Anti-inflammatory enzyme digestion hemorrhoid cream and preparation method thereof

Abstract

The invention provides an anti-inflammatory enzyme digestion hemorrhoid cream and a preparation method thereof. The hemorrhoid cream is prepared from the following raw materials: an anti-inflammatory enzyme compound, a plant extract, sodium hyaluronate, a humectant, a gel matrix, a skin repair factor, a polymer slow-release agent, water and the like. Wherein the anti-inflammatory enzyme compound is formed by mixing alpha-amylase and superoxide dismutase, dissolving by deionized water, adding a silver nitrate solution and a tricholoma gambosum water extract, and irradiating by electron beams. The plant extract is prepared from a tea tree extract, a cortex phellodendri extract and a radix sanguisorbae extract according to a specific mass ratio. The preparation method comprises the steps of preparing the anti-inflammatory enzyme compound, preparing the basic gel, adding the active ingredients and the like. The hemorrhoid ointment has the effects of resisting inflammation, stopping bleeding, promoting wound healing, resisting bacteria and the like, and the polymer sustained-release agent can prolong the action time, improve the bioavailability and stability and improve the patient compliance.

Description

Technical Field

[0001] The invention relates to the technical field of medical external preparations, and in particular to an anti-inflammatory enzyme hemorrhoid cream and a preparation method thereof. Background Art

[0002] Hemorrhoids, as a common anal disease, bring significant pain and discomfort to patients, seriously affecting their quality of life. There are many kinds of ointments for the treatment of hemorrhoids on the market, but most of them have problems such as uneven drug release, short duration of efficacy, and obvious side effects. In particular, the drug ingredients in traditional ointments are often rapidly absorbed or lost in a short period of time, making it difficult to maintain effective concentrations at the lesion site, resulting in unsatisfactory treatment effects.

[0003] Most of the existing hemorrhoid ointments focus on the rapid effect of a single ingredient, while ignoring the sustained-release effect and comprehensive therapeutic effect of the drug. Although some ointments contain anti-inflammatory, anti-edema, analgesic and other ingredients, due to the lack of an effective sustained-release mechanism, the drug has a short duration of action and requires frequent use to maintain the therapeutic effect, which not only increases the medication burden of patients, but may also cause adverse reactions due to excessive use of drugs.

[0004] Traditional hemorrhoid creams often rely on chemical synthetic drugs for anti-inflammatory effects, which may cause side effects such as skin allergies and gastrointestinal discomfort. Moreover, their anti-inflammatory effects are not long-lasting and significant enough to effectively inhibit the inflammatory response in the hemorrhoid area. Existing products are often unable to fully and effectively regulate the complex inflammatory environment caused by multiple inflammatory factors, resulting in repeated inflammation and delaying the patient's recovery process.

[0005] In terms of hemostasis, the existing technology also has shortcomings. The hemostatic effect of some hemorrhoid creams is relatively limited and cannot quickly and effectively control the symptoms of hemorrhoid bleeding. Some products may only be able to stop bleeding temporarily, but cannot fundamentally solve the root cause of the bleeding problem, making patients prone to bleeding again.

[0006] In addition, the targeting effect of existing hemorrhoid treatment products is poor. After use, the drug ingredients of most products are difficult to act accurately on the hemorrhoid site and are easily dispersed into the surrounding normal tissues, resulting in low drug utilization. At the same time, due to the lack of an effective targeting mechanism, the drug may be affected by other metabolic mechanisms of the body when reaching the lesion site, further reducing the treatment effect. Summary of the invention

[0007] In view of this, the present invention provides an anti-inflammatory enzyme hemorrhoid cream and a preparation method thereof to solve the above problems.

[0008] The technical solution of the present invention is achieved as follows: an anti-inflammatory enzyme hemorrhoid cream comprises the following raw materials in parts by weight: 10-20 parts of an anti-inflammatory enzyme complex, 10-15 parts of a plant extract, 5-10 parts of sodium hyaluronate, 30-40 parts of a moisturizer, 10-20 parts of a gel matrix, 5-10 parts of a skin repair factor, 2-4 parts of a polymer sustained-release agent, and 18-22 parts of water; the plant extract is a tea tree extract, a phellodendron extract, and a sanguisorba officinalis extract in a mass ratio of (2-5):(3-8):(1-3).

