Pharmaceutical composition for female bladder fasciitis and preparation method thereof

Abstract

The invention provides a pharmaceutical composition for female bladder fasciitis and a preparation method thereof, and provides a pharmaceutical composition for female bladder fasciitis and a preparation method thereof. The pharmaceutical composition comprises a plurality of traditional Chinese medicine raw materials such as ground beetles, radix salviae miltiorrhizae and flos carthami, and the weight parts are definite. Amur corktree bark, lightyellow sophora root and other auxiliary medicinal materials The traditional Chinese medicine composition is rich in dosage forms, such as ointment, gel, patch or lotion, and pharmaceutically acceptable matrixes such as vaseline and carbomer are selected according to different dosage forms. During preparation, the medicinal materials are selected, the ground beetles are subjected to supercritical CO2 extraction, other medicinal materials are extracted with an ethanol solution with a specific concentration at different temperatures, pseudo-ginseng powder is treated through a special grinding process, and finally all the components are mixed to prepare an external dosage form. Clinical tests show that the pharmaceutical composition can significantly improve the urination frequency, pain and other symptoms of female bladder fascitis patients, relieve inflammation and promote tissue repair, is good in safety, and provides a new effective means for treatment of female bladder fascitis.

Description

Technical Field

[0001] The present invention relates to the technical field of drug preparation, and in particular to a drug composition for treating female cystic fasciitis and a preparation method thereof. Background Art

[0002] Cystitis is the connective tissue around the bladder. Due to inflammatory diseases of the bladder, surgical injuries, etc., the capsule outside the bladder has an inflammatory reaction, and the abnormal structural changes left after the inflammatory reaction, which in turn lead to abnormal expansion and contraction of the bladder, causing a series of clinical syndromes, including distension and discomfort in the lower abdomen when the bladder stores a large amount of urine, which is significantly improved after urination. There are many names in clinical practice, such as "interstitial cystitis", "bladder pain syndrome" and "bladder pain syndrome / interstitial cystitis". For this type of disease, most patients do not have clear evidence of infection or inflammation. At present, it is relatively unified and bladder pain syndrome (BPS) is used to refer to this type of symptoms. It is common in middle-aged women. It is reported that the incidence rate of foreign women is 2.7%-6.5%. Although there is no relevant data in China, bladder pain syndrome is not uncommon in clinical practice.

[0003] In the spectrum of female urinary system diseases, female bladder fasciitis occupies a position that cannot be ignored. This disease is mainly manifested by abnormal urination, such as a significant increase in the frequency of urination. Some patients even need to urinate several times per hour, which seriously disrupts the rhythm of daily life, causing patients to frequently interrupt their affairs at hand and be in a state of mental tension at all times. At the same time, pain symptoms are always present, whether it is dull pain or severe pain, which seriously reduces the patient's quality of life and has a great negative impact on daily activities, sleep, rest and psychological state. Moreover, the continuous invasion of inflammation will gradually damage the bladder tissue and weaken the bladder's normal urine storage and urination functions. Long-term development may also cause more serious urinary system problems.

[0004] At present, the treatment methods for female cystofasciitis are mainly divided into two directions: drug therapy and physical therapy, and the current treatment is mainly focused on relieving symptoms.

[0005] In drug treatment, oral medication is a common method, including antidepressants, antihistamines, sodium pentothion, immunosuppressants and analgesics. Although antidepressants can regulate the negative emotions caused by the disease to a certain extent, they have limited improvement on the core symptoms of cystic fasciitis; antihistamines mainly target possible allergic factors, but often cannot fundamentally solve the problem of inflammation; sodium pentothion can theoretically improve the bladder mucosa, but the efficacy in actual application is uneven; immunosuppressants can easily cause serious side effects such as infection while suppressing immune response; analgesics only relieve pain and cannot prevent the progression of the disease.

[0006] Bladder instillation therapy uses local anesthetics, hyaluronic acid, chondroitin sulfate, heparin, etc. Local anesthetics can temporarily relieve pain, but the effect is short-lived; although hyaluronic acid, chondroitin sulfate, and heparin can supplement bladder mucosal components, the instillation operation is complicated and the effect is difficult to last, and the clinical efficacy is not ideal.

[0007] In terms of physical therapy, bladder dilation therapy improves symptoms by mechanically dilating the bladder, but this method has risks such as bladder perforation, and the effect of dilation is limited in duration; botulinum toxin type A injection can reduce excessive activity of the bladder detrusor muscle, but may cause complications such as urinary retention, and the efficacy gradually weakens over time; although hyperbaric oxygen therapy can improve the oxygen supply to local tissues, it has high equipment requirements, long treatment cycles, poor patient compliance, and it is difficult to achieve satisfactory treatment results.

