External gel for treating prostatitis and preparation method thereof

Abstract

The invention discloses an external gel for treating prostatitis and a preparation method thereof. The external gel is prepared from white pepper, asarum, poria cocos, borneol and menthol. And the auxiliary materials comprise 0.5% of potassium sorbate, carbomer 940, Tween 80 and propylene glycol. 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 gel disclosed by the invention is good in plasticity and can be fully filled in deep tissues; volatilization is not easy, and action time is long; the texture is fine and uniform, no greasy feeling exists, the irritation is small, and coating is easy; water solubility is good, and cleaning is easy. The safety is high and the side effect is small.

Description

Field of the Invention

[0001] The invention relates to an external gel for treating prostatitis and a preparation method thereof, 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 used to treat 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] Gels refer to thick liquid or semisolid preparations made of drugs and excipients that can form gels, such as solutions, suspensions or emulsions. Usually, gels are limited to local use on the skin and body cavities (such as the nasal cavity, vagina and rectum). Emulsion gels are also called latexes. Gels made from polymer matrices (such as tragacanth gum, etc.) can also be called slurries. Gels formed by small particles of small molecule inorganic drugs (such as aluminum hydroxide) existing in a network structure in a liquid are two-phase dispersion systems, also known as suspension gels. Suspension gels can be thixotropic, semisolid when still and liquid when stirred or shaken.

[0005] The invention prepares a two-phase fusion suspension gel through a Chinese medicine formula, which 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, painful urination, incomplete urination, bifurcated urine, white dripping from the urethra, scrotal itching and the like. The gel has good plasticity and can be fully filled in deep tissues; it is not easy to volatilize and has a long action time; it has a fine and uniform texture, no greasy feeling, low irritation, and is easy to apply; it has good water solubility and is easy to clean. It has high safety and small side effects. Summary of the invention

[0006] The technical problem to be solved by the present invention is to provide an external gel for treating prostatitis and a preparation method thereof. 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 symptoms such as frequent urination, urgent urination, painful urination, incomplete urination, bifurcated urine, white dripping from the urethra, and scrotal itching.

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

[0008] An external gel for treating prostatitis, wherein the medicinal effective ingredients thereof are calculated by weight: 100-320 parts of white pepper, 100-320 parts of asarum, 15-45 parts of tuckahoe, 5-30 parts of borneol and 5-30 parts of menthol.

[0009] The above-mentioned external gel for treating prostatitis is prepared from 150-270 parts of white pepper, 150-270 parts of asarum, 20-40 parts of tuckahoe, 8-20 parts of borneol and 8-20 parts of menthol by weight.

[0010] Specifically, the aforementioned external gel for treating prostatitis, its medicinal active ingredients are calculated by weight: 210 parts of white pepper, 210 parts of asarum, 30 parts of Poria, 10 parts of borneol and 10 parts of menthol.

[0011] The preparation method of the external gel for treating prostatitis is carried out according to the following steps:

[0012] (1) Weigh 100-320 g of white pepper, 100-320 g of asarum and 15-45 g of poria, grind into coarse powder, mix evenly, add 65-85% ethanol solution and soak for 14-18 h, the ratio of the total amount of medicinal materials to 75% ethanol is 1 g: 10-30 mL, heat to 40-60° C. and reflux for 1-3 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an extract without residue, and concentrate under normal pressure to an extract with a relative density of 1.10-1.40 at 25° C. to obtain an extract;

[0013] (2) Add 5-15 mL of 0.5% potassium sorbate to the extract and mix well, then add 5-15 g of Carbomer 940 and mix well to obtain an aqueous phase;

[0014] (3) Take 5-30 g of borneol and 5-30 g of menthol, grind and mix them, then add 3-7 mL of Tween 80 and 3-7 mL of propylene glycol and mix well to obtain an oil phase;

[0015] (4) Slowly add the water phase into the oil phase, keep stirring in the same direction, and at the same time, dropwise add triethanolamine to adjust the pH value to 5-7 until condensation occurs to obtain a gel.

