Preparation method of white poria jelly for treating prostatitis

Abstract

The invention discloses a preparation method of white poria jelly for treating prostatitis. The white poria jelly is prepared from white pepper, asarum, poria cocos, borneol and menthol. Potassium sorbate is used as a preservative, polyethylene glycol 400 is used as an emulsifier, and the oil-phase matrix comprises albolene, beeswax, cetyl alcohol and glycerol. The traditional Chinese medicine composition has the effects of eliminating dampness and relieving pain, inducing diuresis to reduce edema and killing parasites to relieve itching, and is used for treating pelvic region pain or discomfort caused by prostatitis with symptoms such as frequent micturition, urgent urination, micturition pain, incomplete urination, white urethral orifice drop and scrotum pruritus. The ointment disclosed by the invention is faint yellow, fine and uniform in texture, good in flowability and easy to coat; water solubility is good, and cleaning is easy; the product has the advantages of good quality, no layering after centrifugation, high safety and small side effect, and is suitable for long-term use.

Description

Field of the Invention

[0001] The invention relates to a preparation method of Bailing Gao for treating prostatitis, belonging to the field of pharmaceutical technology. Background Art

[0002] Prostatitis is a common disease in men. It may be caused by bacterial infection or other factors, including acute bacterial prostatitis, chronic bacterial prostatitis, chronic prostatitis (chronic pelvic pain syndrome), etc. 35%-50% of men from adolescence to old age will be affected by prostatitis. Unclean sexual life, long-term sitting and unhealthy eating habits, such as excessive drinking and spicy food, may all be factors that induce prostatitis. The symptoms of the disease are diverse, ranging from acute pain and frequent urination to sexual dysfunction and mental and psychological disorders. Acute bacterial prostatitis is often manifested by frequent urination, urgency, urethral burning pain, etc. Chronic prostatitis (chronic pelvic pain syndrome) may cause long-term pain and discomfort in the pelvic area, urethral discomfort during urination, sexual dysfunction, and mental and psychological problems.

[0003] At present, most Western medicine drugs for the treatment of prostatitis use antibiotics, including quinolone, cephalosporin, and macrolide antibiotics, such as levofloxacin, ceftriaxone hydrochloride, and roxithromycin. However, long-term treatment of prostatitis with Western medicine may be accompanied by side effects such as sexual dysfunction, mental and neurological symptoms, digestive system discomfort, and allergic reactions. In severe cases, liver damage may occur. Traditional Chinese medicine adopts the method of "treating the site while adjusting and supplementing", and comprehensively treats systemic symptoms through a variety of treatment methods such as Chinese medicine, acupuncture, massage, and diet therapy, so as to achieve the purpose of treating prostatitis. It has high safety and few side effects, and is suitable for long-term use.

[0004] Ointment refers to a topical semi-solid preparation with a certain consistency made by uniformly mixing a drug with a suitable matrix. The drug in the ointment can be dissolved in the matrix or dispersed in the matrix. If a suitable matrix is ​​selected, the drug is dissolved in one phase of the matrix, so that the drug exists in molecular form. When the two phases are mixed, the drug is evenly distributed in the matrix. This not only ensures the drug dosage and efficacy, but also avoids the presence of drug particles that make the ointment drug concentration locally too high, causing irritation to the skin.

[0005] The present invention prepares a two-phase fusion ointment through a Chinese medicine formula, has the effects of drying dampness and relieving pain, diuresis and swelling, and killing insects and relieving itching, and is used for pelvic pain or discomfort caused by prostatitis, accompanied by frequent urination, urgent urination, painful urination, incomplete urination, white dripping from the urethra, scrotal itching, etc. The ointment has a simple preparation method, a uniform paste color, no obvious particles, good product quality, high safety, small side effects, and is suitable for long-term use. Summary of the invention

[0006] The technical problem to be solved by the present invention is to provide a preparation method of Bailing Gao for treating prostatitis. The present invention has the effects of drying dampness and relieving pain, diuresis and detumescence, and killing insects and relieving itching, and is used for pelvic pain or discomfort caused by prostatitis, accompanied by frequent urination, urgent urination, urinary pain, incomplete urination, white discharge from the urethra, scrotal itching and the like. The preparation method of the ointment is simple, the ointment is light yellow, the texture is fine and uniform, the fluidity is good, and it is easy to apply; it has good water solubility and is easy to clean; the product quality is good, there is no stratification after centrifugation, it has high safety, small side effects, and is suitable for long-term use.

[0007] In order to solve the above technical problems, the present invention adopts the following technical solutions:

[0008] A method for preparing Bailing Gao for treating prostatitis, the method for preparing Bailing Gao is carried out according to the following steps:

[0009] (1) Weigh 150-260 g of Asarum sieboldii, crush it into coarse powder, add 95% ethanol for ultrasonic extraction for 20-40 min, the ratio of medicinal material to 95% ethanol is 1 g: 5-15 mL, filter with a filter membrane to obtain Asarum sieboldii volatile oil and Asarum sieboldii residue respectively;

[0010] (2) Weigh 150-260 g of white pepper and 20-40 g of Poria cocos, grind them into coarse powder, add the asarum residue obtained in step (1), mix well, add 2-4 times the amount of 65-85% ethanol solution, soak for 14-18 h, heat and reflux at 40-60° C. for 1-3 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an alcohol extract without residue, evaporate the alcohol extract to obtain a Chinese medicine extract powder, i.e., product A;

[0011] (3) Take 5-15 g of borneol and 5-15 g of menthol, grind and mix them to obtain product B;

[0012] (4) adding 1.5-2.5 g of polyethylene glycol 400 and 0.1-0.3 g of potassium sorbate to 10 g of purified water, heating to 70-90° C., and mixing to obtain an aqueous phase;

[0013] (5) Add 10-20 g of white vaseline, 3-7 g of beeswax, 0.5-1.5 g of cetyl alcohol and 2-4 g of glycerol into an evaporating dish, place it on a heating mantle and heat it at 70-90° C. to melt, thereby obtaining an oil phase;

[0014] (6) Take the water phase at 70-90℃ and add product A to mix evenly, then add product B, and then add the oil phase at 70-80℃, and keep stirring in the same direction. When it cools to 25-35℃, add asarum volatile oil until it condenses, and then you will get Bailing Gao.

