Hemorrhoids ointment and preparation method thereof

Abstract

The invention discloses a hemorrhoid ointment and a preparation method, and relates to the technical field of hemorrhoid ointment preparation. The ointment is prepared from the following raw materials in parts by weight: 20 to 30 parts of rhizoma coptidis, 20 to 30 parts of cortex phellodendri, 15 to 25 parts of radix sophorae flavescentis, 15 to 25 parts of radix sanguisorbae, 8 to 12 parts of dragon's blood, 10 to 15 parts of radix notoginseng, 5 to 10 parts of chitosan, 3 to 6 parts of borneol, 8 to 12 parts of radix arnebiae seu lithospermi, 5 to 8 parts of alum, 120 to 180 parts of sesame oil, 10 to 20 parts of polyethylene glycol 400, 6 to 10 parts of herba portulacae extract, 5 to 9 parts of rhizoma bletillae extract, 4 to 8 parts of herba agrimoniae extract and 3 to 6 parts of calamine. The traditional Chinese medicine extract is a mixed product extracted from coptis chinensis, golden cypress and the like through ultrasonic-reflux combination, chitosan and tannin form a slow-release carrier, the medicine effect is prolonged, and all the components synergistically strengthen the anti-inflammatory, hemostasis and repair effects. The haemorrhoids cream has the advantages of multi-target synergism, full release of effective components through an optimized process, lasting efficacy, excellent effects of diminishing inflammation, stopping bleeding and repairing wounds, low mucous membrane irritation, good biocompatibility, stable storage, adaptation to various haemorrhoids, effective compensation for the shortages of traditional products, and high application value.

Description

Technical Field

[0001] This invention relates to the field of hemorrhoid ointment preparation technology, specifically to a hemorrhoid ointment and its preparation method. Background Technology

[0002] Hemorrhoids, a common anorectal disease, are characterized by swelling, pain, and bleeding, severely impacting patients' quality of life. With changes in dietary habits and the prevalence of sedentary lifestyles, its incidence continues to rise, making treatment increasingly urgent. Currently, clinical treatment primarily focuses on conservative therapies, with topical hemorrhoid creams being the first choice due to their convenience and minimal invasiveness. However, existing products generally suffer from limitations such as single-effect drugs, short duration of action, high recurrence rates, and limited adaptability to different types of hemorrhoids, failing to meet the demands for highly effective clinical treatment.

[0003] The patent application document with patent publication number CN106236906A and patent name "A Hemorrhoid Ointment and Preparation Method" mentions the use of traditional Chinese medicines such as Coptis chinensis, Phellodendron chinense, and Sophora flavescens combined with sesame oil, which are then pulverized and boiled to prepare a hemorrhoid ointment. The ointment achieves anti-inflammatory and hemostatic effects through the synergistic effect of traditional Chinese medicines. However, this technology formula relies solely on traditional Chinese medicine combinations, has a relatively simple function, lacks specific components for the repair of hemorrhoid wounds, and does not construct a drug sustained-release system, resulting in a short duration of efficacy and poor effect on reducing swelling and dissipating nodules in thrombosed external hemorrhoids. At the same time, the preparation process only uses simple boiling, resulting in insufficient extraction of effective components from traditional Chinese medicines, making it difficult to release some fat-soluble components, affecting the therapeutic effect. Furthermore, the ointment has insufficient adhesion and is easily lost during defecation, reducing the utilization rate of the drug.

[0004] The patent application document with patent publication number CN104042646B and patent name "A hemorrhoid ointment and its preparation method" mentions using Patrinia scabiosifolia, which sprouts in spring, as the core raw material, combined with dandelion, prickly ash, etc., and cooking it in a cast iron pot to prepare hemorrhoid ointment, claiming that it can achieve radical cure of hemorrhoids. However, the raw materials of this technology depend on fresh Patrinia scabiosifolia in a specific season, which is limited in source and unstable in quality; the preparation process relies on high-temperature charring reaction to generate special products, and the process conditions are difficult to control precisely, which can easily lead to decomposition or deterioration of effective ingredients; the formula lacks wound repair and mucosal protection ingredients, which has limited effect on healing the damaged mucosa of hemorrhoids, and does not consider the problem of perianal mucosal irritation. Some patients may experience burning discomfort after use, and the recurrence rate control effect is not good.

[0005] The patent application document with patent publication number CN108186741B and patent name "A hemorrhoid ointment and its preparation method" mentions using sesame oil, beeswax, pepper, astragalus, etc. as raw materials, and extracting the effective ingredients at a controlled high temperature of 150-170℃ to prepare a hemorrhoid ointment with antibacterial and anti-inflammatory effects. However, the formula of this technology lacks the core hemostatic ingredient, and its effect on relieving bleeding symptoms of internal hemorrhoids is limited. The ointment relies solely on sesame oil to disperse the drug and does not add adhesive excipients, making it easy to fall off in the moist environment of the anus, and the duration of the drug effect is short. Moreover, the high-temperature extraction process may destroy the heat-sensitive effective ingredients in astragalus and angelica, reducing the drug activity. At the same time, the formula does not add corresponding ingredients targeting the thrombosis mechanism, resulting in poor comprehensive treatment effect on mixed hemorrhoids.

[0006] Furthermore, existing technologies generally suffer from common problems such as a lack of multi-target synergistic formulation design, low extraction efficiency of active ingredients, and insufficient stability and biocompatibility of the ointment. Some processes are complex or limited by seasonal raw material availability, making large-scale production difficult. Therefore, developing a new type of hemorrhoid ointment with a scientifically formulated, comprehensive, long-lasting, and safe formula suitable for various types of hemorrhoids is crucial to overcoming the shortcomings of existing technologies. Summary of the Invention

[0007] (a) Technical problems to be solved

[0008] In view of the shortcomings of existing hemorrhoid ointments, such as single formula, insufficient extraction of effective ingredients, short duration of efficacy, poor storage stability, strong mucosal irritation, and poor treatment effect on complex types such as mixed hemorrhoids, this invention provides a hemorrhoid ointment and its preparation method.

[0009] (II) Technical Solution

[0010] A hemorrhoid ointment is composed of the following ingredients in parts by weight: 20-30 parts Coptis chinensis, 20-30 parts Phellodendron chinense, 15-25 parts Sophora flavescens, 15-25 parts Sanguisorba officinalis, 8-12 parts Dragon's Blood, 10-15 parts Panax notoginseng, 5-10 parts Chitosan, 3-6 parts Borneol, 8-12 parts Lithospermum erythrorhizon, 5-8 parts Alum, 120-180 parts Sesame Oil, 10-20 parts Polyethylene Glycol 400, 6-10 parts Portulaca oleracea extract, 5-9 parts Bletilla striata extract, 4-8 parts Agrimonia pilosa extract, and 3-6 parts Calamine.

[0011] Among them, the Chinese herbal extract refers to the mixed extract containing berberine, berberine, matrine, sanguisorbin and lithospermum, obtained by ultrasonic extraction and reflux extraction of Coptis chinensis, Phellodendron chinense, Sophora flavescens, Sanguisorba officinalis and Lithospermum erythrorhizon. During the extraction process, the mass-volume ratio of solvent to raw material is 1:8-1:12, and the extraction temperature gradient is controlled at 50-60℃ for ultrasonic extraction and 70-80℃ for reflux extraction.

[0012] Chitosan undergoes a cross-linking reaction with tannins in traditional Chinese medicine extracts. Taking gallic acid (C7H6O5) as an example, the reaction molecular formula is: (C6H 11 NO4)n+nC7H6O5→[(C6H 10 NO4)C7H5O5]n+nH2O forms a stable sustained-release carrier structure, extending the duration of drug efficacy to 8-12 hours;

[0013] Purslane extract contains purslane polysaccharides and flavonoids; Bletilla striata extract contains glucomannan and Bletilla striata gum; Agrimonia pilosa extract contains agrimonin; and calamine contains zinc carbonate. These four ingredients work synergistically with the basic raw materials to enhance anti-inflammatory, repairing, hemostatic, and astringent effects, forming a multi-target treatment system.

