Rectum in-situ heating gel for treating chronic prostatitis and preparation method and application thereof

Abstract

The invention provides a rectum in-situ heating gel for treating chronic prostatitis, which is prepared by taking a water extract of wild chrysanthemum as an active ingredient and adding a gel auxiliary material, and the dosage percentage content of the dry powder of the wild chrysanthemum extract and the auxiliary material is as follows: 8% of the wild chrysanthemum extract, 0.3%-1.5% of a matrix material, 70%-80% of a heating material and the balance of pure water. The invention further provides a preparation method and application of the rectum in-situ heating gel. According to the present invention, the problems of inconvenient operation, difficult drug positioning, easy leakage, heat effect loss and the like in the clinical application of the wild chrysanthemum suppository are solved, the combination scheme based on the phase change microemulsion (PCME) and the gel carrier is provided based on the special rectal HGVB prostate drug delivery path, and the innovative rectal in-situ heating gel is developed, the medicine can be delivered to diseased tissues, so that the treatment effect is remarkably improved.

Description

Technical Field

[0001] The invention relates to a rectal in situ heating gel for treating chronic prostatitis and a preparation method and application thereof, belonging to the field of pharmaceutical preparations. Background Art

[0002] Chronic prostatitis (CP) is a common disease in adult men. Epidemiological surveys show that the prevalence of prostatitis in adult men in my country has reached 11.2%. Autopsy results show that the pathological incidence is 24.3%, which often causes frequent urination, urgency, pelvic pain, and sexual dysfunction, seriously affecting the quality of life of patients. Modern medicine mainly uses α-receptor blockers, antibiotics, and nonsteroidal anti-inflammatory drugs for symptomatic treatment, but their effectiveness is still controversial. In addition, the commonly used oral, intramuscular, and intravenous administration methods make it difficult for drugs to be enriched in prostate tissue and prostate fluid to reach effective concentrations, resulting in unsatisfactory efficacy and a lingering course of disease that is difficult to cure. To solve this problem, there are reports of using prostate injection for administration, but there are complications such as fibrosis, tissue adhesion, hematuria, infection, and pain caused by puncturing the capsule. Therefore, modern medicine still lacks definite and effective means to treat prostatitis. Low tissue drug concentration is an important reason. There is an urgent need for innovative drug strategies to improve the distribution of drugs in prostate tissue and the therapeutic effect.

[0003] The method of guiding is a traditional external treatment in traditional Chinese medicine. The Yellow Emperor's Classic of Internal Medicine states that "it can be guided downward". Zhang Zhongjing invented honey decoction and pig bile anus. The Compendium of Materia Medica calls guiding drugs suppositories and suppositories, and includes enema and embolism. They are used for stranguria, constipation, leucorrhea and other lower-jiao diseases. The drugs directly reach the affected area and have the outstanding characteristics of rapid onset and significant effects. Rectal administration can partially avoid the first-pass effect of the liver to improve the bioavailability of drugs. Modern studies have found that there are 2 to 6 hemorrhoidal genital venous branches (HGVB) with an outer diameter of about 2.2 mm between the venous plexus in the posterolateral area of ​​the prostate and the rectal venous plexus, which can transport the venous blood refluxed from the rectum to the prostate tissue, indicating that drugs can be transported to the prostate tissue through the rectal veins in a very short transportation distance and quickly reach the prostate tissue.

[0004] Wild chrysanthemum is the dried inflorescence of Chrysanthemumindicum L., a plant of the Asteraceae family. It is picked when the flowers first bloom in autumn and winter, and then dried in the sun or steamed and then dried in the sun. It tastes bitter and is slightly cold in nature. It enters the liver and heart meridians. It has the effects of clearing away heat and detoxifying, purging fire and calming the liver. It is used to treat carbuncles, ulcers, eczema, cervicitis, prostatitis, anal sinusitis, hypertension, etc. The 2020 edition of the Chinese Pharmacopoeia contains wild chrysanthemum suppositories, which are prepared by extracting wild chrysanthemums with water and precipitating them with alcohol. Indications: antibacterial and anti-inflammatory. Used for diseases such as prostatitis and chronic pelvic inflammatory disease.