[0016] The preparation method of the external gel is carried out according to the following steps:

[0017] (1) Weigh 150-270 g of white pepper, 150-270 g of asarum and 20-40 g of poria, grind into coarse powder, mix evenly, add 70-80% ethanol solution and soak for 15-17 h, the ratio of the total amount of medicinal materials to 75% ethanol is 1 g: 15-25 mL, heat to 45-55° C. and reflux for 1.5-2.5 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an extract without residue, and concentrate at normal pressure to an extract with a relative density of 1.15-1.35 at 25° C., thereby obtaining an extract;

[0018] (2) Take the extract, add 8-12 mL of 0.5% potassium sorbate, mix well, then add 8-12 g of Carbomer 940, mix well, and obtain an aqueous phase;

[0019] (3) Take 8-20 g of borneol and 8-20 g of menthol, grind and mix them, then add 4-6 mL of Tween 80 and 4-6 mL of propylene glycol and mix well to obtain an oil phase;

[0020] (4) Slowly add the aqueous phase into the oil phase, stirring continuously in the same direction, and at the same time, dropwise add triethanolamine to adjust the pH value to 5.5-6.5 until condensation occurs to obtain a gel.

[0021] Specifically, the preparation method of the external gel is carried out according to the following steps:

[0022] (1) Weigh 210 g of white pepper, 210 g of asarum and 30 g of Poria, grind them into coarse powder, mix them evenly, add 75% ethanol solution and soak for 16 h, the ratio of the total amount of medicinal materials to 75% ethanol is 1 g:20 mL, heat to 50° C. and reflux for 2 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an extract without residue, and concentrate at normal pressure to an extract with a relative density of 1.20-1.30 at 25° C. to obtain an extract;

[0023] (2) Add 10 mL of 0.5% potassium sorbate to the extract and mix well, then add 10 g of Carbomer 940 and mix well to obtain an aqueous phase;

[0024] (3) Take 10 g of borneol and 10 g of menthol, grind and mix them, then add 5 mL of Tween 80 and 5 mL of propylene glycol and mix well to obtain an oil phase;

[0025] (4) Slowly add the aqueous phase into the oil phase, stirring continuously in the same direction, and at the same time, dropwise add triethanolamine to adjust the pH value to 6 until condensation occurs to obtain a gel.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The topical gel 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 yellow-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.

[0028] Solution:

[0029] 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.

[0030] The beneficial effects of the gel prepared by the present invention are as follows:

[0031] 1. In the extract extraction process, the extract was prepared using 75% ethanol, a ratio of Chinese medicine to ethanol of 1g:20mL, a soaking time of 16h, a heating reflux temperature of 50°C and a heating reflux time of 2h. The maximum extract yield reached 91.91% and the highest content reached 18.21mg / g.

[0032] 2. The gel of the present invention has good plasticity and can be fully filled into deep tissues; it is not easy to volatilize and has a long action time; it has a fine and uniform texture, good fluidity, and no obvious granular feeling after coating; it has good water solubility and is easy to clean. It has high safety and few side effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 : Appearance of four groups of gels;

[0034] Figure 2 : Four groups of gel coating effect diagrams;

[0035] Figure 3 : Intuitive pictures of gross observation of prostatitis in rats of each group;

[0036] Figure 4 : Light microscopic images of the prostate tissue structure of rats in each group after HE staining. DETAILED DESCRIPTION

[0037] The present invention will be further described below in conjunction with the embodiments, but they are not intended to limit the present invention.

[0038] Example 1. Preparation method of external gel

[0039] (1) Weigh 210 g of white pepper, 210 g of asarum and 30 g of Poria, grind them into coarse powder, mix them evenly, add 75% ethanol solution and soak for 16 h, the ratio of the total amount of medicinal materials to 75% ethanol is 1 g:20 mL, heat to 50° C. and reflux for 2 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an extract without residue, and concentrate at normal pressure to an extract with a relative density of 1.20-1.30 at 25° C. to obtain an extract;

[0040] (2) Add 10 mL of 0.5% potassium sorbate to the extract and mix well, then add 10 g of Carbomer 940 and mix well to obtain an aqueous phase;

[0041] (3) Take 10 g of borneol and 10 g of menthol, grind and mix them, then add 5 mL of Tween 80 and 5 mL of propylene glycol and mix well to obtain an oil phase;

[0042] (4) Slowly add the aqueous phase into the oil phase, stirring continuously in the same direction, and at the same time, dropwise add triethanolamine to adjust the pH value to 6 until condensation occurs to obtain a gel.