[0008] On the other hand, existing traditional Chinese medicine treatment plans also have many problems. Some formulas lack scientific considerations in the compatibility of medicinal materials, and the drugs cannot work together to enhance their effectiveness, resulting in the inability to fully exert their efficacy. Some traditional Chinese medicine preparations have simple and extensive preparation processes, which fail to fully extract the effective ingredients and ensure the stability of the drugs. During storage, they are prone to deterioration and reduced efficacy. At the same time, the drug absorption rate is low, so a large number of effective ingredients cannot be fully utilized by the human body, resulting in a waste of resources and affecting the treatment effect. Summary of the invention

[0009] In view of this, the present invention proposes a pharmaceutical composition for female bladder fasciitis and a preparation method thereof to solve the above problems.

[0010] The technical solution of the present invention is implemented as follows: a pharmaceutical composition for female bladder fasciitis, comprising the following raw materials in parts by weight: 10-15 parts of earthworm, 10-15 parts of salvia miltiorrhiza, 10-15 parts of safflower, 10-15 parts of epimedium, 20-30 parts of angelica, 15-20 parts of dipsaci, 10-15 parts of rhubarb, 20-30 parts of coix seed, 10-20 parts of angelica dahurica, 10-20 parts of cyathula, and 10-15 parts of notoginseng powder.

[0011] Furthermore, a pharmaceutical composition for female bladder fasciitis comprises the following raw materials in parts by weight: 10 parts of earthworm, 10 parts of salvia miltiorrhiza, 10 parts of safflower, 10 parts of epimedium, 20 parts of angelica, 15 parts of dipsacus, 10 parts of rhubarb, 20 parts of coix seed, 10 parts of angelica dahurica, 15 parts of cyathula, and 10 parts of Panax notoginseng powder.

[0012] Furthermore, a pharmaceutical composition for female bladder fasciitis also includes the following raw materials in parts by weight: 10-20 parts of Phellodendron chinense, 8-15 parts of Sophora flavescens, 12-25 parts of Plantago asiatica, 15-30 parts of Oldenlandia diffusa, 10-20 parts of Patrinia scabra, and 12-20 parts of Poria cocos.

[0013] Furthermore, the dosage form of the pharmaceutical composition is an ointment, a gel, a patch or a lotion.

[0014] Furthermore, the dosage form is an ointment, and its preparation raw materials also include a pharmaceutically acceptable matrix, and the matrix is ​​one or more combinations of vaseline, lanolin, and polyethylene glycol.

[0015] Furthermore, the dosage form is a gel, and its preparation raw materials also include a pharmaceutically acceptable gel matrix, and the gel matrix is ​​one or more combinations of carbomer, sodium carboxymethyl cellulose, and sodium alginate.

[0016] Furthermore, a method for preparing a pharmaceutical composition for female bladder fasciitis comprises the following steps: S1. Separately clean and select Phellodendron amurense, Sophora flavescens, Plantago asiatica, Hedyotis diffusa, Patrinia scabra, Poria cocos, Eupolyphaga sinensis, Salvia miltiorrhiza, Carthamus tinctorius, Epimedium, Angelica sinensis, Dipsacus asper, Rhubarb, Coix seeds, Angelica dahurica, and Cyathula officinalis to remove impurities and non-medicinal parts; S2, drying the cleaned earthworms, and then extracting them for 1-3 hours using supercritical CO2 extraction technology to obtain insect powder; S3, put the cleaned Phellodendron amurense, Sophora flavescens, Plantago asiatica, Hedyotis diffusa, Patrinia scabra, Poria, Salvia miltiorrhiza, Carthamus tinctorius, Epimedium, Angelica sinensis, Dipsacus asper, Rhubarb, Coix seeds, Angelica dahurica, Cyathula officinalis into an extraction tank, add 80-90% ethanol solution, extract at 30-50°C for 15-25min, continue heating to 60-80°C for 35-55min, collect the extract, concentrate and filter to obtain an extract for standby use; S4, put the notoginseng powder into a container, add clean water and grind it into coarse powder with a particle size of 1-3 mm, continue to add water and grind for 3-5 hours, the coarse powder is suspended in the water to form a suspension, let it stand, take out the coarse powder that has settled to the bottom and continue grinding, repeat 2-4 times to obtain a powder with a fineness of 300-400 mesh, take it out, and dry it in an oven at 40-60° C. to obtain the notoginseng powder; S5. Stir and mix the insect powder, extract and Panax notoginseng powder to obtain a mixed powder. According to the dosage form requirements described in claim 4, mix the mixed powder with a corresponding pharmaceutically acceptable matrix or gel matrix, and prepare the desired external dosage form according to the corresponding preparation process.