[0014] Furthermore, it also includes 3-5 parts menthol, 2-4 parts vitamin E, and 1-3 parts sodium hyaluronate. Menthol can enhance the cooling and antipruritic effect and relieve the burning sensation around the anus. Its evaporation rate is regulated by vitamin E to prevent rapid loss. Sodium hyaluronate can improve the moisturizing properties and mucosal adhesion of the ointment, prolong the drug residence time, and form a synergistic effect with the sustained-release effect of chitosan to further optimize the drug release curve. Vitamin E can enhance the antioxidant properties of the ointment, delay the degradation of easily oxidized active ingredients such as berberine and shikonin, reduce the rate of ointment deterioration, and ensure the stability of the drug efficacy within the shelf life.

[0015] Furthermore, it also includes 6-10 parts of dandelion extract, 4-8 parts of prunella vulgaris extract, and 3-7 parts of angelica extract. Dandelion extract contains taraxasterol and inulin, while prunella vulgaris extract contains flavonoids and polyphenols. The two work synergistically to enhance the effects of clearing heat and detoxifying, reducing the intensity of hemorrhoid inflammation, and are particularly effective in reducing swelling and dissipating nodules in thrombosed external hemorrhoids. Angelica extract contains ferulic acid and angelica polysaccharides, which can improve local blood circulation around the anus and inhibit platelet aggregation. It complements the blood-activating and hemostatic effects of dragon's blood and Panax notoginseng, and is highly effective for symptoms of bleeding from internal hemorrhoids and congestion in mixed hemorrhoids.

[0016] Furthermore, the content of effective ingredients in the herbal extracts meets the following requirements: berberine ≥ 1.2%, berberine ≥ 0.8%, matrine ≥ 0.6%, sanguisorbin ≥ 3.0%, shikonin ≥ 0.3%, and agrimonyin ≥ 0.2%. The key physical properties of the ointment are: pH 5.5-7.5, which conforms to the physiological environment of the perianal mucosa; viscosity 10000-20000 mPa·s, ensuring that it is not easily lost after application; and centrifugal stability with no stratification or precipitation. This combination of content range and physical property parameters ensures the stable performance of the core efficacy of anti-inflammatory, hemostatic, and repairing effects, avoiding fluctuations in treatment effect due to insufficient effective ingredients or poor ointment stability.

[0017] Furthermore, the purslane extract was prepared using a water extraction-ethanol precipitation-column chromatography process: extraction temperature 70-80℃, extraction time 2-3 hours, the extract was concentrated to a relative density of 1.10-1.15, 95% ethanol was added to adjust the ethanol precipitation concentration to 70-85%, and the mixture was allowed to stand for 12-18 hours. After filtration, the precipitate was purified by D101 macroporous resin column chromatography with 30-50% ethanol solution as the eluent. The eluent was collected, concentrated, and dried, with the purslane polysaccharide content ≥30%. The Bletilla striata extract was prepared using a microwave-assisted enzymatic hydrolysis process: microwave power 200-300W, extraction... Extraction time is 15-25 minutes. After extraction, 0.5-1.0% cellulase is added, and enzymatic hydrolysis is carried out for 30-60 minutes at pH 4.5-5.5 and 50-55℃. After inactivation, the extract is filtered and concentrated, with a glucomannan content ≥25%. Agrimonia pilosa extract is prepared using a combination of ultrasonic and Soxhlet extraction: ultrasonic power 300-400W, extraction time 40-60 minutes, followed by Soxhlet extraction for 2-3 hours, with 70-80% ethanol as the solvent. The agrimony extract has an agrimonin content ≥0.2%, ensuring that the core active ingredients of each extract are fully enriched and exert a synergistic therapeutic effect.

[0018] Furthermore, all raw materials comply with the standards of Part I of the 2020 edition of the Pharmacopoeia of the People's Republic of China and meet the following quality control requirements: heavy metal limits (Pb ≤ 10 mg / kg, Cd ≤ 1 mg / kg, Hg ≤ 0.1 mg / kg); total pesticide residues ≤ 0.5 mg / kg; microbial limits meet the requirements for medical external preparations, with total bacterial count ≤ 10 CFU / g, total mold and yeast count ≤ 1 CFU / g, and no pathogenic bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli detected; in the skin irritation test, the average score of rabbit intact skin and broken skin after application at 24, 48, and 72 hours was ≤ 0.5; the sensitization test results showed no sensitization reaction, meeting the biocompatibility requirements for perianal mucosal contact preparations and ensuring medication safety.

[0019] Furthermore, a method for preparing a hemorrhoid ointment includes the following steps:

[0020] S1. Raw material pretreatment: Coptis chinensis, Phellodendron chinense, Sophora flavescens, Sanguisorba officinalis, and Lithospermum erythrorhizon are washed 3-5 times with deionized water to remove surface impurities and dust. They are then dried in an oven at 60-70℃ for 4-6 hours. After drying, they are mixed and pulverized, and passed through a 200-250 mesh sieve to obtain mixed powder with a particle size D90≤75μm. Dragon's blood and Panax notoginseng are pulverized separately and passed through a 250-300 mesh sieve with a particle size D90≤50μm for later use. Portulaca oleracea, Bletilla striata, Agrimonia pilosa, Taraxacum mongolicum, Prunella vulgaris, and Angelica sinensis are prepared into extracts according to their respective extraction processes. After vacuum drying, they are pulverized and passed through a 180 mesh sieve for later use. Calamine is pulverized and passed through a 300 mesh sieve with a particle size D90≤45μm for later use.

[0021] S2. Preparation of Traditional Chinese Medicine Extract: Add the mixed medicinal powder to sesame oil, stir evenly, and soak for 8-12 hours. During the soaking process, stir for 10-15 minutes every 2 hours to ensure that the medicinal powder is fully wetted. Then, use a combination of ultrasonic extraction and reflux extraction. First, extract with 300-400W ultrasonic power at 50-60℃ for 60-90 minutes, and then transfer to a reflux extraction device for reflux extraction at 70-80℃ for 2-3 hours. Stir once every 30 minutes during the extraction process. After extraction, filter with a plate and frame filter press at a filtration pressure of 0.2-0.3MPa and a filter membrane pore size of 0.45μm. Collect the filtrate to obtain a traditional Chinese medicine extract containing effective components such as berberine and berberine. Discard the residue. Test the extract to ensure that the content of effective components meets the standard specified in claim 4; otherwise, return to the extraction site for re-extraction.

[0022] S3. Cross-linking reaction preparation: Chitosan is added to the traditional Chinese medicine extract, stirred at a rate of 100-150 r / min, heated to 70-80℃, and stirred for 2-3 hours to allow the chitosan to cross-link with the tannins in the traditional Chinese medicine extract to form a sustained-release matrix; nitrogen gas is introduced during the reaction for protection, with a flow rate of 20-30 mL / min, to prevent the effective components of the traditional Chinese medicine from being oxidized and destroyed at high temperatures; the reaction endpoint is judged by: taking a small amount of the reaction solution and dropping it onto a glass slide, drying it at room temperature to form a uniform film without obvious particulate matter; after the reaction, the solution is filtered once through an 80-100 mesh filter to remove unreacted solid particles;

[0023] S4. Mixing of excipients: Crush alum and add it to the above cross-linking reaction system. Continue stirring for 30-40 minutes to ensure the alum is completely dissolved. Then cool to 50-60℃ and add the following ingredients in sequence: dragon's blood powder, Panax notoginseng powder, polyethylene glycol 400, purslane extract, Bletilla striata extract, Agrimonia pilosa extract, calamine, dandelion extract, Prunella vulgaris extract, and Angelica sinensis extract. Stir for 20-30 minutes after adding one ingredient at a time to ensure that all components are fully mixed. Keep warm for 1-2 hours, stirring for 10 minutes every 30 minutes to maintain the homogeneity of the system.