[0009] Furthermore, an anti-inflammatory enzyme hemorrhoid cream includes the following raw materials in parts by weight: 15 parts of anti-inflammatory enzyme complex, 12 parts of plant extract, 8 parts of sodium hyaluronate, 35 parts of moisturizer, 15 parts of gel matrix, 8 parts of skin repair factor, 3 parts of polymer sustained-release agent, and 20 parts of water.

[0010] Furthermore, the anti-inflammatory enzyme complex is α-amylase and superoxide dismutase, both of which have a molecular weight of 22-30 kDa.

[0011] Furthermore, the moisturizing agent is any one or a combination of glycerol, propylene glycol, sorbitol, phosphatidylcholine, palmitoyl pentapeptide-3 or acetyl hexapeptide-8.

[0012] Furthermore, the gel matrix is ​​composed of vaseline, lanolin and beeswax, and the mass ratio thereof is 5-7:2-4:1.

[0013] Furthermore, the skin repair factor is epidermal growth factor, transforming growth factor β or fibroblast growth factor.

[0014] Furthermore, the polymer sustained-release agent includes but is not limited to carbomer, xanthan gum, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, tragacanth gum, and gelatin.

[0015] Further, a method for preparing an anti-inflammatory enzyme hemorrhoid cream comprises the following steps:

[0016] S1. Preparation of anti-inflammatory enzyme complex: α-amylase and superoxide dismutase are mixed in a mass ratio of 3-5:2, deionized water is added and stirred for 10-15 minutes, wherein the mass volume ratio of the mixed enzyme to deionized water is 150-200:10 in mg / mL, to obtain a lysozyme solution, and a silver nitrate solution with a mass concentration of 50-80% and an aqueous extract of Agaricus oleifera are added in an amount of 2.5-5.5% and 0.3-0.5% of the volume of the lysozyme solution, respectively, and the mixture is stirred at 30-35° C. and irradiated with an electron beam for 2-6 hours to form a stable enzyme complex;

[0017] S2. Prepare basic gel: mix sodium hyaluronate, gel matrix, moisturizer and water evenly, heat to 60-70°C, stir until completely dissolved to form a transparent gel;

[0018] S3. Adding active ingredients: Slowly add the anti-inflammatory enzyme complex, natural plant extracts, skin repair factors and polymer sustained-release agents into the basic gel under stirring, stir evenly at a speed of 30-40 rpm, cool to room temperature, and cool naturally to obtain the anti-inflammatory enzyme hemorrhoid cream.

[0019] Furthermore, the electron beam irradiation of S1 is gamma rays, X-rays or ultraviolet rays, the irradiation dose is 0.1-3 kGy, and the output energy is 8-10 MeV.

[0020] Furthermore, the preparation method of the natural plant extract in S3 includes: crushing tea tree, phellodendron and sanguisorba officinalis respectively, passing through a 40-60 mesh sieve, and then adding 60-80% ethanol solution, with a solid-liquid ratio of 1:10-15, reflux extraction at a temperature of 45-65°C for 2-3h, filtering, and concentrating the filtrate under reduced pressure at 50-60°C to obtain the natural plant extract.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] The anti-inflammatory enzyme hemorrhoid cream of the present invention achieves high-efficiency anti-inflammatory, good hemostatic effect and the effect of promoting the long-term sustained release of the skin repair agent through the combination of a specific anti-inflammatory enzyme complex, a plant extract, a gel matrix and a polymer sustained-release agent;

[0023] Highly effective anti-inflammatory: The anti-inflammatory enzyme complex composed of α-amylase and superoxide dismutase can effectively inhibit inflammatory reactions. The two enzymes work synergistically to remove excessive free radicals in the body, reduce the damage to tissues caused by oxidative stress, and relieve inflammation in the hemorrhoid area from the source; the tea polyphenols in the tea tree extract, the alkaloids in the phellodendron extract, and the various active ingredients in the burdock extract work together to inhibit the production and release of inflammatory factors, reduce the activity of inflammatory cells, and relieve local redness, swelling, pain and other symptoms.

[0024] Good hemostatic effect: Anti-inflammatory enzyme complexes and plant extracts may also have an auxiliary effect on hemostasis while exerting anti-inflammatory effects; they can reduce inflammatory responses, reduce vascular permeability, and create a good environment for hemostasis.

[0025] Promote skin repair: Added skin repair factors, these factors can accelerate the skin repair process in the hemorrhoid area, promote cell regeneration and wound healing, and reduce scar formation. Sodium hyaluronate has a moisturizing effect, which can increase the moisture content of the skin and maintain the elasticity and softness of the skin. At the same time, it can also provide a good environment for the normal metabolism of cells and promote the healing of wounds.