[0015] In the above step (1), 190-230 g of Asarum medicinal material is weighed, crushed into coarse powder, added with 95% ethanol for ultrasonic extraction for 25-35 min, the ratio of medicinal material to 95% ethanol is 1 g: 8-12 mL, and filtered using a filter membrane to obtain Asarum volatile oil and Asarum medicinal residue, respectively.

[0016] Specifically, in the above step (1), 210 g of Asarum medicinal material was weighed, crushed into coarse powder, added with 95% ethanol for ultrasonic extraction for 30 min, the ratio of medicinal material to 95% ethanol was 1 g:10 mL, and filtered using a filter membrane to obtain Asarum volatile oil and Asarum medicinal residue, respectively.

[0017] In the above step (2), 190-230 g of white pepper and 25-35 g of Poria cocos are weighed and crushed into coarse powder, and the asarum residue obtained in step (1) is added and mixed evenly, and 2-4 times the amount of 70-80% ethanol solution is added and soaked for 15-17 h, heated and refluxed at 45-55° C. for 1.5-2.5 h, and cooled to obtain an extract, and the extract is filtered to remove the residue to obtain an alcohol extract without residue, and the alcohol extract is evaporated to obtain a Chinese medicine extract powder, i.e., product A.

[0018] Specifically, in the above step (2), 210 g of white pepper and 30 g of Poria cocos are weighed and crushed into coarse powder, and the asarum residue obtained in step (1) is added and mixed evenly, and 3 times the amount of 75% ethanol solution is added and soaked for 16 hours, heated and refluxed at 50° C. for 2 hours, and cooled to obtain an extract, and the extract is filtered to remove the residue to obtain an alcohol extract without residue, and the alcohol extract is evaporated to obtain a Chinese medicine extract powder, i.e., product A.

[0019] In the above step (3), 8-12 g of borneol and 8-12 g of menthol are taken, ground and mixed to obtain product B.

[0020] Specifically, in the above step (3), 10 g of borneol and 10 g of menthol are taken, ground and mixed to obtain product B.

[0021] In the above step (4), 2 g of polyethylene glycol 400 and 0.2 g of potassium sorbate are added to 10 g of purified water, heated to 80° C., and mixed to obtain an aqueous phase.

[0022] Specifically, in the aforementioned step (5), 15 g of white vaseline, 5 g of beeswax, 1 g of cetyl alcohol and 3 g of glycerol are added to an evaporating dish, placed on a heating mantle and heated to 80° C. to melt, thereby obtaining an oil phase.

[0023] In the above step (6), add the water phase at 80°C to product A and mix evenly, then add product B, and then add the oil phase at 75°C, and stir continuously in the same direction. When cooled to 30°C, add asarum volatile oil until condensed, and then obtain Bailing Gao.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] The topical ointment for treating prostatitis of the present invention is prepared from white pepper, asarum, poria, borneol and menthol. White pepper is the dried nearly mature or mature fruit of Piper nigrum L., a plant of the Piperaceae family; the surface is off-white or light yellowish white, smooth, with a plurality of light-colored linear stripes between the top and the base; the smell of white pepper is aromatic, the taste is spicy, the nature is hot, and it enters the stomach and large intestine meridians; its main effects include warming the middle and dispersing cold, lowering qi, and eliminating phlegm, and it is often used to treat symptoms such as stomach cold vomiting, abdominal pain diarrhea, and loss of appetite. Asarum is the dried root and rhizome of Asarum heterotropoides Fr.Schmidt var.mandshuricum (Maxim.)Kitag., Asarum sieboldii Miq.var.seoulense Nakai or Asarwm sieboldii Miq. of the Aquilegiaceae family; the first two species are commonly known as "Liao Asarum"; they are harvested in summer when the fruit is ripe or in early autumn, and the above-ground parts and mud and sand are removed, and then dried in the shade; they are pungent in taste and warm in nature; they enter the heart, lung and kidney meridians; they have the effects of dispelling exterior pathogens and cold, dispelling wind and relieving pain, opening the orifices, warming the lungs and transforming fluid; they are used for colds caused by wind and cold, headaches, toothaches, nasal congestion and runny nose, allergic rhinitis, sinusitis, rheumatic pain, and coughs and wheezing caused by phlegm and fluid. Poria cocos is the dried sclerotium of the fungus Poria cocos (Schw.) Wolf of the Polyporaceae family; it tastes sweet and light, and is neutral in nature; it enters the heart, lung, spleen, and kidney meridians; it has the effects of promoting water and removing dampness, strengthening the spleen, and calming the mind; it is used for edema, oliguria, phlegm and fluid, palpitations, spleen deficiency, poor appetite, loose stools, restlessness, palpitations, and insomnia. Borneol is made by extracting and processing the fresh branches and leaves of the plant Cinnamomum camphora (L.) Presl of the Lauraceae family; it tastes pungent and bitter, and is cool in nature; it enters the heart, spleen, and lung meridians, and has the effects of opening the mind, clearing heat, and relieving pain; it is used for fever, coma, convulsions, stroke, phlegm, sudden syncope, coma caused by evil spirits, chest pain, red eyes, mouth sores, sore throat, and pus in the ear canal. Menthol is a saturated cyclic alcohol obtained by steam distillation, freezing and recrystallization of the fresh stems and leaves of Mentha haplocalyx Briq., a plant of the Lamiaceae family. It is l-1-methyl-4-isopropylcyclohexanol-3-; it has the effects of dispelling wind, clearing heat and detoxifying; it is mainly used to treat headaches, red eyes, exogenous wind-heat, sore throat and teeth, and itchy skin.

[0026] Solution:

[0027] White pepper is the main drug, which has the functions of antibacterial, insecticidal and detumescence, and has the functions of dispersing, descending qi and dredging; Asarum and Poria cocos help the main drug to dispel cold and relieve pain, resolve phlegm and promote diuresis, and remove turbid semen, etc., and are the assistant drugs; Borneol clears heat and relieves pain, and menthol has the functions of cooling and relieving itching, and the two drugs play the role of adjuvant. The combination of these drugs can achieve the functions of drying dampness and relieving pain, diuresis and detumescence, killing insects and relieving itching. It is used for pelvic pain or discomfort caused by prostatitis, accompanied by frequent urination, urgent urination, painful urination, incomplete urination, white dripping from the urethra, scrotal itching, etc. It is suitable for people with prostatitis.