[0005] There are reports about the side effects of wild chrysanthemum suppositories, such as common side effects including diarrhea, dysmenorrhea and allergies. Since wild chrysanthemum suppositories are slightly cold in nature, long-term use by women may cause dysmenorrhea. In addition, if the patient's immunity is too low, the local skin may be irritated after taking the medicine, resulting in allergic symptoms such as skin itching or peeling. In addition, wild chrysanthemum suppositories are easy to deform above 30°C, but it does not affect the efficacy. The suppositories can be cooled before use. In terms of drug absorption, due to the special pathological site of prostatitis, there is a prostate barrier that limits the penetration of drugs into the prostate tissue. There are literature reports on the use of compound sulfamethoxazole combined with wild chrysanthemum suppositories to treat chronic prostatitis (Song Yandong, Observation on the efficacy of wild chrysanthemum suppositories in the treatment of chronic prostatitis, Jilin Traditional Chinese Medicine, Volume 25, Issue 2, February 2005).

[0006] Suppositories are a type of dosage form for rectal administration. They are a treatment method that avoids the "first-pass effect" of the liver and utilizes the characteristics of the rectal venous plexus to facilitate the intestinal mucosa to fully absorb the drug, thereby maintaining a high effective drug concentration in the prostate fluid bed. Rectal administration still has selectivity for drugs, and not all drugs can be effectively absorbed through the rectal mucosa and penetrate the prostate barrier. Literature reports that drugs with good fat solubility, weak alkalinity, and low plasma protein binding rate, such as quinolones and macrolides, are selected. In addition, the absorption capacity of the rectal mucosa may be limited, which may affect the bioavailability and therapeutic effect of the drug. Even if the drug can be absorbed through the rectal mucosa, its distribution in the prostate may be uneven. Rectal administration can also cause discomfort to patients and affect their compliance.

[0007] In order to improve the absorption capacity of the rectal mucosa, the methods reported so far include optimizing the properties of drugs, such as selecting drugs with a higher oil-water partition coefficient (log P) and a smaller molecular weight, which helps the drugs to be quickly absorbed through the rectal mucosa. Lipid-soluble drugs are more easily absorbed than water-soluble drugs, and molecular drugs are more easily absorbed than ionic drugs; improving the solubility of drugs, such as by reducing the particle size, forming salts, using surfactants, or encapsulating them into nanoparticles to increase the hydrophilicity and lipophilicity of the drugs, thereby increasing the dissolution and absorption rate; adding absorption enhancers, such as salicylates, 5-methoxysalicylic acid, surfactants, nonsteroidal anti-inflammatory drugs, bile salts, fatty acids, etc., which can increase cell membrane permeability or absorption through the paracellular pathway, and combining the use of surfactants with new technologies such as liposome nanoparticles, self-microemulsification drug delivery systems, nanomicelles, microcapsules, etc., to improve drug bioavailability and reduce mucosal irritation. The choice of which method to improve the absorption capacity of the rectal mucosa is determined by the properties of the drug. Summary of the invention

[0008] In order to overcome the technical problems existing in the current wild chrysanthemum suppositories, the present invention provides a rectal in situ heating gel for treating chronic prostatitis, and also provides a preparation method and use of the gel.

[0009] The present invention provides a rectal in situ heating gel for treating chronic prostatitis, which is prepared by taking a water extract of wild chrysanthemum as an active ingredient and adding a gel auxiliary material, wherein the percentage content of the wild chrysanthemum extract dry powder and the auxiliary material is:

[0010] Wild chrysanthemum extract 8%, matrix material 0.3% to 1.5%, heating material 70% to 80%, and the rest is pure water;

[0011] Each gram of wild chrysanthemum extract contains 10-15g of the original drug;

[0012] The matrix material is one or a mixture of two or more of carbomer 940, poloxamer 407, sodium alginate, and sodium carboxymethyl cellulose;

[0013] The heating material is one or a mixture of two or more of paraffin, lauric acid, and n-docosane phase change microemulsion PCME.