[0024] S5. Low-temperature mixing: Cool the system to 35-45℃, add borneol, menthol, vitamin E, and sodium hyaluronate, increase the stirring speed to 180-220 r / min, and stir for 40-60 minutes to ensure that the borneol and menthol are completely dissolved and the system is uniform, smooth, and free of particles; control the ambient humidity to ≤60% during the mixing process to prevent moisture from entering the paste and affecting its stability; after mixing, use a colloid mill to grind for 15-20 minutes with a grinding gap of 0.05-0.1mm to further improve the smoothness and application smoothness of the paste;

[0025] S6. Molding and Packaging: The mixed ointment is naturally cooled to room temperature and subjected to multiple tests, including pH value, viscosity, active ingredient content, and microbial limits. After passing the tests, it is filled into disposable applicators using an aseptic filling machine, with 5-8g per applicator, and then sealed. After packaging, it is sterilized by cobalt-60 irradiation at a dose of 5-10kGy. After sterilization, microbial limits are checked again to ensure compliance with standards. The sterilized hemorrhoid ointment can be stored in an environment below 25℃ and with a relative humidity of ≤60% for up to 18 months.

[0026] Furthermore, the ultrasonic extraction process in S2 is performed in two stages. After the first extraction, the mixture is allowed to stand for 30 minutes to allow the powder to settle fully before a second ultrasonic extraction of 30 minutes. The two extracts are then combined. During the reflux extraction, a jacketed kettle is used for heating, with a temperature control accuracy of ±2℃ to avoid local overheating that could lead to the decomposition of active ingredients. The filtered herbal extract must be refrigerated at 4-8℃ for no more than 24 hours to ensure the smooth progress of subsequent cross-linking reactions. The residue generated during the extraction process is dried and disposed of according to medical waste regulations to avoid environmental pollution.

[0027] Furthermore, the stirring device for the crosslinking reaction in S3 adopts an anchor-type stirring paddle, and the stirring speed can be dynamically adjusted according to the viscosity of the system. When the initial viscosity is low, 100 r / min is used, and as the viscosity increases during the reaction, it is gradually increased to 150 r / min. The nitrogen purity is ≥99.9%, and it is dried and purified before being introduced to avoid introducing moisture and impurities. Vacuum filtration is used to assist the filtration after the reaction, with a filtration pressure of -0.06~-0.08 MPa to improve filtration efficiency and filtrate purity. During the grinding process of the colloid mill, the temperature of the paste is controlled not to exceed 45℃, and circulating water cooling is used to avoid the volatilization of camphor and degradation of active ingredients due to high temperature.

[0028] Furthermore, the specific methods for testing the ointment in S6 are as follows: pH value is measured using a precision pH meter; 5g of ointment is added to 45mL of deionized water, stirred evenly, and then measured; viscosity is measured using a rotational viscometer with rotor model N0.4, rotation speed 10r / min, and temperature 25℃; the content of active ingredients is determined using high performance liquid chromatography (HPLC), with berberine detection wavelength 265nm, mobile phase acetonitrile-0.05mol / L potassium dihydrogen phosphate solution (40:60), and flow rate 1.0mL / min; microbial limit testing is performed according to General Chapters 1105, 1106, and 1107 of Part IV of the 2020 edition of the Pharmacopoeia of the People's Republic of China; the filling accuracy error of the filling machine is ≤±2%; the administration device is made of low-density polyethylene and sterilized with ethylene oxide to ensure sterility of the device in contact with the ointment; the packaged hemorrhoid ointment is labeled with product name, specifications, batch number, production date, expiration date, and usage method, etc., for clinical use and quality traceability.

[0029] (iii) Beneficial technical effects

[0030] Compared with existing technologies, the beneficial effects of this invention are:

[0031] In terms of formulation design, this invention breaks through the traditional single-combination model of traditional Chinese medicine, innovatively introducing multiple functional ingredients such as dragon's blood extract, Panax notoginseng, Portulaca oleracea extract, and Bletilla striata extract, forming a multi-target synergistic system with traditional Chinese medicines such as Coptis chinensis and Phellodendron chinense. Each component acts on core pathological aspects such as inflammatory response, bleeding symptoms, thrombosis, and wound repair, achieving comprehensive therapeutic effects of anti-inflammatory, hemostatic, anti-swelling, and repairing, thus overcoming the shortcomings of existing products with single functions. Simultaneously, a sustained-release carrier is constructed through the cross-linking reaction of chitosan and tannins from traditional Chinese medicine, prolonging the duration of efficacy, preventing rapid drug loss, and improving therapeutic efficiency.

[0032] In terms of preparation technology, ultrasonic-reflux extraction combined with gradient temperature control is employed to significantly improve the extraction rate of effective components from traditional Chinese medicine, ensuring the full release of both fat-soluble and water-soluble components and solving the problem of insufficient extraction in traditional decoction processes. The application of cross-linking reactions and colloid milling optimizes the fineness and adhesion of the ointment, allowing it to adhere tightly to the mucosal surface even in the moist perianal environment, making it less susceptible to being washed away by defecation and improving drug utilization. The entire process has well-defined and stable parameters, is not limited by the season of raw materials, and is easy to scale up for production.

[0033] Regarding safety and adaptability, all raw materials comply with the standards of Part I of the 2020 edition of the Pharmacopoeia of the People's Republic of China, with strict control over heavy metal and pesticide residues. Skin irritation and sensitization tests have verified that the product exhibits extremely low irritation and excellent biocompatibility, making it suitable for various perianal mucosal conditions. The product demonstrates significant therapeutic effects on internal hemorrhoids, external hemorrhoids, and mixed hemorrhoids. It exhibits particularly excellent performance in reducing swelling and lumps in thrombosed external hemorrhoids, stopping bleeding and relieving pain in internal hemorrhoids, and providing comprehensive conditioning for mixed hemorrhoids, effectively reducing the recurrence rate and addressing the limited adaptability of existing products.

[0034] Furthermore, the ointment contains excipients such as sodium hyaluronate and vitamin E, which enhance its moisturizing and antioxidant properties, delay the degradation of active ingredients, and strengthen mucosal protection, further optimizing the treatment experience. Overall, this patented product boasts advantages such as comprehensive efficacy, long-lasting effects, high safety, wide applicability, and simple preparation, effectively addressing the shortcomings of existing technologies and providing a superior option for conservative treatment of hemorrhoids. Attached Figure Description

[0035] Figure 1 This is a flowchart of a method for preparing hemorrhoid ointment proposed in this invention;

[0036] Figure 2 This is a bar chart comparing the core therapeutic effects of each embodiment and the comparative example;

[0037] Figure 3 These are line graphs showing the retention rates of active ingredients during storage for each embodiment and comparative example;

[0038] Figure 4 This is a radar chart showing the overall performance of each embodiment and comparative example. Detailed Implementation

[0039] according to Figures 1 to 4 The specific embodiments of the present invention are as follows:

[0040] The following describes the hemorrhoid ointment and its preparation method of the present invention in detail with reference to three embodiments and one comparative example. All operations were carried out in a cleanroom that meets GMP standards, with the workshop temperature controlled at 25±2℃ and relative humidity ≤60%, and aseptic operation procedures were followed throughout the process. All raw materials used comply with the standards of Part I of the 2020 edition of the Pharmacopoeia of the People's Republic of China, and the equipment parameters were strictly set according to the scope of the claims to ensure the repeatability and practicality of the technical solution.

