A traditional Chinese medicine composition and preparation thereof for treating skin diseases of damp-heat accumulating on the skin and wind-toxin stagnation

Abstract

This invention discloses a traditional Chinese medicine composition and its preparation for treating skin diseases caused by damp-heat accumulation and wind-toxin stagnation, relating to the field of traditional Chinese medicine technology. The composition includes: 25-35 parts of Rehmannia glutinosa, 8-12 parts of Gentiana scabra, 15-25 parts of Dictamnus dasycarpus, 15-25 parts of Sophora flavescens, and 25-35 parts of Hedyotis diffusa. Using a combination of Rehmannia glutinosa, Gentiana scabra, Dictamnus dasycarpus, and other traditional Chinese medicines, the composition is prepared into decoctions, capsules, or pills through decoction and concentration. It can significantly inhibit ear swelling, reduce the frequency of itching, lower the level of inflammatory factors, and repair pathological damage to the skin. It has multiple synergistic effects of clearing heat and dampness, dispelling wind and detoxifying, cooling blood and relieving itching, and drying dampness and astringing. Furthermore, it is safe and non-toxic, thus providing a safe and effective traditional Chinese medicine solution for treating skin diseases caused by damp-heat accumulation and wind-toxin stagnation, addressing both the symptoms and the root cause.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a traditional Chinese medicine composition and its preparation for treating skin diseases caused by damp-heat accumulation and wind-toxin stagnation. Background Technology

[0002] Skin diseases such as eczema, dermatitis, urticaria, and pruritus are common chronic inflammatory skin diseases in clinical practice. Their main clinical manifestations include skin erythema, papules, vesicles, exudation, itching, desquamation, and thickening, characterized by recurrent attacks and persistent, difficult-to-cure nature. Modern medical treatments often employ antihistamines, corticosteroids, and immunosuppressants. While these drugs can effectively control itching and inflammation in the short term, long-term use often leads to a series of side effects, such as skin atrophy, pigmentation, steroid-dependent dermatitis, liver and kidney damage, and decreased immune function. Furthermore, the relapse rate after discontinuation of these medications is high.

[0003] From the perspective of Traditional Chinese Medicine (TCM) theory, the core pathogenesis of this type of skin disease is mostly due to damp-heat accumulation in the skin, wind-toxin stagnation, and blood heat generating wind, accompanied by spleen deficiency and dampness accumulation. Treatment should be based on the principles of clearing heat and dampness, dispelling wind and detoxifying, cooling blood and relieving itching, and drying dampness and astringing. However, existing TCM preparations mostly focus on clearing heat or dispelling wind, lacking a comprehensive approach that addresses multiple aspects such as cooling blood, drying dampness, relieving itching, detoxifying, and astringing, resulting in a persistently high recurrence rate. Therefore, there is an urgent need for a well-formulated TCM composition that addresses both the symptoms and the root cause, has definite efficacy, and high safety. Summary of the Invention

[0004] The purpose of this invention is to provide a traditional Chinese medicine composition and preparation thereof for treating skin diseases of the damp-heat accumulation and wind-toxin stagnation type, so as to solve the problem of large side effects of existing drugs for skin diseases of the damp-heat accumulation and wind-toxin stagnation type.

[0005] To achieve the above objectives, the present invention provides the following technical solution: a method for preparing a traditional Chinese medicine composition for treating skin diseases of the damp-heat and wind-toxin stagnation type, comprising the following steps:

[0006] S1. Weigh the following raw materials according to the following parts by weight: Rehmannia glutinosa 25-35 parts, Gentiana scabra 8-12 parts, Dictamnus dasycarpus 15-25 parts, Sophora flavescens 15-25 parts, Hedyotis diffusa 25-35 parts, Phellodendron chinense 15-25 parts, Cicadae periostracum 8-12 parts, Kochia scoparia 15-25 parts, Citrus reticulata 8-12 parts, Lonicera japonica 15-25 parts, Forsythia suspensa 15-25 parts, Saposhnikovia divaricata 8-12 parts, Gypsum fibrosum 25-35 parts, Schizonepeta tenuifolia 8-12 parts, Anemarrhena asphodeloides (salted) 12-18 parts, Tribulus terrestris (salted) 15-25 parts, Portulaca oleracea 25-35 parts, Glycyrrhiza uralensis 8-12 parts.

[0007] S2. Mix the weighed raw materials and decoct them with water;

[0008] S3. Filter, combine the filtrates to obtain the decoction.