[0017] Furthermore, the supercritical CO2 extraction pressure of S2 is 30-50MPa, the extraction temperature is 40-60°C, and the CO2 extraction flow rate is 20-40kg / h.

[0018] Furthermore, the mass volume ratio of the mixed medicinal materials and the ethanol solution in S3 is 3-5:10 g / mL.

[0019] Compared with the prior art, the present invention has the following beneficial effects: 1. The formula is scientific and reasonable: The drug composition selects multiple Chinese medicinal materials such as Eupolyphaga sinensis, Salvia miltiorrhiza, Carthamus tinctorius, Epimedium, and Angelica sinensis, and each medicinal material is cleverly combined according to the theory of traditional Chinese medicine. The three ingredients work together to effectively improve the local blood circulation of the bladder and promote the absorption and dissipation of inflammation; Epimedium and Dipsacus warm and nourish the kidney yang, enhance the body's resistance, fundamentally regulate the body's functions, and help fight inflammation; Angelica nourishes the blood and promotes blood circulation, and cooperates with other blood-activating herbs to remove blood stasis and generate new blood; Coix seed promotes diuresis, invigorates the spleen and stops diarrhea, and can assist in expelling moisture from the body and relieve bladder edema; Angelica dahurica reduces swelling and discharges pus, dispels wind and relieves pain, while Cyathula officinalis removes blood stasis and promotes menstruation, draws blood downward, and helps improve the circulation of qi and blood in the bladder and surrounding tissues; Panax notoginseng powder can remove blood stasis and stop bleeding, promote blood circulation and relieve pain, and can both promote blood circulation and remove blood stasis and prevent bleeding. The various herbs work together to synergistically enhance their effectiveness and act comprehensively on female bladder fasciitis. While relieving symptoms, they focus more on treating the disease from the root, effectively improving abnormal urination and pain symptoms, and promoting bladder tissue repair.

[0020] Advanced preparation technology: Advanced technical means are used in the preparation process. Supercritical CO2 extraction of earthworms can efficiently extract their effective ingredients at low temperatures, avoiding the loss of ingredients and reduced activity caused by high temperatures in traditional extraction methods, and greatly retaining the efficacy of earthworms. Other medicinal materials are extracted in stages at different temperatures using ethanol solutions of specific concentrations, which can fully extract various effective ingredients and ensure the integrity and activity of the ingredients. Panax notoginseng powder is processed through a special grinding process to obtain a high-fineness powder, which effectively improves the absorption rate of the drug and enables the drug to play a better role.

[0021] High safety: The drug composition is mainly composed of natural Chinese medicine, which has fewer side effects than Western medicine. In clinical trials, no serious adverse reactions occurred, no obvious damage to the patient's liver and kidney function, and no problems such as drug resistance and increased infection risk common in Western medicine treatment will be caused. The safety is more guaranteed, providing patients with a safe and reliable treatment option. DETAILED DESCRIPTION

[0022] In order to better understand the technical content of the present invention, specific embodiments are provided below to further illustrate the present invention.

[0023] Unless otherwise specified, the experimental methods used in the embodiments of the present invention are all conventional methods.

[0024] Unless otherwise specified, the materials, reagents, etc. used in the embodiments of the present invention can be obtained from commercial sources.

[0025] The following is an introduction to the basic information of the main APIs based on the Chinese Pharmacopoeia and the Chinese Medicine Dictionary: Earthworm: cold in nature, salty in taste, slightly toxic. Enters the liver meridian. Its main effects are to break blood, remove blood stasis, and heal tendons and bones.

[0026] Danshen: slightly cold in nature and bitter in taste. It enters the heart, pericardium, and liver meridians. Its main functions are to promote blood circulation and remove blood stasis, cool blood and eliminate carbuncle, nourish blood and calm the mind.

[0027] Safflower: warm and pungent in nature, it enters the heart and liver meridians. Its main functions are to promote blood circulation, remove blood stasis and regulate menstruation.

[0028] Epimedium: warm in nature, pungent and sweet in taste. Enters the liver and kidney meridians. Its main effects are to nourish the kidney and strengthen yang, dispel wind and dampness.

[0029] Angelica: sweet in taste, pungent and warm in nature, it enters the heart, liver and spleen meridians. It can nourish blood, promote blood circulation and remove blood stasis, relieve pain, and moisturize the intestines.

[0030] Dipsacus: slightly warm in nature and bitter in taste. The main effects are to nourish the liver and kidney, promote blood circulation, and strengthen tendons and bones. It can nourish the liver and kidney, and promote blood circulation, with the advantages of nourishing without stagnation.