[0026] Long-term sustained release and stability: By introducing polymer sustained release agents, the hemorrhoid cream can effectively control the release rate of drug ingredients, ensuring that anti-inflammatory enzyme complexes, plant extracts and other active ingredients are continuously and stably released at the hemorrhoid site, thereby extending the drug's action time and improving the durability of the treatment effect. This sustained release mechanism allows the drug to maintain an effective concentration for a longer period of time, significantly enhancing the anti-inflammatory, detumescent and analgesic effects on hemorrhoids. DETAILED DESCRIPTION

[0027] In order to better understand the technical content of the present invention, specific embodiments are provided below to further illustrate the present invention.

[0028] Unless otherwise specified, the experimental methods used in the embodiments of the present invention are all conventional methods.

[0029] Unless otherwise specified, the materials, reagents, etc. used in the embodiments of the present invention can be obtained from commercial sources.

[0030] Example 1

[0031] An anti-inflammatory enzyme hemorrhoid cream, comprising the following raw materials in parts by weight: 10 parts of anti-inflammatory enzyme complex, 10 parts of plant extract, 5 parts of sodium hyaluronate, 30 parts of moisturizer, 10 parts of gel matrix, 5 parts of skin repair factor, 2 parts of polymer sustained-release agent, and 18 parts of water;

[0032] The anti-inflammatory enzyme complex is α-amylase and superoxide dismutase, both of which have a molecular weight of 22 kDa;

[0033] The plant extracts are tea tree extract, phellodendron amurense extract, and sanguisorba officinalis extract in a mass ratio of 2:3:1;

[0034] The moisturizing agent is glycerin, propylene glycol, and sorbitol in a mass ratio of 1:1:1;

[0035] The gel matrix is ​​composed of vaseline, lanolin and beeswax in a mass ratio of 5:2:1;

[0036] The skin repair factor is epidermal growth factor;

[0037] The polymer sustained-release agent is carbomer.

[0038] Example 2

[0039] An anti-inflammatory enzyme hemorrhoid cream, comprising the following raw materials in parts by weight: 20 parts of anti-inflammatory enzyme complex, 15 parts of plant extract, 10 parts of sodium hyaluronate, 40 parts of moisturizer, 20 parts of gel matrix, 10 parts of skin repair factor, 4 parts of polymer sustained-release agent, and 22 parts of water;

[0040] The anti-inflammatory enzyme complex is α-amylase and superoxide dismutase, both of which have a molecular weight of 30 kDa;

[0041] The plant extracts are tea tree extract, phellodendron amurense extract, and sanguisorba officinalis extract in a mass ratio of 5:8:3;

[0042] The moisturizing agent is palmitoyl pentapeptide-3 and acetyl hexapeptide-8 in a mass ratio of 1:2;

[0043] The gel matrix is ​​composed of vaseline, lanolin and beeswax in a mass ratio of 7:4:1;

[0044] The skin repair factor is transforming growth factor β;

[0045] The polymer sustained-release agent is sodium carboxymethyl cellulose.

[0046] Example 3

[0047] An anti-inflammatory enzyme hemorrhoid cream, comprising the following raw materials in parts by weight: 15 parts of anti-inflammatory enzyme complex, 12 parts of plant extract, 8 parts of sodium hyaluronate, 35 parts of moisturizer, 15 parts of gel matrix, 8 parts of skin repair factor, 3 parts of polymer sustained-release agent, and 20 parts of water;

[0048] The anti-inflammatory enzyme complex is α-amylase and superoxide dismutase, both of which have a molecular weight of 26 kDa;

[0049] The plant extracts are tea tree extract, phellodendron amurense extract, and sanguisorba officinalis extract in a mass ratio of 3:5:2;

[0050] The moisturizing agent is propylene glycol, phosphatidylcholine and acetyl hexapeptide-8 in a mass ratio of 1:2:1;

[0051] The gel matrix is ​​composed of vaseline, lanolin and beeswax in a mass ratio of 6:3:1;

[0052] The skin repair factor is fibroblast growth factor;

[0053] The polymer sustained-release agent is hydroxypropyl methylcellulose;

[0054] The above examples 1-3 adopt the following preparation method:

[0055] S1. Preparation of anti-inflammatory enzyme complex: α-amylase and superoxide dismutase were mixed in a mass ratio of 4:2, deionized water was added and stirred for 12 min, the mass volume ratio of the mixed enzyme to deionized water was 180:10 in mg / mL, a lysozyme solution was prepared, and a silver nitrate solution with a mass concentration of 70% and an aqueous extract of Agaricus gloeosporium were added in an amount of 4% and 0.4% of the volume of the solution of Rhizoctonia solani, respectively. The mixture was stirred at 33° C. and irradiated with an electron beam for 4 h. The electron beam irradiation was gamma rays, the irradiation dose was 2 kGy, and the output energy was 9 MeV, to form a stable enzyme complex;

[0056] S2. Prepare basic gel: mix sodium hyaluronate, gel matrix, moisturizer and water evenly, heat to 65°C, and stir until completely dissolved to form a transparent gel;

[0057] S3. Adding active ingredients: Slowly add the anti-inflammatory enzyme complex, natural plant extracts, skin repair factors and polymer sustained-release agents into the basic gel under stirring, stir evenly at a speed of 35 rpm, cool to room temperature, and cool naturally to obtain the anti-inflammatory enzyme hemorrhoid cream.

[0058] The preparation method of the above-mentioned natural plant extract includes: crushing tea tree, phellodendron and sanguisorba officinalis respectively, passing through a 50-mesh sieve, then adding 70% ethanol solution, with a solid-liquid ratio of 1:13, reflux extraction at a temperature of 55°C for 2h, filtering, and concentrating the filtrate under reduced pressure at 55°C to obtain the natural plant extract.

[0059] Example 4

[0060] An anti-inflammatory enzyme hemorrhoid cream, comprising the following raw materials in parts by weight: 15 parts of anti-inflammatory enzyme complex, 12 parts of plant extract, 8 parts of sodium hyaluronate, 35 parts of moisturizer, 15 parts of gel matrix, 8 parts of skin repair factor, 3 parts of polymer sustained-release agent, and 20 parts of water;

[0061] The anti-inflammatory enzyme complex is α-amylase and superoxide dismutase, both of which have a molecular weight of 26 kDa;

[0062] The plant extracts are tea tree extract, phellodendron amurense extract, and sanguisorba officinalis extract in a mass ratio of 3:5:2;

[0063] The moisturizing agent is propylene glycol, phosphatidylcholine and acetyl hexapeptide-8 in a mass ratio of 1:2:1;

[0064] The gel matrix is ​​composed of vaseline, lanolin and beeswax in a mass ratio of 6:3:1;

[0065] The skin repair factor is fibroblast growth factor;

[0066] The polymer sustained-release agent is hydroxypropyl methylcellulose;

[0067] The above-mentioned Example 4 adopts the following preparation method:

[0068] S1. Preparation of anti-inflammatory enzyme complex: α-amylase and superoxide dismutase were mixed in a mass ratio of 3:2, deionized water was added and stirred for 10 min, the mass volume ratio of the mixed enzyme to deionized water was 150:10 in mg / mL, a lysozyme solution was prepared, and a silver nitrate solution with a mass concentration of 50% and an aqueous extract of Agaricus gloeosporium were added in an amount of 2.5% and 0.3% of the volume of the solution of Rhizoctonia solani, respectively. The mixture was stirred at 30° C. and irradiated with an electron beam for 2 h. The electron beam irradiation was γ-ray, X-ray or ultraviolet light, the irradiation dose was 0.1 kGy, and the output energy was 8 MeV, to form a stable enzyme complex;

[0069] S2. Prepare basic gel: mix sodium hyaluronate, gel matrix, moisturizer and water evenly, heat to 60°C, and stir until completely dissolved to form a transparent gel;

[0070] S3, adding active ingredients: slowly adding the anti-inflammatory enzyme complex, natural plant extract, skin repair factor and polymer sustained-release agent into the base gel under stirring, stirring evenly at a speed of 30 rpm, cooling to room temperature, and cooling by natural cooling to obtain the anti-inflammatory enzyme hemorrhoid cream;

[0071] The preparation method of the natural plant extract comprises: crushing tea tree, phellodendron amurense and sanguisorba officinalis respectively, passing through a 40-mesh sieve, then adding 60% ethanol solution with a solid-liquid ratio of 1:10, refluxing and extracting at a temperature of 45°C for 2h, filtering, and concentrating the filtrate under reduced pressure at 50°C to obtain the natural plant extract.