[0028] The beneficial effects of the ointment prepared by the present invention are:

[0029] 1. In the extract extraction process, 95% ethanol is used to ultrasonically extract the volatile oil of Asarum, and the maximum content of the extracted volatile oil (asarone) of Asarum reaches 0.077%.

[0030] 2. The extract was prepared using 75% ethanol, Chinese medicine (white pepper, Poria cocos and asarum residue) and ethanol in a ratio of 1g:20mL, soaking time 16h, heating reflux temperature 50℃ and heating reflux time 2h. The maximum extract yield reached 91.77%, and the highest piperine content reached 18.38mg / g.

[0031] 3. The ointment of the present invention has good plasticity, fine and uniform texture, good fluidity, and is easy to apply; it has good water solubility and is easy to clean; the product quality is good, it does not stratify after centrifugation, it has high safety, small side effects, and is suitable for long-term use. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 : Four groups of ointment appearance pictures;

[0033] Figure 2 : Light microscopic images of the prostate tissue structure of rats in each group after HE staining. DETAILED DESCRIPTION

[0034] The present invention will be further described below in conjunction with the embodiments, but they are not intended to limit the present invention.

[0035] Example 1.

[0036] Preparation method of Bailing Gao:

[0037] (1) Weigh 210 g of Asarum sieboldii, crush it into coarse powder, add 95% ethanol for ultrasonic extraction for 30 min, the ratio of medicinal material to 95% ethanol is 1 g: 10 mL, filter with a filter membrane to obtain Asarum sieboldii volatile oil and Asarum sieboldii residue respectively;

[0038] (2) Weigh 210 g of white pepper and 30 g of Poria cocos, grind them into coarse powder, add the asarum residue obtained in step (1), mix well, add 3 times the amount of 75% ethanol solution, soak for 16 h, heat and reflux at 50° C. for 2 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an alcohol extract without residue, evaporate the alcohol extract to obtain product A;

[0039] (3) Take 10 g of borneol and 10 g of menthol, grind and mix them to obtain product B;

[0040] (4) Add 2 g of polyethylene glycol and 0.2 g of potassium sorbate to 10 g of purified water, heat to 80° C., and mix to obtain an aqueous phase;

[0041] (5) Add 15 g of white vaseline, 5 g of beeswax, 1 g of cetyl alcohol and 3 g of glycerin into an evaporating dish, place it on a heating mantle and heat it at 80°C to melt to obtain the oil phase;

[0042] (6) Take the water phase at 80°C and add product A to mix evenly, then add product B, and then add the oil phase at 75°C, and continue stirring in the same direction. When it cools to 30°C, add asarum volatile oil until it condenses, and Bailing Gao is obtained.

[0043] Dosage and Administration: Apply to the navel once a day, 2-4g each time, 7 days as a course of treatment.

[0044] Indications: Pain or discomfort in the pelvic area caused by prostatitis, accompanied by frequent urination, urgency, pain, incomplete urination, white discharge from the urethra, and scrotal itching.

[0045] Example 2.

[0046] Preparation method of Bailing Gao:

[0047] (1) Weigh 150 g of Asarum sieboldii, grind it into coarse powder, add 95% ethanol for ultrasonic extraction for 40 min, the ratio of medicinal material to 95% ethanol is 1 g: 5 mL, filter with a filter membrane to obtain Asarum sieboldii volatile oil and Asarum sieboldii residue respectively;

[0048] (2) Weigh 260 g of white pepper and 20 g of Poria cocos, grind them into coarse powder, add the asarum residue obtained in step (1), mix well, add 2 times the amount of 65% ethanol solution, soak for 14 h, heat and reflux at 40° C. for 3 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an alcohol extract without residue, evaporate the alcohol extract to obtain product A;

[0049] (3) Take 5 g of borneol and 15 g of menthol, grind and mix them to obtain product B;

[0050] (4) Add 1.5 g of polyethylene glycol and 0.1 g of potassium sorbate to 10 g of purified water, heat to 90° C., and mix to obtain an aqueous phase;

[0051] (5) Add 20 g of white vaseline, 7 g of beeswax, 1.5 g of cetyl alcohol and 2 g of glycerin into an evaporating dish, place it on a heating mantle and heat it at 90°C to melt to obtain the oil phase;

[0052] (6) Take the water phase at 90°C and add product A to mix evenly, then add product B, and then add the oil phase at 80°C, and continue stirring in the same direction. When it cools to 35°C, add asarum volatile oil until it condenses, and you will get Bailing Gao.

[0053] Dosage and Administration: Apply to the navel once a day, 2-4g each time, 7 days as a course of treatment.

[0054] Indications: Pain or discomfort in the pelvic area caused by prostatitis, accompanied by frequent urination, urgency, pain, incomplete urination, white discharge from the urethra, and scrotal itching.

[0055] Example 3.

[0056] Preparation method of Bailing Gao:

[0057] (1) Weigh 260 g of Asarum sieboldii, grind it into coarse powder, add 95% ethanol for ultrasonic extraction for 20 min, the ratio of medicinal material to 95% ethanol is 1 g:15 mL, filter with a filter membrane to obtain Asarum sieboldii volatile oil and Asarum sieboldii residue respectively;

[0058] (2) Weigh 150 g of white pepper and 40 g of Poria cocos, grind them into coarse powder, add the asarum residue obtained in step (1), mix well, add 4 times the amount of 85% ethanol solution, soak for 18 h, heat and reflux at 60° C. for 1 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an alcohol extract without residue, evaporate the alcohol extract to obtain product A;

[0059] (3) Take 15 g of borneol and 5 g of menthol, grind and mix them to obtain product B;

[0060] (4) Add 2.5 g of polyethylene glycol and 0.3 g of potassium sorbate to 10 g of purified water, heat to 70° C., and mix to obtain an aqueous phase;

[0061] (5) Take 10 g of white vaseline, 3 g of beeswax, 0.5 g of cetyl alcohol and 4 g of glycerin and add them to an evaporating dish. Heat it on a heating mantle at 70°C to melt to obtain the oil phase.