[0009] Furthermore, the specific operation of adding water for decoction is as follows: add 1000-1400mL of water and soak for 20-40 minutes, bring to a boil over high heat and then simmer over low heat for 20-40 minutes, and filter the decoction; add 600-1000mL of water to the dregs and decoct for 15-25 minutes, and filter the decoction; combine the two filtrates.

[0010] Furthermore, it also includes concentrating the combined filtrate under reduced pressure to a thick paste with a relative density of 1.15-1.25 at 60°C, drying it to obtain a dry extract powder, and adding excipients to prepare capsules or pills.

[0011] Furthermore, glutinous rice flour of 10%-20% of the total weight of the raw materials is added during the preparation of the pills.

[0012] Furthermore, the capsule is prepared by mixing dry extract powder with microcrystalline cellulose and magnesium stearate and then filling the capsule shell.

[0013] Furthermore, the dregs of the decoction are used for external washing or wet compresses on the affected area.

[0014] Application of a traditional Chinese medicine composition in the preparation of a drug for treating skin diseases caused by damp-heat accumulation and wind-toxin stagnation.

[0015] Furthermore, the skin condition is eczema, dermatitis, urticaria, or pruritus.

[0016] The application of a traditional Chinese medicine composition in the preparation of drugs that have anti-inflammatory, antipruritic, astringent, exudative, or recurrent skin inflammation effects.

[0017] Compared with existing technologies, the present invention provides a traditional Chinese medicine composition and preparation for treating skin diseases of the damp-heat and wind-toxin stagnation type. It uses a combination of multiple traditional Chinese medicines such as Rehmannia glutinosa, Gentiana scabra, and Dictamnus dasycarpus, and is prepared into decoctions, capsules or pills through decoction and concentration. It can significantly inhibit ear swelling, reduce the frequency of itching, reduce the level of inflammatory factors and repair pathological damage to the skin. It has multiple synergistic effects of clearing heat and dampness, dispelling wind and detoxifying, cooling blood and relieving itching, and drying dampness and astringing. Moreover, it is safe and non-toxic, thus providing a safe and effective traditional Chinese medicine solution for the treatment of skin diseases of the damp-heat and wind-toxin stagnation type. Detailed Implementation

[0018] To enable those skilled in the art to better understand the technical solution of the present invention, the present invention will be further described in detail below.

[0019] Example 1:

[0020] Preparation of decoction

[0021] Prescription: Rehmannia glutinosa 30g, Gentiana scabra 10g, Dictamnus dasycarpus 20g, Sophora flavescens 20g, Hedyotis diffusa 30g, Phellodendron chinense 20g, Cicadae periostracum 10g, Kochia scoparia 20g, Citrus reticulata 10g, Lonicera japonica 20g, Forsythia suspensa 20g, Saposhnikovia divaricata 10g, Gypsum fibrosum 30g, Schizonepeta tenuifolia 10g, Anemarrhena asphodeloides 15g, Tribulus terrestris 20g, Portulaca oleracea 30g, Glycyrrhiza uralensis 10g.

[0022] Preparation method:

[0023] 1. Weigh all the medicinal materials according to the prescription;

[0024] 2. Add 1200mL of drinking water and soak for 30 minutes;

[0025] 3. After bringing to a boil over high heat, reduce to low heat and simmer for 30 minutes;

[0026] 4. Filter through a 200-mesh sieve and collect approximately 400 mL of the liquid.

[0027] 5. Add 800mL of water to the dregs and continue to decoct for 20 minutes;

[0028] 6. Filter and collect approximately 300 mL of the liquid.

[0029] 7. Combine the two decoctions, mix well, and you will have a decoction. Take one dose daily, divided into two warm doses, morning and evening. The dregs can be wrapped in gauze while still warm and used for external washing or as a wet compress on the affected area for 15-20 minutes each time.

[0030] Example 2:

[0031] Preparation of capsules

[0032] Prescription: Rehmannia glutinosa 30g, Gentiana scabra 10g, Dictamnus dasycarpus 20g, Sophora flavescens 20g, Hedyotis diffusa 30g, Phellodendron chinense 20g, Cicadae periostracum 10g, Kochia scoparia 20g, Citrus reticulata 10g, Lonicera japonica 20g, Forsythia suspensa 20g, Saposhnikovia divaricata 10g, Gypsum fibrosum 30g, Schizonepeta tenuifolia 10g, Anemarrhena asphodeloides 15g, Tribulus terrestris 20g, Portulaca oleracea 30g, Glycyrrhiza uralensis 10g.