[0014] Further preferably, the percentage content of wild chrysanthemum extract dry powder and auxiliary materials is:

[0015] Wild chrysanthemum extract 8%, matrix material 0.6% to 1.4%, heating material 73% to 78%, and the rest is pure water;

[0016] The matrix material is sodium carboxymethyl cellulose; the heating material is n-docosane phase change microemulsion.

[0017] More preferably, the percentage content of wild chrysanthemum extract dry powder and auxiliary materials is:

[0018] Wild chrysanthemum extract 8%, matrix material 1.2%, heat-generating material 75.54%, and the rest is pure water.

[0019] Wherein, the n-docosane phase change microemulsion is obtained by emulsifying n-docosane with an emulsifier solution;

[0020] The emulsifier is one or a mixture of two or more of polyethylene glycol-600 (PEG-600), polyvinyl alcohol-1788 (PVA1788), and methylcellulose (MC);

[0021] The weight ratio of the emulsifier to n-docosane is 3:10;

[0022] The weight ratio of the core material of the heating material, n-docosane, to the phase change microemulsion is 2:5, wherein the microemulsion formula contains 10 parts of n-docosane, 3 parts of emulsifier, and 12 parts of water.

[0023] The present invention also provides a method for preparing the rectal in situ heating gel for treating chronic prostatitis, which comprises the following steps:

[0024] a. Weigh the raw materials of each weight ratio;

[0025] b. Dissolve the wild chrysanthemum extract powder in water;

[0026] c. Add the matrix material to the solution of step b, stir, and place at a low temperature not exceeding 4° C. until it is completely swollen;

[0027] d. Add the heating material to the solution in step c and grind evenly to obtain the rectal in situ heating gel.

[0028] The heating material is a n-docosane phase change microemulsion, which is obtained by emulsifying n-docosane with an emulsifier solution; the emulsifier is polyethylene glycol-600 (PEG-600) and polyvinyl alcohol-1788 (PVA1788), and the emulsification parameters are: the initial emulsification rate is 400rpm and the homogenization emulsification rate is 12000rpm.

[0029] The present invention also provides the use of the rectal in-situ heating gel in preparing a drug for rectal administration to treat chronic prostatitis.

[0030] The local thermal therapy effect of the rectal in situ heating gel of the present invention can improve the vascular permeability of the part, promote local blood circulation, relieve pelvic floor muscle spasms, accelerate metabolism, and enhance the drug delivery capacity of the channel.

[0031] The drug of the present invention solves the problems of inconvenient operation, difficult drug positioning, easy leakage, lack of thermal effect, etc. of wild chrysanthemum suppositories in clinical applications, while separate thermal therapy requires the use of corresponding equipment, which is inconvenient for clinical treatment. The present invention combines drug therapy with thermal therapy, and proposes a combination scheme based on phase change microemulsion (PCME) and gel carrier based on the special HGVB prostate drug delivery pathway of the rectum, and develops an innovative rectal in situ heating gel, which enables the drug to be delivered to the diseased tissue to significantly improve the treatment effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 Temperature control curves, DSC curves, water separation rate and particle size of n-docosane emulsions with different prescriptions (where A is the temperature control curve; B is the DSC curve; C is the water separation rate; D is the particle size diagram);

[0033] Figure 2 Flow chart of the preparation of the heating material in the wild chrysanthemum rectal in situ heating gel;

[0034] Figure 3 In vitro release diagram of active ingredients (where A is the in vitro release result of montanol, and B is the in vitro release result of chlorogenic acid);

[0035] Figure 4Results of effective ingredients permeating through the membrane;

[0036] Figure 5 Results of rectal pathology examination (among which: a, b, c are rectal tissue sections of the blank group, normal saline group and experimental group 14 days after administration; d, e, f are rectal tissue sections of the blank group, normal saline group and experimental group 7 days after drug withdrawal);

