Traditional Chinese medicine composition for preventing or treating chronic non-bacterial prostatitis, preparation method and application thereof

Abstract

The application discloses a traditional Chinese medicine composition for preventing or treating chronic non-bacterial prostatitis and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicines. In view of the fact that existing traditional Chinese medicine prescriptions have the problems of being biased towards 'attacking evil' and lacking'supporting healthy qi and tonifying the body', the indications are prone to acute attack, and the core pathogenesis of CNP is not completely matched, and the prescriptions are not suitable for long-term treatment of CNP, the traditional Chinese medicine composition comprises Poria cocos, Alisma orientalis (Sam.) Juzep, sea golden sand, talc powder, salt plantago seed, Akebia quinata, Gardenia jasminoides Ellis, Polygonum aviculare, Potentilla atrosanguinea and lophatherum gracile. The raw materials are mixed and soaked, then decocted, concentrated, dried and crushed to obtain the traditional Chinese medicine composition. The traditional Chinese medicine composition can effectively improve the pain and pathological changes of the prostate tissue of a chronic non-bacterial prostatitis mouse model. The preparation method of the application can obtain the traditional Chinese medicine composition with high effective component content in an economic and applicable range, prolongs the method of traditional Chinese medicine decoction for maintaining efficacy, and is more convenient.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a traditional Chinese medicine composition for the prevention or treatment of chronic nonbacterial prostatitis, its preparation method, and its application. Background Technology

[0002] Chronic nonbacterial prostatitis (CNP) is the most common type of prostatitis, accounting for over 90%-95% of cases. It is often equivalent to type III prostatitis and is also known as chronic pelvic pain syndrome. The core clinical manifestation of this disease is long-term or recurrent pain and discomfort in the pelvic region. The pain can affect the perineum, suprapubic region, groin, scrotum, and lower abdomen, and is often accompanied by varying degrees of urinary abnormalities and sexual dysfunction, seriously affecting the patient's physical and mental health. The pathogenesis of chronic nonbacterial prostatitis is not fully understood, and effective intervention methods are currently lacking in clinical practice.

[0003] Chronic nonbacterial prostatitis (CNP) falls under the categories of "spermatorrhea," "leukorrhea," and "urinary tract infection" in Traditional Chinese Medicine (TCM). Its pathogenesis is largely attributed to damp-heat accumulation in the lower abdomen, qi stagnation and blood stasis, and kidney deficiency leading to weak seminal control. Among these, damp-heat descending and blood stasis obstructing the meridians are key pathogenic factors causing pelvic pain and urinary abnormalities. Based on this, clearing heat and dampness, promoting blood circulation and relieving urinary tract infection, and resolving stasis and relieving pain have become the basic principles of TCM treatment for this disease. The *Taiping Huimin Heji Jufang* records the Bazheng San formula, which includes Plantago seed, Dianthus superbus, Polygonum aviculare, Talcum, Gardenia, Akebia stem, Rhubarb, and Licorice. It is mainly used to treat damp-heat urinary tract infection, corresponding to the symptoms of damp-heat descending in modern acute prostatitis and acute exacerbations of chronic prostatitis, such as urinary frequency, urgency, dysuria, urethral burning, and perineal distension. However, this formula has the following shortcomings in treating CNP:

[0004] 1. The prescription focuses too much on "attacking the pathogenic factors" and lacks the ability to "strengthen the body's resistance and consolidate its foundation."

[0005] While the medicine is potent and effective at expelling excess heat, CNP is a chronic, persistent disease with a long course and frequent relapses. Patients often suffer from varying degrees of spleen and stomach weakness and yin deficiency. Bazheng San lacks spleen-strengthening and dampness-draining ingredients, and long-term use can easily damage the spleen and stomach, leading to decreased digestive function and increased internal dampness. Furthermore, the large amount of bitter and cold purgatives can deplete yin fluids, making long-term use detrimental to the recovery of chronic disease patients. Therefore, it is unsuitable for patients with weak constitutions or those requiring long-term maintenance therapy.

[0006] 2. Some medications are not suitable for the long-term treatment needs of modern CNP.

[0007] The original formula of Bazheng San includes rhubarb, which is used for its bitter and cold properties to clear heat and promote bowel movement. However, rhubarb has a strong purgative effect and can easily cause gastrointestinal discomfort in patients with deficiency and cold in the middle jiao (middle burner) or poor spleen and stomach function, making it unsuitable as a long-term medication choice for patients with chronic diseases. In addition, licorice, which is also included in Bazheng San, has the effect of harmonizing the various herbs and relieving pain, but in some patients with prostatitis who may also have lower jiao water retention, edema, or hypertension, licorice poses a potential risk of causing water and sodium retention, which is not conducive to the safety management of long-term medication.

[0008] 3. The indications tend to focus on acute attacks, which does not fully align with the core pathogenesis of CNP.