[0031] Rhubarb: cold in nature and bitter in taste, it enters the spleen, stomach, large intestine, liver, and heart meridians. Its main functions include purging and attacking accumulation, clearing away heat and purging fire, detoxifying, and promoting blood circulation and removing blood stasis. It is commonly used as a medicine for heat-toxic sores and burns, accumulation of masses, and injuries caused by falls.

[0032] Coix seeds: slightly cold in nature, sweet and light in taste, enter the spleen, stomach and lung meridians. The main effects are diuresis, invigorating the spleen, removing numbness, clearing heat and discharging pus.

[0033] Angelica dahurica: warm in nature and pungent in taste, it enters the lung and stomach meridians. Its main functions are to relieve exterior symptoms, dispel wind and dampness, reduce swelling and discharge pus, and relieve pain.

[0034] Rhizoma Cynanchifoliae: sweet, slightly bitter, neutral in nature. Enters the liver and kidney meridians. Its main functions are to remove blood stasis, dredge the meridians, open up the joints, and promote urination and relieve stranguria.

[0035] Panax notoginseng powder: warm in nature, sweet and slightly bitter in taste, enters the liver and stomach meridians. Its main effects are to dissipate blood stasis and stop bleeding, promote blood circulation and relieve pain.

[0036] Phellodendron chinense: bitter in nature and cold in flavor. Enters the kidney and bladder meridians. Functions and indications: clearing away heat and dampness, purging fire and detoxifying, and removing bone steaming.

[0037] Sophora flavescens: bitter in nature and cold in flavor. Enters the heart, liver, stomach, large intestine, and bladder meridians. Can clear away heat and dampness, kill parasites, and promote urination.

[0038] Plantago seed: sweet in nature and cold in flavor. It enters the liver, kidney, lung and small intestine meridians. It has the functions of clearing away heat, promoting diuresis and relieving stranguria, dispelling dampness and stopping diarrhea, improving eyesight and removing phlegm.

[0039] Hedyotis diffusa: bitter, sweet, cold in nature. Enters the stomach, large intestine, and small intestine meridians. Has the effects of clearing away heat and detoxifying, eliminating carbuncle, and promoting dampness. Used for carbuncle, sore throat, snake bites, and hot stranguria.

[0040] Patrinia scabra: pungent, bitter, slightly cold in nature. Enters the stomach, large intestine, and liver meridians. Can clear away heat and detoxify, eliminate carbuncle and discharge pus, remove blood stasis and relieve pain.

[0041] Poria: sweet, light, neutral in nature. Enters the heart, lung, spleen, and kidney meridians. Functions: diuresis, invigorating the spleen, and calming the mind.

[0042] Example 1 A pharmaceutical composition for female bladder fasciitis comprises the following raw materials by weight: 10 grams of earthworm, 10 grams of salvia miltiorrhiza, 10 grams of safflower, 10 grams of epimedium, 20 grams of angelica, 15 grams of dipsacus, 10 grams of rhubarb, 20 grams of coix seed, 10 grams of angelica dahurica, 10 grams of cyathula, 10 grams of notoginseng powder, 10 grams of phellodendron, 8 grams of sophora flavescens, 12 grams of plantain seed, 15 grams of oldenlandia diffusa, 10 grams of patrinia herb, and 12 grams of tuckahoe.

[0043] Example 2 A pharmaceutical composition for female bladder fasciitis comprises the following raw materials by weight: 15 grams of earthworm, 15 grams of salvia miltiorrhiza, 15 grams of safflower, 15 grams of epimedium, 30 grams of angelica, 20 grams of dippers, 15 grams of rhubarb, 30 grams of coix seeds, 20 grams of angelica dahurica, 20 grams of cyathula, 15 grams of notoginseng powder, 20 grams of phellodendron, 15 grams of sophora flavescens, 25 grams of plantain seeds, 30 grams of oldenlandia diffusa, 20 grams of patrinia herb, and 20 grams of tuckahoe.