[0062] (6) Take the water phase at 70°C and add product A to mix evenly, then add product B, and then add the oil phase at 70°C, and continue stirring in the same direction. When it cools to 25°C, add asarum volatile oil until it condenses, and Bailing Gao is obtained.

[0063] Dosage and Administration: Apply to the navel once a day, 2-4g each time, 7 days as a course of treatment.

[0064] Indications: Pain or discomfort in the pelvic area caused by prostatitis, accompanied by frequent urination, urgency, pain, incomplete urination, white discharge from the urethra, and scrotal itching.

[0065] Example 4.

[0066] Preparation method of Bailing Gao:

[0067] (1) Weigh 190 g of Asarum sieboldii, grind it into coarse powder, add 95% ethanol for ultrasonic extraction for 25 min, the ratio of medicinal material to 95% ethanol is 1 g:12 mL, filter with a filter membrane to obtain Asarum sieboldii volatile oil and Asarum sieboldii residue respectively;

[0068] (2) Weigh 230 g of white pepper and 35 g of Poria cocos, grind them into coarse powder, add the asarum residue obtained in step (1), mix well, add 2 times the amount of 70% ethanol solution, soak for 17 h, heat and reflux at 55° C. for 1.5 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an alcohol extract without residue, evaporate the alcohol extract to obtain product A;

[0069] (3) Take 8 g of borneol and 12 g of menthol, grind and mix them to obtain product B;

[0070] (4) Add 2.2 g of polyethylene glycol and 0.25 g of potassium sorbate to 10 g of purified water, heat to 85° C., and mix to obtain an aqueous phase;

[0071] (5) Add 13 g of white vaseline, 6 g of beeswax, 1.0 g of cetyl alcohol and 3.5 g of glycerin into an evaporating dish, place it on a heating mantle and heat it at 85°C to melt to obtain an oil phase;

[0072] (6) Take the water phase at 85°C and add product A to mix evenly, then add product B, and then add the oil phase at 85°C, and continue stirring in the same direction. When it cools to 32°C, add asarum volatile oil until it condenses, and Bailing Gao is obtained.

[0073] Dosage and Administration: Apply to the navel once a day, 2-4g each time, 7 days as a course of treatment.

[0074] Indications: Pain or discomfort in the pelvic area caused by prostatitis, accompanied by frequent urination, urgency, pain, incomplete urination, white discharge from the urethra, and scrotal itching.

[0075] Example 5.

[0076] Preparation method of Bailing Gao:

[0077] (1) Weigh 230 g of Asarum sieboldii, grind it into coarse powder, add 95% ethanol for ultrasonic extraction for 35 min, the ratio of medicinal material to 95% ethanol is 1 g: 8 mL, filter with a filter membrane to obtain Asarum sieboldii volatile oil and Asarum sieboldii residue respectively;

[0078] (2) Weigh 1900 g of white pepper and 25 g of Poria cocos, grind them into coarse powder, add the asarum residue obtained in step (1), mix well, add 4 times the amount of 80% ethanol solution, soak for 15 h, heat and reflux at 45° C. for 2.5 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an alcohol extract without residue, evaporate the alcohol extract to obtain product A;

[0079] (3) Take 12 g of borneol and 8 g of menthol, grind and mix them to obtain product B;

[0080] (4) Add 1.9 g of polyethylene glycol and 0.15 g of potassium sorbate to 10 g of purified water, heat to 75° C., and mix to obtain an aqueous phase;

[0081] (5) Add 18 g of white vaseline, 4 g of beeswax, 0.5 g of cetyl alcohol and 2.5 g of glycerin into an evaporating dish, place it on a heating mantle and heat to 75°C to melt to obtain the oil phase;

[0082] (6) Take the water phase at 75°C and add product A to mix evenly, then add product B, and then add the oil phase at 75°C, and continue stirring in the same direction. When it cools to 28°C, add asarum volatile oil until it condenses, and Bailing Gao is obtained.

[0083] Dosage and Administration: Apply to the navel once a day, 2-4g each time, 7 days as a course of treatment.

[0084] Indications: Pain or discomfort in the pelvic area caused by prostatitis, accompanied by frequent urination, urgency, pain, incomplete urination, white discharge from the urethra, and scrotal itching.

[0085] The present invention has carried out a lot of experimental studies, and the following are the results of the experimental studies of the present invention:

[0086] 1. Optimization of extraction and preparation process

[0087] 1.1 Chinese medicine prescription

[0088] The traditional Chinese medicine prescription is prepared from 210g of white pepper, 210g of asarum, 30g of Poria, 10g of borneol and 10g of menthol.

[0089] 1.2 Extraction process optimization

[0090] 1.2.1 Optimization of Asarum Extraction Process

[0091] Experimental method: Weigh the medicinal materials of Asarum according to the prescribed amount, grind the medicinal materials into coarse powder, add ethanol for ultrasonic extraction, and obtain Asarum volatile oil and Asarum residue.

[0092] The extracted Asarum volatile oil was used to investigate the three variables of different concentrations of ethanol, the ratio of Chinese medicine to ethanol, and ultrasonic extraction time. The three variables were designed according to the following schemes: the ethanol concentration was 75% ethanol, 95% ethanol or anhydrous ethanol, the ratio of Asarum medicinal materials to ethanol was 1g:5mL, 1g:10mL, 1g:15mL, and the ultrasonic extraction time was 20, 30, and 40min, respectively. Nine groups of experiments were carried out according to the experimental method, and the content of Asarum volatile oil (asarone) in each group of experiments was calculated. The detection method was the volatile oil determination method of the Chinese Pharmacopoeia 2020 edition, and the determination results are shown in Table 1.

[0093] Table 1 Experimental groups and results

[0094] Experimental Grouping Ethanol concentration Asarum to ethanol ratio Ultrasonic extraction time Content results 1 75% ethanol 1g:5mL 20min 0.048％ 2 75% ethanol 1g:10mL 30min 0.073％ 3 75% ethanol 1g:15mL 40min 0.069％ 4 85% ethanol 1g:5mL 30min 0.050％ 5 85% ethanol 1g:10mL 20min 0.070％ 6 85% ethanol 1g:15mL 40min 0.067％ 7 95% ethanol 1g:5mL 40min 0.052％ 8 95% ethanol 1g:10mL 30min 0.077％ 9 95% ethanol 1g:15mL 20min 0.074％

[0095] As shown in Table 1, the Asarum content extracted in the 8th experimental group was the highest. The ethanol concentration, the ratio of medicinal materials to ethanol and the ultrasonic extraction time had a great influence on the extraction rate of the volatile oil of the Asarum medicinal materials. When the amount of 95% ethanol added was 10 mL, the ratio of Asarum to ethanol was 1 g:10 mL, and the ultrasonic time was 30 min, the maximum content of the extracted Asarum volatile oil (asarone) reached 0.077%.