[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, urgent urination, painful urination, incomplete urination, white discharge from the urethra, and scrotal itching.

[0045] Example 2. Preparation method of external gel

[0046] (1) Weigh 320 g of white pepper, 100 g of asarum and 45 g of Poria, grind them into coarse powder, mix them evenly, add 85% ethanol solution and soak them for 18 h, the ratio of the total amount of medicinal materials to 75% ethanol is 1 g:30 mL, heat to 40° C. and reflux for 3 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an extract without residue, and concentrate under normal pressure to an extract with a relative density of 1.10-1.20 at 25° C. to obtain an extract;

[0047] (2) Add 15 mL of 0.5% potassium sorbate to the extract and mix well, then add 5 g of Carbomer 940 and mix well to obtain an aqueous phase;

[0048] (3) Take 30 g of borneol and 5 g of menthol, grind and mix them, then add 7 mL of Tween 80 and 3 mL of propylene glycol and mix well to obtain an oil phase;

[0049] (4) Slowly add the aqueous phase into the oil phase, keep stirring in the same direction, and at the same time, dropwise add triethanolamine to adjust the pH value to 5 until condensation occurs to obtain a gel.

[0050] Dosage and Administration: Apply to the navel once a day, 2-4g each time, 7 days as a course of treatment.

[0051] Indications: Pain or discomfort in the pelvic area caused by prostatitis, accompanied by frequent urination, urgent urination, painful urination, incomplete urination, white discharge from the urethra, and scrotal itching.

[0052] Example 3. Preparation method of external gel

[0053] (1) Weigh 100 g of white pepper, 320 g of asarum and 15 g of poria, grind into coarse powder, mix evenly, add 65% ethanol solution and soak for 14 h, the ratio of total amount of medicinal materials to 75% ethanol is 1 g:10 mL, heat to 60° C. and reflux for 1 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an extract without residue, and concentrate under normal pressure to an extract with a relative density of 1.30-1.40 at 25° C. to obtain an extract;

[0054] (2) Take the extract, add 5 mL of 0.5% potassium sorbate, mix well, then add 15 g of Carbomer 940, mix well to obtain an aqueous phase;

[0055] (3) Take 5 g of borneol and 30 g of menthol, grind and mix them, then add 3 mL of Tween 80 and 7 mL of propylene glycol and mix well to obtain an oil phase;

[0056] (4) Slowly add the aqueous phase into the oil phase, stirring continuously in the same direction, and at the same time, dropwise add triethanolamine to adjust the pH value to 7 until condensation occurs to obtain a gel.

[0057] Dosage and Administration: Apply to the navel once a day, 2-4g each time, 7 days as a course of treatment.

[0058] Indications: Pain or discomfort in the pelvic area caused by prostatitis, accompanied by frequent urination, urgent urination, painful urination, incomplete urination, white discharge from the urethra, and scrotal itching.

[0059] Example 4. Preparation method of external gel

[0060] (1) Weigh 270 g of white pepper, 150 g of asarum and 20 g of Poria, grind them into coarse powder, mix them evenly, add 70% ethanol solution and soak for 17 h, the ratio of the total amount of medicinal materials to 75% ethanol is 1 g:15 mL, heat to 55° C. and reflux for 1.5 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an extract without residue, and concentrate at normal pressure to an extract with a relative density of 1.25-1.35 at 25° C. to obtain an extract;

[0061] (2) Add 12 mL of 0.5% potassium sorbate to the extract and mix well, then add 8 g of Carbomer 940 and mix well to obtain an aqueous phase;

[0062] (3) Take 8 g of borneol and 20 g of menthol, grind and mix them, then add 4 mL of Tween 80 and 6 mL of propylene glycol and mix well to obtain an oil phase;

[0063] (4) Slowly add the aqueous phase into the oil phase, keep stirring in the same direction, and at the same time, dropwise add triethanolamine to adjust the pH value to 5.5 until condensation occurs to obtain a gel.

