Hydrocortisone compound ointment preparation for treating haemorrhoids

Abstract

The invention discloses a hydrocortisone compound ointment preparation for treating haemorrhoids, and belongs to the technical field of medicines. The technical problem to be solved is to provide a hydrocortisone compound ointment preparation which has a good hemorrhoid treatment effect and is stable. The hydrocortisone compound ointment preparation comprises the following components in percentage by weight: 0.15%-1% of corticoid, 0.025%-0.1% of a vasoconstrictor, 2%-4% of a local anesthetic, 0.1%-1.5% of L-menthol, 0.02%-0.5% of chlorhexidine acetate and 0.05%-1% of allantoin. The hydrocortisone compound ointment preparation disclosed by the invention has the medicinal effects of relieving pain and discomfort of patients suffering from haemorrhoids, promoting healing and repairing of haemorrhoids tissues, preventing infection and relieving inflammatory response, and has obvious effects of stopping bleeding and relieving swelling and pain in haemorrhoids treatment.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology and relates to a hydrocortisone compound ointment preparation for treating hemorrhoids. Background Technology

[0002] Hemorrhoids are a common disease located in the anal area, referring to the dilation and expansion of veins in the submucosa of the rectum, anal canal, and anal margin, forming soft, hemangioma-like lesions. Based on their location, they can be classified as internal hemorrhoids, external hemorrhoids, and mixed hemorrhoids. Patients may experience symptoms such as pain, rectal bleeding, a feeling of heaviness or pressure, and prolapse, which seriously affect their health and quality of life.

[0003] There are many methods for treating hemorrhoids. Traditional Chinese medicine treatments include fumigation, external application, sitz baths, and rectal suppositories, often used for mild to moderate hemorrhoids. These can quickly relieve pain, but their effectiveness alone is not ideal, and they are often combined with Western medicine treatments. Western medicine treatments include internal and external therapies. Internal therapies use medication; external therapies are surgical treatments, which are the fastest way to treat hemorrhoids. With the continuous improvement of modern medical technology, some non-surgical therapies have emerged, such as laser and infrared therapy, which can also eliminate hemorrhoids, allowing traditional medicine to fully leverage its significant advantages in treating hemorrhoids. However, this method has disadvantages such as slow recovery, high recurrence rate, and postoperative bleeding, especially when treating severe hemorrhoids, as it may cause excessive tissue damage and affect recovery.

[0004] Relevant patent documents retrieved: Patent CN102579569A discloses a pharmaceutical composition for treating hemorrhoids, its preparation method, and its application. The technical solution comprises 80-20 parts berberine hydrochloride, 7-20 parts procaine hydrochloride, 1.5-4.2 parts hydrocortisone, 7-18 parts borneol, 3.5-6.5 parts menthol, and a lipid-soluble matrix to bring the total to 1000 parts. Compared with this application, it does not contain vasoconstrictors, chlorhexidine acetate, or allantoin, but it still contains borneol and berberine hydrochloride; furthermore, the content of hydrocortisone and menthol (or L-menthol) differs from that in this application.

[0005] Patent CN1813766A discloses a hemorrhoid ointment, which is prepared by sequentially adding 89%-98% petrolatum, 0.1%-0.9% nifedipine, 0.5%-4% hydrocortisone, 1%-6.04% lidocaine, and 0.01%-0.07% menthol into a sterile container and stirring until homogeneous. Compared with this application, it does not contain vasoconstrictors, chlorhexidine acetate, or allantoin, but it still contains nifedipine; in addition, the content of hydrocortisone and menthol (or L-menthol) in it is different from that in this application.

[0006] Patent CN102579457A discloses a compound tetracaine composition, its preparation method, and its application. The composition comprises the following active pharmaceutical ingredients: tetracaine, ephedrine, phenobarbital, diphenhydramine, hydrocortisone, and borneol; wherein the weight parts of each component are: tetracaine 20-40 parts, ephedrine 20-40 parts, phenobarbital 20-40 parts, diphenhydramine 10-25 parts, hydrocortisone 2-15 parts, and borneol 3-15 parts. Compared to this application, it does not contain chlorhexidine acetate or allantoin, but still contains tetracaine, ephedrine, phenobarbital, diphenhydramine, and borneol; furthermore, the content of hydrocortisone differs from that in this application.

[0007] Relevant non-patent literature retrieved: The literature, "A Study on the Effective Components of the Classic Formula Sanhuang Ointment and Its Therapeutic Effect on Experimental Hemorrhoids in Rats," discloses that this study used the classic Chinese formula Sanhuang Ointment as the research object, and used berberine hydrochloride, aloe-emodin, baicalin, coptisine, baicalin, and rhein as indicators. Combining single-factor experiments and response surface methodology, and based on the guidance of modern TCM theory and the traditional preparation method of *Yixin Fang*, the study optimized the preparation process (determining the optimal parameters such as soaking for 12 hours and frying for 60 minutes at 140℃) and established an HPLC fingerprint (calibrating 13... The study identified 6 peaks and used liquid chromatography-mass spectrometry (LC-MS) to identify 706 chemical components (41 with similarity exceeding 90%), clarifying their pharmacodynamic substances. Combined with network pharmacology, molecular docking (identifying core targets such as CGRP and component affinity), and animal experiments (mouse ear swelling and rat anorectal models), it was confirmed that Sanhuang Ointment can exert anti-inflammatory and hemorrhoid-treating effects by inhibiting inflammatory factors and promoting the secretion of healing-related cytokines. This provides a basis for its development into a stable and effective traditional Chinese medicine compound external preparation.

[0008] This document contains at least the following unresolved technical problems or defects: The formulation lacks stability, as evidenced by the following: In the literature "Study on the Effective Components of the Classic Formula Sanhuang Ointment and Its Use in Treating Experimental Hemorrhoids in Rats", only the relative standard deviation (RSD) value from 0 to 48 hours was measured. It did not verify whether the ointment was easy to spread on the skin surface, whether it clumped or separated, which directly affects the user experience and efficacy. It did not assess whether the ointment was sticky or easily absorbed after application. Poor skin feel may lead to decreased user compliance, indirectly affecting the treatment effect. It did not verify whether the formulation separated or precipitated through centrifugation tests (such as centrifugation at 3000 rpm for 30 minutes), which could not rule out the risk of physical instability after being subjected to force (such as shaking or vibration). This indicates that the stability of the formulation needs to be fully verified and improved. Summary of the Invention

[0009] Terminology Explanation: Unless otherwise defined, all technical terms in this document have the same meanings as commonly understood by one of ordinary skill in the art to which the subject matter of the claims pertains. Unless otherwise stated, all patents, patent inventions, and publications cited in this document are incorporated herein by reference in their entirety. If multiple definitions exist for terms in this document, the definitions in this chapter shall prevail.