[0096] 1.2.2 Optimization of white pepper and Poria cocos extraction process

[0097] Experimental method: Weigh white pepper and Poria cocos according to the prescribed amount, crush them into coarse powder, add the residue of Asarum after ultrasonic extraction with 95% ethanol, mix evenly, then add different concentrations of ethanol as solvent, soak first, heat under reflux, cool to obtain the extract, filter the extract, filter out the residue to obtain the extract without residue, and concentrate at normal pressure to 1.20-1.30 extract.

[0098] The five variables of ethanol concentration, ratio of Chinese medicine to ethanol, soaking time, heating reflux time and heating reflux temperature were investigated in order to obtain the extract yield. The five variables were designed according to the following schemes: the concentration of the added ethanol solvent was 65%, 75% and 85% respectively, the ratio of the total amount of medicinal materials to the ethanol solvent was 1g:15mL, 1g:20mL and 1g:25mL respectively, the soaking time was 15h, 16h and 17h respectively, the heating reflux temperature was 45℃, 50℃ and 55℃ respectively, and the heating reflux time was 1.5h, 2h and 2.5h respectively. Nine groups of experiments were carried out according to the experimental method, and the extract yield of each group of experiments was calculated. The extract yield was calculated according to the following formula:

[0099] Extract yield = (extract mass ÷ total mass of Chinese medicine) × 100%;

[0100] The total mass of Chinese medicine is the sum of the mass of white pepper, asarum and poria in the prescription.

[0101] Table 1 Experimental combinations and results

[0102]

[0103] The results are shown in Table 2. It can be seen that ethanol concentration, the ratio of Chinese medicine to ethanol, soaking time, heating reflux temperature and heating reflux time all have an effect on the extraction rate of Chinese medicine extract. The extract yield of Group 5 is the highest. The extract yield of 75% ethanol, the ratio of Chinese medicine to ethanol is 1g:20mL, the soaking time is 16h, the heating reflux temperature is 50℃ and the heating reflux time is 2h is the largest, reaching 91.77%, and the piperine content reaches 18.38mg / g.

[0104] 1.2.3 Discussion

[0105] The optimal extraction process of traditional Chinese medicine is obtained according to the extraction process verification:

[0106] (1) Weigh 210 g of Asarum sieboldii, grind it into coarse powder, add 95% ethanol for ultrasonic extraction for 30 min, the ratio of medicinal material to 95% ethanol is 1 g: 10 mL, filter with a filter membrane to obtain Asarum sieboldii volatile oil and Asarum sieboldii residue respectively;

[0107] (2) Weigh 210 g of white pepper and 30 g of Poria cocos, grind them into coarse powder, add the asarum residue obtained in step (1), mix well, add 3 times the amount of 75% ethanol solution, soak for 16 h, heat and reflux at 50° C. for 2 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an alcohol extract without residue, evaporate the alcohol extract to obtain a Chinese medicine extract powder.

[0108] 1.3 Optimization of ointment preparation process

[0109] 1.3.1 Aqueous matrix

[0110] Potassium sorbate was determined as the preservative, water was the solvent, different emulsifiers (polyethylene glycol 400, polyethylene glycol 800 or polyethylene glycol 4000) were selected, potassium sorbate and emulsifier were added to 10g of water, added to an evaporating dish, heated to 80°C, mixed, and the aqueous phase was obtained. The dry powder of the Chinese medicine extract prepared by the method of "1.2.3" was added to the aqueous phase and mixed evenly, and its appearance, fluidity, fineness and other indicators were investigated, so as to select a matrix with good hydrophilicity that can be made in a short time. The results are shown in Table 3:

[0111] Table 3 Performance comparison of different aqueous matrices

[0112]

[0113] It can be seen that the aqueous phase prepared with 0.1 g of sorbic acid and 2 g of polyethylene glycol 400 has a transparent yellow-brown appearance, a uniform and delicate texture, and moderate viscosity, and does not separate after centrifugation.

[0114] 1.3.2 Selection of oil phase matrix

[0115] Potassium sorbate was determined to be the preservative, water to be the solvent, and polyethylene glycol 400 to be the emulsifying base. The preparation method was determined as follows: first, 0.1 g of potassium sorbate and 2 g of polyethylene glycol 400 were added to 10 g of water, and added to an evaporating dish to obtain an aqueous phase. Then weigh different proportions of oil phase (the oil phase can be white vaseline, beeswax, cetyl alcohol, glycerin, liquid paraffin, glyceryl monostearate and sodium lauryl sulfate) and add them to another evaporating dish. Place the two evaporating dishes of the water phase and the oil phase on two heating jackets for heating respectively. Use a thermometer to control the temperature of the two phases at 80°C. After the substances in the evaporating dishes are heated and melted and the temperature reaches the requirement, add the dry powder of the Chinese medicine extract prepared by the method in "1.2.3" to the water phase and mix evenly. Then add 10g of ground borneol and 10g of menthol. After mixing, slowly add to the oil phase and stir continuously in the same direction. When cooled to 25-35°C, add the asarum volatile oil prepared by the method in "1.2.3", and continue stirring until condensed. Observe the appearance and properties of the ointments obtained with different prescriptions and determine their relevant physical and chemical parameters. The color, properties, consistency, stratification and coating of the ointment are used as indicators to select the best prescription. The grouping of different oil phase ratios is shown in Table 4, and the results are shown in Table 5. Figure 1 .

[0116] Table 4 Grouping of different oil ratios

[0117]

[0118]

[0119] Table 5 Properties of ointments prepared with different oil phases

[0120]

[0121] From the results, it can be seen that in Group 4, the best effect is achieved when the oil phase is white vaseline, beeswax, cetyl alcohol and glycerin. The appearance is light yellow, the texture is fine and uniform, the fluidity is good, there is no stratification after centrifugation, and there is no granularity after coating.