[0033] Preparation method:

[0034] 1. Weigh the medicinal materials according to the prescription amount, and combine the two filtrates according to the decoction method in Example 1;

[0035] 2. Place the filtrate in a rotary evaporator and concentrate it under reduced pressure at 60℃ and -0.08MPa until the relative density of the concentrate at 60℃ is 1.18 to 1.22, to obtain a thick paste;

[0036] 3. Spray dry the thick paste at an inlet air temperature of 160℃ and an outlet air temperature of 80℃ to obtain dry extract powder;

[0037] 4. Take 100g of dry extract powder, add 20g of microcrystalline cellulose and 1g of magnesium stearate, and mix well;

[0038] 5. Using a fully automatic capsule filling machine, fill the No. 0 gelatin capsules with 0.5g of gelatin per capsule;

[0039] 6. Polishing, screening, and aluminum-plastic packaging. Dosage and administration: Oral administration, 4 capsules each time, 3 times a day.

[0040] Example 3:

[0041] Preparation of water pills

[0042] Prescription: Rehmannia glutinosa 30g, Gentiana scabra 10g, Dictamnus dasycarpus 20g, Sophora flavescens 20g, Hedyotis diffusa 30g, Phellodendron chinense 20g, Cicadae periostracum 10g, Kochia scoparia 20g, Citrus reticulata 10g, Lonicera japonica 20g, Forsythia suspensa 20g, Saposhnikovia divaricata 10g, Gypsum fibrosum 30g, Schizonepeta tenuifolia 10g, Anemarrhena asphodeloides 15g, Tribulus terrestris 20g, Portulaca oleracea 30g, Glycyrrhiza uralensis 10g.

[0043] Preparation method:

[0044] 1. Weigh the medicinal materials according to the prescription amount, and combine the two filtrates according to the decoction method in Example 1;

[0045] 2. Concentrate the filtrate under reduced pressure to a thick paste with a relative density of 1.20–1.25 at 60°C;

[0046] 3. Take the thick paste, add glutinous rice flour (15% of the total weight of the raw materials) and an appropriate amount of purified water, stir and knead repeatedly to make a soft material;

[0047] 4. Place the soft material in a water pellet making machine, extrude it into strips, roll it into pellets, and make water pellets with a diameter of about 4mm;

[0048] 5. Place the wet pellets in a 50℃ oven and dry at a low temperature for 12 hours until constant weight is achieved;

[0049] 6. Polish the dried water pellets with a polishing machine to remove surface burrs;

[0050] 7. Package into composite film bags, 10g per bag. Dosage and administration: Oral administration, 1 bag each time, 3 times a day.

[0051] Example 4:

[0052] Preparation of decoction

[0053] Prescription: Rehmannia glutinosa 25g, Gentiana scabra 8g, Dictamnus dasycarpus 15g, Sophora flavescens 15g, Hedyotis diffusa 25g, Phellodendron chinense 15g, Cicadae periostracum 8g, Kochia scoparia 15g, Citrus reticulata 8g, Lonicera japonica 15g, Forsythia suspensa 15g, Saposhnikovia divaricata 8g, Gypsum fibrosum 25g, Schizonepeta tenuifolia 8g, Anemarrhena asphodeloides (salted) 12g, Tribulus terrestris (salted) 15g, Portulaca oleracea 25g, Glycyrrhiza uralensis 8g.

[0054] Preparation method:

[0055] 1. Weigh all the medicinal materials according to the prescription;

[0056] 2. Add 1200mL of drinking water and soak for 30 minutes;

[0057] 3. After bringing to a boil over high heat, reduce to low heat and simmer for 30 minutes;

[0058] 4. Filter through a 200-mesh sieve and collect approximately 400 mL of the liquid.

[0059] 5. Add 800mL of water to the dregs and continue to decoct for 20 minutes;

[0060] 6. Filter and collect approximately 300 mL of the liquid.

[0061] 7. Combine the two decoctions, mix well, and you will have a decoction. Take one dose daily, divided into two warm doses, morning and evening. The dregs can be wrapped in gauze while still warm and used for external washing or as a wet compress on the affected area for 15-20 minutes each time.