[0010] It should be understood that the above brief description and the following detailed description are exemplary and for illustrative purposes only, and do not limit the subject matter of the invention in any way. In this invention, the singular is used in conjunction with the plural unless otherwise specifically stated. It should also be noted that, unless otherwise stated, the use of “or” or “or” means “and / or”. Furthermore, the use of the term “comprising” and other forms such as “including,” “containing,” and “contains” are not limiting.

[0011] Definitions of standard chemical terms can be found in the reference books "Pharmacology, People's Medical Publishing House, authors: Yang Baofeng and Chen Jianguo, 2018-9" and "New Pharmacology, People's Medical Publishing House, authors: Chen Xinqian, Jin Youyu, and Tang Guang, 2011-17".

[0012] Unless otherwise stated, conventional methods within the scope of the art, such as crushing, shall be used.

[0013] Unless specifically defined herein, the use of all commercially available products herein employs standard techniques. For example, it may be carried out using the manufacturer's instructions for use with the kit, or in accordance with methods known in the art or the description of this invention. The techniques and methods described herein can generally be implemented according to conventional methods well known in the art, based on the descriptions in the various summary and more specific documents cited and discussed in this specification.

[0014] The terms "optional / arbitrary" or "optionally / arbitrarily" mean that an event or situation subsequently described may or may not occur, including both the occurrence and non-occurrence of the event or situation. For example, according to the definition below: "The local anesthetic is selected from any one or more of lidocaine hydrochloride, promocaine hydrochloride, and benzocaine hydrochloride," for example: This refers to the statement that "the local anesthetic is selected from lidocaine hydrochloride"; Or, “The local anesthetic agent mentioned is selected from lidocaine hydrochloride and promocaine hydrochloride”; Or, “The local anesthetic is selected from lidocaine hydrochloride, promocaine hydrochloride, and benzocaine hydrochloride.”

[0015] The term "corticosteroids" used in this article refers to steroid hormones secreted by the adrenal cortex or synthesized artificially, and are divided into three categories: glucocorticoids, mineralocorticoids, and sex hormones. Among them, glucocorticoids are the most widely used in clinical practice, and have anti-inflammatory and anti-allergic effects, reducing inflammation by inhibiting the activation of inflammatory cells.

[0016] The term "hydrocortisone" used in this article refers to a naturally occurring glucocorticoid with anti-inflammatory and anti-allergic functions, capable of relieving various symptoms caused by inflammation or allergies. Clinically, it can be administered orally, by injection, or topically. Topical preparations are mostly suitable for local non-infectious skin inflammations such as eczema and dermatitis.

[0017] The term "hydrocortisone butyrate" as used in this article refers to a synthetic topical derivative of hydrocortisone, which is a glucocorticoid. It is primarily used to treat non-infectious inflammatory skin diseases such as contact dermatitis and eczema, effectively relieving symptoms such as redness, swelling, and itching, and has low irritation.

[0018] The term "vasoconstrictor" as used in this article refers to drugs that cause vasoconstriction, narrowing of the lumen, increased vascular resistance, and elevated blood pressure. They have wide clinical applications, relieving tissue congestion, controlling bleeding, and treating shock. When used in combination with local anesthetics, they can delay absorption, prolong efficacy, and reduce the risk of toxicity.

[0019] The term "phenylephrine" as used in this article refers to a synthetic alpha-adrenergic receptor agonist, classified as a vasoconstrictor. Clinically, it is used to treat hypotension; when applied topically, it constricts blood vessels in the eye and nasal mucosa, relieving eye congestion and nasal congestion.

[0020] The term "oxymetazoline hydrochloride" as used in this article refers to a potent and long-lasting local vasoconstrictor, belonging to the α-adrenergic receptor agonist class. Common dosage forms are nasal drops / sprays and eye drops, used to treat nasal congestion caused by rhinitis, etc., and to relieve conjunctival congestion caused by eye fatigue, allergies, etc., respectively.

[0021] The term "naphthazolium hydrochloride" as used in this article refers to a synthetically produced local vasoconstrictor, belonging to the α-adrenergic receptor agonist class. Nasal drops can quickly improve nasal congestion caused by acute rhinitis, while eye drops can relieve conjunctival congestion and redness caused by eye inflammation such as conjunctivitis or fatigue.

[0022] The term "xylometazoline hydrochloride" as used in this article refers to a selective α1-adrenergic receptor agonist, a local vasoconstrictor with rapid onset and long-lasting effect. It is primarily used in nasal drops and sprays to treat nasal congestion caused by acute and chronic rhinitis, with minimal impact on systemic blood pressure and heart rate.

[0023] The term "local anesthetic" as used in this article refers to an agent that reversibly blocks nerve impulse transmission at the application site, causing temporary loss of sensation such as pain without affecting consciousness. It is widely used in minor surgical procedures, dental treatments, and other medical settings to reduce patient pain.

[0024] The term "lidocaine hydrochloride" as used in this article refers to a commonly used amide-type local anesthetic that also has antiarrhythmic effects. As a local anesthetic, it can be administered via various routes and is used in surgical, dental, and other procedures; as an antiarrhythmic drug, it can treat premature ventricular contractions and stabilize myocardial electrical activity.

[0025] The term "promocaine hydrochloride" as used in this article refers to prilocaine, an ester-based local anesthetic that has a rapid onset of action, low irritation, and strong penetrability. It is commonly used for surface anesthesia of the skin and mucous membranes, and is suitable for minor dermatological surgeries, analgesia for oral mucosal ulcers, etc.

[0026] The term "benzocaine hydrochloride" as used in this article refers to a commonly used ester-based topical anesthetic that has a rapid onset of action, direct effect, and high lipid solubility. It is primarily used for skin and mucous membrane anesthesia and analgesia, such as relieving burn pain and oral ulcer pain. It can also be used for pre-operative anesthesia in otolaryngology and ophthalmology procedures.