[0072] Example 5

[0073] An anti-inflammatory enzyme hemorrhoid cream, comprising the following raw materials in parts by weight: 15 parts of anti-inflammatory enzyme complex, 12 parts of plant extract, 8 parts of sodium hyaluronate, 35 parts of moisturizer, 15 parts of gel matrix, 8 parts of skin repair factor, 3 parts of polymer sustained-release agent, and 20 parts of water;

[0074] The anti-inflammatory enzyme complex is α-amylase and superoxide dismutase, both of which have a molecular weight of 26 kDa;

[0075] The plant extracts are tea tree extract, phellodendron amurense extract, and sanguisorba officinalis extract in a mass ratio of 3:5:2;

[0076] The moisturizing agent is propylene glycol, phosphatidylcholine and acetyl hexapeptide-8 in a mass ratio of 1:2:1;

[0077] The gel matrix is ​​composed of vaseline, lanolin and beeswax in a mass ratio of 6:3:1;

[0078] The skin repair factor is fibroblast growth factor;

[0079] The polymer sustained-release agent is hydroxypropyl methylcellulose;

[0080] The above-mentioned Example 5 adopts the following preparation method:

[0081] S1. Preparation of anti-inflammatory enzyme complex: α-amylase and superoxide dismutase were mixed in a mass ratio of 5:2, deionized water was added and stirred for 15 min, the mass volume ratio of the mixed enzyme to deionized water was 200:10 in mg / mL, a lysozyme solution was prepared, and a silver nitrate solution with a mass concentration of 80% and an aqueous extract of Agaricus gloeosporium were added in an amount of 5.5% and 0.5% of the volume of the solution of Rhizoctonia solani, respectively. The mixture was stirred at 35° C. and irradiated with an electron beam for 6 h. The electron beam irradiation was γ-ray, X-ray or ultraviolet light, the irradiation dose was 3 kGy, and the output energy was 10 MeV, to form a stable enzyme complex;

[0082] S2. Prepare basic gel: mix sodium hyaluronate, gel matrix, moisturizer and water evenly, heat to 70°C, and stir until completely dissolved to form a transparent gel;

[0083] S3, adding active ingredients: slowly adding the anti-inflammatory enzyme complex, natural plant extract, skin repair factor and polymer sustained-release agent to the base gel under stirring, stirring evenly at a speed of 40 rpm, cooling to room temperature, and cooling by natural cooling to obtain the anti-inflammatory enzyme hemorrhoid cream;

[0084] The preparation method of the natural plant extract comprises: crushing tea tree, phellodendron amurense and sanguisorba officinalis respectively, passing through a 60-mesh sieve, then adding 80% ethanol solution with a solid-liquid ratio of 1:15, refluxing extraction at a temperature of 65°C for 3h, filtering, and concentrating the filtrate under reduced pressure at 60°C to obtain the natural plant extract.

[0085] Comparative Example 1

[0086] The difference between this comparative example and Example 3 is that the anti-inflammatory enzyme hemorrhoid cream comprises the following raw materials in parts by weight: 2 parts of anti-inflammatory enzyme complex, 5 parts of plant extract, 15 parts of sodium hyaluronate, 25 parts of moisturizer, 3 parts of gel matrix, 12 parts of skin repair factor, 5 parts of polymer sustained-release agent, and 15 parts of water.

[0087] Comparative Example 2

[0088] The difference between this comparative example and Example 3 is that the raw materials of the anti-inflammatory enzyme hemorrhoid cream do not contain plant extracts.

[0089] Comparative Example 3

[0090] The difference between this comparative example and Example 3 is that the plant extracts are tea tree extract and phellodendron amurense extract in a mass ratio of 3:5.

[0091] Comparative Example 4

[0092] The difference between this comparative example and Example 3 is that the raw materials of the anti-inflammatory enzyme hemorrhoid cream do not contain skin repair factors.

[0093] Comparative Example 5

[0094] The difference between this comparative example and Example 3 is that the raw materials of the anti-inflammatory enzyme hemorrhoid cream do not contain a polymer sustained-release agent.

[0095] Comparative Example 6

[0096] The difference between this comparative example and Example 3 is that in the preparation method of the anti-inflammatory enzyme hemorrhoid cream, electron beam irradiation is not performed in the preparation of the anti-inflammatory enzyme complex.