[0122] 1.3.3 Amount of oil phase matrix

[0123] The oil phase was determined to be composed of white vaseline, beeswax, cetyl alcohol and glycerol. The appearance properties of the ointment obtained at different dosages of white vaseline, beeswax, cetyl alcohol and glycerol and at different temperatures were investigated and their relevant physicochemical parameters were determined. The color, properties, consistency, stratification and coating conditions of the ointment were used as indicators to screen the optimal oil phase formula dosage. The results are shown in Table 6.

[0124] Table 6 Grouping of different oil ratios

[0125]

[0126] From the results, it can be seen that in Group 2, the amount of oil phase used is 15g white vaseline, 5g beeswax, 1g cetyl alcohol and 3g glycerol, and the effect is best when the preparation temperature is 80°C. The appearance is light yellow, the texture is fine and uniform, the fluidity is good, there is no stratification after centrifugation, and there is no granularity after coating.

[0127] 1.3.3 Discussion:

[0128] This experiment uses appearance texture, fluidity, stratification, and the presence or absence of particles as evaluation indicators to screen the amount of auxiliary materials used in the ointment process. It is found that the ointment prepared using polyethylene glycol 400 as an emulsifier, white vaseline, beeswax, cetyl alcohol, and glycerol as the oil phase matrix has a uniform and delicate texture, moderate viscosity, and is not stratified after centrifugation. If the amount of white vaseline is too small, the texture of the ointment is slightly thin, the coating and ductility are poor, and the stability is reduced. If the amount of white vaseline is too large, the texture will be thicker, resulting in reduced fluidity. In addition, too high a temperature during preparation will also reduce fluidity, and too much beeswax will be difficult to apply, and the coating and ductility will be poor.

[0129] Finally, the optimal preparation process conditions of the ointment were obtained. The preparation process is as follows: first, add 0.1g of potassium sorbate and 2g of polyethylene glycol 400 to 10g of water, add to an evaporating dish, heat to 80°C, mix well, and obtain a water phase. Then weigh 15g of white vaseline, 5g of beeswax, 1g of cetyl alcohol, and 3g of glycerol respectively, add to another evaporating dish, heat to 80°C, and obtain an oil phase. Add the dry powder of the Chinese medicine extract prepared by the method of "1.2.3" to the water phase and mix well. Then add 10g of ground borneol and 10g of menthol. After mixing, slowly add to the oil phase, stir continuously in the same direction, and add the volatile oil of Asarum prepared by the method of "1.2.3" when cooled to 25-35°C, and stir until condensed.

[0130] 2. Drug efficacy experiment

[0131] 2.1 Materials and methods

[0132] 2.1.1 Experimental animals

[0133] 40 male SD rats (specific pathogen free, SPF grade) were provided by Beijing Weitong Lihua Co., Ltd., weighing 300-400g, with production license number: SCXK (Beijing) 2021-0011. The animals were kept in the barrier area animal room of Chongqing Institute of Traditional Chinese Medicine, and were given standard pelleted feed for rodents (provided by the Experimental Animal Center) and tap water to drink freely, with 12h light and dark cycle, constant temperature (24±2℃), and humidity (40%-70%). The experimental plan was approved by the Animal Ethics Committee of Chongqing Institute of Traditional Chinese Medicine.

[0134] 2.1.2 Experimental instruments and reagents

[0135] Bailing Gao (prepared by the method in Example 1) was prepared by the Institute of Medicinal Chemistry of Chongqing Institute of Traditional Chinese Medicine; carrageenan (Sigma, USA, production batch number: C1013-25G); 0.9% sodium chloride injection (Guizhou Kelun Pharmaceutical Co., Ltd., production batch number: D23052505); 10% chloral hydrate (The First Hospital of Lanzhou University, production batch number: H04000035); penicillin G sodium salt (Beijing Boosen Biotechnology Co., Ltd., production batch number: D21004); 10% formaldehyde fixative (Nanchang Yulu Experimental Equipment Co., Ltd., production batch number: 190515); hematoxylin-eosin (HE) staining solution set (Nanchang Yulu Experimental Equipment Co., Ltd., production batch number: 190601); disposable syringe (Shandong Weigao Group Medical Polymer Products Co., Ltd., production batch number: 20220221).

[0136] XD-685 electrolyte analyzer, Shanghai Xunda Medical Instrument Co., Ltd. ASP300S advanced intelligent dehydrator, Germany's TUKA Instrument Co., Ltd. HistoCore Arcadia H paraffin embedding machine, Leica Microsystems (Shanghai) Co., Ltd. TK-218 constant temperature slide baking machine, Hubei Taiwei Technology Industry Co., Ltd. RM2235 rotary slicer, Germany's TUKA Instrument Co., Ltd. DP260 fully automatic intelligent staining machine, Dakoway (Shenzhen) Medical Equipment Co., Ltd. Mias-2000 pathological image processing system, National Institute of Image Processing, Sichuan University. YZ11 ophthalmoscope, Suzhou Liuliu Vision Technology Co., Ltd. KJ5S1 handheld slit lamp microscope, Suzhou Industrial Park Kangjie Medical Equipment Co., Ltd. BX53 biological microscope, Olympus Corporation.

[0137] 2.1.2 Experimental Grouping

[0138] The model was established and the drug administration was referred to the literature. The grouping and establishment of the model: 40 rats were adaptively raised for 5 days, and then anesthetized by intraperitoneal injection of 10% chloral hydrate (0.3ml / 100g). Five rats were taken as the normal control group. After anesthesia, the lower abdomen was smeared with iodine disinfection and placed on a sterile operating table. The abdominal wall of the rat was cut open, and the bladder and the seminal vesicles on both sides were lifted with forceps to expose the dorsal lobe of the prostate. Except for the blank group rats, which were injected with 0.1ml of normal saline on both sides of the dorsal lobe of the prostate, the other groups were injected with 0.1ml of 3% carrageenan solution on both sides of the prostate, with a total of 0.2ml on both sides. Sterile cotton balls were used to press the needle hole for 1min, the abdominal wall was sutured, iodine disinfection was performed, and 0.2ml of 300,000 units / ml penicillin injection was dripped on the external wound. After the rats woke up, 20 animals with successful modeling were randomly divided into 4 groups, namely the model group, the high-, medium-, and low-dose groups of Bailing Gao, with 10 rats in each group. After grouping, the high, medium and low dose groups of Bailing Gao were applied to the navel at 2.0, 1.0 and 0.5 g / animal (4, 2 and 1 times of the human clinical equivalent dose), respectively, and the blank group and model group were applied with normal saline to the navel once a day. After 7 consecutive days of administration.

