is composed of the following ingredients in parts by weight: 9 parts cinnamon twig, 9 parts poria cocos, 9 parts peony bark, 9 parts peach kernel, 9 parts white peony root, 15 parts Sichuan teaspoon, 10 parts prepared epimedium and 10 parts sparganium. Alternatively, it may be composed of the following ingredients in parts by weight: 3 parts cinnamon twig, 3 parts poria cocos, 3 parts peony bark, 3 parts peach kernel, 3 parts white peony root, 5 parts Sichuan teaspoon, 3 parts prepared epimedium, and 3 parts sparganium rhizome.

5. A traditional Chinese medicine extract, obtained by extraction from the composition according to any one of claims 1 to 4.

6. The method for preparing the traditional Chinese medicine extract according to claim 5, characterized in that, Cinnamon twig, Poria cocos, Moutan bark, peach kernel, white peony root, Dipsacus asper, processed Epimedium and Sparganium rhizome were added to water and extracted by reflux. The extract was then concentrated and dried to obtain a traditional Chinese medicine extract.

7. The preparation method according to claim 6, characterized in that, Add 4 to 12 times the amount of water to the cinnamon twig, poria cocos, peony bark, peach kernel, white peony root, Sichuan teasel root, processed epimedium, and sparganium rhizome, and reflux extract 1 to 3 times, each time for 0.5 to 3 hours. Combine the extracts and concentrate under reduced pressure to obtain a water extract.

8. The use of the composition according to any one of claims 1 to 4, the traditional Chinese medicine extract according to claim 5, or the traditional Chinese medicine extract prepared by the method according to claim 6 or 7 in the preparation of a drug for treating benign prostatic hyperplasia.

9. The application according to claim 8, characterized in that, The prostate hyperplasia mentioned is benign prostatic hyperplasia, including castration-induced prostatic hyperplasia or androgen-induced prostatic hyperplasia.

10. A drug for treating benign prostatic hyperplasia, comprising the composition according to any one of claims 1 to 4, the traditional Chinese medicine extract according to claim 5, or the traditional Chinese medicine extract prepared by the method according to claim 6 or 7.

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