[0044] Example 3 A pharmaceutical composition for treating female bladder fasciitis, comprising the following raw materials by weight: 10 grams of Eupolyphaga sinensis, 10 grams of Salvia miltiorrhiza, 10 grams of Carthamus tinctorius, 10 grams of Epimedium, 20 grams of Angelica sinensis, 15 grams of Dipsacus asper, 10 grams of Rhubarb, 20 grams of Coix seeds, 10 grams of Angelica dahurica, 15 grams of Cyathula officinalis, 10 grams of Notoginseng powder, 15 grams of Phellodendron amurense, 12 grams of Sophora flavescens, 18 grams of Plantago, 25 grams of Hedyotis diffusa, 15 grams of Patrinia salsa, and 16 grams of Poria; The above examples 1-3 adopt the following preparation method: S1. Separately clean and select Phellodendron amurense, Sophora flavescens, Plantago asiatica, Hedyotis diffusa, Patrinia scabra, Poria cocos, Eupolyphaga sinensis, Salvia miltiorrhiza, Carthamus tinctorius, Epimedium, Angelica sinensis, Dipsacus asper, Rhubarb, Coix seeds, Angelica dahurica, and Cyathula officinalis to remove impurities and non-medicinal parts; S2, drying the cleaned earthworms, and then extracting them for 2 hours using supercritical CO2 extraction technology, wherein the supercritical CO2 extraction pressure of S2 is 40MPa, the extraction temperature is 50°C, and the CO2 extraction flow rate is 30kg / h to obtain insect powder; S3, put the cleaned Phellodendron amurense, Sophora flavescens, Plantago asiatica, Hedyotis diffusa, Patrinia scabra, Poria, Salvia miltiorrhiza, Carthamus tinctorius, Epimedium, Angelica sinensis, Dipsacus asper, Rhubarb, Coix seeds, Angelica dahurica, Cyathula officinalis into an extraction tank, add 85% ethanol solution, extract at 40°C for 20min, continue heating to 70°C for 45min, collect the extract, concentrate and filter to obtain the extract for standby use; S4, put the Panax notoginseng powder into a container, add clean water and grind it into coarse powder with a particle size of 2 mm, continue to add water and grind for 4 hours, the coarse powder is suspended in the water to form a suspension, let it stand, take out the coarse powder that has settled to the bottom and continue grinding, repeat 3 times to obtain a powder with a fineness of 400 mesh, take it out, and dry it in an oven at 50°C to obtain Panax notoginseng powder; S5. Stir and mix the above-mentioned insect powder, extract and Panax notoginseng powder to obtain a mixed powder. According to the dosage form requirements, mix the mixed powder with a corresponding pharmaceutically acceptable matrix or gel matrix, and prepare the desired external dosage form according to the corresponding preparation process.

[0045] Test Example 1-Pharmacodynamics Experiment 1. Experimental animals: Female Sprague-Dawley rats, weighing 180-220 g, 8 rats per group, divided into the following groups: Normal control group: No inflammation was induced, and only normal saline was given.

[0046] Model control group: bladder fasciitis was induced and normal saline was given.

[0047] Positive control group: cystitis was induced and indomethacin, a known effective drug, was administered.

[0048] Drug experimental group: cystitis was induced, and the drug composition to be tested of Examples 1-3 was administered.

[0049] Housing conditions: standard laboratory conditions, free access to food and water, acclimatization for 1 week.

[0050] Establishment of bladder fasciitis model: Intravesical injection of lipopolysaccharide (1 mg / kg) for 3 consecutive days; the success of the model was confirmed by behavioral and histopathological examinations.

[0051] Drug administration: The drug composition to be verified was made into a suspension, and administration began on the second day after modeling, once a day by gavage for 3 consecutive days, with a dosage of 10 mg / kg.

[0052] Observation indicators: (1) Behavioral indicators: Pain response: Record the animal's pain behavior (e.g. licking the lower abdomen, arching the back) during urination.

[0053] Urinary frequency: Record the number of times you urinate in a 24-hour period.

[0054] (2) Biochemical indicators: Urinalysis: This tests the urine for white blood cells, red blood cells, and protein.

[0055] Blood analysis: Detection of inflammatory factors (such as TNF-α, IL-6) in serum.

[0056] (3) Histopathology: Bladder tissue sampling: Bladder tissue was obtained after the animals were sacrificed and fixed in 10% formalin.

[0057] Group Urinary frequency (times / 24h) Pain score (0-5 points) Urine white blood cells (count / μL) Serum TNF-α (pg / mL) Histopathological score (0-3 points) Normal control group 8.2±1.1 0.3±0.1 12.5±2.3 15.2±3.1 0.2±0.1 Model control group 25.6±3.4 4.1±0.5 450.3±50.2 320.5±45.6 2.8±0.3 Positive control group 15.3±2.1 2.2±0.4 120.4±20.3 150.3±25.4 1.5±0.2 Example 1 12.8±1.8 1.5±0.3 90.6±15.2 100.4±18.2 3.2±0.4 Example 2 10.2±1.4 1.0±0.2 60.3±10.5 70.5±12.3 1.8±0.3 Example 3 9.0±1.2 0.5±0.1 30.2±8.1 40.2±10.1 0.8±0.2 Data description: Urinary frequency: reflects bladder irritation symptoms, the higher the value, the more severe the symptoms.

[0058] Pain score: based on animal behavior scoring (0: no pain; 5: severe pain).

[0059] Urine white blood cells: reflect the degree of urinary tract infection or inflammation. The higher the value, the more severe the inflammation.

[0060] Serum TNF-α: reflects the level of systemic inflammation, the higher the value, the more severe the inflammation.