[0009] The "damp-heat strangury syndrome" treated by Bazheng Powder mainly corresponds to acute prostatitis or the acute exacerbation of chronic prostatitis in modern medicine, characterized by urinary irritation symptoms such as frequent urination, urgency, and painful urination. However, the core symptom of CNP (chronic pelvic pain syndrome) is primarily pelvic pain. Its pathogenesis, besides damp-heat, is closely related to blood stasis ("pain due to obstruction") and deficiency ("pain due to lack of nourishment"). Bazheng Powder is relatively weak in its effects on promoting blood circulation, removing blood stasis, strengthening the spleen, eliminating dampness, and nourishing yin, thus having significant limitations in improving persistent chronic pelvic pain and addressing the root cause of damp-heat constitution in patients. Summary of the Invention

[0010] To address the aforementioned problems, this invention aims to provide a traditional Chinese medicine composition for the prevention or treatment of chronic nonbacterial prostatitis, its preparation method, and its application, thereby resolving the technical issues described above.

[0011] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0012] On one hand, the present invention provides a traditional Chinese medicine composition for the prevention or treatment of chronic nonbacterial prostatitis, comprising the following raw materials in parts by weight: 80-100 parts of Poria cocos, 80-100 parts of Alisma plantago-aquatica, 80-100 parts of Lygodium japonicum, 80-100 parts of talc, 80-100 parts of Plantago asiatica, 50-70 parts of Akebia quinata, 80-100 parts of Gardenia jasminoides, 80-100 parts of Polygonum aviculare, 80-100 parts of Dianthus superbus, and 80-100 parts of Lophatherum gracile.

[0013] Preferably, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 90 parts Poria cocos, 90 parts Alisma plantago-aquatica, 90 parts Lygodium japonicum, 90 parts talc, 90 parts Plantago asiatica (salted), 60 parts Akebia quinata, 90 parts Gardenia jasminoides, 90 parts Polygonum aviculare, 90 parts Dianthus superbus, and 90 parts Lophatherum gracile.

[0014] Furthermore, the present invention also provides a method for preparing the traditional Chinese medicine composition as described above, the method comprising the following steps:

[0015] Mix the raw materials Poria cocos, Alisma plantago-aquatica, Lygodium japonicum, talc powder, salt-processed Plantago asiatica, Akebia quinata, Gardenia jasminoides, Polygonum aviculare, Dianthus superbus, and Lophatherum gracile, add 10 times the amount of ultrapure water, soak for 30 minutes, and then decoct.

[0016] The filtrate after decoction is filtered to remove impurities, and then concentrated to obtain a Chinese herbal extract with a relative density of 1.15~1.20 at 25℃; the Chinese herbal extract is then dried, pulverized, and sieved.

[0017] Furthermore, the decocting operation specifically includes:

[0018] Boil for 2 hours the first time, filter, and collect the filtrate from the first decoction for later use;

[0019] Collect the dregs from the first decoction, add 8 times the total weight of the raw materials in ultrapure water, decoct for 1.5 hours, filter, and collect the filtrate from the second decoction for later use.

[0020] The filtrate from the first and second decoctions was combined to obtain the filtrate after decoction.

[0021] In another aspect, the present invention also provides the use of the aforementioned traditional Chinese medicine composition in the preparation of a medicament for the prevention or treatment of chronic nonbacterial prostatitis.

[0022] In another aspect, the present invention also provides a medicament for the prevention or treatment of chronic nonbacterial prostatitis, the medicament comprising the traditional Chinese medicine composition as described above.

[0023] Furthermore, the drug also includes pharmaceutically acceptable excipients.

[0024] Furthermore, the dosage form of the drug includes decoction, capsule, pill, elixir, or granule.

[0025] Furthermore, the dosage of the drug is 1.2 g of the traditional Chinese medicine composition / kg / day.

[0026] The beneficial effects of this invention are: compared with the prior art, the improvement of this invention lies in that...