[0027] The term "L-menthol" as used in this article refers to a monoterpenoid compound extracted from the essential oil of peppermint plants or synthesized artificially, possessing a minty aroma and a cooling sensation. In the pharmaceutical field, it is commonly used in topical preparations to provide cooling relief from itching, assist in local analgesia, and improve nasal dryness and bad breath, exhibiting a relatively high safety profile.

[0028] The term "chlorhexidine acetate" as used in this article refers to: also known as chlorhexidine acetate, a cationic surfactant disinfectant that is broad-spectrum, highly effective, and low in toxicity. It is available in various formulations and is widely used for skin and mucous membrane disinfection, medical device disinfection, and as an adjunct treatment for oral diseases such as gingivitis.

[0029] The term "allantoin" as used in this article refers to substances that are naturally found in plants and animals, but are now mostly synthesized artificially. These substances promote tissue repair, moisturize and soothe, and reduce inflammation. They are commonly used in topical preparations to treat dry skin, eczema, burns, etc., accelerating wound healing and reducing scar formation.

[0030] The term "liquid paraffin" as used in this article refers to a mixture of hydrocarbons refined from petroleum, also known as mineral oil. It can be taken orally as a laxative to treat habitual constipation; externally, it can be used as an excipient in pharmaceutical preparations, or as a skin lubricant and moisturizer to relieve dry and rough skin.

[0031] The term "white petrolatum" as used in this article refers to an ointment-like substance refined from petroleum, which is a common base for topical preparations. It can moisturize and protect the skin, treat dry skin, and can also be used as a protective dressing for burns and injuries, helping to stabilize and locally absorb medications.

[0032] The term "weight percentage" used in this article refers to the content of a component in a mixture, expressed as % (w / w). It is calculated by dividing the component's mass by the total mass and then multiplying by 100%. It is widely used in many fields such as chemistry and medicine, facilitating a direct comparison of the component content of different mixtures.

[0033] In a first aspect, the present invention provides: a hydrocortisone compound ointment formulation for treating hemorrhoids.

[0034] Among them, the technical features include: hemorrhoid and hydrocortisone compound ointment preparation.

[0035] Among them, the technical characteristics of hemorrhoids include: internal hemorrhoids, external hemorrhoids, or mixed hemorrhoids.

[0036] Among them, the technical features of the hydrocortisone compound ointment preparation include: corticosteroids, vasoconstrictors, local anesthetics, L-menthol, chlorhexidine acetate, and allantoin.

[0037] Specifically, the weight percentages of the corticosteroids, vasoconstrictors, local anesthetics, L-menthol, chlorhexidine acetate, and allantoin are 0.15%-1%: 0.025%-0.1%: 2%-4%: 0.1%-1.5%: 0.02%-0.5%: 0.05%-1%.

[0038] Preferably, the weight percentages of the corticosteroid, vasoconstrictor, local anesthetic, L-menthol, chlorhexidine acetate, and allantoin are 0.25%:0.025%:4%:0.5%:0.02%:0.1%.

[0039] Specifically, the corticosteroid is selected from any one or more of hydrocortisone and hydrocortisone butyrate.

[0040] Specifically, the vasoconstrictor is selected from any one or more of phenylephrine, oxymetazoline hydrochloride, naphazoline hydrochloride, and xylometazoline hydrochloride.

[0041] Specifically, the local anesthetic is selected from any one or more of lidocaine hydrochloride, promocaine hydrochloride, and benzocaine hydrochloride.

[0042] Preferably, the corticosteroid is hydrocortisone.

[0043] Preferably, the vasoconstrictor is phenylephrine or oxymetazoline hydrochloride.

[0044] Preferably, the local anesthetic is lidocaine hydrochloride or promocaine hydrochloride.

[0045] Among them, the technical features of hydrocortisone compound ointment formulations also include: pharmaceutical matrix.

[0046] Specifically, the pharmaceutical matrix includes any one or more of liquid paraffin and white petrolatum.

[0047] Based on further solutions to the technical problems of the present invention, or simultaneous solutions to multiple technical problems, the preferred solution in the technical solution provided in the first aspect of the present invention includes: The first preferred option is a hydrocortisone compound ointment for treating hemorrhoids, comprising a corticosteroid, a vasoconstrictor, a local anesthetic, L-menthol, chlorhexidine acetate, and allantoin, wherein the weight percentages of the corticosteroid, vasoconstrictor, local anesthetic, L-menthol, chlorhexidine acetate, and allantoin are 0.25%:0.025%:4%:0.5%:0.02%:0.1%. This technical solution, in addition to addressing the technical problem of "insufficient stability of existing formulations," further addresses the technical problem of "which formulation has strong stability."

[0048] Secondly, the present invention provides: a preparation method.

[0049] Among them, the technical feature is the preparation method.

[0050] The technical feature preparation method is selected from the preparation method of the above-mentioned hydrocortisone compound ointment.

[0051] Specifically, the preparation method includes the following steps: S1. Crush the corticosteroids, vasoconstrictors, local anesthetics, L-menthol, allantoin, and chlorhexidine acetate into powders and set aside. S2. Add the crushed L-menthol to the liquid paraffin, stir to dissolve, add allantoin, stir to homogenize, and mix evenly. S3: Add white petrolatum to an emulsification tank and heat it. Add the local anesthetic in four batches, stirring and homogenizing each time. Add the raw materials corticosteroid, vasoconstrictor and chlorhexidine acetate in sequence, stirring and homogenizing after each addition to obtain a uniform dispersion phase. S4: Keep the uniformly dispersed phase under vacuum and stir to homogenize it; S5: After preparation, cool, fill and seal.

[0052] Based on further solutions to the technical problems of the present invention, or simultaneous solutions to multiple technical problems, the preferred solution in the technical solution provided in the second aspect of the present invention includes: The first preferred solution is a method for preparing the above-mentioned hydrocortisone compound ointment formulation. This solution, in addition to solving the technical problem of "insufficient stability of existing formulations," further addresses the technical problem of "which preparation method to use to prepare a highly stable formulation."

[0053] Thirdly, the present invention provides: an application.

[0054] This includes technical features: applications.

[0055] The technical features are selected from the application of the above-mentioned hydrocortisone compound ointment in the preparation of drugs for the prevention, treatment or adjunctive treatment of hemorrhoids.

[0056] Among them, the technical characteristics of hemorrhoids include: internal hemorrhoids, external hemorrhoids, or mixed hemorrhoids.

[0057] Specifically, the hydrocortisone compound ointment is administered rectally or applied perianally.