[0139] 2.2 Observation indicators

[0140] 2.2.1 Urine output

[0141] One day before the last administration, the mice were gavaged with 10 ml of normal saline and placed in a metabolic cage, and the urine output was measured 1, 2, and 4 h after administration.

[0142] 2.2.2 Sample collection and testing

[0143] One hour after the last administration, blood was collected from the abdominal aorta of the rats, centrifuged at 4°C and 3000r / min for 10min, and serum was collected. The ELISA method was used to detect prostaglandin E2 (PGE2), interleukin-6 (IL-6), interleukin-8 (IL-8), etc. in the serum. The prostate tissue was removed and weighed, and the prostate index was calculated using the formula of prostate index = prostate mass / body weight. The supernatant after the prostate tissue was homogenized was used to determine the indicators such as PGE2, IL-6, IL-8, superoxide dismutase (SOD) and malondialdehyde (MDA) in the prostate tissue according to the kit.

[0144] 2.2.3 Gross morphology examination, i.e. light microscopy

[0145] The color, morphology and adhesion of the prostate tissue of the rats were observed with the naked eye, and then the right lobe of the prostate tissue was taken for HE staining, and the pathological changes of the prostate tissue were observed under a light microscope.

[0146] 2.2.4 Statistical analysis

[0147] The research data were analyzed and processed using SPSS 22.0 statistical software, and the quantitative data that conformed to the normal distribution were The inter-group comparison was analyzed by one-way ANOVA and Dunnett's t test (Dunnett method). When the difference between the groups was statistically significant (P<0.05),

[0148] 2.3 Test results

[0149] 2.3.1 Effect on urine output in rats with prostatitis

[0150] From the results in Table 7, we can see that compared with the normal control group, the urine volume in the model group increased significantly, which was statistically significant (P<0.01). After applying Bailing Gao to the navel skin, the urine volume in the high, medium and low dose groups was significantly lower than that in the model control group, which was statistically significant.

[0151] Table 7 Effect on urine output of model rats

[0152]

[0153] Note: Compared with the model control group, * indicates P < 0.05; ** indicates P < 0.01.

[0154] 2.3.2 Effects on the appearance, weight and index of the prostate in rats with prostatitis

[0155] According to naked eye observation, the surface of the prostate of the rats in the blank control group was ruddy, the gland was soft and elastic, there was no adhesion with the surrounding tissues, and it was easy to separate. The prostate of the rats in the model group was dark red, hard, poor in elasticity, large in size, widely adhered to the surrounding tissues, and difficult to separate. Compared with the model control group, the prostate of each dose group of the drug was redder, softer, and had restored elasticity, and the degree of adhesion with the surrounding tissues was improved. As shown in Table 8, compared with the normal control group, the prostate weight index of the model group increased significantly, with significant statistical significance (P<0.01). After applying Bailing Gao, the prostate weight index of the high and medium dose groups was significantly lower than that of the model control group, with significant statistical differences.

[0156] Table 8 Effects on prostate weight and index of model rats

[0157]

[0158] Note: Compared with the model control group, * indicates P < 0.05; ** indicates P < 0.01.

[0159] 2.3.3 ELISA determination of PGE2 changes in rat serum and prostate tissue

[0160] From the results in Table 9, it can be seen that compared with the normal control group, the PGE2 levels in serum and prostate tissue of the model group were significantly increased, with significant statistical significance (P<0.01). After applying Bailing Gao, the PGE2 levels in high, medium and low doses of serum were significantly lower than those in the model control group, and the PGE2 in the prostate tissue of the high dose of Bailing Gao group was significantly lower than that in the model control group, with significant statistical differences.

[0161] Table 9 Effects on serum and prostate tissue PGE2 in model rats

[0162]

[0163] Note: Compared with the blank control group, * indicates P < 0.05; ** indicates P < 0.01.

[0164] 2.3.4 Changes of IL-2 and IL-8 in serum and prostate tissue of rats with prostatitis

[0165] From the results in Table 10, it can be seen that compared with the blank control group, the IL-2 levels in the serum and prostate tissue of the model control group were significantly increased (p<0.01). Compared with the model control group, the IL-2 levels in the serum and tissue of the high-dose Bailing Gao group were significantly reduced, with significant statistical differences (P<0.01), and the IL-2 in the serum of the medium-dose Bailing Gao group was significantly reduced.

[0166] Table 10 Effects on IL-2 in serum and prostate tissue of model rats

[0167]

[0168] Note: Compared with the blank control group, * indicates P < 0.05; ** indicates P < 0.01.

[0169] As shown in Table 11, compared with the blank control group, the IL-8 levels in the serum and prostate tissue of the model control group were significantly increased (p<0.01). Compared with the model control group, the IL-8 levels in the serum and tissue of the high-dose Bailing Gao group were significantly reduced, with significant statistical differences (P<0.01), and the IL-8 levels in the serum of the medium-dose Bailing Gao group were significantly reduced (P<0.05).

[0170] Table 11 Effects on IL-8 in serum and prostate tissue of model rats

[0171]

[0172] Note: Compared with the blank control group, * indicates P < 0.05; ** indicates P < 0.01.

[0173] 2.3.5 Effects on SOD and MDA in prostate tissue of rats with prostatitis

[0174] From the results in Table 12, it can be seen that compared with the normal control group, the SOD level in the prostate tissue of the model group was significantly reduced and the MDA level was significantly increased, which was statistically significant (P<0.01). After applying Bailing Gao, the MDA levels in the high, medium and low doses of serum were significantly lower than those in the model control group, and the SOD in the prostate tissue of the high dose of Bailing Gao group was significantly higher than that in the model control group, which was statistically significant.

[0175] Table 12 Effects on SOD and MDA in prostate tissue of model rats

[0176]

[0177] Note: Compared with the blank control group, * indicates P < 0.05; ** indicates P < 0.01.