[0064] Dosage and Administration: Apply to the navel once a day, 2-4g each time, 7 days as a course of treatment.

[0065] Indications: Pain or discomfort in the pelvic area caused by prostatitis, accompanied by frequent urination, urgent urination, painful urination, incomplete urination, white discharge from the urethra, and scrotal itching.

[0066] Example 5. Preparation method of external gel

[0067] (1) Weigh 150 g of white pepper, 270 g of asarum and 40 g of Poria, grind them into coarse powder, mix them evenly, add 80% ethanol solution and soak for 15 h, the ratio of the total amount of medicinal materials to 75% ethanol is 1 g:25 mL, heat to 45° C. and reflux for 2.5 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an extract without residue, and concentrate at normal pressure to an extract with a relative density of 1.15-1.25 at 25° C. to obtain an extract;

[0068] (2) Take the extract, add 8 mL of 0.5% potassium sorbate, mix well, then add 12 g of Carbomer 940, mix well to obtain an aqueous phase;

[0069] (3) Take 20 g of borneol and 8 g of menthol, grind and mix them, then add 6 mL of Tween 80 and 4 mL of propylene glycol and mix well to obtain an oil phase;

[0070] (4) Slowly add the aqueous phase into the oil phase, keep stirring in the same direction, and at the same time, dropwise add triethanolamine to adjust the pH value to 6.5 until condensation occurs to obtain a gel.

[0071] Dosage and Administration: Apply to the navel once a day, 2-4g each time, 7 days as a course of treatment.

[0072] Indications: Pain or discomfort in the pelvic area caused by prostatitis, accompanied by frequent urination, urgent urination, painful urination, incomplete urination, white discharge from the urethra, and scrotal itching.

[0073] Example 6. Preparation method of external gel

[0074] (1) Weigh 190 g of white pepper, 220 g of asarum and 30 g of Poria, grind them into coarse powder, mix them evenly, add 75% ethanol solution and soak for 15.5 h, the ratio of the total amount of medicinal materials to 75% ethanol is 1 g:20 mL, heat to 50° C. and reflux for 2.5 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an extract without residue, and concentrate at normal pressure to an extract with a relative density of 1.20-1.30 at 25° C. to obtain an extract;

[0075] (2) Add 10 mL of 0.5% potassium sorbate to the extract and mix well, then add 10 g of Carbomer 940 and mix well to obtain an aqueous phase;

[0076] (3) Take 15 g of borneol and 15 g of menthol, grind and mix them, then add 5 mL of Tween 80 and 5 mL of propylene glycol and mix well to obtain an oil phase;

[0077] (4) Slowly add the aqueous phase into the oil phase, stirring continuously in the same direction, and at the same time, dropwise add triethanolamine to adjust the pH value to 6 until condensation occurs to obtain a gel.

[0078] Dosage and Administration: Apply to the navel once a day, 2-4g each time, 7 days as a course of treatment.

[0079] Indications: Pain or discomfort in the pelvic area caused by prostatitis, accompanied by frequent urination, urgent urination, painful urination, incomplete urination, white discharge from the urethra, and scrotal itching.

[0080] 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:

[0081] 1. Optimization of extraction and preparation process

[0082] 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.

[0083] 1.1 Optimization of white pepper and Poria cocos extraction process

[0084] 1.1.1 Extraction process experimental method

[0085] Weigh white pepper, asarum and poria according to the prescribed amount, crush them into coarse powder, mix them evenly, add different concentrations of ethanol as a solvent, soak them first, heat them under reflux, cool them to obtain an extract, filter the extract, filter out the residue to obtain a residue-free extract, and concentrate them at normal pressure to an extract of 1.20-1.30.

[0086] The five variables of ethanol concentration, ratio of Chinese medicine to ethanol, soaking time, heating reflux time and heating reflux temperature were investigated according to the yield of the extract obtained by extraction. 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 medicinal materials to ethanol solvent was 1g:15mL, 1g:20mL, and 1g:25mL, respectively, the soaking time was 15h, 16h, and 17h, respectively, the heating reflux temperatures were 45℃, 50℃, and 55℃, respectively, and the heating reflux times were 1.5h, 2h, and 2.5h, respectively.

