Externally applied medicine for treating haemorrhoids and preparation method thereof

Abstract

The invention discloses an externally applied medicine for treating haemorrhoids and a preparation method thereof. The externally applied medicine is prepared from the following raw materials in parts by weight: 11-18 parts of bothriospermum chinense, 9-16 parts of green vegetables, 11-18 parts of dandelion, 6-15 parts of lotus root sticks, 4-13 parts of black fungus, 6-15 parts of folium artemisiae argyi, 2-8 parts of pepper, 80-120 parts of white vinegar, 4-13 parts of Chinese chive roots and 9-16 parts of sophora flowers. According to the medicine for external application disclosed by the invention, through reasonable compatibility of various traditional Chinese medicinal materials, pharmacological effects and synergistic effects of all the components are fully exerted, and the medicine has remarkable curative effects of resisting inflammation, diminishing swelling, stopping bleeding, relieving pain and promoting tissue repair. The formula is remarkable in curative effect, high in safety and convenient to use, and an effective treatment choice is provided for patients suffering from haemorrhoids.

Description

Technical Field

[0001] The invention relates to the technical field of medical drugs, in particular to an external application medicine for treating hemorrhoids and a preparation method thereof. Background Art

[0002] Hemorrhoids are common diseases in anorectal medicine, and their incidence rate increases significantly with age. Clinical manifestations include blood in stool, pain, and prolapse, which seriously affect the quality of life of patients. Currently, the treatment methods are mainly divided into two categories: surgical resection and conservative drug treatment. Among them, topical preparations have become the main choice because of their convenience and high patient acceptance. However, the existing hemorrhoid topical drugs still have the following key defects:

[0003] Efficacy limitations: Most topical medications can only relieve symptoms (such as hemostasis and pain relief) but cannot cure the lesions, resulting in a high recurrence rate. For example, although the formula using traditional ingredients such as taro and borneol claims to be cured once, its clinical data lacks large sample verification, and the actual recurrence rate is still over 30%4; while the combination containing rhubarb and Artemisia suspensa shortens the course of treatment, it needs to be combined with injection treatment, which increases the complexity of the operation.

[0004] Insufficient bioavailability: Conventional topical drugs have poor permeability of active ingredients and are difficult to effectively act on deep tissues. For example, formulas using alcohol as a solvent can promote the dissolution of some ingredients, but are prone to cause mucosal irritation, and fat-soluble ingredients (such as volatile oil from mugwort leaves) are difficult to release stably.

[0005] Unreasonable combination of ingredients: Some formulas rely too much on toxic medicinal materials (such as Aconitum kusnezoffii and Strychnos nux vomica), and long-term use may cause liver and kidney damage; while relying solely on a single effective ingredient (such as Glauber's salt for clearing heat) makes it difficult to achieve multi-target synergy of anti-inflammatory and repair.

[0006] Therefore, an external compress for treating hemorrhoids and a preparation method thereof are proposed to solve the current deficiencies. Summary of the invention

[0007] The technical problem to be solved by the present invention is to overcome the defects of the above-mentioned technology and provide an external compress medicine for treating hemorrhoids and a preparation method thereof.

[0008] To solve the above technical problems, the technical solution provided by the present invention is an external compress for treating hemorrhoids, which is prepared from the following raw materials in weight ratio: 11-18 parts of toad grass, 9-16 parts of green vegetables, 11-18 parts of dandelions, 6-15 parts of lotus root sticks, 4-13 parts of black fungus, 6-15 parts of wormwood leaves, 2-8 parts of pepper, 80-120 parts of white vinegar, 4-13 parts of leek roots, and 9-16 parts of Sophora japonica flowers.

[0009] As an improvement, it is made from the following raw materials in the following weight ratio: 15 parts of toad grass, 12 parts of green vegetables, 15 parts of dandelions, 10 parts of lotus root sticks, 8 parts of black fungus, 10 parts of mugwort, 5 parts of pepper, 100 parts of white vinegar, 8 parts of leek roots, and 12 parts of locust flowers.

[0010] An external compress for treating hemorrhoids comprises the following steps:

[0011] S1. Raw material pretreatment: Toad grass, green vegetables, dandelion, and leek roots are cleaned and processed respectively to remove impurities and non-medicinal parts, dried in a circulating hot air drying oven at 45-50°C to a moisture content of ≤8%, and then crushed to a particle size of 80-100 meshes to obtain primary powder A;

[0012] S2. Preparation of composite extract: Sophora japonica, Artemisia argyi and Zanthoxylum bungeanum were mixed in proportion, 6 times the amount of purified water was added, and gradient extraction was carried out in a multifunctional extraction tank. In the first stage, the constant temperature of 55-65° C. was maintained for 35-45 min. In the second stage, the temperature was raised to 80-90° C. for reflux extraction for 55-65 min. The mixture was double filtered through a 180-220 mesh filter cloth, the combined filtrate was collected, and the mixture was concentrated under reduced pressure to a relative density of 1.15-1.20 to obtain extract B.

[0013] S3, solid matrix treatment: After the black fungus is soaked in purified water and expanded, it is placed in an ultrafine grinder together with the lotus root stick, and the cell wall is broken at a low temperature of -10°C to control the particle size distribution D90≤15μm to obtain composite ultrafine powder C;

[0014] S4, vinegar production reaction: white vinegar is placed in a reactor with a stirring function, primary powder A and composite ultrafine powder C are added in sequence, a constant temperature environment of 25-30°C is maintained, and dynamic mixing is performed at a speed of 100-140 r / min for 55-65 min to form a homogeneous suspension system D;

[0015] S5. Preparation of finished product: The extract B was slowly added to the suspension system D three times, and ultrasonic treatment (frequency 40 kHz, power 300 W) was performed for 15 minutes after each addition. Finally, it was treated in a vacuum degassing machine at -0.08 MPa for 20 minutes to obtain a semi-solid topical preparation with thixotropy.

[0016] As an improvement, in S2, an intelligent temperature control system is used during gradient extraction, and the temperature deviation is controlled within the range of ±1°C.

[0017] As an improvement, in S3, food-grade nitrogen is continuously introduced into the cryogenic pulverization process for protection, and the oxygen content is maintained below 500 ppm.

[0018] As an improvement, in S5, the ultrasonic treatment adopts an intermittent working mode, with a frequency of 40kHz and a power of 300W, and a working cycle of running for 5 seconds / stopping for 2 seconds.

[0019] The present invention also provides an external compress for treating hemorrhoids, wherein the external compress comprises the external compress or other pharmaceutically acceptable physical forms.

[0020] As an improvement, the medicine is in the form of gel, foam, spray or ointment.

[0021] As an improvement, the present invention also provides the use of the above-mentioned external application medicine in preparing a medicine capable of treating hemorrhoids.

[0022] The pharmacological properties of the Chinese medicinal materials used are as follows:

[0023] Toad grass: It contains flavonoids, phenolic acids and other ingredients, which have significant anti-inflammatory effects and can effectively inhibit the release of inflammatory mediators. It also has inhibitory effects on a variety of bacteria and fungi, helping to prevent infection. It can also be used to treat redness, swelling, heat and pain caused by hemorrhoids.

[0024] It can be used in combination with heat-clearing and detoxifying drugs such as dandelion and green onion to enhance the overall anti-inflammatory and swelling-reducing effects.

[0025] Greens: Rich in ω-3 fatty acids and flavonoids, they have anti-inflammatory effects. They have inhibitory effects on a variety of pathogens. They are used to treat damp-heat symptoms caused by hemorrhoids. They can also relieve hemorrhoid bleeding symptoms.

[0026] It can be used together with other hemostatic drugs such as Sophora japonica flower and Artemisia argyi to enhance the hemostatic effect.

[0027] It works synergistically with heat-clearing and detoxifying drugs such as Toad Grass and Dandelion to enhance the overall therapeutic effect.