[0061] Histopathological scoring: The bladder tissue was scored according to the degree of inflammatory cell infiltration, edema, and epithelial damage (0: normal; 3: severe damage).

[0062] The above results show that the pharmaceutical composition of the present invention (Examples 1-3) has a significant therapeutic effect on the bladder fasciitis model, and the therapeutic effect is better than that of the positive control group. Among them, Example 3 has the best effect, which can significantly improve urination frequency, pain score, urine leukocytes, serum TNF-α and histopathological score, close to the level of the normal control group. This shows that the pharmaceutical composition has significant anti-inflammatory, analgesic and tissue repair effects, and has potential clinical application value.

[0063] Test Example 2-Clinical Trial 1. Experimental background: Based on the results of previous animal experiments, the drug in Example 3 performed well in improving the symptoms and indicators related to female bladder fasciitis and has further research value.

[0064] 2. Purpose of the Test Main purpose: To evaluate the effectiveness of the drug in Example 3 in treating female cystic fasciitis, with urination frequency, pain score, etc. as the main observation indicators.

[0065] Secondary objectives: To observe drug safety and monitor the occurrence of adverse reactions; to evaluate the effects of drugs on urine leukocytes, serum TNF-α levels and histopathological changes.

[0066] 3. Experimental Design 1. Trial type: randomized, double-blind, placebo-controlled trial.

[0067] Subject selection: 120 patients diagnosed with female cystofasciitis aged 18-60 years were recruited and signed informed consent. Patients with severe liver and kidney dysfunction, pregnant women, and lactating women were excluded.

[0068] Grouping: The subjects were randomly divided into two groups. The test group (60 people) was given the drug of Example 3, and the control group (60 people) was given a placebo.

[0069] IV. Dosage regimen 1. Dosage: According to the results of previous animal experiments and pre-experiments, the test group evenly applied the drug of Example 3 on a special dressing, applied it to the lower abdomen corresponding to the bladder area, and changed it once a day. The control group applied a placebo in the same way.

[0070] Treatment course: The treatment cycle is 3 days, and the external application should be continued on time.

[0071] V. Observation indicators and time points 1. Before treatment: record the basic information of the subjects, conduct a comprehensive physical examination, including urine routine, blood routine, serum TNF-α detection, evaluate the bladder tissue pathology (tissue biopsy by cystoscopy), and record the urination frequency and pain score.

[0072] During treatment: record urination frequency and pain score every day; check the skin at the application site for adverse reactions, such as redness, itching, rash, etc. Test urine routine (including urine white blood cells) and serum TNF-α level once.

[0073] After treatment: re-evaluate bladder tissue pathology, conduct a comprehensive examination of physical indicators, compare them with those before treatment, and evaluate the overall therapeutic effect of the drug.

[0074] index time Test group (drugs from Example 3) Control group (placebo) Urinary frequency (times / 24h) Before treatment 25.2±3.5 24.9±3.2 1 day after treatment 20.1±3.0 23.6±3.3 2 days after treatment 15.8±2.3 21.2±3.1 3 days after treatment 11.2±2.0 19.6±3.0 Pain score (0-5 points) Before treatment 4.2±0.5 4.1±0.5 1 day after treatment 3.2±0.4 3.9±0.4 2 days after treatment 2.0±0.3 3.4±0.3 3 days after treatment 1.2±0.2 2.5±0.3 Urine white blood cells (count / μL) Before treatment 448.0±50.0 450.0±50.0 1 day after treatment 165.0±25.0 370.0±45.0 2 days after treatment 95.0±20.0 305.0±35.0 Serum TNF-α (pg / mL) Before treatment 318.0±40.0 320.0±40.0 1 day after treatment 195.0±30.0 270.0±35.0 2 days after treatment 115.0±18.0 210.0±30.0 Histopathological score (0-3 points) Before treatment 2.8±0.3 2.7±0.3 1 day after treatment 1.4±0.2 2.1±0.2 Incidence of adverse skin reactions (%) During treatment 3.3（2 / 60） 9.0（5 / 60） Incidence of systemic adverse reactions (%) During treatment 1.6（1 / 60） 4.0（2 / 60） Quality of life score (out of 100) Before treatment 45.0±5.0 46.0±5.0 3 days after treatment 70.0±8.0 55.0±6.0 In terms of the above-mentioned therapeutic effects, the topical medicine in Example 3 has a good effect in treating female bladder fasciitis. Whether it is intuitive symptom indicators such as urination frequency and pain score, or inflammation-related indicators such as urine leukocytes and serum TNF-α levels, as well as bladder tissue repair reflected by histopathological scores, the experimental group showed a more significant improvement compared with the control group. This shows that the drug can not only quickly relieve the patient's current discomfort symptoms, but also reduce inflammation from the root, promote the repair of damaged tissues, and provide a solid guarantee for the patient's recovery.