[0037] Figure 6 Prostate tissue pathology test results (where: a, b, c are prostate tissue sections of the blank group, normal saline group and experimental group 14 days after administration; d, e, f are prostate tissue sections of the blank group, normal saline group and experimental group 7 days after drug withdrawal);

[0038] Figure 7 Active ingredient prostate tissue drug concentration-time curve (wherein: A is the prostate tissue drug concentration-time curve of lignoside, B is the prostate tissue drug concentration-time curve of chlorogenic acid, C is the plasma drug concentration-time curve of lignoside, and D is the plasma drug concentration-time curve of chlorogenic acid);

[0039] Figure 8 Pharmacodynamic experimental results (wherein: A is the COX-2 content in prostate tissue, B is the TNF-α content in prostate tissue, C is the IL-6 content in prostate tissue, and D is the prostate index). DETAILED DESCRIPTION

[0040] Example 1: Preparation of the wild chrysanthemum rectal in situ heating gel of the present invention

[0041] Prescription (based on 100g of finished gel)

[0042] Wild chrysanthemum extract 8g

[0043] Sodium carboxymethyl cellulose (base material) 1.2g

[0044] n-Docosane phase change microemulsion (heat-generating material) 75.54g

[0045] The rest is pure water.

[0046] Preparation process:

[0047] a. Weigh the raw materials according to the above ratio;

[0048] b. Wild chrysanthemum extract is dissolved in water;

[0049] c. Add the matrix material to the solution of step b, stir it slightly, and place it at a low temperature not exceeding 4°C until it is completely swollen;

[0050] d. Add the heating material to the solution in step c and grind evenly.

[0051] Example 2 Preparation of the heating material n-docosane phase change microemulsion in the wild chrysanthemum rectal in situ heating gel of the present invention

[0052] Taking the key parameters of optical microscopic characteristics, particle size, temperature control performance, thermodynamic properties and repeated heating stability as indicators, single-factor experiments were used to investigate factors such as emulsifier type, emulsifier ratio, emulsifier dosage, n-docosane dosage and homogenization emulsification rate. Finally, a process for preparing heat-generating materials that best meets the gel requirements was proposed.

[0053] The ratio of the key factors PVA1788 and PEG-600 is examined as follows:

[0054] Five phase change emulsion samples with a n-docosane mass fraction of 30% were prepared under the conditions of a composite emulsifier dosage of 30% of n-docosane, an emulsification temperature of 85°C, a homogenization emulsification rate of 12000rpm, an emulsification time of 5min, and a mass ratio of PVA1788 to PEG-600 of 3:7, 4:6, 5:5, 6:4 and 7:3, respectively; the particle size, temperature control performance, thermodynamic properties and repeated heating stability were characterized and analyzed, and the results are as follows Figure 1 As shown in the figure, according to the results, the optimal ratio of PVA1788 and PEG-600 is 6:4. However, when the ratio of PVA1788 and PEG-600 is increased to 6:4, the fluidity is poor and the viscosity is high, which does not meet the requirements of subsequent gel preparation. Considering the particle size, viscosity, stability and thermal properties of the n-docosane phase change emulsion, the mass ratio of PVA 1788 and PEG-600 is finally selected as 5:5.

[0055] The best preparation process of the heat-generating material of the present invention is:

[0056] PVA1788 and PEG-600 were selected as composite emulsifiers, the ratio of PVA1788 to PEG-600 was 5:5, the amount of composite emulsifier was 30% of the mass of n-docosane, the proportion of n-docosane was 40% of the total mass of phase change microemulsion, the initial emulsification rate was 400 rpm, and the homogenization emulsification rate was 12000 rpm;

[0057] The obtained n-docosane phase change emulsion has no supercooling phenomenon, clear composition, suitable particle size, phase change temperature of 42.94℃~43.57℃, phase change latent heat of 98.43J / g~100.41J / g, and can effectively control the temperature for about 30min.

[0058] Preparation flow chart see Figure 2 .