[0097] Comparative Example 7

[0098] The difference between this comparative example and Example 3 is that the specific method for preparing the anti-inflammatory enzyme complex in the preparation method of the anti-inflammatory enzyme hemorrhoid cream is:

[0099] Alpha-amylase and superoxide dismutase were mixed in a mass ratio of 4:2, and the mixture was stirred at 33° C. and 50-80 rpm to obtain an anti-inflammatory enzyme complex.

[0100] Test Example 1-Anti-inflammatory Test

[0101] 1. Cell culture: Human umbilical vein endothelial cells (HUVEC) were cultured in a 37°C constant temperature incubator to ensure that the cells were in good condition.

[0102] 2. Inflammatory stimulation: Induce inflammatory response with lipopolysaccharide (LPS) stimulation. HUVEC cells were stimulated with 1 μg / mL LPS for 12 hours to induce inflammatory response.

[0103] 3. Hemorrhoid cream treatment: The hemorrhoid cream prepared in Examples 1-5 and Comparative Examples 1-7 was diluted to 1% (w / v); the cells in the treatment group were stimulated with LPS and the hemorrhoid cream solution was added, the model group was stimulated with LPS only, and the control group was not stimulated with LPS.

[0104] 4. Detection indicators:

[0105] Detection of inflammatory factors: The content of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in cell culture fluid was detected by enzyme-linked immunosorbent assay (ELISA);

[0106] Detection of intracellular signaling molecules: Western blot was used to detect the expression and activation of intracellular inflammation-related signaling molecules, such as nuclear factor κB (NF-κB).

[0107] Reactive oxygen species (ROS) detection: Fluorescent probes are used to detect the level of intracellular ROS. Intracellular ROS usually increases under inflammatory conditions. If hemorrhoid cream has anti-inflammatory effects, it may reduce the level of ROS.

[0108] 5. Experimental results:

[0109]

[0110]

[0111] The levels of TNF-α, IL-6, and IL-1β in the model group were significantly higher than those in the control group, indicating that LPS stimulation successfully induced an inflammatory response, causing cells to secrete a large number of inflammatory factors. The degree of NF-κB activation and ROS levels also increased significantly in the model group, further confirming the activation of intracellular inflammatory signaling pathways and the enhancement of oxidative stress under inflammatory conditions.

[0112] Compared with the model group, the content of inflammatory factors, degree of NF-κB activation, and level of ROS in the embodiment group and the comparative example group were all reduced, among which the level in embodiment 3 was the lowest, indicating that it has a better effect in inhibiting the secretion of inflammatory factors, has an inhibitory effect on the NF-κB signaling pathway, thereby reducing the inflammatory response, and also has a certain antioxidant effect, which can reduce the oxidative stress in cells;

[0113] The content of inflammatory factors in the comparative group was higher than that in the embodiment group as a whole, but lower than that in the model group. There were also some differences in the content of inflammatory factors between the comparative groups, but the variation was relatively small; the degree of NF-κB activation and ROS level in the comparative group were also higher than those in the embodiment group but lower than those in the model group, indicating that the hemorrhoid cream in the comparative group can also inhibit inflammation and oxidative stress to a certain extent, but the effect is not as good as that in the embodiment group. These results show that hemorrhoid cream containing specific ingredients has the potential to treat hemorrhoids, and there are differences in the effects of different formulas.

[0114] Test Example 2-Hemostatic Effect Test

[0115] 1. Tail bleeding model: Several healthy mice were selected and randomly divided into 14 groups, with 10 mice in each group. The tails of the mice were cut with surgical scissors at about 5 mm from the tip of the tail to allow natural bleeding.

[0116] 2. Drug administration

[0117] Control group: Apply normal saline to the bleeding site.

[0118] Groups of Examples 1-5: The hemorrhoid creams prepared in Examples 1-5 were applied respectively, with an application amount of 1 g.

[0119] Comparative Examples 1-7: The hemorrhoid ointment prepared in Comparative Examples 1-6 was applied respectively, with an application amount of 1 g.

[0120] Positive control drug group: Apply a drug known to have hemostatic effect, Mayinglong Hemorrhoid Ointment, with an application amount of 1g.

[0121] 3. Detection indicators:

[0122] Bleeding time: the time from the start of bleeding to the cessation of bleeding, usually measured in seconds. The shorter the bleeding time, the better the hemostasis effect.

[0123] Amount of bleeding: The amount of bleeding can be determined by weighing or volume measurement. The less the amount of bleeding, the stronger the hemostatic effect of the hemorrhoid cream.