[0058] Based on further solutions to the technical problems of the present invention, or simultaneous solutions to multiple technical problems, the preferred solution in the technical solution provided in the third aspect of the present invention includes: The first preferred option is the application of the aforementioned hydrocortisone compound ointment formulation in the preparation of a drug for the prevention, treatment, or adjunctive treatment of hemorrhoids. This technical solution, building upon the existing technical problem of "insufficient stability of formulations," further addresses the technical problem of "what are the applications of highly stable formulations."

[0059] The present invention has at least the following beneficial effects: Compared with existing technologies, the present invention has better technical effects in improving anal ulcers.

[0060] Under the same dosage and after a period of treatment, the present invention has a far superior repair effect on anal ulcers than existing technologies, and can achieve faster and more thorough healing of the ulcer surface. Attached Figure Description

[0061] Figure 1 The cumulative in vitro permeation of lidocaine hydrochloride in different dosages of hydrocortisone compound ointment.

[0062] Figure 2 This shows the dispersion of allantoin in the matrix at different dosages in hydrocortisone compound ointment.

[0063] Figure 3 The cumulative in vitro release of promocaine hydrochloride, benzocaine hydrochloride, and lidocaine hydrochloride from hydrocortisone compound ointment.

[0064] Figure 4 The pathological morphology of anal tissue stained with HE in different treatment groups. Detailed Implementation

[0065] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection claimed by the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, and such changes should also fall within the scope of protection claimed by the present invention.

[0066] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all instruments, devices, equipment, reagents, products, etc., used in the embodiments of the present invention are obtained through conventional commercial means.

[0067] Example 1 1. A hydrocortisone compound ointment preparation for treating hemorrhoids. This embodiment provides prescriptions 1-1 to 1-5. The difference between prescriptions 1-1 to 1-5 is that the hydrocortisone content is different. The specific prescription ingredients (g) are shown in Table 1.

[0068] Table 1

[0069] 2. The preparation methods for hydrocortisone compound ointment formulations of prescriptions 1-1 to 1-5 are as follows: (1) All raw materials are crushed and passed through a 200-mesh sieve to obtain raw materials with a particle size of less than 60μm.

[0070] (2) Add L-menthol to liquid paraffin and stir to dissolve. Then set aside. Then add allantoin while stirring. Control the stirring speed at 30 rpm, the homogenization rate at 2500 rpm, and the homogenization time at 10 min. Mix evenly.

[0071] (3) Add white petrolatum to an emulsification tank and heat to 45-55℃. Add lidocaine hydrochloride in four batches. Stir and homogenize each batch. Control the stirring speed at 30 rpm, the homogenization rate at 2500 rpm, and the stirring and homogenization time at 10 min. Then add the raw materials hydrocortisone, phenylephrine hydrochloride and chlorhexidine acetate in sequence. Stir and homogenize each batch after each addition. Stir at 30 rpm, the homogenization rate at 2500 rpm, and the stirring and homogenization time at 10 min to obtain a uniform dispersed phase.

[0072] (4) The obtained uniformly dispersed phase was stirred and homogenized under vacuum (-0.04~-0.08MPa) at a stirring rate of 30 rpm and a homogenization rate of 2500 rpm for 25 min.

[0073] (5) After preparation, cool down to 35-45℃ and fill each container. The amount of each container should be no less than 93% of the theoretical amount, and the average amount of each container should be no less than 10g of the indicated amount. After filling, seal the container.

[0074] 3. The appearance, skin feel, and centrifugal stability (centrifugal stability test conditions: centrifuge speed 3000 rpm, 10 min) of the hydrocortisone compound ointment preparations obtained by the above prescriptions and preparation methods were determined. The results are shown in Table 2. Prescriptions 1-1, 1-2, 1-3, and 1-4 had uniform color, no grainy feel when applied, and did not separate into layers upon centrifugation. However, prescription 1-5 had uneven color, a grainy feel when applied, and separated into layers upon centrifugation. Therefore, the weight percentage of hydrocortisone was selected to be 0.15%-1%.

[0075] Table 2

[0076] Example 2 1. A compound ointment preparation of hydrocortisone for treating hemorrhoids. This embodiment provides prescriptions 1-2, 2-2 to 2-5. The difference between the above prescriptions is that the content of phenylephrine is different. The specific prescription ingredients (g) are shown in Table 3.

[0077] Table 3

[0078] 2. The preparation methods of the hydrocortisone compound ointment formulations of prescriptions 1-2, 2-2 to 2-5 are as described in Example 1.

[0079] 3. The appearance, skin feel, and centrifugal stability (centrifugal stability test conditions: centrifuge speed 3000 rpm, 10 min) of the hydrocortisone compound ointment preparations obtained by the above prescriptions and preparation methods were determined. The results are shown in Table 4. Prescriptions 1-2, 2-2, and 2-3 had uniform color, no grainy feel when applied, and did not separate into layers upon centrifugation. Prescriptions 2-4 and 2-5 showed uneven color, a grainy feel when applied, and separation upon centrifugation. Therefore, the weight percentage of phenylephrine was selected as 0.025%-0.1%.

[0080] Table 4

[0081] Example 3 1. A compound ointment preparation of hydrocortisone for treating hemorrhoids. This embodiment provides prescriptions 1-2, 3-1 to 3-4. The difference between the above prescriptions is that the content of lidocaine hydrochloride is different. The specific prescription ingredients (g) are shown in Table 5.

[0082] Table 5

[0083] 2. The preparation methods of the hydrocortisone compound ointment formulations of prescriptions 1-2, 3-1 to 3-4 are as described in Example 1.

[0084] 3. The hydrocortisone compound ointment formulations of prescriptions 1-2, 3-1 to 3-4 obtained by the above prescriptions and preparation methods were subjected to in vitro lidocaine release assay. The assay procedure is as follows: Apparatus: Vertical diffusion cell; Temperature: 32℃; Rotation speed: 600 rpm; Release medium: pH 6.8 phosphate buffer solution; Sample loading amount: 300mg (2mm quantitative loop); Artificial membrane: PES (polyethersulfone) pore size: 0.45μm; Medium volume: 10ml; Sampling time: 1h, 2h, 3h, 4h, 5h, 6h; Sampling volume: 1 ml; Replenishment volume: 1 ml; Diffusion cell orifice diameter: 15 mm; Diffusion cell orifice area: 1.77 cm² 2 ; HPLC chromatographic conditions using Agilent ZORBAX C18 (4.6×250mm, 5μm) column; acetonitrile-water (50:30) as mobile phase; flow rate 1.0 ml / min; detection wavelength 250 nm; column temperature 30℃; injection volume 10 μl.