[0059] Example 3 Evaluation of the effect of different amounts of auxiliary materials on the quality of heating gel

[0060] Fourteen wild chrysanthemum rectal in situ heating gel experimental groups were set up, with wild chrysanthemum extract, sodium carboxymethyl cellulose (CMCNa) and n-docosane phase change microemulsion (PCME) as raw materials and auxiliary materials;

[0061] The content of the main drug wild chrysanthemum extract is 8g / 100g, and the heating gel is prepared according to the amount of auxiliary materials in Table 1;

[0062] Specifically, take pure water, add the corresponding amount of each component into it, and add wild chrysanthemum extract and sodium carboxymethyl cellulose in the order of addition. The subsequent components can be added only after the drug is dissolved, and placed at 4°C until it is completely swollen. Finally, add the heating material and grind it evenly. Measure the tensile stress, shear stress and temperature control time of each experimental group.

[0063] Table 1: Determination results of indexes of wild chrysanthemum rectal in situ heating gel prepared according to different amounts of excipients

[0064]

[0065]

[0066] The results showed that the AHP-CRITIC comprehensive weighted method was used to process the experimental data, calculate the comprehensive score, and import it into the Design-Expert 11 software. The mass concentrations of CMCNa (A) and PCME (B) in the prescription were used as independent variables, and the comprehensive scores of tensile stress, shear stress and temperature control time were used as dependent variables. The mathematical model obtained by analysis was as follows:

[0067] Z=87.92-6.56A-12.81B-8.05AB-4.42A^2-9.24B^2,r 2 =0.9608, P<0.001.

[0068] By r 2 The results of the P value show that the model fits well. The optimized formula is calculated to be PCME75.54% and CMCNa1.20%.

[0069] The beneficial effects of the present invention are demonstrated by specific performance tests and efficacy tests.

[0070] Test Example 1 In vitro performance test of the wild chrysanthemum rectal in situ heating gel of the present invention

[0071] 1. In vitro release results of wild chrysanthemum heating gel and wild chrysanthemum suppository

[0072] The in vitro release results of wild chrysanthemum rectal in situ heating gel and wild chrysanthemum suppository (commercially available, Hubei Dongxin Pharmaceutical Co., Ltd., 20230315) are shown in Table 2, Table 3, Figure 3As shown, the results show that the cumulative release rate of montenoside from the wild chrysanthemum rectal in situ heating gel is 69.20% and the cumulative release rate of chlorogenic acid is 93.70% within 12 hours; the cumulative release rate of montenoside from the wild chrysanthemum suppository is 63.72% and the cumulative release rate of chlorogenic acid is 92.98% within 12 hours.

[0073] Table 2: Cumulative release percentage of montanol ( n=3)

[0074]

[0075]

[0076] Table 3 Cumulative release percentage of chlorogenic acid ( n=3)

[0077]

[0078] 2. Results of rectal retention study

[0079] The retention of the wild chrysanthemum rectal in situ heating gel is shown in Table 4, indicating that the wild chrysanthemum rectal in situ heating gel can be retained in the rat body for about 6 hours, with good rectal retention performance, and subsequent performance studies such as membrane permeability, fever and temperature control, irritation and tissue pharmacokinetics can be carried out.

[0080] Table 4 Retention of different preparations in rats ( n=6)

[0081]

[0082] Note: * indicates significant difference compared with the suppository group.

[0083] 3. Results of membrane permeability test

[0084] The results of the membrane permeability test are shown in Table 5. Figure 4 As shown, about 69% of mongosides can be penetrated after 12 hours, and more than 90% of chlorogenic acid can be penetrated, indicating that the wild chrysanthemum rectal in situ heating gel can effectively penetrate the rectal membrane. Therefore, it is speculated that the active ingredients of wild chrysanthemum can reach the prostate tissue through rectal administration.