[0041] General Raw Material and Equipment Parameter Specifications

[0042] Regarding the core raw material parameters, Coptis chinensis is from Sichuan, the traditional producing area, with a berberine content ≥7.0%, and is pulverized and passed through a 200-mesh sieve; Phellodendron amurense is from Liaoning, the traditional producing area, with a berberine content ≥0.6%, and is pulverized and passed through a 200-mesh sieve; Sophora flavescens is from Shanxi, the traditional producing area, with a matrine content ≥1.0%, and is pulverized and passed through a 200-mesh sieve; Sanguisorba officinalis is from Gansu, the traditional producing area, with a tannin content ≥8.0%, and is pulverized and passed through a 200-mesh sieve; Dragon's blood is imported natural dragon's blood, with a sclerotinum content ≥1.0%, and is pulverized and passed through a 300-mesh sieve; Panax notoginseng is... The authentic producing area is Yunnan. The total saponin content of Panax notoginseng is ≥5.0%, and it is sieved through a 300-mesh sieve after pulverization. The degree of deacetylation of chitosan is ≥90%, the molecular weight is 50,000-80,000 Da, and the particle size is ≤50μm. The borneol is natural borneol with a content ≥96%, and it is sieved through a 300-mesh sieve after pulverization. The authentic producing area is Xinjiang. The shikonin content is ≥0.8%, and it is sieved through a 200-mesh sieve after pulverization. The purity of alum is ≥99.0%, and the particle size is ≤45μm. The sesame oil is cold-pressed grade one, with an acid value ≤1.0mgKOH / g, and it is sieved through a 300-mesh sieve. Oxidation value ≤ 6.0 mmol / kg; Polyethylene glycol 400 purity ≥ 99.5%, hydroxyl value 255-312 mg KOH / g; Purslane extract prepared by water extraction, alcohol precipitation, and column chromatography, purslane polysaccharide content ≥ 30%, moisture ≤ 5.0%; Bletilla striata extract prepared by microwave-assisted enzymatic hydrolysis, glucomannan content ≥ 25%, moisture ≤ 5.0%; Agrimonia pilosa extract prepared by ultrasonic-Soxhlet extraction, agrimonin content ≥ 0.2%, moisture ≤ 5.0%; Calamine natural carbonate Zinc content ≥98%, pulverized and passed through a 300-mesh sieve; menthol is naturally extracted, purity ≥99.0%; vitamin E purity ≥96.0%, tocopherol content ≥90%; sodium hyaluronate molecular weight 800,000-1,200,000 Da, purity ≥98.0%; dandelion extract flavonoid content ≥5.0%, moisture ≤5.0%; *Gnaphalium affine* extract polyphenol content ≥4.0%, moisture ≤5.0%; angelica extract ferulic acid content ≥0.1%, moisture ≤5.0%.

[0043] Regarding key equipment parameters, the ultrasonic extractor has a power adjustment range of 100-500W, a temperature control accuracy of ±2℃, and an extraction tank volume of 50L; the reflux extraction device uses a jacketed kettle for heating, with a temperature control range of 30-100℃, a condensation efficiency of ≥95%, and a volume of 100L; the plate and frame filter press has a filtration pressure adjustment range of 0.1-0.5MPa, a filter membrane pore size of 0.45μm, and a filtration area of ​​0.5m²; the anchor-type stirring paddle has a speed adjustment range of 50-300r / min, a blade diameter of 20cm, and is made of 316L stainless steel; the colloid mill has a grinding gap adjustment range of 0.01- 0.2mm diameter, 3000r / min rotation speed, 50L / h throughput; aseptic filling machine with filling accuracy error ≤±2%, filling speed 100 tubes / min, material 316L stainless steel; cobalt-60 irradiation sterilization equipment with irradiation dose adjustment range 1-20kGy, irradiation uniformity ≤±10%; rotational viscometer rotor model N0.4, rotation speed adjustment range 5-100r / min, temperature control accuracy ±0.1℃; high performance liquid chromatograph with detection wavelength range 190-800nm, flow rate accuracy ±0.01mL / min, column temperature control accuracy ±0.1℃.

[0044] Example 1

[0045] Process parameter settings

[0046] The raw materials are as follows by weight: 25 parts Coptis chinensis, 25 parts Phellodendron chinense, 20 parts Sophora flavescens, 20 parts Sanguisorba officinalis, 10 parts Dragon's Blood, 12 parts Panax notoginseng, 8 parts Chitosan, 5 parts Borneol, 10 parts Lithospermum erythrorhizon, 6 parts Alum, 150 parts Sesame Oil, 15 parts Polyethylene Glycol 400, 8 parts Portulaca oleracea extract, 7 parts Bletilla striata extract, 6 parts Agrimonia pilosa extract, 5 parts Calamine, 4 parts Menthol, 3 parts Vitamin E, 2 parts Sodium Hyaluronate, 8 parts Taraxacum mongolicum extract, 6 parts Lysimachia christinae extract, and 5 parts Angelica sinensis extract.

[0047] Ultrasonic extraction power: 350W; extraction temperature: 55℃; first extraction: 60 minutes; second extraction: 30 minutes; reflux extraction temperature: 75℃; extraction time: 2.5 hours; cross-linking reaction temperature: 75℃; stirring speed: 120r / min; holding time: 2.5 hours; nitrogen flow rate: 25mL / min; excipient mixing temperature: 55℃; stirring for 25 minutes after each addition; holding time: 1.5 hours; low-temperature blending temperature: 40℃; stirring speed: 200r / min; stirring time: 50 minutes; ambient humidity: 55%; colloid mill grinding gap: 0.08mm; grinding time: 18 minutes; cobalt-60 irradiation dose: 8kGy.

[0048] Detailed preparation process

[0049] S1. Raw Material Pretreatment: Coptis chinensis, Phellodendron chinense, Sophora flavescens, Sanguisorba officinalis, and Lithospermum erythrorhizon were washed four times with deionized water to remove surface impurities and dust. They were then dried in a 65℃ oven for 5 hours. After drying, they were mixed, pulverized, and passed through a 220-mesh sieve to obtain a mixed powder with a particle size D90 of 68μm. Dragon's blood and Panax notoginseng were separately pulverized and passed through a 280-mesh sieve, with a particle size D90 of 45μm, for later use. Portulaca oleracea, Bletilla striata, Agrimonia pilosa, Taraxacum mongolicum, Prunella vulgaris, and Angelica sinensis were used to prepare extracts according to their respective extraction processes. After vacuum drying at 55℃ and a vacuum degree of -0.085MPa, they were pulverized and passed through a 180-mesh sieve for later use. Calamine was pulverized and passed through a 300-mesh sieve, with a particle size D90 of 42μm, for later use.

[0050] S2. Preparation of Traditional Chinese Medicine Extract: The mixed medicinal powder was added to sesame oil, stirred evenly, and soaked for 10 hours, stirring for 12 minutes every 2 hours during soaking to ensure the powder was fully moistened. Then, an ultrasonic extractor was started, extracting at 350W power and 55℃ for 60 minutes. After standing for 30 minutes, it was ultrasonically extracted again for 30 minutes, and the two extracts were combined. The extract was transferred to a reflux extraction device and refluxed at 75℃ for 2.5 hours, stirring every 30 minutes during extraction. After extraction, a plate and frame filter was started, filtering at 0.25MPa pressure. The filtrate was collected to obtain the traditional Chinese medicine extract, and the residue was discarded. The extract was analyzed by high-performance liquid chromatography (HPLC), confirming that the contents of berberine (1.4%), berberine (0.9%), matrine (0.7%), sanguisorbin (3.5%), shikonin (0.4%), and agrimonyin (0.3%) met the requirements. The extract was stored at 6℃ for no more than 24 hours.

[0051] S3. Cross-linking reaction preparation: Chitosan was added to the traditional Chinese medicine extract. An anchor-type stirrer was started, with an initial speed of 100 r / min, gradually increasing to 120 r / min as the system viscosity increased. The temperature was raised to 75℃ and stirred for 2.5 hours to allow the chitosan to undergo a cross-linking reaction with the tannins in the traditional Chinese medicine extract, with the reaction represented by gallic acid proceeding fully. During the reaction, 99.9% pure nitrogen gas was introduced at a flow rate of 25 mL / min. The nitrogen gas was dried and purified before introduction. The reaction endpoint was determined by dropping a small amount of the reaction solution onto a glass slide, drying it at room temperature to form a uniform film without obvious particulate matter. After the reaction, the mixture was filtered through a 90-mesh filter, with the assistance of -0.07 MPa vacuum filtration, to remove incompletely reacted solid particles.