[0027] 1. This invention proposes a traditional Chinese medicine composition for the prevention or treatment of chronic nonbacterial prostatitis, with Lygodium japonicum, Plantago asiatica, and Akebia trifoliata as the principal herbs: Lygodium japonicum clears damp-heat, promotes urination and relieves pain, specifically treating urinary tract infections, hematuria, and leukorrhea; Plantago asiatica drains dampness, promotes urination and promotes urination, guiding damp-heat downwards; Akebia trifoliata clears heart fire and drains damp-heat. The three herbs combined allow damp-heat to be eliminated through urination. The adjuvant herbs are Polygonum aviculare, Dianthus superbus, Poria cocos, and Alisma plantago-aquatica: Polygonum aviculare is bitter and descending, with the special function of promoting urination; Dianthus superbus is bitter and cold, descending and breaking up blood stasis and promoting menstruation; Poria cocos strengthens the spleen and drains dampness, promoting the flow of Qi through the Triple Burner and consolidating the body's foundation, while also regulating damp-heat constitution; Alisma plantago-aquatica promotes urination and drains dampness while also nourishing Yin, preventing excessive urination from damaging Yin fluids. The adjuvant herbs are Lophatherum gracile and Gardenia jasminoides, which clear heat from the Triple Burner and promote urination, enhancing the dampness-draining and urination-promoting effects of the principal and adjuvant herbs. With talc as an adjuvant, this herbal composition promotes urination, clears damp-heat, and effectively relieves dribbling and painful urination. Targeting the pathological characteristics of chronic nonbacterial prostatitis—characterized by the absence of bacterial infection and simple damp-heat stagnation—this composition eliminates the need for antibacterial herbs, focusing solely on clearing heat and dampness while simultaneously strengthening the spleen and protecting Yin. Animal experiments have shown that this herbal composition can dose-dependently increase the mechanical pain threshold in the lower abdomen of CNP mice, effectively improving symptoms of chronic pelvic pain. Furthermore, it significantly reduces the prostate wet weight index in model mice and inhibits CNP-induced abnormal prostate hyperplasia and inflammatory swelling. Histopathological observations reveal that this herbal composition significantly reduces pathological damage to the prostate tissue, including inflammatory cell infiltration, acinar structure destruction, and abnormal epithelial hyperplasia, improving glandular stenosis and restoring the prostate tissue morphology to a more normal state.

[0028] 2. Compared with the existing Bazheng Powder, this invention removes rhubarb and licorice, adds Poria to strengthen the spleen and eliminate dampness, and adds Alisma to promote diuresis and eliminate dampness while nourishing Yin, and adds Lygodium japonicum to specifically relieve urination and pain in the lower Jiao without harming the body's vital energy. This achieves "eliminating dampness without harming Yin and clearing heat without damaging the stomach". The overall formula focuses more on clearing damp-heat and turbid evil accumulated in the lower Jiao, while also taking into account the spleen, stomach and Yin fluids. It is especially suitable for treating chronic diseases such as CNP that require long-term management.

[0029] 3. The present invention also provides a method for preparing the traditional Chinese medicine composition. The extraction process is simple and stable, and it continues the traditional method of maintaining efficacy by decocting traditional Chinese medicine. It can obtain a traditional Chinese medicine composition with a high content of effective ingredients within an economic and applicable range. It can be directly adapted to hospital in-house preparations and pharmaceutical industrial production. It is compatible with multiple dosage forms and meets the medication needs of different groups of people. Attached Figure Description

[0030] Figure 1 The results of the Vonfrey experiment in Example 2 of this invention, which detected the effect of different stages of administration of the traditional Chinese medicine composition on the pain threshold of CNP mice, are shown.

[0031] Figure 2 The results show the statistical results of body weight and prostate wet weight index of mice in each group in Example 2 of the present invention.

[0032] Figure 3 The results of staining of prostate tissue from mice in each group in Example 2 of this invention are shown. Detailed Implementation

[0033] To enable those skilled in the art to better understand the technical solutions of the present invention, the technical solutions of the present invention will be further described below in conjunction with the accompanying drawings and embodiments.

[0034] Example 1:

[0035] Example 1 provides a traditional Chinese medicine composition for the prevention or treatment of chronic nonbacterial prostatitis. The traditional Chinese medicine composition includes the following raw materials by weight: Poria cocos 90g, Alisma plantago-aquatica 90g, Lygodium japonicum 90g, Talcum powder 90g, Plantago asiatica 90g, Akebia quinata 60g, Gardenia jasminoides 90g, Polygonum aviculare 90g, Dianthus superbus 90g, and Lophatherum gracile 90g.

[0036] It should be noted that all Chinese medicinal materials in this formula meet the quality standards for processed medicinal materials in the Pharmacopoeia of the People's Republic of China (2025 Edition). Salt-processed Plantago asiatica is processed using the standard salt-processing technique in the Pharmacopoeia to avoid the disadvantages of raw products being cold and damaging to the spleen. All medicinal materials are free from quality defects such as mold, insect infestation, and sulfur fumigation.

[0037] Chronic nonbacterial prostatitis falls under the categories of "spermatorrhea," "leukorrhea," and "urinary tract infection" in Traditional Chinese Medicine (TCM). Its pathogenesis is often attributed to damp-heat accumulation in the lower burner, qi stagnation and blood stasis, kidney deficiency and weakened seminal control. Prolonged illness may also manifest as dampness affecting the spleen and depletion of yin fluids. The TCM composition in this invention follows the core principles of TCM: clearing heat and dampness, promoting urination and relieving pain, strengthening the spleen and protecting yin, and unblocking the three burners. It strictly adheres to the principles of monarch-minister-assistant-guide formula composition, employing both tonifying and purging methods, promoting dampness without harming yin, and clearing heat without damaging the stomach. The specific mechanism of action is as follows:

[0038] The formula uses Lygodium japonicum, Plantago asiatica, and Akebia trifoliata as the principal herbs: Lygodium japonicum is cold in nature and sweet and salty in taste, entering the bladder and small intestine meridians. Its core function is to clear damp-heat in the lower burner, promote urination and relieve pain, directly targeting the affected area. It specifically improves typical symptoms of prostatitis such as leukorrhea, frequent urination, and urethral pain, and is particularly effective for treating heat strangury, hematuria, and seminal vesicle turbidity caused by damp-heat in the lower burner. Salt-processed Plantago asiatica guides the medicine to the kidney and bladder meridians, enhancing its diuretic, dampness-draining, and heat-clearing effects. It can guide damp-heat in the lower burner out with urine, while also astringing semen and stopping turbidity, and improving abnormal prostate secretions. Akebia trifoliata is bitter and cold, clearing stagnant heat in the heart meridian and draining damp-heat in the bladder, thus promoting the smooth flow of water throughout the body's three burners. The combined use of these three principal herbs directly targets the core pathogenesis of this disease, opening up the water pathways so that damp-heat and turbid pathogens in the body can be directly excreted through urine, thus resolving the core problem of damp-heat in the lower burner from the root.

[0039] The formula uses Polygonum aviculare, Dianthus superbus, Poria cocos, and Alisma plantago-aquatica as assistant herbs to enhance the diuretic and urination-clearing effects of the principal herbs, while also taking into account the need to strengthen the spleen and prevent the diuretic from damaging the body's vital energy: Polygonum aviculare is bitter and slightly cold in nature, and its bitterness descends and enters the bladder meridian, which can enhance the overall diuretic, urination-clearing, dampness-drying, and turbidity-clearing effects of the formula; Dianthus superbus is bitter, cold, and descending, which can not only clear the urination but also promote blood circulation and remove blood stasis, addressing the symptoms of pelvic congestion and perineal distension and pain associated with chronic nonbacterial prostatitis; Poria cocos is neutral in nature, which can strengthen the spleen and replenish qi, eliminate dampness and promote diuresis, clear the water passages of the triple burner while tonifying the spleen and stomach, and eliminate the source of internal dampness, thus addressing both the root cause and symptoms of damp-heat-prone constitution; Alisma plantago-aquatica promotes diuresis and eliminates dampness, clears deficiency heat in the lower burner, and also has the effect of nourishing yin and protecting fluids, neutralizing the dryness of the large number of diuretic herbs in the formula and preventing the long-term diuretic treatment from depleting the body's yin fluids. The four herbs, when used together, not only enhance the ability to clear urination and expel pathogens, but also strengthen the spleen, consolidate the foundation, and protect yin and preserve fluids.

[0040] The formula is supplemented with Lophatherum gracile and Gardenia jasminoides: Gardenia jasminoides, being bitter and cold, clears and drains heat from the upper, middle, and lower jiao (upper, middle, and lower burners), eliminating the source of internal heat and blocking the pathological process of heat consuming dampness to form damp-heat turbidity; Lophatherum gracile clears heart fire and promotes urination, guiding the deficiency heat of the heart meridian and lower jiao through urination. The combination of these two herbs clears heat throughout the body, assisting the principal and assistant herbs in further unblocking the water passages, strengthening the overall effects of clearing heat and dampness, relieving urinary tract infections and pain, and eliminating accompanying symptoms such as irritability, insomnia, and dark yellow urine.

[0041] Talc is used as an adjuvant. Talc is sweet, bland and cold in nature. It is slippery and can open the orifices. It can not only promote urination and relieve strangury, clear damp heat in the lower jiao, but also lubricate the urinary tract, quickly relieving the core discomforts of patients with chronic nonbacterial prostatitis such as dribbling urination, urethral stinging and difficulty in urination. At the same time, it can harmonize the properties of all the medicines in the whole prescription, and moderate the bitter and cold nature of the principal and assistant medicines, so that the whole prescription can clear heat without harming the stomach and promote diuresis without being too strong, taking into account both efficacy and medication safety.

[0042] In this invention, a method for preparing the traditional Chinese medicine composition is also provided, specifically including the following steps:

[0043] Step 1: Weigh and mix the Chinese medicinal materials according to the prescription ratio, add 10 times the amount of ultrapure water and soak for 30 minutes to fully moisten the internal tissues of the medicinal materials, fully dissolve the effective ingredients, and improve the extraction rate;

[0044] Step 2: Heat to boiling and then simmer for 2 hours. After simmering, filter while hot using a 200-mesh filter to separate the dregs from the filtrate. Collect the first decoction filtrate for later use.

[0045] Step 3: Add 8 times the total weight of the raw materials of ultrapure water to the separated dregs, heat to boiling again, and simmer for 1.5 hours. After simmering, filter while hot under the same conditions and collect the second decoction filtrate.

[0046] Step 4: Combine all the filtrates obtained from the two decoctions and perform a second fine filtration using 4 layers of medical sterile gauze to thoroughly remove suspended medicinal residue particles and colloidal impurities from the filtrate, thereby improving the purity of the subsequent ointment and the stability of the finished product.