[0178] 2.3.6 Effect on prostate histopathology in rats with prostatitis

[0179] From the results in Table 13, it can be seen that gross morphological examination, i.e., light microscopic examination and HE staining observation under a light microscopy, the blank control group had normal prostate tissue structure, normal gland arrangement and distribution, and no inflammatory cell infiltration was observed in the interstitium.

[0180] Model control group: Part of the prostate gland was destroyed, a small amount of glandular cavity had secretions, the interstitial tissue became wider, and the interstitial tissue was filled with a large number of diffuse lymphocytes and monocytes.

[0181] Drug group: The arrangement and distribution of prostate glands were basically normal, with secretions in some glandular cavities and a small amount of inflammatory cell infiltration. Compared with the model group, the lymphocyte infiltration in the interstitium was significantly reduced.

[0182] Table 13 Effects on prostate weight and index of model rats

[0183]

[0184] Note: Compared with the blank control group, * indicates P < 0.05; ** indicates P < 0.01.

Claims

1. A method for preparing Bailing Gao for treating prostatitis, characterized in that: The preparation method of the Bailing Gao is carried out according to the following steps: (1) Weigh 150-260 g of Asarum sieboldii, crush it into coarse powder, add 95% ethanol for ultrasonic extraction for 20-40 min, the ratio of medicinal material to 95% ethanol is 1 g: 5-15 mL, filter with a filter membrane to obtain Asarum sieboldii volatile oil and Asarum sieboldii residue respectively; (2) Weigh 150-260 g of white pepper and 20-40 g of Poria cocos, grind them into coarse powder, add the asarum residue obtained in step (1), mix well, add 2-4 times the amount of 65-85% ethanol solution, soak for 14-18 h, heat and reflux at 40-60° C. for 1-3 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an alcohol extract without residue, evaporate the alcohol extract to obtain a Chinese medicine extract powder, i.e., product A; (3) Take 5-15 g of borneol and 5-15 g of menthol, grind and mix them to obtain product B; (4) adding 1.5-2.5 g of polyethylene glycol 400 and 0.1-0.3 g of potassium sorbate to 10 g of purified water, heating to 70-90° C., and mixing to obtain an aqueous phase; (5) Add 10-20 g of white vaseline, 3-7 g of beeswax, 0.5-1.5 g of cetyl alcohol and 2-4 g of glycerol into an evaporating dish, place it on a heating mantle and heat it at 70-90° C. to melt, thereby obtaining an oil phase; (6) Take the water phase at 70-90℃ and add product A to mix evenly, then add product B, and then add the oil phase at 70-80℃, and keep stirring in the same direction. When it cools to 25-35℃, add asarum volatile oil until it condenses, and then you will get Bailing Gao.

2. The preparation method of Bailing Gao for treating prostatitis as claimed in claim 1, characterized in that: In the step (1), 190-230 g of Asarum medicinal material is weighed, crushed into coarse powder, added with 95% ethanol for ultrasonic extraction for 25-35 min, the ratio of medicinal material to 95% ethanol is 1 g: 8-12 mL, and filtered using a filter membrane to obtain Asarum volatile oil and Asarum medicinal residue, respectively.

3. The preparation method of Bailing Gao for treating prostatitis as claimed in claim 2, characterized in that: In the step (1), 210 g of Asarum medicinal material is weighed, crushed into coarse powder, added with 95% ethanol for ultrasonic extraction for 30 min, the ratio of medicinal material to 95% ethanol is 1 g:10 mL, and filtered using a filter membrane to obtain Asarum volatile oil and Asarum medicinal residue, respectively.

4. The preparation method of Bailing Gao for treating prostatitis as claimed in claim 1, characterized in that: In the step (2), 190-230 g of white pepper and 25-35 g of Poria cocos are weighed and crushed into coarse powder, the asarum residue obtained in the step (1) is added, the mixture is mixed evenly, 2-4 times the amount of 70-80% ethanol solution is added, the mixture is soaked for 15-17 h, the mixture is heated and refluxed at 45-55° C. for 1.5-2.5 h, the mixture is cooled to obtain an extract, the extract is filtered, the residue is filtered off to obtain an alcohol extract without residue, the alcohol extract is evaporated to obtain a Chinese medicine extract powder, i.e., product A.

5. The preparation method of Bailing Gao for treating prostatitis as claimed in claim 4, characterized in that: In the step (2), 210 g of white pepper and 30 g of Poria cocos are weighed and crushed into coarse powder, the asarum residue obtained in the step (1) is added, the mixture is mixed evenly, 3 times the amount of 75% ethanol solution is added and soaked for 16 h, the mixture is heated under reflux at 50° C. for 2 h, and the mixture is cooled to obtain an extract, the extract is filtered, the residue is filtered off to obtain an alcohol extract without residue, and the alcohol extract is evaporated to obtain a Chinese medicine extract powder, i.e., product A.

6. The preparation method of Bailing Gao for treating prostatitis as claimed in claim 1, characterized in that: In the step (3), 8-12 g of borneol and 8-12 g of menthol are taken, ground and mixed to obtain product B.

7. The method for preparing the Bailing Gao for treating prostatitis as claimed in claim 6, characterized in that: In the step (3), 10 g of borneol and 10 g of menthol are taken, ground and mixed to obtain product B.

8. The preparation method of Bailing Gao for treating prostatitis as claimed in claim 1, characterized in that: In the step (4), 2 g of polyethylene glycol 400 and 0.2 g of potassium sorbate are added to 10 g of pure water, heated to 80° C., and mixed to obtain an aqueous phase.

9. The method for preparing the Bailing Gao for treating prostatitis as claimed in claim 1, characterized in that: In the step (5), 15 g of white vaseline, 5 g of beeswax, 1 g of cetyl alcohol and 3 g of glycerol are added to an evaporating dish, placed on a heating mantle and heated to 80° C. to melt, thereby obtaining an oil phase.

10. The method for preparing Bailing Gao for treating prostatitis according to claim 1, characterized in that: In the step (6), add the water phase at 80°C to product A and mix evenly, then add product B, and then add the oil phase at 75°C, and stir continuously in the same direction. When the mixture is cooled to 30°C, add asarum volatile oil until condensation, and obtain Bailing Gao.

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