[0087] Nine groups of experiments were carried out according to the experimental method, and the piperine content in the extract and the extract yield of each group of experiments were calculated.

[0088] 1) The content of piperine is tested according to the Chinese Pharmacopoeia 2020 Edition Part 1 (determined by high performance liquid chromatography (General Rule 0512)):

[0089] 2) The extract yield is calculated according to the following formula:

[0090] Extract yield = (extract mass ÷ total mass of Chinese medicine) × 100%;

[0091] The total mass of Chinese medicine is the sum of the mass of white pepper, asarum and poria in the prescription.

[0092] Table 1 Extraction experiment combinations and results

[0093]

[0094] The results are shown in Table 1. It can be seen that ethanol concentration, the ratio of medicinal materials to ethanol, soaking time, heating reflux temperature and heating reflux time all have an impact on the extraction rate of medicinal material extracts. The extract yield of Group 5 was the highest. The extract yield of 75% ethanol, the ratio of Chinese medicine to ethanol was 1g:20mL, the soaking time was 16h, the heating reflux temperature was 50℃ and the heating reflux time was 2h reached a maximum of 91.91%, and the highest content reached 18.21mg / g.

[0095] 1.1.2 Discussion

[0096] In this experiment, the extract yield and piperine content were used as evaluation indicators. The ethanol concentration of the extraction process, the ratio of medicinal materials to ethanol, the soaking time, the heating reflux temperature and the heating reflux time were screened to obtain the optimal extraction process conditions of the gel. The optimal extraction method was: weigh 210g of white pepper, 210g of asarum and 30g of Poria, crush them into coarse powder, mix them evenly, add 75% ethanol solution and soak for 16h, the ratio of the total amount of medicinal materials to 75% ethanol is 1g:20mL, then heat to 50℃ and reflux for 2h, cool to obtain an extract, filter the extract, filter out the residue to obtain an extract without residue, and concentrate at normal pressure to an extract with a relative density of 1.20-1.30 at 25℃.

[0097] 1.2 Optimization of gel preparation process

[0098] 1.2.1 Water phase preparation process

[0099] 0.5% potassium sorbate was determined as the preservative, and different gel matrices were selected. First, 10 mL of 0.5% potassium sorbate was added to the extract, and then 10 g of different gel matrices were added to prepare the aqueous phase. The selected gel matrices were sodium carboxymethyl cellulose, carbomer 940, poloxamer and gelatin. The aqueous phase was prepared according to the formula, and its appearance, fluidity, fineness and other indicators were investigated, so as to select the matrix that can be made into a good spreadability and hydrophilicity in a short time. The results are shown in Table 2:

[0100] Table 2 Performance comparison of aqueous phase made of different matrices and extracts

[0101]

[0102] It can be seen that the water phase prepared by Carbomer 940 has a transparent yellow-brown appearance, a uniform and delicate texture, and moderate viscosity.

[0103] 1.2.2 Gel preparation process

[0104] Carbomer 940 is determined as the matrix, and the preparation method is determined as follows: first, 10 mL of 0.5% potassium sorbate is added to the extract, and then 10 g of Carbomer 940 is added to prepare an aqueous phase. At the same time, borneol and menthol in the prescribed amount are taken, ground and mixed, and then Tween 80 and propylene glycol are added, and mixed evenly to obtain an oil phase. The aqueous phase is slowly added to the oil phase, and stirred continuously in the same direction, and triethanolamine is added dropwise to adjust the pH value to 5-7 until condensation occurs, thereby obtaining a gel.

[0105] Experimental design: Orthogonal experiments were designed with the dosage of Carbomer 940, Tween 80 and propylene glycol as the main factors, and the addition of triethanolamine to adjust the pH value. The four groups of experiments designed were used to evaluate the gel in terms of appearance and texture, fluidity, and the presence of particles after coating, as shown in Table 3. Figure 1 , Figure 2 .