[0052] S4. Mixing of excipients: Crush alum and add it to the cross-linking reaction system, stirring for 35 minutes to ensure complete dissolution. Then cool to 55°C and add the following ingredients in sequence: dragon's blood powder, Panax notoginseng powder, polyethylene glycol 400, purslane extract, Bletilla striata extract, Agrimonia pilosa extract, calamine, dandelion extract, Prunella vulgaris extract, and Angelica sinensis extract. Stir for 25 minutes after each addition to ensure thorough mixing. Maintain the temperature for 1.5 hours, stirring for 10 minutes every 30 minutes to ensure system homogeneity.

[0053] S5. Low-Temperature Blending: Cool the system to 40℃, add borneol, menthol, vitamin E, and sodium hyaluronate. Increase the stirring speed to 200 rpm and stir for 50 minutes to ensure that the borneol and menthol are completely dissolved and the system is homogeneous, smooth, and free of granules. Maintain an ambient humidity of 55% during blending to prevent moisture from entering the paste. After blending, transfer the paste to a colloid mill with a grinding gap of 0.08 mm and a grinding time of 18 minutes. Use circulating water for cooling during grinding to control the paste temperature to not exceed 45℃.

[0054] S6. Molding and Packaging: The mixed ointment was allowed to cool naturally to room temperature and then subjected to multiple tests. The pH value was 6.5, and the viscosity, measured using a rotational viscometer at 25℃ and 10r / min, was 15000mPa·s. The content of the active ingredient met the requirements. Microbial limit tests showed a total bacterial count of 2 CFU / g, a total mold and yeast count of 0 CFU / g, and no pathogenic bacteria were detected. After passing the tests, the ointment was aseptically filled into disposable applicators, each containing 6g. The applicators were made of low-density polyethylene and sterilized with ethylene oxide. After sealing and packaging, the ointment was sterilized by cobalt-60 irradiation at a dose of 8kGy. Microbial limit tests were performed again after sterilization, confirming compliance with standards. The sterilized hemorrhoid ointment was labeled with relevant information and stored in an environment below 25℃ and with a relative humidity ≤60%.

[0055] Example 2

[0056] Process parameter settings

[0057] The raw materials are as follows by weight: 20 parts Coptis chinensis, 20 parts Phellodendron chinense, 15 parts Sophora flavescens, 15 parts Sanguisorba officinalis, 8 parts Dragon's Blood, 10 parts Panax notoginseng, 5 parts Chitosan, 3 parts Borneol, 8 parts Lithospermum erythrorhizon, 5 parts Alum, 120 parts Sesame Oil, 10 parts Polyethylene Glycol 400, 6 parts Portulaca oleracea extract, 5 parts Bletilla striata extract, 4 parts Agrimonia pilosa extract, 3 parts Calamine, 3 parts Menthol, 2 parts Vitamin E, 1 part Sodium Hyaluronate, 6 parts Taraxacum mongolicum extract, 4 parts Lysimachia christinae extract, and 3 parts Angelica sinensis extract.

[0058] Ultrasonic extraction power 300W, extraction temperature 50℃, first extraction 60 minutes, second extraction 30 minutes; reflux extraction temperature 70℃, extraction time 2 hours; cross-linking reaction temperature 70℃, stirring speed 100r / min, holding time 2 hours, nitrogen flow rate 20mL / min; excipient mixing temperature 50℃, stirring for 20 minutes after each addition, holding for 1 hour; low-temperature blending temperature 35℃, stirring speed 180r / min, stirring time 40 minutes, ambient humidity 50%; colloid mill grinding gap 0.05mm, grinding time 15 minutes; cobalt-60 irradiation dose 5kGy.

[0059] Detailed preparation process

[0060] S1. Raw Material Pretreatment: Coptis chinensis, Phellodendron chinense, Sophora flavescens, Sanguisorba officinalis, and Lithospermum erythrorhizon were washed three times with deionized water to remove surface impurities and dust. They were then dried in a 60℃ oven for 4 hours. After drying, they were mixed, pulverized, and passed through a 200-mesh sieve to obtain a mixed powder with a particle size D90 of 72μm. Dragon's blood and Panax notoginseng were separately pulverized and passed through a 250-mesh sieve, with a particle size D90 of 48μm, for later use. Portulaca oleracea, Bletilla striata, Agrimonia pilosa, Taraxacum mongolicum, Prunella vulgaris, and Angelica sinensis were used to prepare extracts according to their respective extraction processes. After vacuum drying at 50℃ and a vacuum degree of -0.08MPa, they were pulverized and passed through a 180-mesh sieve for later use. Calamine was pulverized and passed through a 300-mesh sieve, with a particle size D90 of 44μm, for later use.

[0061] S2. Preparation of Traditional Chinese Medicine Extract: The mixed medicinal powder was added to sesame oil, stirred evenly, and soaked for 8 hours, stirring for 10 minutes every 2 hours to ensure the powder was fully moistened. Then, an ultrasonic extractor was started at 300W power and 50℃ for 60 minutes. After standing for 30 minutes, it was ultrasonically extracted again for 30 minutes, and the two extracts were combined. The extract was transferred to a reflux extraction device and refluxed at 70℃ for 2 hours, stirring every 30 minutes during extraction. After extraction, a plate and frame filter was started and filtered at 0.2MPa pressure. The filtrate was collected to obtain the traditional Chinese medicine extract, and the residue was discarded. The extract was analyzed by high-performance liquid chromatography (HPLC), confirming that the contents of berberine (1.2%), berberine (0.8%), matrine (0.6%), sanguisorbin (3.0%), shikonin (0.3%), and agrimonyin (0.2%) met the requirements. The extract was stored at 4℃ for no more than 24 hours.

[0062] S3. Cross-linking reaction preparation: Chitosan was added to the traditional Chinese medicine extract. An anchor-type stirrer was started, with an initial speed of 100 r / min, and maintained at this speed until the reaction was completed. The temperature was raised to 70℃ and stirred for 2 hours to allow the chitosan to undergo a cross-linking reaction with the tannins in the traditional Chinese medicine extract. During the reaction, 99.9% pure nitrogen gas was introduced at a flow rate of 20 mL / min. The nitrogen gas was dried and purified before introduction. The reaction endpoint was determined by dropping a small amount of the reaction solution onto a glass slide, drying it at room temperature to form a uniform film with no obvious particulate matter. After the reaction, the mixture was filtered through an 80-mesh filter, with the assistance of -0.06 MPa vacuum filtration, to remove unreacted solid particles.

[0063] S4. Mixing of excipients: Crush alum and add it to the cross-linking reaction system, stirring for 30 minutes to ensure complete dissolution. Then cool to 50°C and add the following ingredients in sequence: dragon's blood powder, Panax notoginseng powder, polyethylene glycol 400, purslane extract, Bletilla striata extract, Agrimonia pilosa extract, calamine, dandelion extract, Prunella vulgaris extract, and Angelica sinensis extract. Stir for 20 minutes after each addition to ensure thorough mixing. Keep warm for 1 hour, stirring for 10 minutes every 30 minutes to maintain system homogeneity.

[0064] S5. Low-Temperature Mixing: Cool the system to 35℃, add borneol, menthol, vitamin E, and sodium hyaluronate. Increase the stirring speed to 180 rpm and stir for 40 minutes to ensure that the borneol and menthol are completely dissolved and the system is homogeneous, smooth, and free of granules. Maintain ambient humidity at 50% during mixing to prevent moisture from entering the paste. After mixing, transfer the paste to a colloid mill with a grinding gap of 0.05 mm and a grinding time of 15 minutes. Use circulating water for cooling during grinding to control the paste temperature to not exceed 45℃.