[0085] The measurement results are as follows Figure 1 As shown, the results indicated that in the hydrocortisone compound ointment formulation of prescription 3-1, the cumulative permeation of lidocaine hydrochloride did not reach 15.00 μg / cm³ after 24 hours. 2 In prescriptions 1-2, 3-2 to 3-4, the cumulative permeation of lidocaine hydrochloride reached 20.00 μg / cm³ within 24 hours. 2 Therefore, the weight percentage of lidocaine hydrochloride is chosen to be 2%-4%.

[0086] Example 4 1. A compound ointment preparation of hydrocortisone for treating hemorrhoids. This embodiment provides prescriptions 1-2, 4-1 to 4-4. The difference between the above prescriptions is that the content of L-menthol is different. The specific prescription ingredients (g) are shown in Table 6.

[0087] Table 6

[0088] 2. The preparation methods of the hydrocortisone compound ointment formulations of prescriptions 1-2, 4-1 to 4-4 are as described in Example 1.

[0089] 3. During the stirring and dissolution process of the above formulation: After L-menthol is added to liquid paraffin and stirred until dissolved, allantoin is added. The stirring speed is controlled at 25-30 rpm, the homogenization rate at 2000-2500 rpm, and the homogenization time is 5-10 minutes until the mixture is homogeneous. After performing the above steps, white crystals precipitate in formulation 4-4. This may be due to the limited dissolution of the matrix in the raw materials, leading to the precipitation of the material. Therefore, the weight percentage of L-menthol is selected as 0.1%-1.5%.

[0090] Example 5 1. A compound ointment preparation of hydrocortisone for treating hemorrhoids. This embodiment provides prescriptions 1-2, 5-1 to 5-4. The difference between the above prescriptions is that the content of chlorhexidine acetate is different. The specific prescription ingredients (g) are shown in Table 7.

[0091] Table 7

[0092] 2. The preparation methods of the hydrocortisone compound ointment formulations of prescriptions 1-2, 5-1 to 5-4 are as described in Example 1.

[0093] 3. The hydrocortisone compound ointment formulations of formulations 1-2 and 5-1 to 5-4 obtained by the above formulations and preparation methods were tested for their antibacterial activity against Staphylococcus aureus ATCC25923, Escherichia coli ATCC25922, and Streptococcus mutans ATCC25175 using the inhibition zone method. The inhibition zone test method is as follows: (1) Bottom layer: Use a sterile pipette (20ml) to draw about 20ml of melted culture medium and pour it into the double dish. After all the double dishes have been filled with the bottom layer, cover them with ceramic lids and wait for solidification before use.

[0094] (2) Bacterial layer: Take out the pre-tested Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa bacterial suspensions respectively, and use a sterile pipette (or sterile syringe) to draw 2 ml of bacterial suspension (0.5%) and add it to the culture medium that has been melted and kept warm in a water bath (48℃). Shake well to prepare the bacterial layer. Use a sterile wide-mouth pipette to draw 2 ml of culture medium with added bacteria, spread the culture medium evenly on the bottom culture medium, place it on a water platform, cover it with a ceramic tile lid, and let it solidify before use.

[0095] (3) Placing the steel pipe: Place the steel pipe into the stainless steel cup in the steel pipe holder, turn on the switch, place the double plate on the operating table of the steel pipe holder, align the interface, press the handle to make the steel pipe fall steadily on the culture medium. After the steel pipe is placed properly, let it stand and allow the steel pipe to sink and stabilize in the culture medium. Then add 0.1g of ointment of prescription 5-1, prescription 1-2, prescription 5-2, prescription 5-3 and prescription 5-4 respectively.

[0096] (4) Sample addition: Add ointments of prescriptions 5-1, 1-2, 5-2, 5-3, and 5-4 to a petri dish, ensuring the ointments are level with the top edge of the small steel tube. Incubate at 30°C for 8 hours. The results are shown in Table 8. Table 8

[0097] Chlorhexidine acetate is a broad-spectrum antibacterial disinfectant, mainly used to kill or inhibit bacteria, fungi, and other microorganisms. It can be used for disinfection of skin and mucous membrane surfaces. Test results showed that formulations 1-2, 5-2 to 5-4 exhibited good inhibitory activity against Staphylococcus aureus, Escherichia coli, and Streptococcus mutans, while formulation 5-1 showed poor inhibitory effect. Therefore, a weight percentage of chlorhexidine acetate of 0.02%-0.5% was selected.

[0098] Example 6 1. A hydrocortisone compound ointment preparation for treating hemorrhoids. This embodiment provides prescriptions 1-2, 6-1 to 6-4. The difference between the above prescriptions is that the allantoin content is different. The specific prescription ingredients (g) are shown in Table 9.

[0099] Table 9

[0100] 2. The preparation methods of the hydrocortisone compound ointment formulations of prescriptions 1-2, 6-1 to 6-4 are as described in Example 1.

[0101] 3. After adding allantoin to the above prescription, observe the dispersion of allantoin in the matrix, and based on... Figure 2 Microscopic examination revealed that allantoin in prescription 6-4 comprised 1.5% by weight, with numerous particle clusters observed in the field of view. Therefore, an allantoin weight percentage of 0.05%-1% was selected.

[0102] Example 7 1. A compound ointment preparation of hydrocortisone for treating hemorrhoids. This embodiment provides prescription 7-1, which uses 10g of hydrocortisone butyrate to replace hydrocortisone in prescription 1-2. The specific prescription ingredients (g) are shown in Table 10.

[0103] Table 10

[0104] 2. In prescription 7-1, hydrocortisone is replaced with hydrocortisone butyrate, and the preparation method is the same as in Example 1.

[0105] 3. The appearance, skin feel, and centrifugal stability (centrifugal stability test conditions: centrifuge speed 3000 rpm, 10 min) of the hydrocortisone compound ointment preparation of prescription 7-1 obtained by the above prescription and preparation method were determined. The results are shown in Table 11. Prescription 7-1 has a uniform color, no grainy feel when applied, and does not separate into layers after centrifugation, which is consistent with the stability of prescription 1-2. Therefore, hydrocortisone butyrate can be used to replace hydrocortisone.