[0085] Table 5 Percent release through the membrane results ( n=6)

[0086]

[0087]

[0088] 5. Results of irritation test

[0089] The rectum and prostate tissues of each group were observed with the naked eye after continuous administration for 14 days and 7 days after drug withdrawal. No congestion or edema was found, and no obvious deformation or necrosis was found. The score summary table is shown in Table 6 and Table 7. The experimental results show that it is mildly irritating to the rectum and non-irritating to the prostate. The pathological test results are as follows Figure 5 , Figure 6 As shown in the figure, the rectal mucosa of the blank group was intact, the glandular structure was clear, and there was no inflammatory cell infiltration. However, after 14 days of administration in the saline group and the experimental group, the intestinal tissue structure was clear, the mucosal epithelial structure was intact, and it was a single-layer columnar epithelium. The cell morphology and structure were normal. The number of intestinal glands in the lamina propria was abundant, and many goblet cells were visible. The local intestinal glands were arranged irregularly. Multiple lymph nodes were seen in the lamina propria and submucosal layer, and a small amount of vascular congestion was seen in the submucosal layer. The muscular layer was stained evenly, and the morphology and structure of the muscle fibers were normal and arranged regularly. There was improvement after 7 days of drug withdrawal. The prostate and glandular cavity structures of the blank group, saline group, and experimental group were intact, and there was no glandular cavity atrophy or inflammatory cell infiltration, and no obvious pathological changes were caused.

[0090] Table 6 Summary of rectal mucosal irritation scoring results ( n=6)

[0091]

[0092] Table 7 Summary of prostate irritation scoring results ( n=6)

[0093]

[0094] Test Example 2 Performance evaluation of wild chrysanthemum rectal in situ heating gel Prostate targeted drug delivery effect evaluation Tissue pharmacokinetics study results:

[0095] The drug concentration-time curves of chlorogenic acid and chlorogenic acid in prostate tissue are shown in Figure 2. Figure 7As shown in Table 4 and Table 5, the main pharmacokinetic parameters are shown. For the poorly soluble active ingredient, lignoside, the prostate targeting efficiency (Te) of the heating gel group reached 6.58, which was much higher than 2.01 of the gel group and 4.23 of the suppository group. Taking the suppository as the control, the relative uptake rate (Re) of lignoside in the prostate tissue of the heating gel group was 2.53, and the prostate peak concentration ratio (Ce) was 2.55, which were significantly higher than the conventional gel group without heating effect. For another effective ingredient, chlorogenic acid, the prostate targeting efficiency (Te) of the heating gel group was 2.62, which was higher than 2.22 of the gel group and 1.06 of the suppository group. Relative to the suppository, the relative uptake rate (Re) of chlorogenic acid in the prostate tissue of the heating gel group was 2.32, and the prostate peak concentration ratio (Ce) was 1.73, which were higher than the conventional gel group. On the other hand, the prostate tissue Tmax of lignoside and chlorogenic acid in the heating gel was less than that of the suppository group, showing a faster absorption and distribution speed. The experimental results show that the rectal in situ heating gel prepared by combining the gel dosage form carrier and phase change microemulsion significantly improves the prostate distribution targeting of the active ingredients in the wild chrysanthemum extract.

[0096] Table 7 Main pharmacokinetic parameters and targeting parameters of different dosage forms of mongoside (n=6)

[0097]

[0098] Table 8 Main pharmacokinetic parameters and targeting parameter results of chlorogenic acid in different dosage forms (n=6)

[0099]

[0100] Test Example 3 Performance evaluation and pharmacodynamic effect evaluation of wild chrysanthemum rectal in situ heating gel

[0101] Pharmacodynamic results:

[0102] The experimental results are shown in Table 9. Figure 8 As shown in the results, in the comparison of the contents of inflammatory factors COX-2, TNF-α, IL-6 and the prostate index, there were extremely significant differences between the model group and the blank control group, proving that the prostatitis model was successfully established; compared with the model group, the contents of inflammatory factors COX-2, TNF-α, IL-6 and the prostate index in the wild chrysanthemum suppository group and the wild chrysanthemum fever gel group were decreased, and the differences were significant, and the contents of inflammatory factors COX-2, TNF-α, IL-6 in the wild chrysanthemum fever gel group were significantly lower than those in the wild chrysanthemum suppository group, and the differences were significant; the prostate index of the wild chrysanthemum gel group was lower, indicating that the wild chrysanthemum fever gel showed obvious therapeutic advantages in inhibiting the expression of inflammatory factors and reducing the prostate index.