[0065] S6. Molding and Packaging: The mixed ointment was naturally cooled to room temperature and subjected to multiple tests. The pH value was 5.8, and the viscosity, measured using a rotational viscometer at 25℃ and 10r / min, was 12000mPa·s. The content of the active ingredient met the requirements. Microbial limit tests showed a total bacterial count of 3 CFU / g, a total mold and yeast count of 0 CFU / g, and no pathogenic bacteria were detected. After passing the tests, the ointment was aseptically filled into disposable applicators, 5g per applicator. The applicators were made of low-density polyethylene and sterilized with ethylene oxide. After sealing and packaging, the ointment was sterilized by cobalt-60 irradiation at a dose of 5kGy. Microbial limit tests were performed again after sterilization, confirming compliance with standards. The sterilized hemorrhoid ointment was labeled with relevant information and stored in an environment below 25℃ and with a relative humidity ≤60%.

[0066] Example 3

[0067] Process parameter settings

[0068] The raw materials are as follows by weight: Coptis chinensis 30 parts, Phellodendron chinense 30 parts, Sophora flavescens 25 parts, Sanguisorba officinalis 25 parts, Daemonorops draco 12 parts, Panax notoginseng 15 parts, chitosan 10 parts, borneol 6 parts, Lithospermum erythrorhizon 12 parts, alum 8 parts, sesame oil 180 parts, polyethylene glycol 400 20 parts, Portulaca oleracea extract 10 parts, Bletilla striata extract 9 parts, Agrimonia pilosa extract 8 parts, calamine 6 parts, menthol 5 parts, vitamin E 4 parts, sodium hyaluronate 3 parts, Taraxacum mongolicum extract 10 parts, Prunella vulgaris extract 8 parts, Angelica sinensis extract 7 parts.

[0069] Ultrasonic extraction power 400W, extraction temperature 60℃, first extraction 60 minutes, second extraction 30 minutes; reflux extraction temperature 80℃, extraction time 3 hours; cross-linking reaction temperature 80℃, stirring speed 150r / min, holding time 3 hours, nitrogen flow rate 30mL / min; excipient mixing temperature 60℃, stirring for 30 minutes after each addition, holding for 2 hours; low-temperature blending temperature 45℃, stirring speed 220r / min, stirring time 60 minutes, ambient humidity 58%; colloid mill grinding gap 0.1mm, grinding time 20 minutes; cobalt-60 irradiation dose 10kGy.

[0070] Detailed preparation process

[0071] S1. Raw Material Pretreatment: Coptis chinensis, Phellodendron chinense, Sophora flavescens, Sanguisorba officinalis, and Lithospermum erythrorhizon were washed five times with deionized water to remove surface impurities and dust. They were then dried in a 70℃ oven for 6 hours. After drying, they were mixed, pulverized, and passed through a 250-mesh sieve to obtain a mixed powder with a particle size D90 of 65μm. Dragon's blood and Panax notoginseng were separately pulverized and passed through a 300-mesh sieve, with a particle size D90 of 42μm, for later use. Portulaca oleracea, Bletilla striata, Agrimonia pilosa, Taraxacum mongolicum, Prunella vulgaris, and Angelica sinensis were used to prepare extracts according to their respective extraction processes. After vacuum drying at 60℃ and a vacuum degree of -0.09MPa, they were pulverized and passed through a 180-mesh sieve for later use. Calamine was pulverized and passed through a 300-mesh sieve, with a particle size D90 of 40μm, for later use.

[0072] S2. Preparation of Traditional Chinese Medicine Extract: The mixed medicinal powder was added to sesame oil, stirred evenly, and soaked for 12 hours, stirring for 15 minutes every 2 hours during soaking to ensure the powder was fully moistened. Then, an ultrasonic extractor was started, extracting at 400W power and 60℃ for 60 minutes. After standing for 30 minutes, it was ultrasonically extracted again for 30 minutes, and the two extracts were combined. The extract was transferred to a reflux extraction device and refluxed at 80℃ for 3 hours, stirring every 30 minutes during extraction. After extraction, a plate and frame filter was started, filtering at 0.3MPa pressure. The filtrate was collected to obtain the traditional Chinese medicine extract, and the residue was discarded. The extract was analyzed by high-performance liquid chromatography (HPLC), confirming that the contents of berberine (1.6%), berberine (1.0%), matrine (0.8%), sanguisorbin (4.0%), shikonin (0.5%), and agrimonyin (0.4%) met the requirements. The extract was stored at 8℃ for no more than 24 hours.

[0073] S3. Cross-linking reaction preparation: Chitosan was added to the traditional Chinese medicine extract. An anchor-type stirrer was started, with an initial speed of 100 r / min, gradually increasing to 150 r / min as the system viscosity increased. The temperature was raised to 80℃ and stirred for 3 hours to allow the chitosan to undergo a cross-linking reaction with the tannins in the traditional Chinese medicine extract. During the reaction, 99.9% pure nitrogen gas was introduced at a flow rate of 30 mL / min. The nitrogen gas was dried and purified before introduction. The reaction endpoint was determined by dropping a small amount of the reaction solution onto a glass slide, drying it at room temperature to form a uniform film without obvious particulate matter. After the reaction, the mixture was filtered through a 100-mesh filter, with the assistance of -0.08 MPa vacuum filtration, to remove unreacted solid particles.

[0074] S4. Mixing of excipients: Crush alum and add it to the cross-linking reaction system, stirring for 40 minutes to ensure complete dissolution. Then cool to 60°C and add the following ingredients in sequence: dragon's blood powder, Panax notoginseng powder, polyethylene glycol 400, purslane extract, Bletilla striata extract, Agrimonia pilosa extract, calamine, dandelion extract, Prunella vulgaris extract, and Angelica sinensis extract. Stir for 30 minutes after adding one ingredient at a time to ensure thorough mixing. Keep warm for 2 hours, stirring for 10 minutes every 30 minutes to maintain system homogeneity.

[0075] S5. Low-Temperature Blending: Cool the system to 45℃, add borneol, menthol, vitamin E, and sodium hyaluronate. Increase the stirring speed to 220 rpm and stir for 60 minutes to ensure that the borneol and menthol are completely dissolved and the system is homogeneous, smooth, and free of granules. Maintain an ambient humidity of 58% during blending to prevent moisture from entering the paste. After blending, transfer the paste to a colloid mill with a grinding gap of 0.1 mm and a grinding time of 20 minutes. Use circulating water for cooling during grinding to control the paste temperature to not exceed 45℃.

[0076] S6. Molding and Packaging: The mixed ointment was allowed to cool naturally to room temperature and then subjected to multiple tests. The pH value was 7.2, and the viscosity, measured using a rotational viscometer at 25℃ and 10 r / min, was 18000 mPa·s. The content of the active ingredient met the requirements. Microbial limit tests showed a total bacterial count of 1 CFU / g, a total mold and yeast count of 0 CFU / g, and no pathogenic bacteria were detected. After passing the tests, the ointment was aseptically filled into disposable applicators, each containing 8g. The applicators were made of low-density polyethylene and sterilized with ethylene oxide. After sealing and packaging, the ointment was sterilized by cobalt-60 irradiation at a dose of 10 kGy. Microbial limit tests were performed again after sterilization, confirming compliance with standards. The sterilized hemorrhoid ointment was labeled with relevant information and stored in an environment below 25℃ and with a relative humidity ≤60%.

[0077] Comparative Example

[0078] Process parameter settings

[0079] The raw materials are in the following weight parts: 25 parts Coptis chinensis, 25 parts Phellodendron chinense, 20 parts Sophora flavescens, 20 parts Sanguisorba officinalis, 5 parts Borneol, 10 parts Lithospermum erythrorhizon, 6 parts Alum, 150 parts Sesame oil, and 15 parts Polyethylene glycol 400.

[0080] It adopts a traditional decoction process, without ultrasonic-reflux extraction, cross-linking reaction, colloid milling, or cobalt-60 irradiation sterilization. The decoction temperature is 100℃, the decoction time is 3 hours, and it is directly filled after cooling to room temperature.

[0081] Detailed preparation process

[0082] S1. Raw material pretreatment: Coptis chinensis, Phellodendron chinense, Sophora flavescens, Sanguisorba officinalis, and Lithospermum erythrorhizon were washed three times with deionized water, dried in a 65℃ oven for 5 hours, mixed and pulverized after drying, and passed through a 100-mesh sieve to obtain mixed medicinal powder. Borneol and alum were pulverized separately and passed through a 100-mesh sieve for later use.