[0124] 4. Test results:

[0125]

[0126]

[0127] The bleeding time of embodiment 1 to 5 is respectively 108 ± 11s, 103 ± 10s, 90 ± 7s, 100 ± 8s, 105 ± 9s, which is significantly lower than the control group, indicating that the hemorrhoid cream in these embodiments has a positive effect in shortening the bleeding time of tail. Wherein the bleeding time of embodiment 3 is the shortest, and the effect is relatively best. The bleeding volume of embodiment group is between 0.03 ± 0.007g and 0.07 ± 0.011g, which is significantly lower than the control group. It shows that the hemorrhoid cream in the embodiment can effectively reduce the bleeding volume of tail bleeding.

[0128] In summary, Example 3 has the best anti-inflammatory and hemostatic effects, which, compared with Comparative Example 1, shows that the formula of the anti-inflammatory enzyme hemorrhoid cream of the present invention can coordinately exert its effects under a specific ratio.

[0129] Compared with comparative examples 2 and 3, the tea tree extract, Phellodendron chinense extract and Sanguisorba officinalis extract of the present invention in a mass ratio of 3:5:2 have synergistic beneficial effects in the anti-inflammatory enzyme hemorrhoid cream, which can enhance anti-inflammatory, hemostatic, wound healing and antibacterial effects, wherein the tea tree extract contains ingredients such as tea polyphenols, and has antioxidant and anti-inflammatory activity. It can inhibit the release of inflammatory mediators; the main ingredients in the Phellodendron chinense extract, such as alkaloids such as berberine, have significant anti-inflammatory effects. It can inhibit the production of inflammatory cytokines; Sanguisorba officinalis extract is rich in ingredients such as tannins and has astringent and anti-inflammatory effects. It can reduce vascular permeability, reduce tissue edema, and inhibit the infiltration of inflammatory cells; when these three extracts are combined in a specific ratio, they synergistically exert anti-inflammatory effects through different mechanisms. Tea tree extract and Phellodendron chinense extract can inhibit the activation of inflammatory signaling pathways, while Sanguisorba officinalis extract can reduce tissue damage caused by inflammation. This synergistic effect can more effectively reduce inflammation at the site of hemorrhoids and relieve symptoms such as pain and swelling.

[0130] Compared with comparative example 4, the increase of skin repair factor can stimulate the proliferation of damaged skin and mucosal cells. This helps to quickly fill the wounds such as ulcers and damages caused by hemorrhoids, accelerate the tissue regeneration process; promote the synthesis of extracellular matrix components such as collagen and elastin; contribute to the formation of new blood vessels, provide sufficient nutrition and oxygen supply for wound repair; can regulate inflammatory response, reduce the release of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), etc.; can cooperate with anti-inflammatory enzymes to play a better therapeutic effect. Anti-inflammatory enzymes mainly act to reduce inflammatory reactions, while skin repair factors focus on promoting wound healing and enhancing skin barrier function. The synergistic effect of the two can treat hemorrhoids more comprehensively and improve the overall efficacy of hemorrhoid cream.

[0131] Compared with Comparative Example 5, the polymer sustained-release agent of the present invention can create a microenvironment suitable for drug release, can control the release rate of active ingredients such as anti-inflammatory enzymes, so that they can continue to play a role for a long time, and can encapsulate the active ingredients to prevent the active ingredients from direct contact with the external environment, thereby improving the stability of the drug.

[0132] Compared with Comparative Examples 6 and 7, in the process of preparing the anti-inflammatory enzyme complex, electron beam irradiation can trigger a series of chemical reactions, promote the interaction between α-amylase and superoxide dismutase, and between the silver nitrate solution and the water extract of Agaricus oleifera, and accelerate the formation of the enzyme complex; at the same time, it induces cross-linking reactions between enzyme molecules and between enzymes and other components, and cross-linking can form a more solid three-dimensional structure to prevent the depolymerization and inactivation of enzyme molecules; in addition, electron beam irradiation can cause silver nitrate to produce antibacterial activity. Silver nitrate may release silver ions under irradiation, which has antibacterial effect, thereby enhancing the antibacterial properties of the enzyme complex; electron beam irradiation may produce synergistic effects with active ingredients in the water extract of Agaricus oleifera, such as polysaccharides, phenolic compounds, etc., and irradiation can promote the interaction between these ingredients and enzymes, and enhance the anti-inflammatory, antioxidant and other properties of the enzyme complex.