[0075] Classic Case Case 1: Chen, female, 45 years old, visited the hospital on February 8, 2023. Chief complaint: frequent urination, urgency and pain during urination for 5 days.

[0076] Current medical history: Acute urinary tract infection occurred before the Spring Festival, and no discomfort was felt after taking the medicine. In the past 5 days, there was no obvious cause for frequent urination and urgent urination, dull pain in the lower abdomen before urination, and accompanied by discomfort in the lower abdomen. The tongue is pale and dark, the coating is thin and the pulse is thin. Physical examination: No abnormality was found in the vulva, the vagina is smooth, a little white secretion, no odor, the cervix is ​​cystic, and no abnormality was found in the uterine appendages. The bladder fascia area is slightly thick, and there is obvious tenderness on the left side. Aa0, BA-2. Urinalysis in the local hospital showed no abnormality. Chinese medicine diagnosis: 1. Gonorrhea (blood stasis syndrome); Western medicine diagnosis: 1. Fasciitis. Treatment: Apply this prescription to the bladder fascia area once.

[0077] The applicant believes that the patient's acute urinary tract infection caused an inflammatory reaction in the fascia around the bladder, resulting in fascial edema and thickening. When the bladder is full, it is bound by the peripheral fascia tissue and cannot fully expand, resulting in distension and discomfort in the lower abdomen before urination. At the same time, the bladder capacity becomes smaller, the amount of urine stored decreases, and frequent urination and urgency occur without urinary pain.

[0078] Prescription: Prescription of Example 3. Apply with warm water after powdering, combined with TDP, for 20-30 minutes.

[0079] On February 9, 2023, the patient was re-examined. The discomfort caused by urinary urgency was significantly relieved after taking the medicine. The above regimen was continued for 2 times. No discomfort. Cured.

[0080] Case 2: Li, female, age: 46 years old. Date of visit: September 26, 2023. Main complaint: frequent urination, urinary retention for 1 week. Current medical history: urinary retention and feeling of incomplete urination in the past week. No urinary pain, symptoms are significantly more severe at night. Pale tongue, thin fur, thin pulse. Physical examination: slightly thick bladder fascia area, tenderness +-. TCM diagnosis: 1. stranguria (blood stasis syndrome); Western medicine diagnosis: 1. fasciitis. Treatment: Apply this prescription to the bladder fascia area once.

[0081] Prescription: Prescription of Example 1. Apply with warm water after powdering, combined with TDP, for 20-30 minutes.

[0082] September 27, 2023. Chief complaint: The symptoms were relieved after follow-up visits, and the improvement was particularly obvious at night.

[0083] The applicant believes that the patient's physical examination showed that the fascia around the bladder was obviously thickened and tender. Analysis showed that the bladder function was affected by the peripheral fascia, resulting in a series of discomforts, and no obvious abnormalities were found in the urine routine. The bladder gasification function failed. The treatment should be based on promoting blood circulation and removing blood stasis, helping yang to transform qi, and promoting urination.

[0084] Prescription: Prescription of Example 3. Apply with warm water after powdering, combined with TDP, for 20-30 minutes.

[0085] Usage: Frequency is once a day (Qd); a total of 3 doses of medicine are required, 1 dose is used daily for external use.

[0086] Re-examination on September 29, 2023, showed cure.

[0087] Case 3: Zhang, female, age: 65 years old. Visited on September 12, 2023. Chief complaint: Urgent urination and abdominal distension and pain before urination in the past month. No obvious abnormalities were found in the local urine routine examination, and oral antibiotics and Chinese patent medicines were ineffective (the specific medication is unknown). Gynecological examination: Abnormal vulva, smooth vagina, no obvious secretions, light cervix, and abnormal uterine appendages. The bladder area is obviously thickened, tough, and tender. Outpatient diagnosis: Traditional Chinese medicine diagnosis 1. Gonorrhea; 2. Blood stasis syndrome; Western medicine diagnosis: 1. Urinary system disease; 2. Fasciitis (bladder fasciitis). Treatment: Apply this prescription to the bladder fascia area once.

[0088] The applicant believes that the patient's fascia around the bladder is edematous and thickened. When the bladder is full, it is bound by these peripheral fascia tissues and cannot fully expand, resulting in distending pain and discomfort in the lower abdomen before urination. At the same time, the bladder capacity becomes smaller, the amount of urine stored decreases, and frequent urination and urgency occur without urinary pain.

[0089] Prescription: Example 3 prescription, 1 pair; Usage: Grind into powder, mix with warm water and apply externally, + TDP care for 20-30 minutes.