[0106] Table 11

[0107] Example 8 1. A compound ointment preparation of hydrocortisone for treating hemorrhoids. This embodiment provides prescriptions 8-1 to 8-3, in which oxymetazoline hydrochloride, naphazoline hydrochloride, and xylometazoline hydrochloride are used respectively to replace phenylephrine in prescriptions 1-2. The specific prescription ingredients (g) are shown in Table 12.

[0108] Table 12

[0109] 2. In prescriptions 8-1 to 8-3, norepinephrine is replaced with oxymetazoline hydrochloride, naphazoline hydrochloride, and xylometazoline hydrochloride, respectively. The preparation method is the same as in Example 1.

[0110] 3. The appearance, skin feel, and centrifugal stability (centrifugal stability test conditions: centrifuge speed 3000 rpm, 10 min) of the hydrocortisone compound ointment preparations of prescriptions 8-1 to 8-3 obtained by the above prescriptions and preparation methods were determined. The results are shown in Table 13. Prescriptions 8-1 to 8-3 have uniform color, no grainy feel when applied, and do not separate into layers when centrifuged. Their stability is consistent with or similar to that of prescriptions 1-2. Therefore, oxymetazoline hydrochloride, naphazoline hydrochloride, and xylometazoline hydrochloride can be used to replace phenylephrine.

[0111] Table 13

[0112] Example 9 1. A compound ointment preparation of hydrocortisone for treating hemorrhoids. This embodiment provides prescription 9-1 and prescription 9-2. Prescription 9-1 and prescription 9-2 use promocaine hydrochloride and benzocaine hydrochloride, respectively, to replace lidocaine hydrochloride in prescription 1-2. The specific prescription components (g) are shown in Table 14.

[0113] Table 14

[0114] 2. In prescriptions 9-1 and 9-2, lidocaine hydrochloride is replaced with promocaine hydrochloride and benzocaine hydrochloride, respectively. The preparation method is the same as in Example 1.

[0115] 3. The hydrocortisone compound ointment preparations of prescriptions 1-2, 9-1 and 9-2 obtained by the above prescriptions and preparation methods were subjected to in vitro release assays. Lidocaine hydrochloride, promocaine hydrochloride and benzocaine hydrochloride were measured respectively. The assay process was the same as the in vitro release assay method for lidocaine hydrochloride in Example 3.

[0116] The measurement results are as follows Figure 3 As shown, the results indicated that the cumulative permeation of lidocaine hydrochloride, promocaine hydrochloride, and benzocaine hydrochloride in the hydrocortisone compound ointment formulations of prescriptions 1-2, 9-1, and 9-2 reached 25.00 μg / cm³ at 24 hours. 2 Therefore, promocaine hydrochloride and benzocaine hydrochloride can be used to replace lidocaine hydrochloride.

[0117] Comparative Example 1 1. A compound ointment preparation of hydrocortisone for the treatment of hemorrhoids. The difference between Comparative Example 1 and Formulas 1-2 is that the raw materials do not contain chlorhexidine acetate or allantoin. The specific formula ingredients (g) of Comparative Example 1 are shown in Table 15.

[0118] Table 15

[0119] 2. Comparative Example 1 did not include chlorhexidine acetate or allantoin, and the preparation method was the same as in Example 1.

[0120] Comparative Example 2 1. A hydrocortisone compound ointment preparation for treating hemorrhoids, the difference between Comparative Example 2 and Formula 1-2 is that it does not contain allantoin in the raw materials. The specific formula ingredients (g) of Comparative Example 2 are shown in Table 16.

[0121] Table 16

[0122] 2. Comparative Example 2 did not include allantoin; the preparation method was the same as in Example 1. Comparative Example 3 1. A compound ointment preparation of hydrocortisone for the treatment of hemorrhoids, wherein the difference between Comparative Example 3 and Formulas 1-2 is that chlorhexidine acetate is not present in the raw materials. The specific formula components (g) of Comparative Example 3 are shown in Table 17.

[0123] Table 17

[0124] 2. Comparative Example 3 did not include chlorhexidine acetate; the preparation method was the same as in Example 1. Experiment 1: Verification of a rat anal swelling model The animals used in the experiment were 6-week-old SD rats, half male and half female.

[0125] The croton oil mixture was prepared using 1 part distilled water, 4 parts pyridine, 5 parts ether, and 10 parts 6% croton oil ether solution. To create the model, a cotton ball soaked in 0.16 mL of the croton oil mixture was inserted into the anus of a 6-week-old rat anesthetized with chloral hydrate for 40 seconds, thus obtaining a croton oil-induced anal swelling model in rats.

[0126] After successful model establishment, the rats were immediately divided into groups, and drug administration began. The drugs were administered intrarectally using cotton swabs. The dosage for prescriptions 1-2, 8-1, 9-1, and comparative examples 1, 2, and 3 was 0.2 g / kg. Based on a rat weight of 300 g, the dosage per rat was 0.06 g. The normal control group and the model group received the drug via saline solution using cotton swabs. Administered the drugs three times daily for 14 consecutive days.

[0127] The diameter of the swelling in the entire perianal tissue was measured using vernier calipers before film formation and 2 and 4 days after film formation and drug administration. The mean of the anal diameter at different time points after modeling and the anal diameter before modeling was used as an indicator of the degree of swelling. Since the anal swelling of the model rats disappeared after 4 days, the anal diameter was no longer measured after 4 days.

[0128] The results are shown in Table 18.

[0129] Table 18 Effect of croton oil on anal swelling degree in rats (±S, mm, n=10)

[0130] Note: && p＜0.05 The model group was compared with the normal control group; * p＜0.05 The examples were compared with the model control group; # p＜0.05 The examples are compared with the comparative examples.

[0131] Conclusion: Preliminary experiments on anal swelling using ointments with different raw material compositions showed a significant difference in the degree of anal swelling between the model group and the normal group, indicating successful model establishment. Compared with prescriptions 1-2, 8-1, and 9-1, prescriptions 1-2, 8-1, and 9-1 showed significant therapeutic effects on croton oil-induced anal swelling in rats, reducing the degree of anal swelling. Compared with comparative examples 1, 2, and 3, comparative examples 1, 2, and 3 showed almost no significant difference in the croton oil-induced anal swelling model compared to the model control group, failing to reduce the degree of anal swelling. Compared with comparative examples 1, 2, and 3, prescriptions 1-2, 8-1, and 9-1 showed significant therapeutic effects on croton oil-induced anal swelling in rats, reducing the degree of anal swelling.