[0133] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. An anti-inflammatory enzyme hemorrhoid cream, characterized in that: The invention comprises the following raw materials in parts by weight: 10-20 parts of anti-inflammatory enzyme complex, 10-15 parts of plant extract, 5-10 parts of sodium hyaluronate, 30-40 parts of moisturizer, 10-20 parts of gel matrix, 5-10 parts of skin repair factor, 2-4 parts of polymer sustained-release agent and 18-22 parts of water; the plant extract is tea tree extract, phellodendron amurense extract and sanguisorba officinalis extract in a mass ratio of (2-5):(3-8):(1-3).

2. An anti-inflammatory enzyme hemorrhoid cream as claimed in claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 15 parts of anti-inflammatory enzyme complex, 12 parts of plant extract, 8 parts of sodium hyaluronate, 35 parts of moisturizer, 15 parts of gel matrix, 8 parts of skin repair factor, 3 parts of polymer sustained-release agent and 20 parts of water.

3. An anti-inflammatory enzyme hemorrhoid cream as claimed in claim 1 or 2, characterized in that: The anti-inflammatory enzyme complex is α-amylase and superoxide dismutase, both of which have molecular weights of 22-30 kDa.

4. An anti-inflammatory enzyme hemorrhoid cream as claimed in claim 1 or 2, characterized in that: The moisturizing agent is any one or a combination of glycerin, propylene glycol, sorbitol, phosphatidylcholine, palmitoyl pentapeptide-3 or acetyl hexapeptide-8.

5. An anti-inflammatory enzyme hemorrhoid cream as claimed in claim 1 or 2, characterized in that: The gel matrix consists of vaseline, lanolin and beeswax, and the mass ratio thereof is 5-7:2-4:

1.

6. An anti-inflammatory enzyme hemorrhoid cream as claimed in claim 1 or 2, characterized in that: The skin repair factor is epidermal growth factor, transforming growth factor β or fibroblast growth factor.

7. An anti-inflammatory enzyme hemorrhoid cream as claimed in claim 1 or 2, characterized in that: The polymer sustained-release agent includes, but is not limited to, carbomer, xanthan gum, sodium carboxymethylcellulose, hydroxypropyl methylcellulose, tragacanth gum, and gelatin.

8. The method for preparing an anti-inflammatory enzyme hemorrhoid cream as claimed in claim 1, characterized in that: The following steps are involved: S1. Preparation of anti-inflammatory enzyme complex: α-amylase and superoxide dismutase are mixed in a mass ratio of 3-5:2, deionized water is added and stirred for 10-15 minutes, wherein the mass volume ratio of the mixed enzyme to deionized water is 150-200:10 in mg / mL, to obtain a lysozyme solution, and a silver nitrate solution with a mass concentration of 50-80% and an aqueous extract of Agaricus oleifera are added in an amount of 2.5-5.5% and 0.3-0.5% of the volume of the lysozyme solution, respectively, and the mixture is stirred at 30-35° C. and irradiated with an electron beam for 2-6 hours to form a stable enzyme complex; S2. Prepare basic gel: mix sodium hyaluronate, gel matrix, moisturizer and water evenly, heat to 60-70°C, stir until completely dissolved to form a transparent gel; S3. Adding active ingredients: Slowly add the anti-inflammatory enzyme complex, natural plant extracts, skin repair factors and polymer sustained-release agents into the basic gel under stirring, stir evenly at a speed of 30-40 rpm, cool to room temperature, and cool naturally to obtain the anti-inflammatory enzyme hemorrhoid cream.

9. The method for preparing an anti-inflammatory enzyme hemorrhoid cream as claimed in claim 1, wherein: The electron beam irradiation of S1 is gamma ray, X-ray or ultraviolet ray, the irradiation dose is 0.1-3 kGy, and the output energy is 8-10 MeV.

10. The method for preparing an anti-inflammatory enzyme hemorrhoid cream as claimed in claim 1, characterized in that: The preparation method of the natural plant extract in S3 comprises: crushing tea tree, phellodendron amurense and sanguisorba officinalis respectively, passing through a 40-60 mesh sieve, then adding 60-80% ethanol solution, with a solid-liquid ratio of 1:10-15, refluxing extraction at a temperature of 45-65°C for 2-3h, filtering, and concentrating the filtrate under reduced pressure at 50-60°C to obtain the natural plant extract.

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