[0047] Step 5: The refined filtrate is placed in a vacuum concentration tank for low-temperature concentration, with the concentration temperature controlled at 60~70℃ and the vacuum degree at -0.06~-0.08MPa. The final concentration yields a traditional Chinese medicine extract with a relative density of 1.15~1.20 at 25℃. The traditional Chinese medicine extract is then placed in a 60℃ oven and dried at constant temperature and pressure until constant weight is obtained to obtain a dried extract. The dried extract is then pulverized using a universal pulverizer and passed through a 100-mesh standard pharmaceutical sieve. The fine powder after sieving is mixed evenly to obtain the raw material powder of the traditional Chinese medicine composition of this invention.

[0048] The raw material powder of the traditional Chinese medicine composition of the present invention can be prepared into commonly used oral dosage forms in clinical practice, including but not limited to decoctions, hard capsules, pills, elixirs, and granules, according to clinical needs and in combination with pharmaceutically acceptable conventional excipients. The preparation process of different types adopts conventional methods in the field of traditional Chinese medicine, which will not be described in detail in this invention.

[0049] Example 2:

[0050] Example 2 verifies the therapeutic effect of the traditional Chinese medicine composition in Example 1 on chronic nonbacterial prostatitis through animal experiments.

[0051] 1. Materials and Methods

[0052] 1.1 Research Subjects and Experimental Reagents

[0053] Six 8-week-old adult male SD rats (weighing 200-300 g) and 36 6-8-week-old male Kunming mice were purchased from Hefei Qingyuan Biotechnology Co., Ltd., animal license number SCXK(Liaoning) 2025-0001. The experimental animals were housed in an SPF-grade environment, maintaining good ventilation, a room temperature of 21-23℃, and a relative humidity of 45%-55% according to Chinese requirements for experimental animal housing. The room was kept under alternating light and dark conditions for 12 hours each. The mice had free access to food and water, and were housed in cages of 5. The Chinese medicinal herbs were purchased from Beijing Tongrentang (Anguo) Chinese Herbal Pieces Co., Ltd., and Freund's Complete Adjuvant (CFA) and celecoxib were purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.

[0054] 1.2 Preparation of Traditional Chinese Medicine Compositions

[0055] According to the prescription ratio in Example 1: Poria cocos 90g, Alisma plantago-aquatica 90g, Lygodium japonicum 90g, Talcum powder 90g, Plantago asiatica 90g, Akebia quinata 60g, Gardenia jasminoides 90g, Polygonum aviculare 90g, Dianthus superbus 90g, Lophatherum gracile 90g, weigh and mix the medicinal slices, add 10 times the amount of ultrapure water and soak for 30 minutes, heat to boiling and then simmer for 2 hours, filter and collect the filtrate; add 8 times the amount of ultrapure water to the residue, boil and then continue to simmer for 1.5 hours, filter again; combine the two filtrates, filter through 4 layers of gauze to remove impurities, concentrate the filtrate to a clear herbal extract with a relative density of 1.15~1.20 (25℃), dry in an oven at 60℃, pulverize the dried material into fine powder, pass through a 100-mesh sieve and weigh, add 1.5% magnesium stearate and 3.5% silica, mix evenly and fill into capsules to obtain a capsule-form traditional Chinese medicine composition.

[0056] 1.3 Experimental grouping and treatment of each group

[0057] The method described in the reference ("Study on the Effect of Compound Lysimachia Granules on Autoimmune Chronic Nonbacterial Prostatitis") uses purified rat prostate protein solution supplemented with an immunoadjuvant to construct a CNP mouse model. Six experimental rats were anesthetized and sacrificed. Prostate tissue was separated, weighed, and rinsed with pre-cooled physiological saline. Physiological saline containing 0.5% Triton X-100 was added to the tissue, and the mixture was placed in an ice-water bath and thoroughly homogenized using a glass homogenizer to prepare a tissue homogenate. The tissue homogenate was centrifuged at 10,000 r / min for 30 min, and the protein content was determined using the Coomassie Brilliant Blue method. The homogenate was diluted with PBS buffer to a protein concentration of 2 mg / mL to obtain the purified rat prostate protein solution. This purified rat prostate protein solution was then mixed with Freund's complete adjuvant (CFA) at a 1:1 ratio, and the resulting emulsion was prepared so that when dropped onto water, it remained in a bead-like shape without spreading. This emulsion could then be used for subsequent animal immunization, thereby constructing the CNP mouse model.

[0058] Kunming mice were randomly divided into 6 groups: blank control group, model group, positive control group, low-dose group of traditional Chinese medicine composition, medium-dose group of traditional Chinese medicine composition, and high-dose group of traditional Chinese medicine composition, with 6 mice in each group.