[0106] Table 3 Preparation experimental combinations and results

[0107]

[0108] From the results, we can see that in experimental group No. 2, the dosage of Carbomer 940 is 10g, the dosage of Tween 80 is 5mL, the dosage of propylene glycol is 5mL, and the effect is best when the pH value is adjusted to 6 by triethanolamine. The appearance is light yellow, the texture is fine and uniform, the fluidity is good, and there is no obvious granularity after coating.

[0109] 1.2.3 Discussion

[0110] This experiment uses appearance, fluidity, coating properties, and the presence or absence of particles as evaluation indicators to screen the amount of auxiliary materials used in the gel process. It is found that if the amount of Carbomer 940 is too little, the gel texture is uneven, and if the amount of Carbomer 940 is too much, the fluidity will be reduced. If the amount of Tween 80 and propylene glycol is too much, there will be occasional granular feeling after coating, the coating property and ductility will deteriorate, and the stability will decrease. Finally, the optimal preparation process conditions of the gel are obtained. The preparation process is: take the extract and add 10mL of 0.5% potassium sorbate to mix well, then add 10g of Carbomer 940 and mix well to obtain the water phase; take 10g of borneol and 10g of menthol, grind and mix, add 5mL of Tween 80 and 5mL of propylene glycol and mix well to obtain the oil phase; slowly add the water phase to the oil phase, stir continuously in the same direction, and add triethanolamine to adjust the pH value to 6 until condensation, and the gel is obtained.

[0111] 2. Drug efficacy experiment

[0112] 2.1 Materials and methods

[0113] 2.1.1 Experimental animals

[0114] 40 male SD rats (specific pathogen free, SPF) 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.

[0115] 2.1.2 Experimental instruments and reagents

[0116] Example 1 Preparation method The prepared gel (prepared by the Institute of Medicinal Chemistry, Chongqing Institute of Traditional Chinese Medicine); carrageenan (Sigma, USA, production batch number: C1013-25G); 0.9% sodium chloride injection (Guizhou Kelun Pharmaceutical Co., Ltd., batch number: D23052505); 10% chloral hydrate (The First Hospital of Lanzhou University, production batch number: H04000035); penicillin G sodium salt (Beijing Bo Ao Sen Biotechnology Co., Ltd., production batch number: D21004); 10% formaldehyde fixative (Nanchang Yu Lu Experimental Equipment Co., Ltd., production batch number: 190515); hematoxylin-eosin (HE) staining solution (Nanchang Yu Lu Experimental Equipment Co., Ltd., production batch number: 190601); disposable syringe (Shandong Weigao Group Medical Polymer Products Co., Ltd., production batch number: 20220221).

[0117] 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.

[0118] 2.1.2 Experimental Grouping

[0119] 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 to disinfect and placed on a sterile operating table. The abdominal wall of the rat was cut open, and the bladder and both sides of the seminal vesicle 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 was disinfected, and 0.2ml of 300,000 units / ml penicillin injection was dripped on the external wound. After the rats woke up, the 20 animals with successful modeling were randomly divided into 4 groups, namely the model group, the high-dose, medium-dose and low-dose groups of Bailing gel, with 10 rats in each group. After grouping, the high, medium and low dose groups of Bailing gel were applied to the navel skin at 2.0, 1.0 and 0.5 g / mouse (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 skin once a day. After 7 consecutive days of administration.

[0120] 2.2 Observation indicators

[0121] 2.2.1 Urine output

[0122] 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.

[0123] 2.2.2 Sample collection and testing

[0124] 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 PGE2, IL-6, IL-8, etc. in the serum were detected by ELISA. 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 PGE2, IL-6, IL-8, SOD, MDA and other indicators in the prostate tissue according to the kit.

[0125] 2.2.3 Gross morphology examination, i.e. light microscopy

[0126] 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.

[0127] 2.2.4 Statistical analysis

[0128] 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 data were expressed as follows, and the comparison among the groups was analyzed by one-way ANOVA, and the comparison was performed by Dunnett's t test (Dunnett's method), when the differences among the groups were statistically significant (P < 0.05).