[0028] Dandelion: Contains taraxasterol, taraxacin and other ingredients, which have significant anti-inflammatory effects. It has inhibitory effects on a variety of bacteria and fungi. It is used to treat inflammation and infection caused by hemorrhoids. It can also relieve swelling and induration caused by hemorrhoids.

[0029] It can be used in combination with heat-clearing and detoxifying drugs such as Toad Grass and Green Vegetables to enhance the overall anti-inflammatory and swelling effects.

[0030] It works synergistically with other drugs such as mugwort and Sichuan pepper to enhance the local analgesic effect.

[0031] Lotus root stick: It is rich in tannins and vitamin K, and has a significant hemostatic effect. It has an inhibitory effect on inflammatory reactions. It is used to treat hemorrhoidal bleeding. It can also relieve swelling and pain caused by hemorrhoids.

[0032] It can be used in combination with hemostatic drugs such as Sophora japonica and Scutellaria baicalensis to enhance the hemostatic effect.

[0033] It works synergistically with black fungus and other drugs to promote tissue repair.

[0034] Black Fungus: Contains black fungus polysaccharide, which has anticoagulant effect, enhances the body's immunity, promotes tissue repair, promotes blood circulation, accelerates wound healing, and relieves constipation symptoms caused by hemorrhoids.

[0035] It can be used in combination with lotus root sticks and other drugs to enhance the effects of hemostasis and promoting tissue repair.

[0036] Works synergistically with other ingredients to promote overall therapeutic effects.

[0037] Mugwort: Contains volatile oils and flavonoids, which have anti-inflammatory effects. It has an inhibitory effect on bleeding. It is used to treat hemorrhoidal bleeding. It can also relieve pain and discomfort caused by hemorrhoids.

[0038] It can be used together with Sophora japonica flower, Zanthoxylum bungeanum and other drugs to enhance the hemostatic and analgesic effects.

[0039] Works synergistically with other ingredients to enhance overall efficacy.

[0040] Zanthoxylum bungeanum: Contains volatile oil, which has local anesthetic effect. It has inhibitory effect on many bacteria and fungi. It can relieve the cold and dampness symptoms caused by hemorrhoids, and can also relieve the pain caused by hemorrhoids.

[0041] It can be used together with other drugs such as mugwort and dandelion to enhance the analgesic effect.

[0042] Works synergistically with other ingredients to enhance overall efficacy.

[0043] White vinegar: provides an acidic environment, which helps dissolve and absorb drug ingredients. It has an inhibitory effect on many bacteria. It can soften hemorrhoid tissue and promote drug absorption. It can also prevent drug deterioration and extend the shelf life.

[0044] As a solvent and reaction medium, it works synergistically with other ingredients to promote the dissolution and absorption of drugs.

[0045] Leek root: Promotes blood circulation, relieves swelling and pain caused by hemorrhoids. It can enhance the body's immunity, promote tissue repair, and relieve inflammation and infection caused by hemorrhoids.

[0046] It can be used in combination with black fungus and other drugs to enhance the effects of promoting blood circulation, removing blood stasis and promoting tissue repair.

[0047] Works synergistically with other ingredients to enhance overall efficacy.

[0048] Sophora japonica flower: Contains rutin, quercetin and other ingredients, which have significant hemostatic effects and inhibit inflammatory reactions. It is used to treat hemorrhoidal bleeding. It can also relieve inflammation and infection caused by hemorrhoids.

[0049] It can be used in combination with hemostatic drugs such as lotus root sticks and green vegetables to enhance the hemostatic effect.

[0050] It works synergistically with other drugs such as mugwort and Sichuan pepper to enhance the overall efficacy.

[0051] The advantages of the present invention compared with the prior art are:

[0052] 1. Clearing away heat, detoxifying, reducing swelling and relieving pain: The combination of drugs such as Toad Grass, Green Vegetables, and Dandelion can jointly play the role of clearing away heat, detoxifying, reducing swelling and relieving pain, and effectively relieve the redness, swelling, heat, pain and inflammatory response caused by hemorrhoids.

[0053] 2. Hemostasis and blood circulation: Sophora japonica flower, lotus root stick, mugwort leaf and other drugs are used together to synergistically play a hemostatic effect. At the same time, black fungus, leek root and other drugs promote blood circulation and accelerate wound healing.

[0054] 3. Local anesthesia and analgesia: The combination of drugs such as Sichuan pepper and mugwort can exert local anesthetic and analgesic effects, effectively relieving the pain caused by hemorrhoids.

[0055] 4. Acidic environment and drug absorption: White vinegar provides an acidic environment, promotes the dissolution and absorption of drug ingredients, and also has antibacterial effects to prevent infection.

[0056] 5. Promote tissue repair: The combination of black fungus, lotus root sticks, leek roots and other drugs can promote blood circulation and tissue repair, and accelerate wound healing.

[0057] 6. The topical medicine of the present invention gives full play to the pharmacological effects and synergistic effects of each component by rationally combining multiple Chinese medicinal materials, and has significant anti-inflammatory, detumescent, hemostatic, analgesic and tissue repair effects. The formula is not only effective, but also highly safe and easy to use, providing an effective treatment option for hemorrhoid patients. DETAILED DESCRIPTION

[0058] The content of the present invention can be more easily understood by selecting the following detailed description of the preferred implementation method of the present invention and the embodiments included. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those of ordinary skill in the art to which the present invention belongs. When there is a conflict, the definition in this specification shall prevail.

[0059] As used herein, the term "prepared from" is synonymous with "comprising." As used herein, the terms "comprising," "including," "having," "containing," or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a composition, process, method, article, or apparatus that comprises the listed elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, process, method, article, or apparatus.

[0060] The conjunction "consisting of excludes any unspecified element, step, or component. If used in a claim, this phrase renders the claim closed-ended so that it does not include materials other than those described, except for conventional impurities associated therewith. When the phrase "consisting of" appears in a clause of the body of a claim rather than immediately following the subject matter, it limits only the elements described in that clause; other elements are not excluded from the claim as a whole.

[0061] When amount, concentration or other value or parameter is expressed as range, preferred range or a series of upper preferred value and lower preferred value limit range, this should be understood as specifically disclosing all ranges formed by any pairing of any range upper limit or preferred value and any range lower limit or preferred value, regardless of whether the range is disclosed separately. For example, when disclosing range "1 to 5", described range should be interpreted as including range "1 to 4", "1 to 3", "1 to 2", "1 to 2 and 4 to 5", "1 to 3 and 5" etc. When numerical range is described in this article, unless otherwise stated, the range is intended to include its end value and all integers and fractions within the range.

[0062] Singular forms include plural references unless the context clearly indicates otherwise. "Optional" or "either" means that the subsequently described event or incident may or may not occur, and that the description includes instances where the event occurs and instances where it does not.

[0063] Approximate terms in the specification and claims are used to modify quantities, indicating that the present invention is not limited to the specific quantity, but also includes acceptable and modified parts close to the quantity without causing changes in the relevant basic functions. Accordingly, the use of "about", "approximately", etc. to modify a numerical value means that the present invention is not limited to the exact numerical value. In some examples, the approximate terms may correspond to the accuracy of the instrument for measuring the numerical value. In the specification and claims of this application, range limitations can be combined and / or interchanged, and if not otherwise stated, these ranges include all subranges contained therein.

[0064] In addition, the indefinite articles "a" and "an" before the elements or components of the present invention have no restrictions on the quantity requirements (i.e. the number of occurrences) of the elements or components. Therefore, "a" or "an" should be interpreted as including one or at least one, and the elements or components in the singular form also include the plural form, unless the number is obviously intended to be in the singular form.

[0065] "Polymer" means a polymeric compound prepared by polymerizing monomers of the same or different types. The general term "polymer" includes the terms "homopolymer", "copolymer", "terpolymer" and "interpolymer". "Interpolymer" means a polymer prepared by polymerizing at least two different monomers. The general term "interpolymer" includes the term "copolymer" (which is generally used to refer to a polymer prepared from two different monomers) and the term "terpolymer" (which is generally used to refer to a polymer prepared from three different monomers). It also includes polymers made by polymerizing more monomers. "Blend" means a polymer formed by mixing two or more polymers together by physical or chemical methods.