[0059] First, a mouse CNP model was constructed. Except for the blank control group mice which were subcutaneously injected with PBS, all other groups of mice were subcutaneously injected on days 1, 8, 15, and 22 with the emulsion formed by the mixture of purified rat prostate protein and CFA described above. Each injection was 0.2 mL / mouse, containing 200 μg of rat prostate protein. Starting from day 23 of modeling, mice in the positive control group were given celecoxib 0.02 g / kg / d (SL-20mg), mice in the low-dose group of the traditional Chinese medicine composition were given 0.6 g of dried extract of the traditional Chinese medicine composition / kg / d (HZ-0.6) by gavage, mice in the medium-dose group of the traditional Chinese medicine composition were given 1.2 g of dried extract of the traditional Chinese medicine composition / kg / d (HZ-1.2) by gavage, mice in the high-dose group of the traditional Chinese medicine composition were given 2.4 g of dried extract of the traditional Chinese medicine composition / kg / d (HZ-2.4) by gavage, mice in the blank group and the model group were given 0.9% (10 mL / kg) physiological saline by gavage. The corresponding drugs were administered by gavage for 14 consecutive days, once a day. It should be noted that the dried material extracted in this invention is the raw material powder of the traditional Chinese medicine composition obtained after drying, pulverizing and sieving in Example 1. When administering the powder to mice via gavage, the corresponding weight of the raw material powder of the traditional Chinese medicine composition is mixed with water to form a liquid before being administered via gavage.

[0060] 1.4 Behavioral examination of mice

[0061] The Von Frey needle pain kit was used to assess the pain response of mice to mechanical stimulation. Mice were placed in a transparent plastic chamber with a stainless steel mesh floor and allowed to acclimatize for 30 minutes. A series of standardized Von Frey fibers (0.008, 0.02, 0.04, 0.16, 0.4, 0.6, 1.0, 2.0, and 4.0 g, a total of 9 fibers) were used, with the median dose of 0.6 g, to stimulate the lower abdomen of the prostate region of the mice using the Up and Down method. The mice's responses to stimulation were recorded, including abrupt abdominal contraction (indicating visceral pain), licking / scratching of the stimulation site (indicating superficial pain), and jumping (indicating severe discomfort). Each fiber was tested 5 times, with 15-second intervals between each test. A response was considered to have occurred if there were three positive results out of five tests. No response was marked as "O", and a response as "X". For no response, a fiber with a slightly higher intensity was applied; for a response, a fiber with a slightly lower intensity was applied, and so on. When the mouse exhibits "OX" or "XO" straddling, repeat the previous steps and measure four more times to obtain a sequence of "O" or "X". Input this sequence and the number of the last test wire into the animal 50% foot withdrawal threshold formula to calculate the mouse's 50% foot withdrawal threshold.

[0062] 1.5 Prostate Wet Weight Index

[0063] After 14 days of drug administration, mice were euthanized by cervical dislocation, the prostate was dissected, weighed, and the prostate wet weight index (PWI) was calculated. PWI = prostate wet weight (mg) / mouse body weight (g).

[0064] 1.6 Hematoxylin-eosin (HE) staining

[0065] After mouse sacrifice, prostate tissue was isolated and fixed with 4% paraformaldehyde at room temperature for 24 hours. The fixed prostate tissue was then dehydrated in an automated tissue dehydrator, followed by paraffin infiltration and embedding. Before preparing 5 μm sections, the prepared paraffin blocks were frozen at -20°C for 5 min to increase their hardness and reduce sectioning errors. The prepared tissue sections were then baked in a 98°C oven for 20 min to prevent tissue detachment. The sections were then sequentially immersed in xylene I, xylene II, and xylene III for 10 min each, followed by hydration in a gradient of ethanol solutions: 100% ethanol, 95% ethanol, and 75% ethanol, for 5 min each. The sections were then rinsed with distilled water for 2 min. For staining, hematoxylin was first applied for 5 min, followed by rinsing with tap water. The sections were then placed in differentiation solution for 20 seconds, followed by a 50°C water bath for 5 minutes to re-blue, then immersed in eosin solution for 30 seconds, and rinsed and soaked in tap water for 5 minutes. Gradual ethanol dehydration was performed, with concentrations of 75%, 95%, and 100% ethanol, for 1 minute each time. Xylene clearing was then performed, with xylene I, xylene II, and xylene III, for 1 minute each time. Finally, the sections were mounted with neutral resin. The structural changes and inflammatory infiltration of the prostate tissue in each group were observed and photographed under a Leica light microscope. The severity of CNP inflammation was assessed using a histological scoring system, with a score of 0-4 representing the degree of inflammation. The specific scoring criteria are shown in Table 1 below.

[0066] Table 1 Scoring criteria for prostate tissue inflammation

[0067]

[0068] 1.7 Statistical Methods

[0069] All data are expressed as mean ± SEM. GraphPad Prism 9.0 software was used to analyze the data or perform t-tests, with P < 0.05 considered statistically significant.