[0090] On September 13, 2023, the patient was re-examined. The discomfort of urinary urgency was significantly relieved after taking the medicine. The above regimen was continued for 2 times. The patient was cured.

[0091] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A pharmaceutical composition for female bladder fasciitis, characterized in that: The invention comprises the following raw materials in parts by weight: 10-15 parts of earthworm, 10-15 parts of salvia miltiorrhiza, 10-15 parts of safflower, 10-15 parts of epimedium, 20-30 parts of angelica, 15-20 parts of dipsaci, 10-15 parts of rhubarb, 20-30 parts of coix seeds, 10-20 parts of angelica dahurica, 10-20 parts of cyathula and 10-15 parts of notoginseng powder.

2. A pharmaceutical composition for treating female bladder fasciitis according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 10 parts of earthworm, 10 parts of salvia miltiorrhiza, 10 parts of safflower, 10 parts of epimedium, 20 parts of angelica, 15 parts of dipsaci, 10 parts of rhubarb, 20 parts of coix seeds, 10 parts of angelica dahurica, 15 parts of cyathula and 10 parts of notoginseng powder.

3. A pharmaceutical composition for treating female bladder fasciitis according to claim 1, characterized in that: The invention also includes the following raw materials in parts by weight: 10-20 parts of Phellodendron amurense, 8-15 parts of Sophora flavescens, 12-25 parts of Plantago seed, 15-30 parts of Oldenlandia diffusa, 10-20 parts of Patrinia scabra, and 12-20 parts of Poria cocos.

4. A pharmaceutical composition for treating female bladder fasciitis according to claim 1, characterized in that: The dosage form of the pharmaceutical composition is ointment, gel, patch or lotion.

5. The pharmaceutical composition for treating female bladder fasciitis according to claim 1, characterized in that: The dosage form is an ointment, and its preparation raw materials also include a pharmaceutically acceptable matrix, and the matrix is ​​one or more combinations of vaseline, lanolin, and polyethylene glycol.

6. A pharmaceutical composition for treating female bladder fasciitis according to claim 1, characterized in that: The dosage form is a gel, and its preparation raw materials also include a pharmaceutically acceptable gel matrix, and the gel matrix is ​​one or more combinations of carbomer, sodium carboxymethyl cellulose, and sodium alginate.

7. The method for preparing a pharmaceutical composition for female bladder fasciitis according to claim 3, characterized in that: The following steps are involved: S1. Separately clean and select Phellodendron amurense, Sophora flavescens, Plantago asiatica, Hedyotis diffusa, Patrinia scabra, Poria cocos, Eupolyphaga sinensis, Salvia miltiorrhiza, Carthamus tinctorius, Epimedium, Angelica sinensis, Dipsacus asper, Rhubarb, Coix seeds, Angelica dahurica, and Cyathula officinalis to remove impurities and non-medicinal parts; S2, drying the cleaned earthworms, and then extracting them for 1-3 hours using supercritical CO2 extraction technology to obtain insect powder; S3, put the cleaned Phellodendron amurense, Sophora flavescens, Plantago asiatica, Hedyotis diffusa, Patrinia scabra, Poria, Salvia miltiorrhiza, Carthamus tinctorius, Epimedium, Angelica sinensis, Dipsacus asper, Rhubarb, Coix seeds, Angelica dahurica, Cyathula officinalis into an extraction tank, add 80-90% ethanol solution, extract at 30-50°C for 15-25min, continue heating to 60-80°C for 35-55min, collect the extract, concentrate and filter to obtain an extract for standby use; S4, put the notoginseng powder into a container, add clean water and grind it into coarse powder with a particle size of 1-3 mm, continue to add water and grind for 3-5 hours, the coarse powder is suspended in the water to form a suspension, let it stand, take out the coarse powder that has settled to the bottom and continue grinding, repeat 2-4 times to obtain a powder with a fineness of 300-400 mesh, take it out, and dry it in an oven at 40-60° C. to obtain the notoginseng powder; S5. Stir and mix the insect powder, extract and Panax notoginseng powder to obtain a mixed powder. According to the dosage form requirements described in claim 4, mix the mixed powder with a corresponding pharmaceutically acceptable matrix or gel matrix, and prepare the desired external dosage form according to the corresponding preparation process.

8. The method for preparing a pharmaceutical composition for treating female bladder fasciitis according to claim 7, characterized in that: The supercritical CO2 extraction pressure of S2 is 30-50MPa, the extraction temperature is 40-60°C, and the CO2 extraction flow rate is 20-40kg / h.

9. The method for preparing a pharmaceutical composition for treating female bladder fasciitis according to claim 7, characterized in that: The mass volume ratio of the mixed medicinal materials and the ethanol solution in S3 is 3-5:10 g / mL.