[0062] Example 5:

[0063] Preparation of decoction

[0064] Prescription: Rehmannia glutinosa 35g, Gentiana scabra 12g, Dictamnus dasycarpus 25g, Sophora flavescens 25g, Hedyotis diffusa 35g, Phellodendron chinense 25g, Cicadae periostracum 12g, Kochia scoparia 25g, Citrus reticulata 12g, Lonicera japonica 25g, Forsythia suspensa 25g, Saposhnikovia divaricata 12g, Gypsum fibrosum 35g, Schizonepeta tenuifolia 12g, Anemarrhena asphodeloides 18g, Tribulus terrestris 25g, Portulaca oleracea 35g, Glycyrrhiza uralensis 12g.

[0065] Preparation method:

[0066] 1. Weigh all the medicinal materials according to the prescription;

[0067] 2. Add 1200mL of drinking water and soak for 30 minutes;

[0068] 3. After bringing to a boil over high heat, reduce to low heat and simmer for 30 minutes;

[0069] 4. Filter through a 200-mesh sieve and collect approximately 400 mL of the liquid.

[0070] 5. Add 800mL of water to the dregs and continue to decoct for 20 minutes;

[0071] 6. Filter and collect approximately 300 mL of the liquid.

[0072] 7. Combine the two decoctions, mix well, and you will have a decoction. Take one dose daily, divided into two warm doses, morning and evening. The dregs can be wrapped in gauze while still warm and used for external washing or as a wet compress on the affected area for 15-20 minutes each time.

[0073] Example 6:

[0074] Preparation of water pills

[0075] Prescription: Rehmannia glutinosa 25g, Gentiana scabra 8g, Dictamnus dasycarpus 15g, Sophora flavescens 15g, Hedyotis diffusa 25g, Phellodendron chinense 15g, Cicadae periostracum 8g, Kochia scoparia 15g, Citrus reticulata 8g, Lonicera japonica 15g, Forsythia suspensa 15g, Saposhnikovia divaricata 8g, Gypsum fibrosum 25g, Schizonepeta tenuifolia 8g, Anemarrhena asphodeloides (salted) 12g, Tribulus terrestris (salted) 15g, Portulaca oleracea 25g, Glycyrrhiza uralensis 8g.

[0076] Preparation method:

[0077] 1. Weigh the medicinal materials according to the prescription amount, and combine the two filtrates according to the decoction method in Example 1;

[0078] 2. Concentrate the filtrate under reduced pressure to a thick paste with a relative density of 1.20–1.25 at 60°C;

[0079] 3. Take the thick paste, add 20% of the total weight of the raw materials in glutinous rice flour and an appropriate amount of purified water, stir and knead repeatedly to make a soft material;

[0080] 4. Place the soft material in a water pellet making machine, extrude it into strips, roll it into pellets, and make water pellets with a diameter of about 4mm;

[0081] 5. Place the wet pellets in a 50℃ oven and dry at a low temperature for 12 hours until constant weight is achieved;

[0082] 6. Polish the dried water pellets with a polishing machine to remove surface burrs;

[0083] 7. Package into composite film bags, 10g per bag. Dosage and administration: Oral administration, 1 bag each time, 3 times a day.

[0084] Example 7:

[0085] Effects of DNCB on mouse eczema model

[0086] 1. Test materials

[0087] Animals: SPF-grade Kunming mice, half male and half female, weighing 18-22g.

[0088] Drugs and reagents: Water pills prepared using the preparation method provided in Example 3, which were prepared to the appropriate concentration with 0.5% sodium carboxymethyl cellulose before use; loratadine tablets (positive control drug, 10 mg / kg); 2,4-dinitrochlorobenzene (DNCB), acetone, and olive oil.

[0089] Main instruments: electronic analytical balance (accuracy 0.1mg), 8mm punch, microplate reader, upright microscope.

[0090] 2. Model establishment, grouping, and drug administration

[0091] Model establishment: 24 hours before the experiment, a 2cm × 2cm area of ​​hair was removed from the abdomen of mice using depilatory cream. On day 1 (sensitization), 100μL of 5% DNCB solution (prepared with acetone:olite = 3:1) was evenly applied to the hair-removed area on the mouse abdomen for initial sensitization. Sensitization was repeated once on day 2. Challenge was initiated on day 5 by evenly applying 20μL of 0.5% DNCB solution to both sides of the right ear auricle of the mice, with an equal amount of solution applied to the left ear as a control. Challenge was performed every 3 days for a total of 3 times.