[0083] S2. Traditional preparation: Pour sesame oil into a jacketed kettle and heat to 100°C. Add the mixed medicinal powder, stir well, and maintain the temperature at 100°C for 3 hours, stirring every 30 minutes to prevent burning and clumping. After simmering, cool to 60°C, add borneol powder and alum powder, and stir for 30 minutes to dissolve them.

[0084] S3. Filtration and Filling: Filter the boiled mixture naturally through a 100-mesh filter, collect the filtrate, and allow it to cool naturally to room temperature. Fill the filtrate directly into disposable applicators using a filling machine, 6g per applicator. Seal the package, do not sterilize, and store in an environment below 25℃ and with a relative humidity ≤60%.

[0085] Core performance test results table

[0086]

[0087] The test results table comprehensively presents the performance differences between the embodiments and the comparative examples of this invention. Examples 1-3, employing an ultrasonic-reflux extraction process, achieved more thorough extraction of the effective components. Combined with the cross-linking reaction of chitosan and tannins to form a sustained-release carrier, their anti-inflammatory, hemostatic, and wound-healing effects were significantly superior to the comparative examples. Example 3, benefiting from optimal raw material ratios and process parameters, exhibited the lowest degree of anti-inflammatory swelling, the shortest hemostatic time, and the highest wound-healing rate. Regarding safety, Examples 1-3 strictly controlled the quality of raw materials and the preparation process, resulting in significantly lower levels of heavy metals and pesticide residues compared to the comparative examples. The mucosal irritation level was 0, demonstrating excellent biocompatibility. In contrast, the comparative examples, lacking control over raw material impurities and sterilization, exhibited some irritation. In terms of stability, Examples 1-3, after colloid milling and cobalt-60 irradiation sterilization, maintained a stable ointment structure, showing no stratification or deterioration after 18 months of storage, demonstrating a long shelf life. The comparative examples, lacking core process steps, showed slight stratification after 6 months and severe deterioration after 18 months, rendering them unusable. The comparative example, due to its traditional single-process boiling method, lacks sufficient extraction of effective ingredients, construction of sustained-release carriers, refinement treatment, and sterilization. As a result, its performance is significantly inferior to that of the embodiments of the present invention. This fully demonstrates that the formulation innovation and process optimization of the present invention have a significant synergistic effect, which can comprehensively improve the therapeutic effect, safety, and stability of hemorrhoid ointment and solve many shortcomings of traditional products.

[0088] Comparison of treatment effects for different types of hemorrhoids

[0089]

[0090] This table presents the differences in the therapeutic effects of the hemorrhoid ointment of this invention on different types of hemorrhoids. In terms of symptom relief time, Example 3 showed the best performance, with internal hemorrhoids (grades I-II) relieving symptoms in only 1-2 days, and thrombosed external hemorrhoids and mixed hemorrhoids in only 2-3 days and 3-4 days respectively, far faster than the 5-15 days in the comparative example. Regarding cure time, Example 3 cured internal hemorrhoids in 12-18 days, external hemorrhoids in 18-22 days, and mixed hemorrhoids in 22-28 days. Examples 1 and 2 were also superior to the 30-60 days in the comparative example. This difference stems from the multi-target formulation design of this invention. Basic ingredients such as Coptis chinensis and Phellodendron amurense synergistically reduce inflammation with Portulaca oleracea and Prunella vulgaris extracts; Dragon's Blood and Panax notoginseng combined with Agrimonia pilosa extract enhance hemostasis; and Bletilla striata extract and sodium hyaluronate promote wound repair, forming a precise treatment targeting the core pathological symptoms of different types of hemorrhoids. In contrast, the comparative example, due to its single formulation and insufficient effective ingredients, could not quickly relieve inflammation and bleeding, resulting in a significantly prolonged cure period. Furthermore, the therapeutic effect of the embodiments on mixed hemorrhoids is particularly obvious, indicating that the formula and process of the present invention can simultaneously address the combined symptoms of internal hemorrhoid bleeding and external hemorrhoid swelling, with wider applicability, and solves the problem of poor treatment effect of traditional hemorrhoid ointments on mixed hemorrhoids.

[0091] Table of changes in active ingredients during storage

[0092]

[0093] This table reflects the retention of active ingredients in each experimental group during the 18-month storage period. The core active ingredients berberine, shikonin, and agrimony extract in Examples 1-3 all maintained high retention rates. After 18 months, the content of berberine remained at 1.05%-1.45%, shikonin at 0.24%-0.42%, and agrimony extract at 0.15%-0.34%, with only minor decreases. This is attributed to the addition of vitamin E and sodium hyaluronate to the formulation of this invention. Vitamin E acts as an antioxidant, delaying the oxidative degradation of the active ingredients, while sodium hyaluronate forms a protective film, reducing the loss of active ingredients. Simultaneously, the sustained-release matrix formed by the cross-linking reaction also encapsulates and protects the active ingredients, further enhancing stability. In contrast, the comparative example did not contain any antioxidants or protective components and lacked a cross-linking structure, resulting in rapid degradation of the active ingredients. After 18 months, the berberine content was only 0.35%, and the shikonin content was 0.08%, almost losing its therapeutic activity. Furthermore, the comparative example did not contain agrimony extract, lacking the corresponding hemostatic active ingredient, thus its therapeutic function was inherently limited. The results fully demonstrate that the present invention, in terms of formula design and process optimization, not only focuses on immediate therapeutic effects but also takes into account the long-term stability of the product, ensuring that the efficacy does not diminish during the shelf life, and solving the problems of easy loss of effective ingredients and rapid decline in efficacy during the storage of traditional hemorrhoid ointments.

[0094] refer to Figure 2 The bar chart visually illustrates the core therapeutic differences between the hemorrhoid ointment of this invention and traditional hemorrhoid ointments. Examples 1-3 significantly outperformed the comparative example in three key indicators: anti-inflammatory, hemostatic, and wound healing. Example 3 showed the best performance, exhibiting the lowest degree of inflammation and swelling, the shortest hemostatic time, and the highest wound healing rate. This is attributed to the multi-target formulation design and optimized process of this invention. The synergistic effect of traditional Chinese medicines such as Coptis chinensis and Phellodendron chinense, along with extracts of Portulaca oleracea and Agrimonia pilosa, combined with ultrasonic-reflux extraction and cross-linking reaction, fully releases the effective components and prolongs the therapeutic effect. In contrast, the comparative example, due to its simple formulation and rudimentary process, showed significantly inferior therapeutic effects, fully demonstrating that the technical solution of this invention can effectively improve the overall therapeutic effect of hemorrhoids.

[0095] refer to Figure 3The line graph clearly shows the retention of active ingredients in the hemorrhoid ointment during an 18-month storage period. In Examples 1 and 3, the retention rates of berberine and shikonin remained at a high level, still above 84% after 18 months. Example 3 showed the best retention effect, attributed to the antioxidant effect of vitamin E and the protective matrix formed by chitosan cross-linking in the formulation. In the comparative examples, the retention rate of active ingredients decreased rapidly over time; after 18 months, berberine was only 31.8% and shikonin was only 22.9%, almost losing their therapeutic activity. The graph fully demonstrates that the storage stability of the hemorrhoid ointment of this invention is significantly better than that of traditional products, maintaining efficacy for a long time and extending shelf life.

[0096] refer to Figure 4 This radar chart comprehensively reflects the differences in overall performance among the experimental groups. Examples 1-3 all performed excellently in all five core dimensions, with scores all above 8.3. Among them, Example 3, with its optimal raw material ratio and process parameters, achieved the highest scores in anti-inflammatory, hemostatic, repair, and stability dimensions, and its mucosal safety was also close to perfect, demonstrating the best overall performance. The comparative examples generally scored lower in all dimensions, especially in storage stability (3.5 points) and mucosal safety (6.0 points), indicating significant shortcomings. The chart visually demonstrates the synergistic effect of the innovative formulation and optimized process of this invention, which not only achieves outstanding single-treatment effects but also achieves a comprehensive balance of anti-inflammatory, hemostatic, repair, stability, and safety, solving the problem of insufficient overall performance of traditional hemorrhoid ointments.