[0132] Therefore, it can be seen that prescriptions 1-2, 8-1 and 9-1 have significant therapeutic effects on the rat anal swelling model and can reduce the degree of anal swelling.

[0133] Experiment Example 2: Results and Analysis of a Rat Anal Ulcer Model The animals used in the experiment were 6-week-old SD rats, half male and half female.

[0134] 1. Route of administration The test sample is used clinically for perianal or intraanal application; therefore, this study uses rectal administration in rats to simulate clinical administration conditions and obtain evaluation data.

[0135] 2. Dosage design and basis The proposed clinical dosage for each prescription is 2g three times daily. Based on the equivalent dose coefficient for rats and humans, this is approximately 2 × 0.018 × 5 ≈ 0.2g / kg. This experiment uses the clinically equivalent dose of 0.2g / kg. Assuming each rat weighs 300g, the dosage per rat is 0.06g, administered three times daily.

[0136] The clinical dosage and administration of Mayinglong Musk Hemorrhoid Ointment are as follows: 2-3 times daily, 2-3g each time. Based on the equivalent dose coefficient between rats and humans, the formula is: 2 × 0.018 × 5 ≈ 0.2g / kg. Assuming each rat weighs 300g, the dosage per rat can be set at 0.06g, administered 3 times daily.

[0137] 3. Animal identification after grouping Each animal was identified using animal tagging and box tagging methods.

[0138] 3.1 Animal Marking Each group of animals was numbered 1-10, and different parts of the animals' fur were rubbed with picric acid for marking. See Table 19 for details.

[0139] Table 19 Animal Markings

[0140] 3.2 Box Label After grouping the animals, different groups are labeled with different colored tags. The tags include: project number, tag number, sex, group, animal number, project leader, contact number, and experiment start and end dates. The completed tags are hung on the front of the enclosure.

[0141] 4. Acetic acid-induced rat anal ulcer model experiment 4.1 Model Preparation Filter paper with an inner diameter of 6 mm was made using a punch. After being fully soaked in 99.0% acetic acid solution (overnight soaking), the filter paper was placed around the anus of 50 membrane-forming rats to ensure close contact between the filter paper and the perianal skin and mucous membrane. One filter paper was used each time, and the filter paper was replaced once every 0.5 min for each rat, for a total of 1 min per rat.

[0142] 4.2 Animal grouping Group design: A total of 6 groups were set up, namely normal animal group, model control group, prescription 1-2 group, prescription 8-1 group, prescription 9-1 group, and positive control group.

[0143] Number of animals: 10 animals per group, totaling 60 animals; Sex ratio: 50% male and 50% female; Grouping method: The anal diameter was measured the day after modeling, and the samples were evenly grouped according to the anal diameter. See Table 20 below for specific grouping information.

[0144] Table 20 Dosing Regimen and Grouping Information

[0145] Note: The first digit of the animal number represents the group, the second letter represents acetic acid (C), and the last two digits represent the animal serial number.

[0146] 4.3 Animal administration After grouping, medication was administered. For each prescription (1-2, 8-1, and 9-1), the dosage was 0.2 g / kg. 0.06 g of each prescription was thoroughly mixed with the medication and then applied to the anus using a cotton swab. For the positive control group, the dosage was 0.06 g / animal. For the normal and model groups, the dosage was applied with a cotton swab soaked in physiological saline. Administered three times daily for 14 consecutive days.

[0147] 4.4 Indicator Testing 4.4.1 Weight Measurement Weigh yourself once a week.

[0148] 4.4.2 Ulcer Score Measurement The healing of the ulcer was observed at 2, 4, 8, 10, 12, and 14 days after medication, and an ulcer score was assigned (assignment criteria: exudate criteria: 3 points for ulcer exudate; 2 points for a small amount of ulcer exudate; 1 point for eschar and basic healing; 0 points for complete healing. Redness and swelling criteria: 3 points for redness and swelling ≥1mm and extending beyond the ulcer surface; 2 points for the edge protruding above the skin; 1 point for barely visible redness and swelling; 0 points for no redness or swelling). Photos were taken at each observation.

[0149] 4.4.3 Ulcer surface and measurement The long and short diameters of the ulcer were observed at 2, 4, 8, 10, 12, and 14 days after medication, and the product of the long and short diameters was taken as the ulcer area.

[0150] 4.4.4 Pathological and histological examination Testing time: End of test Animals tested: All surviving animals Detection method: After euthanasia by chloral hydrate anesthesia, skin around the anus and the ulcer site was excised, fixed in formalin, and stained with hematoxylin and eosin (HE) for pathological histological examination. 5. Results Analysis 5.1 Weight Before administration, there was no significant difference in body weight between the three dosage groups (Ma Yinglong Hemorrhoid Ointment, Prescription 1-2, Prescription 8-1, and Prescription 9-1) and the model group (P>0.05). After modeling, the model group showed slower weight gain compared to the normal group. On days 7 and 14 after administration, the body weight of the Ma Yinglong Hemorrhoid Ointment group and the test sample groups (Prescription 1-2, Prescription 8-1, and Prescription 9-1) was basically the same as that of the model group (p>0.05). The results are shown in Table 21.

[0151] Table 21 Effect of acetic acid on body weight in rats with anal ulcer model ( (±S, g, n=10)

[0152] Note: & p < 0.05, compared with the normal control group.

[0153] 5.2 Ulcer Score Compared with the normal control group, all animals developed perianal exudation and swelling after modeling. Compared with the model group, the perianal exudation and swelling of the Ma Yinglong Hemorrhoid Ointment and the three dosage groups (Prescription 1-2, Prescription 8-1, and Prescription 9-1) decreased from day 4 after administration, and the ulcer score gradually decreased. Statistically significant differences were observed between the Ma Yinglong Hemorrhoid Ointment and the three dosage groups (Prescription 1-2, Prescription 8-1, and Prescription 9-1) starting from day 8 (p < 0.01). Compared with Ma Yinglong Hemorrhoid Ointment, there were no significant differences in ulcer scores at any test point among the three dosage groups (Prescription 1-2, Prescription 8-1, and Prescription 9-1) (P > 0.05); the results are shown in Table 22.

[0154] Table 22 Effects of different formulations on ulcer scores in acetic acid-induced anal ulcer model rats (±S, n=10)

[0155] Note: && p < 0.01, compared with the normal control group; *p<0.05, **p<0.01 Comparison between each treatment group and the model control group; p>0.05, compared with the positive control group for each dose group of prescriptions 1-2, 8-1, and 9-1.