[0092] Grouping and Administration: Mice with successfully induced modeling were randomly divided into 5 groups of 10 mice each, with an additional normal control group (unsensitized, treated only with solvent). The groups were as follows: normal control group, model control group, positive control group (loratadine, 10 mg / kg), low-dose group (25 mg / kg), medium-dose group (50 mg / kg), and high-dose group (100 mg / kg). Each administration group was administered the drug by gavage 1 hour before each challenge, while the normal control group and model group were administered an equal volume of physiological saline by gavage. The administration was continued for 7 days.

[0093] 3. Detection indicators

[0094] Ear swelling determination: 24 hours after the last administration, mice were euthanized by cervical dislocation, and both ears were cut off along the auricular baseline. Ear pieces were punched out at the same location in both ears using an 8mm punch and weighed quickly. Ear swelling degree was calculated as follows: Ear swelling degree (mg) = Right ear weight - Left ear weight.

[0095] Behavioral observation of pruritus: After the final provocation, mice were placed in a transparent observation box. After acclimatization for 10 minutes, the number of times the mice scratched their right ear within 30 minutes was recorded. Scratching criteria: The mouse continuously raised its hind limb to scratch its head or ear, and each time the hind limb was raised and scratched was counted as one scratch.

[0096] Serum inflammatory factor detection: Before euthanizing mice, blood was collected by enucleation. After standing for 2 hours, the blood was centrifuged at 3000 rpm for 15 minutes to separate the serum. The levels of IL-4, IL-6, and TNF-α in the serum were detected according to the ELISA kit instructions.

[0097] Histopathological observation: Right ear tissues of mice in each group were taken, fixed with 4% paraformaldehyde, routinely dehydrated, embedded in paraffin, sectioned (4μm thick), stained with HE, and observed under a light microscope for epidermal thickening, dermal edema and inflammatory cell infiltration. Semi-quantitative scoring was performed from 0 to 4 points (0 points: no change; 1 point: mild; 2 points: moderate; 3 points: severe; 4 points: very severe).

[0098] 4. Statistical Methods

[0099] All data are expressed as mean ± standard deviation (x ± s). One-way ANOVA was performed using SPSS 22.0 software, and LSD-t test was used for comparisons between groups. P < 0.05 was considered statistically significant.

[0100] 5. Results

[0101] Table 1. Statistics on Ear Swelling

[0102] Group Ear swelling degree (mg, ±s) normal control group 8.2±1.1 Model control group 28.5±3.2 Positive drug group 14.3±1.8 low-dose group 19.6±2.1 medium dose group 15.2±1.7 High-dose group 12.8±1.5

[0103] Compared with the normal control group, the ear swelling of mice in the model control group was significantly increased (P<0.01), indicating that the DNCB-induced eczema model was successfully established. Compared with the model group, the medium-, high-dose and positive control groups of the water pills of this invention significantly reduced ear swelling (P<0.01), and the low-dose group also showed a reducing effect (P<0.05). Among them, the ear swelling in the high-dose group was reduced to 12.8 mg, which was better than that in the positive control group (14.3 mg), and the difference was statistically significant (P<0.05). This indicates that the water pills have a significant inhibitory effect on DNCB-induced skin inflammation in a dose-dependent manner.

[0104] Table 2. Statistics on the frequency of itching

[0105] Group Frequency of itching (times / 30 minutes) ±s) normal control group 5.2±1.0 Model control group 42.5±5.3 Positive drug group 18.2±2.4 low-dose group 26.8±3.1 medium dose group 20.5±2.6 High-dose group 15.6±2.1

[0106] The number of itching episodes in the model control group mice increased approximately 8 times compared to the normal group (P<0.01), indicating significant itching behavior in the model mice. All treatment groups significantly reduced the number of itching episodes. The high-dose group showed the most significant effect, reducing the number of itching episodes to 15.6, significantly lower than the 18.2 episodes in the positive control group (P<0.05). This indicates that the water pills have a rapid and potent antipruritic effect, and its mechanism may be related to inhibiting the release of inflammatory mediators and regulating nerve sensitivity.