[0066] In addition, any methods and materials similar or equivalent to those described herein can be applied to the present invention. The preferred implementation methods and materials described herein are for demonstration purposes only and cannot limit the content of this application.

[0067] The experimental methods in the following examples are conventional methods unless otherwise specified; the experimental materials and test strains used in the following examples are purchased from commercial channels unless otherwise specified.

[0068] Embodiment 1

[0069] An external compress for treating hemorrhoids is prepared from the following raw materials in weight proportion: 11 parts of toad grass, 9 parts of green vegetables, 11 parts of dandelions, 6 parts of lotus root sticks, 4 parts of black fungus, 6 parts of wormwood leaves, 2 parts of pepper, 80 parts of white vinegar, 4 parts of leek roots, and 9 parts of Sophora japonica flowers.

[0070] An external compress for treating hemorrhoids comprises the following steps:

[0071] S1. Raw material pretreatment: Toad grass, green vegetables, dandelion, and leek roots are cleaned and processed respectively to remove impurities and non-medicinal parts to ensure the purity and efficacy of the medicinal materials; dried in a circulating hot air drying oven at 45°C to a moisture content of ≤8%, and then crushed to a particle size of 80 mesh to obtain primary powder A;

[0072] During the cleaning and sorting operation of raw materials, the purity of medicinal materials is significantly improved through cleaning and sorting, which reduces the impact of impurities on subsequent extraction and reaction, removes non-medicinal parts, ensures the stability of the active ingredient content of medicinal materials, and is conducive to the subsequent efficacy of the medicine.

[0073] Specific:

[0074] Toad grass: Remove dead leaves, dirt and other impurities, and keep the whole grass for medicinal use.

[0075] Green vegetables: Remove yellow leaves, dead leaves and dirt, and keep fresh leaves.

[0076] Dandelion: Remove dead leaves, dirt and impurities from the roots, and keep the whole plant for medicinal use.

[0077] Leek roots: Remove the soil and fibrous roots, and keep the roots for medicinal use.

[0078] The raw materials are dried in a circulating hot air drying oven to remove excess moisture from the medicinal materials, prevent mildew and bacterial growth, and extend the shelf life. At the same time, reducing the moisture content can improve the chemical stability of the medicinal materials, reduce the degradation of the active ingredients, and the dried medicinal materials are easier to crush, which is conducive to the subsequent crushing operation.

[0079] The crushing of raw materials significantly increases the surface area of ​​the medicinal materials, which is conducive to the subsequent extraction and reaction of active ingredients. At the same time, the solubility of fine powder is higher, which is conducive to the dissolution of active ingredients, and the crushed fine powder is easier to mix evenly with other ingredients to ensure the uniformity of the preparation.

[0080] The quality of the primary powder A obtained after cleaning, drying and pulverization is stable, which is beneficial to the subsequent preparation process. At the same time, the increased surface area and solubility improve the reactivity of the primary powder A, which is beneficial to the subsequent extraction and reaction.

[0081] S2. Preparation of composite extract: Sophora japonica, Artemisia argyi and Zanthoxylum bungeanum were mixed in proportion, 6 times the amount of purified water was added, and gradient extraction was carried out in a multifunctional extraction tank. In the first stage, the constant temperature of 55°C was maintained for 35 minutes, and in the second stage, the temperature was raised to 80°C for reflux extraction for 55 minutes. The mixture was double filtered through a 180-mesh filter cloth, the combined filtrate was collected, and the mixture was concentrated under reduced pressure to a relative density of 1.15 to obtain extract B;

[0082] During implementation, an intelligent temperature control system was used during gradient extraction, and the temperature deviation was controlled within the range of ±1°C.

[0083] By mixing, the active ingredients of different medicinal materials can work together in the extraction process to improve the extraction efficiency. The use of purified water provides sufficient solvent to fully dissolve the active ingredients in the medicinal materials, avoid the influence of impurities on the extraction process, and ensure the purity of the extract.

[0084] In the gradient extraction process, the first stage of low-temperature immersion helps soften the medicinal materials and initially dissolve the active ingredients, avoids the damage of heat-sensitive ingredients by high temperature, and protects the activity of the active ingredients. The second stage of high-temperature reflux can accelerate the dissolution of the active ingredients and improve the extraction efficiency. The reflux process can recycle the solvent and reduce solvent consumption.

[0085] Moreover, the temperature deviation is controlled within the range of ±1°C through the intelligent temperature control system, which can ensure precise temperature control during the extraction process and avoid the influence of temperature fluctuations on the extraction effect. At the same time, it improves the stability and repeatability of the extraction process and ensures the consistent quality of the extract.

[0086] The final extract B has a relative density of 1.15, which ensures that the concentration of the extract is moderate and is beneficial to the subsequent preparation process.

[0087] S3, solid matrix treatment: After the black fungus is soaked in purified water and expanded, it is placed in an ultrafine grinder together with the lotus root stick, and the cell wall is broken at a low temperature of -10°C to control the particle size distribution D90≤15μm to obtain composite ultrafine powder C;

[0088] In the soaking and swelling process of black fungus, soaking in purified water can make the black fungus fully absorb water and swell, soften its texture, and facilitate the subsequent crushing and wall breaking process. At the same time, the cell wall of the expanded black fungus is more easily broken, which is conducive to the release of effective ingredients.

[0089] In the low-temperature ultrafine grinding and cell wall breaking process of black fungus, the plant cell wall is destroyed through ultrafine grinding and low-temperature treatment, so that the effective ingredients in the cells are fully released. The low temperature environment can reduce the degradation of the effective ingredients and protect the activity of heat-sensitive ingredients. Grinding the raw materials into ultrafine powder can increase the surface area and improve bioavailability.

[0090] At the same time, the particle size distribution D90 is controlled to be ≤15μm to ensure uniform powder fineness and improve its solubility and bioavailability.

[0091] During implementation, food-grade nitrogen is continuously introduced into the low-temperature pulverization process to protect the oxygen content below 500ppm. Specifically, nitrogen is an inert gas that can isolate oxygen in the air and prevent oxidative degradation of active ingredients. During the processing, maintaining a low-oxygen environment can protect the activity of heat-sensitive and easily oxidized ingredients and improve the stability of the product. The use of food-grade nitrogen can ensure the safety and quality of the product.

[0092] The obtained composite ultrafine powder C has a particle size distribution D90≤15μm and has high fineness, high solubility and good bioavailability.

[0093] S4, vinegar production reaction: white vinegar is placed in a reactor with a stirring function, primary powder A and composite ultrafine powder C are added in sequence, a constant temperature environment of 25°C is maintained, and dynamic mixing is performed at a speed of 100 r / min for 55 minutes to form a homogeneous suspension system D;

[0094] Specifically, the vinegar production reaction is to fully react the white vinegar with the primary powder A and the composite ultrafine powder C through dynamic mixing and constant temperature reaction to form a homogeneous suspension system D.

[0095] The use of white vinegar, as an acidic medium, can promote the dissolution and reaction of the active ingredients in medicinal materials. At the same time, the acidic environment of white vinegar helps to adjust the pH value of the system and create suitable reaction conditions.

[0096] In the process of adding primary powder A and composite ultrafine powder C, adding them in sequence can ensure that the two powders are in full contact with the white vinegar to avoid agglomeration and aggregation. At the same time, since the two powders contain different effective ingredients, adding them in sequence can ensure that each ingredient can fully react with the white vinegar.

[0097] In terms of temperature control, a constant temperature of 25°C is maintained. The reaction rate can be controlled by appropriate temperature to avoid overly fast or slow reactions, avoid high temperature damage to heat-sensitive components, and protect the activity of effective ingredients. At the same time, a constant temperature environment can ensure that the reaction is carried out at the optimal temperature, thereby improving reaction efficiency.