[0103] Table 9 Comparison of inflammatory factor contents and prostate index in prostate tissues of each group

[0104]

[0105] Note: Compared with the blank control group, *P<0.05, **P<0.01; compared with the model group, #P<0.05, ##P<0.01; compared with the positive control group, ▲P<0.05, ▲▲P<0.01.

Claims

1. A rectal in situ heating gel for treating chronic prostatitis, characterized in that: The invention is prepared by taking the water extract of wild chrysanthemum as the active ingredient and adding gel excipients, wherein the percentage content of the wild chrysanthemum extract dry powder and the excipients is: Wild chrysanthemum extract 8%, matrix material 0.3% to 1.5%, heating material 70% to 80%, and the rest is pure water; Each gram of wild chrysanthemum extract contains 10-15g of the original drug; The matrix material is one or a mixture of two or more of carbomer 940, poloxamer 407, sodium alginate, and sodium carboxymethyl cellulose; The heating material is one or a mixture of two or more of paraffin, lauric acid, and n-docosane phase change microemulsion PCME.

2. The rectal in situ heating gel for treating chronic prostatitis according to claim 1, characterized in that: The percentage content of wild chrysanthemum extract dry powder and auxiliary materials is: Wild chrysanthemum extract 8%, matrix material 0.6% to 1.4%, heating material 73% to 78%, and the rest is pure water; Each gram of the wild chrysanthemum extract contains 12.5 grams of the original drug; The matrix material is sodium carboxymethyl cellulose; the heating material is n-docosane phase change microemulsion.

3. The rectal in situ heating gel for treating chronic prostatitis according to claim 2, characterized in that: The percentage content of wild chrysanthemum extract dry powder and auxiliary materials is: Wild chrysanthemum extract 8%, matrix material 1.2%, heat-generating material 75.54%, and the rest is pure water.

4. The rectal in situ heating gel for treating chronic prostatitis according to any one of claims 1 to 3, characterized in that: The n-docosane phase change microemulsion is obtained by emulsifying n-docosane with an emulsifier solution; The emulsifier is one or a mixture of two or more of polyethylene glycol-600 (PEG-600), polyvinyl alcohol-1788 (PVA1788), and methylcellulose (MC); The weight ratio of the emulsifier to n-docosane is 3:10; The weight ratio of the core material of the heating material n-docosane to the phase change microemulsion is 2:

5.

5. The rectal in situ heating gel for treating chronic prostatitis according to claim 4, characterized in that: The emulsifiers are PVA1788 and PEG-600, and the weight ratio is 5:

5.

6. A method for preparing the rectal in situ heating gel for treating chronic prostatitis according to any one of claims 1 to 5, characterized in that: It includes the following steps: a. Weigh the raw materials of each weight ratio; b. Dissolve the wild chrysanthemum extract powder in water; c. Add the matrix material to the solution of step b, stir, and place at a low temperature not exceeding 4° C. until it is completely swollen; d. Add the heating material to the solution in step c and grind evenly to obtain the rectal in situ heating gel.

7. The method for preparing the rectal in situ heating gel for treating chronic prostatitis according to claim 6, characterized in that: The heating material is a n-docosane phase change microemulsion, which is obtained by emulsifying n-docosane with an emulsifier solution; the emulsifier is polyethylene glycol-600 (PEG-600) and polyvinyl alcohol-1788 (PVA1788), and the emulsification parameters are: the initial emulsification rate is 400rpm and the homogenization emulsification rate is 12000rpm.

8. Use of the rectal in situ heating gel according to any one of claims 1 to 5 in the preparation of a drug for rectal administration to treat chronic prostatitis.

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