[0070] 2. Experimental Results

[0071] 2.1 Effects of Traditional Chinese Medicine Composition on Pain Symptoms in CNP Mice

[0072] To assess pain hypersensitivity in the prostate region of mice, this study used a series of standardized Von Frey fibers to stimulate the prostate region of mice using the Up and Down method at the end of model establishment, before drug administration, one week after drug administration, and two weeks after drug administration. The mice's responses to the stimulation were recorded. The establishment of the CNP mouse model and the effect of the traditional Chinese medicine composition on pain symptoms in CNP mice were assessed by comparing changes in pain sensitivity among the groups. The results are attached. Figure 1 As shown. In the appendix Figure 1 In the figures, A represents the results of pain symptom detection in each group of mice before the end of modeling and before drug administration; B represents the results of pain symptom detection in each group of mice one week after the end of modeling and drug administration; and C represents the results of pain symptom detection in each group of mice two weeks after the end of modeling and after drug administration.

[0073] From the appendix Figure 1 As can be seen from A, after modeling, the withdrawal threshold of the modeled mice was lower than that of normal control mice, indicating that the model was successfully constructed; from the appendix Figure 1 As can be seen from B, one week after administration, compared with the model group mice, the paw withdrawal threshold of the high-dose group of mice in the traditional Chinese medicine composition began to increase; from the appendix Figure 1 As shown in Figure C, after two weeks of administration, compared with the model group mice, the paw withdrawal threshold of mice in the positive control group, the medium-dose group of the traditional Chinese medicine composition, and the high-dose group of the traditional Chinese medicine composition all increased significantly. These results indicate that the medium and high doses of the traditional Chinese medicine composition in this invention can effectively improve pain symptoms in CNP mice. However, the low-dose group (0.6g of dried extract of the traditional Chinese medicine composition / kg / d) did not significantly improve the mechanical analgesia of the lower abdomen in CNP mice after either one or two weeks of administration, failing to reach an effective therapeutic concentration. Only when the dose was increased to a medium dose (1.2g of dried extract of the traditional Chinese medicine composition / kg / d) and a high dose (2.4g of dried extract of the traditional Chinese medicine composition / kg / d) could the pain threshold of CNP mice be effectively increased, achieving the therapeutic goal of improving chronic pelvic pain.

[0074] 2.2 Effects of Traditional Chinese Medicine Composition on Body Weight and Prostate Wet Weight in CNP Mice

[0075] After 14 days of drug administration, the body weight and prostate wet weight of mice in each group were recorded. The results are shown in the attached figure. Figure 2 As shown, A represents the average body weight of mice in each group, and B represents the average wet weight of the prostate gland in each group.

[0076] From the appendix Figure 2 As can be seen from Figure A, there was no significant difference in body weight among the mice in each group 14 days after administration. (See Appendix...) Figure 2As shown in Figure B, the prostate wet weight (PWI) of the model group mice was significantly higher than that of the normal control group, indicating that the CNP model was successfully established. The PWI of the positive control group, the medium-dose group of the traditional Chinese medicine composition, and the high-dose group of the traditional Chinese medicine composition were all significantly lower than those of the model mice. These results indicate that medium and high doses of the traditional Chinese medicine composition can effectively inhibit CNP-induced prostatic hyperplasia.

[0077] 2.3 Effects of Traditional Chinese Medicine Composition on Prostate Pathological Changes in CNP Mice

[0078] Fourteen days after drug administration, mice were euthanized by cervical dislocation, and prostate tissue was isolated. The prostate tissue was then stained with hematoxylin and eosin (HE). The staining results are attached. Figure 3 As shown.

[0079] From the appendix Figure 3 As can be seen, the normal prostate structure is relatively intact, with uniform acini distribution, normal lumen morphology, and no inflammatory cell infiltration or epithelial hyperplasia. In contrast, the model group mice exhibited severe narrowing of the prostate acinar lumen, papillary hyperplasia of the epithelium, diffuse infiltration of numerous inflammatory cells around blood vessels and in the stroma, accompanied by acinar structure destruction, consistent with the typical pathological features of chronic nonbacterial prostatitis, confirming the successful establishment of the CNP model. In the positive control group, the prostate acinar structure was basically normal, with minimal interstitial inflammatory cell infiltration, and the pathological damage was significantly improved compared to the model group. In the low-dose group of the traditional Chinese medicine composition, the prostate showed disordered epithelial cell arrangement, papillary hyperplasia, lumen narrowing, and extensive interstitial inflammatory cell infiltration, with pathological damage similar to the model group. In the medium-dose group of the traditional Chinese medicine composition, the prostate lumen structure remained basically intact, with only a small amount of inflammatory cell interstitial infiltration, and the pathological damage was significantly reduced compared to the model group. In the medium-dose group of the traditional Chinese medicine composition, the prostate acinar structure was basically normal, with very little inflammatory cell infiltration, and the pathological state was close to the blank control group. The prostate tissue inflammation score results showed that, compared with the control group, the prostate inflammation score of the model group mice was significantly increased. Compared with the model group, the inflammation scores of each treatment group decreased to varying degrees. Among them, there was no statistically significant difference in the low-dose group of the traditional Chinese medicine composition (P>0.05), the inflammation scores of the positive control group and the medium-dose group of the traditional Chinese medicine composition decreased significantly, and the inflammation score of the high-dose group of the traditional Chinese medicine composition decreased significantly. This further confirms that the medium and high doses of the traditional Chinese medicine composition in this invention can improve CNP-induced prostate tissue pathological damage.