[0098] During the mixing process, stirring can ensure that the white vinegar and the two powders are fully mixed, which can promote the dissolution and reaction of the effective ingredients. Continuous stirring can prevent powder precipitation and maintain the uniformity of the system. At the same time, it can increase the contact area of ​​the reactants and improve the reaction rate.

[0099] The components of the finally formed homogeneous suspension system D are evenly distributed, without obvious precipitation and agglomeration, and have good stability, are not easy to stratify and precipitate, and can ensure that the effective ingredients react fully with the white vinegar and the active ingredients are effectively released.

[0100] S5. Preparation of finished product: slowly add extract B into suspension system D three times, perform ultrasonic treatment for 15 minutes after each addition, and finally treat it in a vacuum degassing machine at -0.08 MPa for 20 minutes to obtain a semi-solid topical preparation with thixotropy.

[0101] During implementation, the ultrasonic treatment was performed in an intermittent working mode, with a frequency of 40 kHz and a power of 300 W, and a working cycle of 5 seconds on / 2 seconds off.

[0102] Specifically, the finished product is prepared by adding extract B in batches, ultrasonic treatment and vacuum degassing process, fully mixing extract B with suspension system D, and finally obtaining a semi-solid topical preparation with thixotropy.

[0103] The portion-wise addition of extract B can avoid adding too much extract B at one time, which may lead to uneven mixing or excessive local concentration. At the same time, slow addition can prevent agglomeration of extract B and suspension system D, ensuring uniform distribution of each component. Moreover, the portion-wise addition can better control the reaction process and avoid excessively violent reaction.

[0104] During ultrasonic treatment, high-frequency vibration can promote the full mixing and dispersion of extract B and suspension system D, eliminate agglomeration and precipitation, and at the same time, the mechanical action of ultrasound can increase the solubility of the active ingredients and promote their uniform distribution. In addition, ultrasonic treatment can enhance the stability of the system and prevent stratification or precipitation during subsequent storage.

[0105] At the same time, an intermittent working mode is adopted to prevent overheating of the material during the ultrasonic process and to avoid degradation of the effective ingredients. The efficiency of the ultrasonic treatment can be improved through appropriate running and stopping time to ensure sufficient mixing.

[0106] During the vacuum degassing process, the vacuum environment can effectively remove bubbles in the system and prevent the appearance of bubbles in the preparation, which would affect its appearance and stability. After removing the bubbles, the density of the preparation is more uniform, which is conducive to subsequent application and use. At the same time, vacuum degassing can improve the thixotropy of the preparation, making it easier to apply and absorb.

[0107] The obtained semi-solid topical preparation has uniform distribution of components, no obvious precipitation and agglomeration, and can ensure the efficacy of the drug. It also has good stability and is not easy to delaminate and deteriorate.

[0108] It has a certain shape and stability when it is still, but it can flow under the action of external force (such as smearing) and is easy to use.

[0109] The present invention also provides an external compress for treating hemorrhoids, wherein the external compress comprises the external compress or other pharmaceutically acceptable physical forms.

[0110] Specifically, in the present invention, in addition to the semi-solid topical preparation obtained by the above-mentioned preparation method, other pharmaceutically acceptable physical forms are also provided to meet the needs of different patients and usage scenarios.

[0111] In this embodiment, the drug is in the form of a gel, foam, spray or ointment.

[0112] The present invention also provides use of the external application medicine in preparing medicine capable of treating hemorrhoids.

[0113] Embodiment 2

[0114] An external compress for treating hemorrhoids is prepared from the following raw materials in weight proportion: 15 parts of toad grass, 12 parts of green vegetables, 15 parts of dandelions, 10 parts of lotus root sticks, 8 parts of black fungus, 10 parts of wormwood leaves, 5 parts of pepper, 100 parts of white vinegar, 8 parts of leek roots, and 12 parts of Sophora japonica flowers.

[0115] An external compress for treating hemorrhoids comprises the following steps:

[0116] S1. Raw material pretreatment: Toad grass, green vegetables, dandelion, and leek roots are cleaned and processed respectively to remove impurities and non-medicinal parts to ensure the purity and efficacy of the medicinal materials; dried in a circulating hot air drying oven at 47°C to a moisture content of ≤8%, and then crushed to a particle size of 90 mesh to obtain primary powder A;

[0117] During the cleaning and sorting operation of raw materials, the purity of medicinal materials is significantly improved through cleaning and sorting, which reduces the impact of impurities on subsequent extraction and reaction, removes non-medicinal parts, ensures the stability of the active ingredient content of medicinal materials, and is conducive to the subsequent efficacy of the medicine.

[0118] Specific:

[0119] Toad grass: Remove dead leaves, dirt and other impurities, and keep the whole grass for medicinal use.

[0120] Green vegetables: Remove yellow leaves, dead leaves and dirt, and keep fresh leaves.

[0121] Dandelion: Remove dead leaves, dirt and impurities from the roots, and keep the whole plant for medicinal use.

[0122] Leek roots: Remove the soil and fibrous roots, and keep the roots for medicinal use.

[0123] The raw materials are dried in a circulating hot air drying oven to remove excess moisture from the medicinal materials, prevent mildew and bacterial growth, and extend the shelf life. At the same time, reducing the moisture content can improve the chemical stability of the medicinal materials, reduce the degradation of the active ingredients, and the dried medicinal materials are easier to crush, which is conducive to the subsequent crushing operation.

[0124] The crushing of raw materials significantly increases the surface area of ​​the medicinal materials, which is conducive to the subsequent extraction and reaction of active ingredients. At the same time, the solubility of fine powder is higher, which is conducive to the dissolution of active ingredients, and the crushed fine powder is easier to mix evenly with other ingredients to ensure the uniformity of the preparation.

[0125] The quality of the primary powder A obtained after cleaning, drying and pulverization is stable, which is beneficial to the subsequent preparation process. At the same time, the increased surface area and solubility improve the reactivity of the primary powder A, which is beneficial to the subsequent extraction and reaction.

[0126] S2. Preparation of composite extract: Sophora japonica, Artemisia argyi and Zanthoxylum bungeanum were mixed in proportion, 6 times the amount of purified water was added, and gradient extraction was carried out in a multifunctional extraction tank. In the first stage, the constant temperature of 60°C was maintained for 40 minutes, and in the second stage, the temperature was raised to 85°C for reflux extraction for 60 minutes. The mixture was double filtered through a 200-mesh filter cloth, the combined filtrate was collected, and the mixture was concentrated under reduced pressure to a relative density of 1.17 to obtain extract B;

[0127] During implementation, an intelligent temperature control system was used during gradient extraction, and the temperature deviation was controlled within the range of ±1°C.

[0128] By mixing, the active ingredients of different medicinal materials can work together in the extraction process to improve the extraction efficiency. The use of purified water provides sufficient solvent to fully dissolve the active ingredients in the medicinal materials, avoid the influence of impurities on the extraction process, and ensure the purity of the extract.

[0129] In the gradient extraction process, the first stage of low-temperature immersion helps soften the medicinal materials and initially dissolve the active ingredients, avoids the damage of heat-sensitive ingredients by high temperature, and protects the activity of the active ingredients. The second stage of high-temperature reflux can accelerate the dissolution of the active ingredients and improve the extraction efficiency. The reflux process can recycle the solvent and reduce solvent consumption.

[0130] Moreover, the temperature deviation is controlled within the range of ±1°C through the intelligent temperature control system, which can ensure precise temperature control during the extraction process and avoid the influence of temperature fluctuations on the extraction effect. At the same time, it improves the stability and repeatability of the extraction process and ensures the consistent quality of the extract.

[0131] The final extract B has a relative density of 1.157, which ensures that the concentration of the extract is moderate and is beneficial to the subsequent preparation process.

[0132] S3, solid matrix treatment: After the black fungus is soaked in purified water and expanded, it is placed in an ultrafine grinder together with the lotus root stick, and the cell wall is broken at a low temperature of -10°C to control the particle size distribution D90≤15μm to obtain composite ultrafine powder C;

[0133] In the soaking and swelling process of black fungus, soaking in purified water can make the black fungus fully absorb water and swell, soften its texture, and facilitate the subsequent crushing and wall breaking process. At the same time, the cell wall of the expanded black fungus is more easily broken, which is conducive to the release of effective ingredients.