[0097] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A hemorrhoid ointment, characterized in that, It is composed of the following raw materials in parts by weight: Coptis chinensis 20-30 parts, Phellodendron chinense 20-30 parts, Sophora flavescens 15-25 parts, Sanguisorba officinalis 15-25 parts, Daemonorops draco 8-12 parts, Panax notoginseng 10-15 parts, chitosan 5-10 parts, borneol 3-6 parts, Lithospermum erythrorhizon 8-12 parts, alum 5-8 parts, sesame oil 120-180 parts, polyethylene glycol 400 10-20 parts, Portulaca oleracea extract 6-10 parts, Bletilla striata extract 5-9 parts, Agrimonia pilosa extract 4-8 parts, calamine 3-6 parts; Purslane extract contains purslane polysaccharides and flavonoids; Bletilla striata extract contains glucomannan and Bletilla striata gum; Agrimonia pilosa extract contains agrimonin; and calamine contains zinc carbonate.

2. The hemorrhoid ointment according to claim 1, characterized in that, It also includes 3-5 parts menthol, 2-4 parts vitamin E, and 1-3 parts sodium hyaluronate.

3. The hemorrhoid ointment according to claim 1, characterized in that, It also includes 6-10 parts of dandelion extract, 4-8 parts of prickly ash extract, and 3-7 parts of angelica extract.

4. The hemorrhoid ointment according to claim 1, characterized in that, The content of effective components in the Chinese herbal extracts meets the following requirements: berberine content ≥1.2%, berberine content ≥0.8%, matrine content ≥0.6%, sanguisorbin content ≥3.0%, shikonin content ≥0.3%, and agrimonycin content ≥0.2%; the key physical properties of the paste are: pH value 5.5-7.5; viscosity 10000-20000 mPa·s.

5. The hemorrhoid ointment according to claim 1, characterized in that, Purslane extract was prepared using a water extraction-ethanol precipitation-column chromatography process: extraction temperature 70-80℃, extraction time 2-3 hours, the extract was concentrated to a relative density of 1.10-1.15, 95% ethanol was added to adjust the ethanol precipitation concentration to 70-85%, and the mixture was allowed to stand for 12-18 hours. After filtration, the precipitate was purified by D101 macroporous resin column chromatography with 30-50% ethanol solution as the eluent. The eluent was collected, concentrated, and dried. Bletilla striata extract was prepared using a microwave-assisted enzymatic hydrolysis process: microwave power... The extraction process involves using an ultrasonic-Soxhlet extraction process: ultrasonic power 300-400W, extraction time 40-60 minutes, followed by Soxhlet extraction for 2-3 hours, with 70-80% ethanol as the solvent. The agrimony extract contains ≥0.2% agrimonyin.

6. The hemorrhoid ointment according to claim 1, characterized in that, All raw materials meet the following quality control requirements: heavy metal limits are ≤10 mg / kg for Pb, ≤1 mg / kg for Cd, and ≤0.1 mg / kg for Hg; total pesticide residues are ≤0.5 mg / kg; microbial limits meet the requirements for medical topical preparations, with total bacterial count ≤10 CFU / g, total mold and yeast count ≤1 CFU / g, and no pathogenic bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli detected; in the skin irritation test, the average score of rabbit intact skin and broken skin after application at 24, 48, and 72 hours is ≤0.5; the sensitization test results show no sensitization reaction, meeting the biocompatibility requirements for perianal mucosal contact preparations.

7. A method for preparing a hemorrhoid ointment, used to prepare the hemorrhoid ointment according to any one of claims 1-6, characterized in that, Includes the following steps: S1. Raw material pretreatment: Coptis chinensis, Phellodendron chinense, Sophora flavescens, Sanguisorba officinalis, and Lithospermum erythrorhizon are washed 3-5 times with deionized water, dried in an oven at 60-70℃ for 4-6 hours, mixed and pulverized, and passed through a 200-250 mesh sieve to obtain mixed medicinal powder; Dragon's blood and Panax notoginseng are pulverized separately and passed through a 250-300 mesh sieve for later use; Portulaca oleracea, Bletilla striata, Agrimonia pilosa, Taraxacum mongolicum, Prunella vulgaris, and Angelica sinensis are pulverized and passed through a 180 mesh sieve for later use; Calamine is pulverized and passed through a 300 mesh sieve for later use. S2. Preparation of Chinese herbal extracts: Add the mixed herbal powder to sesame oil, stir well, and soak for 8-12 hours; Subsequently, a combined ultrasonic extraction and reflux extraction process was used, followed by transfer to a reflux extraction device; After extraction, the solution was filtered using a plate and frame filter press, and the filtrate was collected to obtain a traditional Chinese medicine extract containing berberine and berberine. Test the extract; if it does not meet the standards, return it for re-extraction. S3. Cross-linking reaction preparation: Chitosan is added to the traditional Chinese medicine extract and stirred at a constant temperature for 2-3 hours to allow the chitosan to undergo a cross-linking reaction with the tannins in the traditional Chinese medicine extract to form a sustained-release matrix; the reaction endpoint is judged by: taking a drop of the reaction solution onto a glass slide, drying it at room temperature to form a uniform film without particulate matter; S4. Mixing of excipients: After crushing alum, add it to the above cross-linking reaction system and continue stirring for 30-40 minutes; then cool to 50-60℃ and add blood powder, Panax notoginseng powder, polyethylene glycol 400, purslane extract, Bletilla striata extract, Agrimonia pilosa extract, calamine, dandelion extract, Prunella vulgaris extract, and Angelica sinensis extract in sequence. Stir for 20-30 minutes after adding one raw material at a time and keep warm for 1-2 hours. S5. Low-temperature blending: Cool the system to 35-45℃, add borneol, menthol, vitamin E, and sodium hyaluronate, and stir for 40-60 minutes; after blending, grind with a colloid mill for 15-20 minutes. S6. Molding and Packaging: The mixed ointment is allowed to cool naturally to room temperature and then tested for indicators including pH value, viscosity, active ingredient content, and microbial limits. After passing the tests, it is filled into disposable administration devices using an aseptic filling machine and then sealed and packaged.

8. The method for preparing hemorrhoid ointment according to claim 7, characterized in that, The ultrasonic extraction process in S2 is carried out in two stages. After the first extraction is 60 minutes, the mixture is allowed to stand for 30 minutes to allow the powder to settle before ultrasonic extraction is performed again for 30 minutes. The two extracts are then combined. During the reflux extraction, a jacketed kettle is used for heating. The filtered herbal extract should be stored at 4-8℃.

9. The method for preparing hemorrhoid ointment according to claim 7, characterized in that, The stirring device for the cross-linking reaction in S3 uses an anchor-type stirring paddle. The stirring paddle speed is dynamically adjusted according to the viscosity of the system. When the initial viscosity is low, it is 100 r / min. As the viscosity increases during the reaction, it is gradually increased to 150 r / min. Before being introduced, the mixture is dried and impurities are removed. After the reaction, the mixture is filtered using vacuum filtration. During the grinding process of the colloid mill, the temperature of the paste is controlled to not exceed 45℃ and is cooled by circulating water.

10. The method for preparing hemorrhoid ointment according to claim 7, characterized in that, The specific methods for testing the ointment in S6 are as follows: pH value is measured using a precision pH meter. Take 5g of ointment, add 45mL of deionized water, stir evenly, and then measure. Viscosity is measured using a rotational viscometer. The content of active ingredients is determined using high-performance liquid chromatography. The applicator is made of low-density polyethylene and sterilized with ethylene oxide. The packaged hemorrhoid ointment is labeled with the product name, specifications, batch number, production date, expiration date, and usage instructions.

Images