[0080] In summary, two weeks after administration, the paw withdrawal threshold of mice in both the medium-dose and high-dose groups significantly increased, showing a marked difference from the model group. This indicates that the dose of 1.2 g of dried extract of the traditional Chinese medicine composition / kg / day had reached or was close to the maximum pharmacological effect in relieving pain. Doubling the dose to 2.4 g of dried extract of the traditional Chinese medicine composition / kg / day did not provide further pain relief. Similarly, HE staining results showed that the pathological state of the medium-dose group was "close to the blank control group," while the high-dose group also "improved CNP-induced pathological damage to prostate tissue." Both groups showed similar protective effects on acinar structure and inhibitory effects on inflammatory infiltration.

[0081] Secondly, CNP is a chronic disease with a long treatment course. Clinically, safety should be prioritized over minor differences in short-term efficacy. The formula contains a large amount of bitter, cold, and dampness-clearing herbs; long-term high-dose use poses a challenge to the patient's spleen and stomach function. Based on the consideration of "clearing heat without harming the stomach," and to reduce the burden on the patient's digestive tract during long-term CNP management, using a medium dose is crucial to ensuring the patient can complete the treatment course. Furthermore, reducing the dosage helps improve patient adherence and lower medical costs.

[0082] Therefore, the medium dose in animal experiments is the optimal inflection point for pharmacological effects, maximizing efficacy with minimal safety risks. In clinical translation, the clinical equivalent dose of 1.2 g of dried extract of the Chinese herbal medicine composition per kg / day in mice via gavage is the most suitable clinical choice.

[0083] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of this invention is defined by the appended claims and their equivalents.

Claims

1. A traditional Chinese medicine composition for the prevention or treatment of chronic nonbacterial prostatitis, characterized in that, The ingredients include the following parts by weight: Poria cocos 80-100 parts, Alisma plantago-aquatica 80-100 parts, Lygodium japonicum 80-100 parts, Talc powder 80-100 parts, Plantago asiatica 80-100 parts, Akebia quinata 50-70 parts, Gardenia jasminoides 80-100 parts, Polygonum aviculare 80-100 parts, Dianthus superbus 80-100 parts, and Lophatherum gracile 80-100 parts.

2. The traditional Chinese medicine composition for the prevention or treatment of chronic nonbacterial prostatitis according to claim 1, characterized in that, The ingredients include the following parts by weight: Poria cocos 90 parts, Alisma plantago-aquatica 90 parts, Lygodium japonicum 90 parts, Talc powder 90 parts, Plantago asiatica 90 parts, Akebia quinata 60 parts, Gardenia jasminoides 90 parts, Polygonum aviculare 90 parts, Dianthus superbus 90 parts, and Lophatherum gracile 90 parts.

3. The method for preparing the traditional Chinese medicine composition as described in claim 1 or 2, characterized in that, The preparation method includes the following steps: Mix the raw materials Poria cocos, Alisma plantago-aquatica, Lygodium japonicum, talc powder, salt-processed Plantago asiatica, Akebia quinata, Gardenia jasminoides, Polygonum aviculare, Dianthus superbus, and Lophatherum gracile, add 10 times the amount of ultrapure water, soak for 30 minutes, and then decoct. The filtrate after decoction is filtered to remove impurities, and then concentrated to obtain a Chinese herbal extract with a relative density of 1.15~1.20 at 25℃; the Chinese herbal extract is then dried, pulverized, and sieved.

4. The method for preparing the traditional Chinese medicine composition according to claim 3, characterized in that: The decocting process specifically includes: Boil for 2 hours the first time, filter, and collect the filtrate from the first decoction for later use; Collect the dregs from the first decoction, add 8 times the total weight of the raw materials in ultrapure water, decoct for 1.5 hours, filter, and collect the filtrate from the second decoction for later use. The filtrate from the first and second decoctions was combined to obtain the filtrate after decoction.

5. The use of the traditional Chinese medicine composition as described in claim 1 or 2 in the preparation of a medicament for the prevention or treatment of chronic nonbacterial prostatitis.

6. A drug for the prevention or treatment of chronic nonbacterial prostatitis, characterized in that: The drug includes the traditional Chinese medicine composition as described in claim 1 or 2.

7. The application according to claim 6, characterized in that: The drug also includes pharmaceutically acceptable excipients.

8. The application according to claim 7, characterized in that: The dosage forms of the drug include decoctions, capsules, pills, elixirs, or granules.

9. The application according to claim 8, characterized in that: The dosage of the drug is 1.2 g of the traditional Chinese medicine composition / kg / day.

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