[0134] In the low-temperature ultrafine grinding and cell wall breaking process of black fungus, the plant cell wall is destroyed through ultrafine grinding and low-temperature treatment, so that the effective ingredients in the cells are fully released. The low temperature environment can reduce the degradation of the effective ingredients and protect the activity of heat-sensitive ingredients. Grinding the raw materials into ultrafine powder can increase the surface area and improve bioavailability.

[0135] At the same time, the particle size distribution D90 is controlled to be ≤15μm to ensure uniform powder fineness and improve its solubility and bioavailability.

[0136] During implementation, food-grade nitrogen is continuously introduced into the low-temperature pulverization process to protect the oxygen content below 500ppm. Specifically, nitrogen is an inert gas that can isolate oxygen in the air and prevent oxidative degradation of active ingredients. During the processing, maintaining a low-oxygen environment can protect the activity of heat-sensitive and easily oxidized ingredients and improve the stability of the product. The use of food-grade nitrogen can ensure the safety and quality of the product.

[0137] The obtained composite ultrafine powder C has a particle size distribution D90≤15μm and has high fineness, high solubility and good bioavailability.

[0138] S4, vinegar production reaction: white vinegar is placed in a reactor with a stirring function, primary powder A and composite ultrafine powder C are added in sequence, the temperature is maintained at 28°C, and dynamic mixing is performed at a speed of 120 r / min for 60 min to form a homogeneous suspension system D;

[0139] Specifically, the vinegar production reaction is to fully react the white vinegar with the primary powder A and the composite ultrafine powder C through dynamic mixing and constant temperature reaction to form a homogeneous suspension system D.

[0140] The use of white vinegar, as an acidic medium, can promote the dissolution and reaction of the active ingredients in medicinal materials. At the same time, the acidic environment of white vinegar helps to adjust the pH value of the system and create suitable reaction conditions.

[0141] In the process of adding primary powder A and composite ultrafine powder C, adding them in sequence can ensure that the two powders are in full contact with the white vinegar to avoid agglomeration and aggregation. At the same time, since the two powders contain different effective ingredients, adding them in sequence can ensure that each ingredient can fully react with the white vinegar.

[0142] In terms of temperature control, a constant temperature of 28°C is maintained. The reaction rate can be controlled through appropriate temperature to avoid overly fast or slow reactions, avoid high temperature damage to heat-sensitive components, and protect the activity of effective ingredients. At the same time, a constant temperature environment can ensure that the reaction is carried out at the optimal temperature, thereby improving reaction efficiency.

[0143] During the mixing process, stirring can ensure that the white vinegar and the two powders are fully mixed, which can promote the dissolution and reaction of the effective ingredients. Continuous stirring can prevent powder precipitation and maintain the uniformity of the system. At the same time, it can increase the contact area of ​​the reactants and improve the reaction rate.

[0144] The components of the finally formed homogeneous suspension system D are evenly distributed, without obvious precipitation and agglomeration, and have good stability, are not easy to stratify and precipitate, and can ensure that the effective ingredients react fully with the white vinegar and the active ingredients are effectively released.

[0145] S5. Preparation of finished product: slowly add extract B into suspension system D three times, perform ultrasonic treatment for 15 minutes after each addition, and finally treat it in a vacuum degassing machine at -0.08 MPa for 20 minutes to obtain a semi-solid topical preparation with thixotropy.

[0146] During implementation, the ultrasonic treatment was performed in an intermittent working mode, with a frequency of 40 kHz and a power of 300 W, and a working cycle of 5 seconds on / 2 seconds off.

[0147] Specifically, the finished product is prepared by adding extract B in batches, ultrasonic treatment and vacuum degassing process, fully mixing extract B with suspension system D, and finally obtaining a semi-solid topical preparation with thixotropy.

[0148] The portion-wise addition of extract B can avoid adding too much extract B at one time, which may lead to uneven mixing or excessive local concentration. At the same time, slow addition can prevent agglomeration of extract B and suspension system D, ensuring uniform distribution of each component. Moreover, the portion-wise addition can better control the reaction process and avoid excessively violent reaction.

[0149] During ultrasonic treatment, high-frequency vibration can promote the full mixing and dispersion of extract B and suspension system D, eliminate agglomeration and precipitation, and at the same time, the mechanical action of ultrasound can increase the solubility of the active ingredients and promote their uniform distribution. In addition, ultrasonic treatment can enhance the stability of the system and prevent stratification or precipitation during subsequent storage.

[0150] At the same time, an intermittent working mode is adopted to prevent overheating of the material during the ultrasonic process and to avoid degradation of the effective ingredients. The efficiency of the ultrasonic treatment can be improved through appropriate running and stopping time to ensure sufficient mixing.

[0151] During the vacuum degassing process, the vacuum environment can effectively remove bubbles in the system and prevent the appearance of bubbles in the preparation, which would affect its appearance and stability. After removing the bubbles, the density of the preparation is more uniform, which is conducive to subsequent application and use. At the same time, vacuum degassing can improve the thixotropy of the preparation, making it easier to apply and absorb.

[0152] The obtained semi-solid topical preparation has uniform distribution of components, no obvious precipitation and agglomeration, and can ensure the efficacy of the drug. It also has good stability and is not easy to delaminate and deteriorate.

[0153] It has a certain shape and stability when it is still, but it can flow under the action of external force (such as smearing) and is easy to use.

[0154] The present invention also provides an external compress for treating hemorrhoids, wherein the external compress comprises the external compress or other pharmaceutically acceptable physical forms.

[0155] Specifically, in the present invention, in addition to the semi-solid topical preparation obtained by the above-mentioned preparation method, other pharmaceutically acceptable physical forms are also provided to meet the needs of different patients and usage scenarios.

[0156] In this embodiment, the drug is in the form of a gel, foam, spray or ointment.

[0157] The present invention also provides use of the external application medicine in preparing medicine capable of treating hemorrhoids.

[0158] Embodiment 3

[0159] An external compress for treating hemorrhoids is prepared from the following raw materials in weight proportion: 18 parts of toad grass, 16 parts of green vegetables, 18 parts of dandelions, 15 parts of lotus root sticks, 13 parts of black fungus, 15 parts of wormwood leaves, 8 parts of pepper, 120 parts of white vinegar, 4-13 parts of leek roots, and 16 parts of Sophora japonica flowers.

[0160] An external compress for treating hemorrhoids comprises the following steps:

[0161] S1. Raw material pretreatment: Toad grass, green vegetables, dandelion, and leek roots are cleaned and processed respectively to remove impurities and non-medicinal parts to ensure the purity and efficacy of the medicinal materials; dried in a circulating hot air drying oven at 50°C to a moisture content of ≤8%, and then crushed to a particle size of 100 mesh to obtain primary powder A;

[0162] During the cleaning and sorting operation of raw materials, the purity of medicinal materials is significantly improved through cleaning and sorting, which reduces the impact of impurities on subsequent extraction and reaction, removes non-medicinal parts, ensures the stability of the active ingredient content of medicinal materials, and is conducive to the subsequent efficacy of the medicine.

[0163] Specific:

[0164] Toad grass: Remove dead leaves, dirt and other impurities, and keep the whole grass for medicinal use.

[0165] Green vegetables: Remove yellow leaves, dead leaves and dirt, and keep fresh leaves.

[0166] Dandelion: Remove dead leaves, dirt and impurities from the roots, and keep the whole plant for medicinal use.

[0167] Leek roots: Remove the soil and fibrous roots, and keep the roots for medicinal use.

[0168] The raw materials are dried in a circulating hot air drying oven to remove excess moisture from the medicinal materials, prevent mildew and bacterial growth, and extend the shelf life. At the same time, reducing the moisture content can improve the chemical stability of the medicinal materials, reduce the degradation of the active ingredients, and the dried medicinal materials are easier to crush, which is conducive to the subsequent crushing operation.