[0129] 2.3 Test results

[0130] 2.3.1 Effect on urine output in rats with prostatitis

[0131] Table 4 Effect on urine output of model rats

[0132]

[0133] Note: Compared with the model control group, * indicates P < 0.05; ** indicates P < 0.01.

[0134] From the results in Table 4, 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 gel for different time periods, 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.

[0135] 2.3.2 Effects on prostate weight and index in rats with prostatitis

[0136] From the results in Table 5, we can see that 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 gel, 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.

[0137] Table 5 Effects on prostate weight and index of model rats

[0138]

[0139] Note: Compared with the model control group, * indicates P < 0.05; ** indicates P < 0.01.

[0140] 2.3.3 Effect on gross observation of prostate in rats with prostatitis

[0141] Depend on Figure 3 Macroscopic observation showed that the surface of the prostate of the rats in the blank control group was ruddy, the gland was soft and elastic, had no adhesion to the surrounding tissues, and was easy to separate. The prostate of the rats in the model group was dark red, hard in texture, 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 in texture, had restored elasticity, and the degree of adhesion to the surrounding tissues was improved.

[0142] 2.3.4 ELISA determination of PGE2 changes in rat serum and prostate tissue

[0143] From the results in Table 6, we can see 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 gel, the PGE2 levels in high and medium doses of serum were significantly lower than those in the model control group, and the PGE2 in prostate tissue of the high dose of Bailing gel group was significantly lower than that in the model control group, with significant statistical differences.

[0144] Table 6 Effects on serum and prostate tissue PGE2 in model rats

[0145]

[0146] Note: Compared with the model control group, * indicates P < 0.05; ** indicates P < 0.01.

[0147] 2.3.5 Changes of IL-2 and IL-8 in serum and prostate tissue of rats with prostatitis

[0148] From the results in Table 7, 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 gel group were significantly reduced, with significant statistical differences (P<0.01), and the IL-2 level in the serum of the medium-dose Bailing gel group was significantly reduced.

[0149] Table 7 Effects on IL-2 in serum and prostate tissue of model rats

[0150]

[0151] Note: Compared with the model control group, * indicates P < 0.05; ** indicates P < 0.01.

[0152] From the results in Table 8, it can be seen that 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 and medium dose groups of Bailing gel were significantly reduced, with significant statistical differences (P<0.01 or P<0.05).

[0153] Table 8 Effects on IL-8 in serum and prostate tissue of model rats

[0154]

[0155] Note: Compared with the model control group, * indicates P < 0.05; ** indicates P < 0.01.

[0156] 2.3.6 Effects on SOD and MDA in prostate tissue of rats with prostatitis

[0157] From the results in Table 9, we can see 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 gel, 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 gel group was significantly higher than that in the model control group, which was statistically significant.

[0158] Table 9 Effects on SOD and MDA in prostate tissue of model rats

[0159]

[0160] Note: Compared with the model control group, * indicates P < 0.05; ** indicates P < 0.01.

[0161] 2.3.7 Effect on prostate histopathology in rats with prostatitis

[0162] From the results in Table 10, it can be seen that the gross morphological examination, i.e., light microscopy, HE staining and light microscopy observation (see Figure 4 ), the blank control group had normal prostate tissue structure, normal glandular arrangement and distribution, and no inflammatory cell infiltration was observed in the interstitium.

[0163] Model control group: Part of the prostate gland was destroyed, large areas of the prostate interstitial edema with a large number of chronic inflammatory cell infiltration, a large number of neutrophil infiltration in the alveoli, a small number of glandular cavities with secretions, interstitial tissue widened, the interstitium was filled with a large number of diffuse lymphocytes and monocytes.

[0164] 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. Especially in the high-dose group compared with the model group, the lymphocyte infiltration in the interstitium was significantly reduced, especially in the high-dose group.

[0165] Table 10 Effects on prostate weight and index of model rats

[0166]

[0167] Note: Compared with the model control group, * indicates P < 0.05; ** indicates P < 0.01.

Claims

1. A topical gel for treating prostatitis, characterized in that: The medicinal effective components are calculated by weight: 100-320 parts of white pepper, 100-320 parts of asarum, 15-45 parts of tuckahoe, 5-30 parts of borneol and 5-30 parts of menthol.