[0156] 5.3 Ulcer area Normal rats have no perianal ulcers. In the model group, rats developed ulcers of varying degrees after modeling. The ulcers reached their final stage on day 8 after modeling, with an incidence rate of 90%. Some animals gradually recovered spontaneously afterward. However, by day 14 after modeling, 60% of the animals still had ulcers that had not healed spontaneously.

[0157] Compared with the model group, the number of animals with ulcers in the Mayinglong Hemorrhoid Ointment and the three dosage groups (Prescription 1-2, Prescription 8-1, and Prescription 9-1) was significantly reduced, and the ulcer area decreased significantly from day 8 of administration. By day 10, all animals in the Prescription 1-2, Prescription 8-1, and Prescription 9-1 groups had ulcers healed, with statistically significant differences in ulcer area (p < 0.05). However, at each time point after administration, there were no statistically significant differences between the three dosage groups (Prescription 1-2, Prescription 8-1, and Prescription 9-1) and the Mayinglong Hemorrhoid Ointment group (p > 0.05), but none of the animals in the Mayinglong Hemorrhoid Ointment group had ulcers healed; the results are shown in Table 23.

[0158] Table 23 Effects of different formulations on ulcer area in acetic acid-induced anal ulcer model rats (±S, mm) 2 (n=10)

[0159] Note: && p < 0.01, compared with the normal control group; *p<0.05, **p<0.01 Comparison between each treatment group and the model control group; p>0.05, compared with the positive control group for each dose group of prescriptions 1-2, 8-1, and 9-1.

[0160] 5.4 Pathological and histological examination Normal control group: The perianal skin and mucous membrane epithelial tissue structure is intact.

[0161] Model control group: Partial mucosal epithelial degeneration and necrosis can be seen, some tissue mucosal surfaces show exudation, interstitial tissue swelling, and submucosal capillary dilation and congestion.

[0162] Positive control group: Anal tissue damage was significantly improved, but telangiectasia and edema were still visible in the interstitial tissue.

[0163] Prescription 1-2 dose group: Significant improvement in anal tissue damage, no obvious mucosal epithelial and skin tissue degeneration and necrosis, no inflammatory cell infiltration and exudation, and no tissue edema.

[0164] Prescription 8-1 dose group: Significant improvement in anal tissue damage, no obvious mucosal epithelial and skin tissue degeneration and necrosis, no inflammatory cell infiltration and exudation, and no tissue edema.

[0165] Prescription 9-1 dosage group: The anal tissue damage was significantly improved, with no obvious degeneration and necrosis of mucosal epithelium and skin tissue, no inflammatory cell infiltration and exudation, and no tissue edema.

[0166] Therefore, it can be seen that the lesions in the model group were more obvious, indicating that the modeling was successful. The three dosage groups (Ma Yinglong Hemorrhoid Ointment, Prescription 1-2, Prescription 8-1, and Prescription 9-1) all showed varying degrees of improvement, with the Prescription 1-2, Prescription 8-1, and Prescription 9-1 showing more significant improvement than the Ma Yinglong Hemorrhoid Ointment group. (See results below.) Figure 4 .

[0167] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A hydrocortisone compound ointment formulation for treating hemorrhoids, characterized in that, The aforementioned hydrocortisone compound ointment formulation comprises corticosteroids, vasoconstrictors, local anesthetics, L-menthol, chlorhexidine acetate, and allantoin, wherein the weight percentages of the corticosteroids, vasoconstrictors, local anesthetics, L-menthol, chlorhexidine acetate, and allantoin are 0.15%-1%: 0.025%-0.1%: 2%-4% and 0.1%-1.5%: 0.02%-0.5%: 0.05%-1%; The corticosteroid is selected from any one or more of hydrocortisone and hydrocortisone butyrate; the vasoconstrictor is selected from any one or more of norepinephrine, oxymetazoline hydrochloride, naphazoline hydrochloride, and xylometazoline hydrochloride; and the local anesthetic is selected from any one or more of lidocaine hydrochloride, promocaine hydrochloride, and benzocaine hydrochloride.

2. The hydrocortisone compound ointment formulation according to claim 1, characterized in that, The weight percentages of the corticosteroids, vasoconstrictors, local anesthetics, L-menthol, chlorhexidine acetate, and allantoin are 0.25%:0.025%:4%:0.5%:0.02%:0.1%.

3. The hydrocortisone compound ointment formulation according to claim 1, characterized in that, The corticosteroid mentioned is hydrocortisone.

4. The hydrocortisone compound ointment formulation according to claim 1, characterized in that, The vasoconstrictor mentioned is phenylephrine or oxymetazoline hydrochloride.

5. The hydrocortisone compound ointment formulation according to claim 1, characterized in that, The local anesthetic is lidocaine hydrochloride or promocaine hydrochloride.

6. The hydrocortisone compound ointment formulation according to claim 1, characterized in that, The aforementioned hydrocortisone compound ointment formulation also includes a pharmaceutical matrix.

7. The hydrocortisone compound ointment formulation according to claim 6, characterized in that, The pharmaceutical matrix includes any one or more of liquid paraffin and white petrolatum.

8. The method for preparing the hydrocortisone compound ointment formulation according to any one of claims 1-7, characterized in that, The preparation method includes the following steps: S1. Crush the corticosteroids, vasoconstrictors, local anesthetics, L-menthol, allantoin, and chlorhexidine acetate into powder and set aside. S2. Add the crushed L-menthol to the liquid paraffin, stir to dissolve, add allantoin, stir to homogenize, and mix evenly. S3. Heat the white petrolatum and add the local anesthetic in four batches. Stir and homogenize each time the material is added. Add the raw materials of corticosteroid, vasoconstrictor and chlorhexidine acetate in sequence. Stir and homogenize after each addition to obtain a uniform dispersion phase. S4. Stir and homogenize the uniformly dispersed phase under vacuum; S5. After preparation, cool down, fill and seal.

9. The use of the hydrocortisone compound ointment formulation according to any one of claims 1-7 in the preparation of a medicament for the prevention, treatment or adjunctive treatment of hemorrhoids.

10. The application according to claim 9, characterized in that, The hemorrhoids mentioned include internal hemorrhoids, external hemorrhoids, or mixed hemorrhoids.

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