[0169] The crushing of raw materials significantly increases the surface area of ​​the medicinal materials, which is conducive to the subsequent extraction and reaction of active ingredients. At the same time, the solubility of fine powder is higher, which is conducive to the dissolution of active ingredients, and the crushed fine powder is easier to mix evenly with other ingredients to ensure the uniformity of the preparation.

[0170] The quality of the primary powder A obtained after cleaning, drying and pulverization is stable, which is beneficial to the subsequent preparation process. At the same time, the increased surface area and solubility improve the reactivity of the primary powder A, which is beneficial to the subsequent extraction and reaction.

[0171] S2. Preparation of composite extract: Sophora japonica, Artemisia argyi and Zanthoxylum bungeanum were mixed in proportion, 6 times the amount of purified water was added, and gradient extraction was carried out in a multifunctional extraction tank. In the first stage, the constant temperature of 65°C was maintained for 45 minutes, and in the second stage, the temperature was raised to 90°C for reflux extraction for 65 minutes. The mixture was double filtered through a 220-mesh filter cloth, the combined filtrate was collected, and the mixture was concentrated under reduced pressure to a relative density of 1.20 to obtain extract B;

[0172] During implementation, an intelligent temperature control system was used during gradient extraction, and the temperature deviation was controlled within the range of ±1°C.

[0173] By mixing, the active ingredients of different medicinal materials can work together in the extraction process to improve the extraction efficiency. The use of purified water provides sufficient solvent to fully dissolve the active ingredients in the medicinal materials, avoid the influence of impurities on the extraction process, and ensure the purity of the extract.

[0174] In the gradient extraction process, the first stage of low-temperature immersion helps soften the medicinal materials and initially dissolve the active ingredients, avoids the damage of heat-sensitive ingredients by high temperature, and protects the activity of the active ingredients. The second stage of high-temperature reflux can accelerate the dissolution of the active ingredients and improve the extraction efficiency. The reflux process can recycle the solvent and reduce solvent consumption.

[0175] Moreover, the temperature deviation is controlled within the range of ±1°C through the intelligent temperature control system, which can ensure precise temperature control during the extraction process and avoid the influence of temperature fluctuations on the extraction effect. At the same time, it improves the stability and repeatability of the extraction process and ensures the consistent quality of the extract.

[0176] The relative density of the extract B finally obtained is within the range of 1.20, which ensures that the concentration of the extract is moderate and is beneficial to the subsequent preparation process.

[0177] S3, solid matrix treatment: After the black fungus is soaked in purified water and expanded, it is placed in an ultrafine grinder together with the lotus root stick, and the cell wall is broken at a low temperature of -10°C to control the particle size distribution D90≤15μm to obtain composite ultrafine powder C;

[0178] In the soaking and swelling process of black fungus, soaking in purified water can make the black fungus fully absorb water and swell, soften its texture, and facilitate the subsequent crushing and wall breaking process. At the same time, the cell wall of the expanded black fungus is more easily broken, which is conducive to the release of effective ingredients.

[0179] In the low-temperature ultrafine grinding and cell wall breaking process of black fungus, the plant cell wall is destroyed through ultrafine grinding and low-temperature treatment, so that the effective ingredients in the cells are fully released. The low temperature environment can reduce the degradation of the effective ingredients and protect the activity of heat-sensitive ingredients. Grinding the raw materials into ultrafine powder can increase the surface area and improve bioavailability.

[0180] At the same time, the particle size distribution D90 is controlled to be ≤15μm to ensure uniform powder fineness and improve its solubility and bioavailability.

[0181] During implementation, food-grade nitrogen is continuously introduced into the low-temperature pulverization process to protect the oxygen content below 500ppm. Specifically, nitrogen is an inert gas that can isolate oxygen in the air and prevent oxidative degradation of active ingredients. During the processing, maintaining a low-oxygen environment can protect the activity of heat-sensitive and easily oxidized ingredients and improve the stability of the product. The use of food-grade nitrogen can ensure the safety and quality of the product.

[0182] The obtained composite ultrafine powder C has a particle size distribution D90≤15μm and has high fineness, high solubility and good bioavailability.

[0183] S4, vinegar production reaction: white vinegar is placed in a reactor with a stirring function, primary powder A and composite ultrafine powder C are added in sequence, the temperature is maintained at 30°C, and dynamic mixing is performed at a speed of 140r / min for 65min to form a homogeneous suspension system D;

[0184] Specifically, the vinegar production reaction is to fully react the white vinegar with the primary powder A and the composite ultrafine powder C through dynamic mixing and constant temperature reaction to form a homogeneous suspension system D.

[0185] The use of white vinegar, as an acidic medium, can promote the dissolution and reaction of the active ingredients in medicinal materials. At the same time, the acidic environment of white vinegar helps to adjust the pH value of the system and create suitable reaction conditions.

[0186] In the process of adding primary powder A and composite ultrafine powder C, adding them in sequence can ensure that the two powders are in full contact with the white vinegar to avoid agglomeration and aggregation. At the same time, since the two powders contain different effective ingredients, adding them in sequence can ensure that each ingredient can fully react with the white vinegar.

[0187] In terms of temperature control, maintain a constant temperature environment of 25-30℃. The reaction rate can be controlled by appropriate temperature to avoid overly fast or slow reactions, avoid high temperature damage to heat-sensitive components, and protect the activity of effective ingredients. At the same time, the constant temperature environment can ensure that the reaction is carried out at the optimal temperature, thereby improving reaction efficiency.

[0188] During the mixing process, stirring can ensure that the white vinegar and the two powders are fully mixed, which can promote the dissolution and reaction of the effective ingredients. Continuous stirring can prevent powder precipitation and maintain the uniformity of the system. At the same time, it can increase the contact area of ​​the reactants and improve the reaction rate.

[0189] The components of the finally formed homogeneous suspension system D are evenly distributed, without obvious precipitation and agglomeration, and have good stability, are not easy to stratify and precipitate, and can ensure that the effective ingredients react fully with the white vinegar and the active ingredients are effectively released.

[0190] S5. Preparation of finished product: slowly add extract B into suspension system D three times, perform ultrasonic treatment for 15 minutes after each addition, and finally treat it in a vacuum degassing machine at -0.08 MPa for 20 minutes to obtain a semi-solid topical preparation with thixotropy.

[0191] During implementation, the ultrasonic treatment was performed in an intermittent working mode, with a frequency of 40 kHz and a power of 300 W, and a working cycle of 5 seconds on / 2 seconds off.

[0192] Specifically, the finished product is prepared by adding extract B in batches, ultrasonic treatment and vacuum degassing process, fully mixing extract B with suspension system D, and finally obtaining a semi-solid topical preparation with thixotropy.

[0193] The portion-wise addition of extract B can avoid adding too much extract B at one time, which may lead to uneven mixing or excessive local concentration. At the same time, slow addition can prevent agglomeration of extract B and suspension system D, ensuring uniform distribution of each component. Moreover, the portion-wise addition can better control the reaction process and avoid excessively violent reaction.

[0194] During ultrasonic treatment, high-frequency vibration can promote the full mixing and dispersion of extract B and suspension system D, eliminate agglomeration and precipitation, and at the same time, the mechanical action of ultrasound can increase the solubility of the active ingredients and promote their uniform distribution. In addition, ultrasonic treatment can enhance the stability of the system and prevent stratification or precipitation during subsequent storage.

[0195] At the same time, an intermittent working mode is adopted to prevent overheating of the material during the ultrasonic process and to avoid degradation of the effective ingredients. The efficiency of the ultrasonic treatment can be improved through appropriate running and stopping time to ensure sufficient mixing.

[0196] During the vacuum degassing process, the vacuum environment can effectively remove bubbles in the system and prevent the appearance of bubbles in the preparation, which would affect its appearance and stability. After removing the bubbles, the density of the preparation is more uniform, which is conducive to subsequent application and use. At the same time, vacuum degassing can improve the thixotropy of the preparation, making it easier to apply and absorb.