2. The external gel for treating prostatitis according to claim 1, characterized in that: The medicinal effective components are calculated by weight: 150-270 parts of white pepper, 150-270 parts of asarum, 20-40 parts of tuckahoe, 8-20 parts of borneol and 8-20 parts of menthol.

3. The external gel for treating prostatitis according to claim 1 or 2, characterized in that: The medicinal effective ingredients are calculated by weight: 210 parts of white pepper, 210 parts of asarum, 30 parts of tuckahoe, 10 parts of borneol and 10 parts of menthol.

4. A method for preparing a topical gel for treating prostatitis as described in claims 1-3, characterized in that: The preparation method of the external gel is carried out according to the following steps: (1) Weigh 100-320 g of white pepper, 100-320 g of asarum and 15-45 g of poria, grind into coarse powder, mix evenly, add 65-85% ethanol solution and soak for 14-18 h, the ratio of the total amount of medicinal materials to 75% ethanol is 1 g: 10-30 mL, heat to 40-60° C. and reflux for 1-3 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an extract without residue, and concentrate under normal pressure to an extract with a relative density of 1.10-1.40 at 25° C. to obtain an extract; (2) Add 5-15 mL of 0.5% potassium sorbate to the extract and mix well, then add 5-15 g of Carbomer 940 and mix well to obtain an aqueous phase; (3) Take 5-30 g of borneol and 5-30 g of menthol, grind and mix them, then add 3-7 mL of Tween 80 and 3-7 mL of propylene glycol and mix well to obtain an oil phase; (4) Slowly add the aqueous phase into the oil phase, stirring continuously in the same direction, and at the same time, dropwise add triethanolamine to adjust the pH value to 5-7 until condensation occurs to obtain a gel.

5. The method for preparing the external gel for treating prostatitis as claimed in claim 4, characterized in that: The preparation method of the external gel is carried out according to the following steps: (1) Weigh 150-270 g of white pepper, 150-270 g of asarum and 20-40 g of poria, grind into coarse powder, mix evenly, add 70-80% ethanol solution and soak for 15-17 h, the ratio of the total amount of medicinal materials to 75% ethanol is 1 g: 15-25 mL, heat to 45-55° C. and reflux for 1.5-2.5 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an extract without residue, and concentrate at normal pressure to an extract with a relative density of 1.15-1.35 at 25° C., thereby obtaining an extract; (2) Take the extract, add 8-12 mL of 0.5% potassium sorbate, mix well, then add 8-12 g of Carbomer 940, mix well, and obtain an aqueous phase; (3) Take 8-20 g of borneol and 8-20 g of menthol, grind and mix them, then add 4-6 mL of Tween 80 and 4-6 mL of propylene glycol and mix well to obtain an oil phase; (4) Slowly add the aqueous phase into the oil phase, keep stirring in the same direction, and at the same time, dropwise add triethanolamine to adjust the pH value to 5.5-6.5 until condensation occurs to obtain a gel.

6. The method for preparing the external gel for treating prostatitis according to claim 5, characterized in that: The preparation method of the external gel is carried out according to the following steps: (1) Weigh 210 g of white pepper, 210 g of asarum and 30 g of Poria, grind them into coarse powder, mix them evenly, add 75% ethanol solution and soak for 16 h, the ratio of the total amount of medicinal materials to 75% ethanol is 1 g:20 mL, heat to 50° C. and reflux for 2 h, cool to obtain an extract, filter the extract, filter out the residue to obtain an extract without residue, and concentrate at normal pressure to an extract with a relative density of 1.20-1.30 at 25° C. to obtain an extract; (2) Add 10 mL of 0.5% potassium sorbate to the extract and mix well, then add 10 g of Carbomer 940 and mix well to obtain an aqueous phase; (3) Take 10 g of borneol and 10 g of menthol, grind and mix them, then add 5 mL of Tween 80 and 5 mL of propylene glycol and mix well to obtain an oil phase; (4) Slowly add the aqueous phase into the oil phase, stirring continuously in the same direction, and at the same time, dropwise add triethanolamine to adjust the pH value to 6 until condensation occurs to obtain a gel.

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