[0197] The obtained semi-solid topical preparation has uniform distribution of components, no obvious precipitation and agglomeration, and can ensure the efficacy of the drug. It also has good stability and is not easy to delaminate and deteriorate.

[0198] It has a certain shape and stability when it is still, but it can flow under the action of external force (such as smearing) and is easy to use.

[0199] The present invention also provides an external compress for treating hemorrhoids, wherein the external compress comprises the external compress or other pharmaceutically acceptable physical forms.

[0200] Specifically, in the present invention, in addition to the semi-solid topical preparation obtained by the above-mentioned preparation method, other pharmaceutically acceptable physical forms are also provided to meet the needs of different patients and usage scenarios.

[0201] In this embodiment, the drug is in the form of a gel, foam, spray or ointment.

[0202] The present invention also provides use of the external application medicine in preparing medicine capable of treating hemorrhoids.

[0203] In order to better illustrate the technical effect of the present invention, the following experiment was conducted.

[0204] Experimental Example 1: Verification of anti-inflammatory and detumescent effects (rat anal swelling experiment)

[0205] 1. Test preparation:

[0206] (1) Test samples: physiological saline, commercially available hemorrhoid cream (containing 1.5% lidocaine), and the sample prepared in Example 2.

[0207] (2) Test animals:

[0208] Healthy ICR mice, SPF grade, mass 22±3g, half male and half female, after 1 week of adaptive feeding of mice, the mice were randomly divided into 5 groups, namely blank control group (normal saline), positive control group (commercially available hemorrhoid cream), low-dose group (10% of the preparation of Example 2), medium-dose group (20% of the preparation of Example 2), and high-dose group (30% of the preparation of Example 2), with 10 mice in each group.

[0209] 3. Model establishment: Before the experiment, rats were deprived of water and food. During the experiment, 0.1 mL of 1% carrageenan saline solution was injected under the anal mucosa of rats. After injection, light pressure was applied for 30 seconds to prevent leakage to establish an acute inflammatory swelling model.

[0210] IV. Grouping treatment: 1 hour after injection, medication was started. Each group applied the drug twice a day, morning and evening (0.5 g / time), and the drug was evenly applied 2 cm around the anus. 2 The area was covered with sterile gauze and secured with medical tape for 7 days.

[0211] 5. Data Collection:

[0212] a) Swelling diameter: The maximum transverse diameter of the anus was measured by a double-blind operator using a digital vernier caliper (accuracy 0.01 mm), and the average of three measurements was taken.

[0213] b) Detection of inflammatory factors: Rats were killed on the 7th day, 100 mg of perianal tissue was collected, quick-frozen in liquid nitrogen and then ground, protein was extracted using RIPA lysis buffer, and the content of inflammatory factors TNF-α and IL-6 was detected using ELISA kits, and the OD value was read using an enzyme reader.

[0214] VI. Test Results

[0215]

[0216] Note: *P<0.05, **P<0.01, #P<0.05;

[0217] The medium and high dose groups showed significant effects within 24 hours, with swelling inhibition rates of 29.3% (medium dose) and 33.7% (high dose), respectively. After 72 hours, the inhibition rates increased to 37.1% and 42.8%, indicating that the drug has rapid penetration and sustained anti-inflammatory properties.

[0218] At the same time, the swelling diameter of the topical application of the present invention was significantly lower than that of the blank control group (p<0.01) and lower than that of the positive control group (p<0.05), indicating that the topical application of the present invention has significant anti-inflammatory and detumescent effects.

[0219] The contents of TNF-α and IL-6 were significantly lower than those of the blank control group (p<0.01) and lower than those of the positive control group (p<0.05), indicating that the topical application medicine of the present invention can effectively inhibit the production of inflammatory factors.

[0220] Test Example 2: Analgesic effect test (acetic acid writhing test in mice)

[0221] 1. Test preparation:

[0222] (1) Test samples: physiological saline, commercially available hemorrhoid cream (containing 1.5% lidocaine), and the sample prepared in Example 2.

[0223] (2) Test animals: healthy ICR mice, SPF grade, weight 22±3 g, half male and half female. After one week of adaptive feeding, the mice were randomly divided into 4 groups, namely, blank control group (normal saline), positive control group (commercially available hemorrhoid cream), medium dose group (20% of the preparation of Example 2), and high dose group (30% of the preparation of Example 2), with 10 mice in each group.

[0224] 2. Model establishment:

[0225] The mice were deprived of water and food before the experiment. During the experiment, 0.6% acetic acid solution (0.1 mL / 10 g) was injected intraperitoneally to induce writhing reaction, with the writhing frequency of 30-35 times / 20 min being the standard.

[0226] 3. Group processing:

[0227] 5 minutes after injection, the corresponding drug (0.3 g / mouse) was evenly applied to the perianal skin (hair removal) of each group of mice, and the mechanical pain threshold (Von Frey fiber needle, pressure range 0.008-300 g) was measured 1h, 2h, and 4h after administration to observe the time effect of the drug on relieving mechanical hyperalgesia.

[0228] 5. Data Collection:

[0229] The experiment was conducted in a soundproof observation room. The writhing reactions (abdominal contraction, hind limb extension) were recorded by a high-definition camera and counted independently by two experimenters. The video recording was reviewed again when the difference was >10%.

[0230] VI. Test Results

[0231]

[0232] Note: *P<0.05, **P<0.01, #P<0.05

[0233] 6.1 Twist reaction inhibition rate:

[0234] Blank control group: The average number of twisting times was 32.5±4.1 times / 20 minutes, indicating that acetic acid injection successfully induced pain response.

[0235] Positive control group: The average number of twisting times was 18.7±3.2 times / 20 minutes, and the inhibition rate was 42.5%, indicating that the positive control drug (hemorrhoid cream) effectively relieved the pain.

[0236] Medium and high-dose groups: The average number of twisting times was 14.6±2.8 times / 20 minutes (medium-dose group) and 12.3±2.1 (high-dose group), and the inhibition rates were 55.1% (medium-dose group) and 62.2% (high-dose group), respectively, which were significantly higher than those of the blank control group and the positive control group, indicating that the topical application of the present invention has a significant effect in relieving pain.

[0237] 6.2 Mechanical pain threshold:

[0238] 1) Rapid onset and sustained analgesia

[0239] 1h pain threshold peak: The pain thresholds of the medium- and high-dose groups increased to 5.03 and 5.48 times the basal value, respectively, which were significantly higher than the positive control group (3.07 times), proving that the drug has a stronger inhibitory effect on mechanical pain.

[0240] 2h maintenance effect: The pain threshold of the high-dose group remained at 5.78g (4.94 times the baseline value), while that of the positive control group dropped to 2.87g (2.43 times), indicating that this preparation has better drug efficacy persistence (P<0.01).

[0241] 2) Central nervous system sensitization intervention

[0242] c-Fos expression in the dorsal horn of the spinal cord: the number of c-Fos positive neurons in the high-dose group was 18.6±3.7, significantly lower than that in the positive control group (32.4±5.1), indicating that the topical application of the present invention can inhibit the central transmission of pain signals.

[0243] Test Example 3: Tissue repair test (rabbit skin irritation test)

[0244] 1. Test preparation:

[0245] (1) Test samples: physiological saline, recombinant human epidermal growth factor (EGF) gel, and the sample prepared in Example 2.

[0246] (2) Test animals: New Zealand rabbits, weighing 2.5±0.5 kg, half male and half female, were randomly divided into three groups after one week of adaptive feeding, namely, a blank control group, a positive control group (recombinant human epidermal growth factor (EGF) gel), and the present preparation group (the sample prepared in Example 2), with 10 rabbits in each group.

[0247] 2. Model establishment:

[0248] The hair on the back of New Zealand rabbits was shaved to expose the skin. Four 4 cm long cuts were made on the back of each rabbit using a sterile scalpel. 2 The wound surfaces were spaced at least 5 cm apart, and full-thickness skin defects were created, reaching the fascia layer.

[0249] 3. Group processing:

[0250] Blank control group: The wound surface was not treated in any way and served as a control.

[0251] Positive control group: recombinant human epidermal growth factor (EGF) gel was applied on the wound surface as a positive control.

[0252] This preparation group: the wound surface is smeared with the external compress of the present invention.

[0253] The drug was administered once daily. A sterile cotton swab was used to evenly apply the drug to the wound surface. 0.5 g of the drug was applied to each wound each time.

[0254] V. Evaluation indicators:

[0255] 5.1 Histological processing

[0256] On the 14th day, wound tissues were obtained, fixed with 4% paraformaldehyde, embedded in paraffin and sectioned (5 μm thick). Masson staining was used to evaluate collagen deposition, and CD31 immunohistochemistry was used to detect angiogenesis;

[0257] 5.2 Quantitative Indicators

[0258] Healing rate = (initial area - remaining unhealed area) / initial area × 100%;

[0259] Collagen maturity: The ratio of type I / III collagen was analyzed using a polarizing microscope (mature collagen exhibits strong birefringence).

[0260] VI. Test Results

[0261]

[0262] Note: *P<0.05, **P<0.01, #P<0.05

[0263] 6.1 Wound healing

[0264] The healing rates of the preparation group on the 3rd, 7th and 14th days were 34.7%, 79.2% and 98.6%, respectively, which were significantly higher than those of the blank control group (p<0.05) and higher than those of the positive control group (p<0.05), indicating that the topical application of the present invention has a significant effect in promoting wound healing.

[0265] Specific:

[0266] 3-day healing rate: The preparation group (34.7%) was significantly higher than the positive control group (26.5%) and the blank control group (18.2%), indicating that early inflammation control and epithelialization process were faster.

[0267] 7-day healing rate: The preparation group reached 79.2%, which was 15.9% higher than the positive control group (68.3%) (P<0.05), indicating that the formation of granulation tissue in the middle stage was accelerated.

[0268] 14-day healing rate: The preparation group was close to complete healing (98.6%), significantly better than the positive control group (95.1%), indicating that the quality of the repair endpoint was higher. At 14 days, the residual area of ​​the wound was only 1.4% (4.9% in the positive group), reducing the risk of scar formation.

[0269] 6.2 Angiogenesis

[0270] Density of new blood vessels: This preparation group (24.6 / mm 2 ) compared with the positive control group (18.7 / mm 2 ) increased by 31.6% (P<0.01), indicating that the drug significantly promoted capillary formation.

[0271] 6.3 Collagen synthesis and maturity

[0272] Collagen density: The density of collagen in the preparation group (85.3%) was 17.2% higher than that in the positive control group (72.8%) (P<0.01), indicating that the synthesis of extracellular matrix was more active.

[0273] Type I / III collagen ratio: The ratio of this preparation group (3.8:1) was significantly higher than that of the positive control group (2.5:1), indicating that the collagen fibers are closer to the normal skin structure (the normal skin type I / III collagen ratio is about 3.5-4:1).

[0274] In summary, the topical application medicine of the present invention has significant anti-inflammatory and detumescent effects, can effectively relieve anal swelling, and inhibit the production of inflammatory factors. It also has significant analgesic effects, can effectively relieve pain, and the analgesia lasts for a long time; moreover, the topical application medicine of the present invention has significant tissue repair effects, can effectively promote wound healing, epidermal regeneration and collagen fiber arrangement.

[0275] Therefore, the topical medicine of the present invention gives full play to the pharmacological effects and synergistic effects of each component by rationally combining multiple Chinese medicinal materials, and has significant curative effects of anti-inflammatory and detumescence, hemostasis, analgesia and promotion of tissue repair. The formula is not only effective, but also highly safe and easy to use.

[0276] The present invention and its implementation methods are described above, but such description is not restrictive, and what is shown is only one of the implementation methods of the present invention, and the actual structure is not limited thereto. In short, if ordinary technicians in the field are inspired by it, without departing from the purpose of the invention, they can design a structure and embodiment similar to the technical solution without creativity, which should belong to the protection scope of the present invention.

Claims

1. An external compress for treating hemorrhoids, characterized in that: The invention is prepared from the following raw materials in weight proportion: 11-18 parts of toad grass, 9-16 parts of green vegetables, 11-18 parts of dandelions, 6-15 parts of lotus root sticks, 4-13 parts of black fungus, 6-15 parts of wormwood leaves, 2-8 parts of pepper, 80-120 parts of white vinegar, 4-13 parts of leek roots and 9-16 parts of locust flowers.

2. The external compress for treating hemorrhoids according to claim 1, characterized in that: The invention is prepared from the following raw materials in weight proportion: 15 parts of toad grass, 12 parts of green vegetables, 15 parts of dandelions, 10 parts of lotus root sticks, 8 parts of black fungus, 10 parts of wormwood leaves, 5 parts of Chinese prickly ash, 100 parts of white vinegar, 8 parts of leek roots and 12 parts of Sophora japonica flowers.

3. The external compress for treating hemorrhoids according to claim 1 or 2, characterized in that: The following steps are involved: S1. Raw material pretreatment: Toad grass, green vegetables, dandelion, and leek roots are cleaned and processed respectively to remove impurities and non-medicinal parts, dried in a circulating hot air drying oven at 45-50°C to a moisture content of ≤8%, and then crushed to a particle size of 80-100 meshes to obtain primary powder A; S2. Preparation of composite extract: Sophora japonica, Artemisia argyi and Zanthoxylum bungeanum were mixed in proportion, 6 times the amount of purified water was added, and gradient extraction was carried out in a multifunctional extraction tank. In the first stage, the constant temperature of 55-65° C. was maintained for 35-45 min. In the second stage, the temperature was raised to 80-90° C. for reflux extraction for 55-65 min. The mixture was double filtered through a 180-220 mesh filter cloth, the combined filtrate was collected, and the mixture was concentrated under reduced pressure to a relative density of 1.15-1.20 to obtain extract B. S3, solid matrix treatment: After the black fungus is soaked in purified water and expanded, it is placed in an ultrafine grinder together with the lotus root stick, and the cell wall is broken at a low temperature of -10°C to control the particle size distribution D90≤15μm to obtain composite ultrafine powder C; S4, vinegar production reaction: white vinegar is placed in a reactor with a stirring function, primary powder A and composite ultrafine powder C are added in sequence, a constant temperature environment of 25-30°C is maintained, and dynamic mixing is performed at a speed of 100-140 r / min for 55-65 min to form a homogeneous suspension system D; S5. Preparation of finished product: slowly add extract B into suspension system D three times, perform ultrasonic treatment for 15 minutes after each addition, and finally treat it in a vacuum degassing machine at -0.08 MPa for 20 minutes to obtain a semi-solid topical preparation with thixotropy.

4. The external compress for treating hemorrhoids according to claim 1, characterized in that: In S2, an intelligent temperature control system is used during gradient extraction, and the temperature deviation is controlled within the range of ±1°C.

5. The external compress for treating hemorrhoids according to claim 1, characterized in that: In S3, food-grade nitrogen is continuously introduced into the cryogenic pulverization process to protect the oxygen content, and the oxygen content is maintained below 500 ppm.

6. The external compress for treating hemorrhoids according to claim 1, characterized in that: In S5, the ultrasonic treatment adopts the intermittent working mode, with a frequency of 40kHz and a power of 300W, and a working cycle of running for 5 seconds / stopping for 2 seconds.

7. An external compress for treating hemorrhoids, the external compress comprising the external compress according to any one of claims 1-2 or the external compress obtained by the preparation method according to claims 3-6 or other pharmaceutically acceptable physical forms.

8. The drug according to claim 4, characterized in that The medicine is in the form of a gel, foam, spray or ointment.

9. Use of the external compress according to any one of claims 1 to 2 or the external compress obtained by the preparation method according to claims 3 to 6 in preparing a medicament capable of treating hemorrhoids.

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