[0107] Table 3. Statistical table of serum inflammatory factors

[0108] Group IL-4 (pg / mL) IL-6 (pg / mL) TNF-α (pg / mL) normal control group 25.3±3.2 30.5±4.1 40.2±5.3 Model control group 128.6±15.7 156.3±18.2 189.5±21.4 Positive drug group 56.2±7.1 68.5±8.3 75.6±9.2 High-dose group 42.8±5.5 51.2±6.7 58.3±7.5

[0109] In the model control group, the serum levels of Th2 cytokine IL-4 and pro-inflammatory factors IL-6 and TNF-α were significantly elevated (P<0.01), indicating that the model mice were in a state of severe immune inflammation. After high-dose treatment with the water pills of this invention, the levels of the above three inflammatory factors decreased significantly, showing a highly significant difference compared with the model group (P<0.01). The high-dose group showed better inhibitory effects on IL-4, IL-6, and TNF-α than the positive control drug loratadine (P<0.05). This indicates that the traditional Chinese medicine composition provided by this invention can not only effectively reduce inflammation but also regulate the Th1 / Th2 immune balance, thereby improving allergic inflammatory responses at their root.

[0110] Table 4 Ear tissue pathology scores

[0111] Group Epidermal thickening (points) Dermal edema (points) Inflammatory cell infiltration (points) normal control group 0.5±0.2 0.3±0.1 0.4±0.2 Model control group 3.8±0.4 3.5±0.3 3.9±0.4 Positive drug group 1.6±0.3 1.4±0.2 1.7±0.3 High-dose group 1.1±0.2 0.9±0.2 1.2±0.2

[0112] As shown in the table above, the ear tissue of the model control group mice showed significant epidermal thickening, edema of the spinous cell layer, and extensive infiltration of lymphocytes and neutrophils in the dermis, with pathological scores significantly higher than those of the normal group (P<0.01). After treatment, the above pathological changes in both the positive drug group and the high-dose group were significantly alleviated. Among them, the high-dose group of this invention showed significantly better scores than the positive drug group in improving epidermal thickening, reducing edema, and inhibiting inflammatory cell infiltration (P<0.05), indicating that its effect on repairing the skin barrier and inhibiting local inflammatory response was more prominent.

[0113] Example 8:

[0114] Acute toxicity test

[0115] 1. Test materials

[0116] Animals: SPF-grade Kunming mice, weighing 18–22g, half male and half female.

[0117] 2. Test Methods

[0118] The maximum tolerated dose method was used. Forty mice were randomly divided into four groups of ten each, with half males and half females. Each group was administered the water-based suspension of this invention via gavage at doses of 20 g / kg, 40 g / kg, and 80 g / kg, respectively. The control group received an equal volume of physiological saline. Mice were observed for 14 consecutive days after gavage, and their general behavior, symptoms of poisoning, mortality, and weight changes were recorded. On day 14, all mice were sacrificed, and their organs (heart, liver, spleen, lungs, kidneys, etc.) were dissected for any visible lesions.

[0119] 3. Test Results

[0120] Table 5. Changes in Body Weight Due to Acute Toxicity

[0121] Group Dosage (g / kg) Weight on day 0 (g) Weight on day 7 (g) Weight on day 14 (g) Death count control group - 20.5±1.2 23.8±1.5 26.2±1.8 0 low-dose group 20 20.3±1.1 23.5±1.4 25.9±1.7 0 medium dose group 40 20.4±1.2 23.6±1.5 26.0±1.8 0 High-dose group 80 20.2±1.1 23.4±1.4 25.8±1.7 0

[0122] During the 14-day observation period, no mice in any of the treatment groups died, and no obvious symptoms of poisoning (such as piloerection, arched back, tremors, ataxia, etc.) were observed. Their diet, water intake, activity, and feces were all normal. There was no significant difference in body weight gain between the treatment groups and the control group (P>0.05). Post-dissection observation revealed no abnormalities in color, size, or texture of the heart, liver, spleen, lungs, kidneys, or other major organs in any group of mice. The calculated LD50 was >80 g / kg. According to the acute toxicity classification standard for chemical substances, the water pills belong to the practically non-toxic category, with a large safety window.

[0123] Example 9:

[0124] Long-term toxicity testing

[0125] 1. Test materials

[0126] Animals: SPF-grade SD rats, half male and half female, weighing 180-220g.

[0127] 2. Test Methods

[0128] Eighty rats were randomly divided into four groups of 20 each, with half males and half females. These groups were: a control group, a low-dose group (1.0 g / kg), a medium-dose group (2.0 g / kg), and a high-dose group (4.0 g / kg). Based on the acute toxicity test results (maximum tolerated dose in mice via single gavage > 80 g / kg), the equivalent dose in rats, calculated by body surface area, was approximately 1 / 6 of that in mice, meaning the acute tolerated dose in rats was approximately 13.3 g / kg. For the long-term toxicity test, the high dose was set at 4.0 g / kg, which was 1 / 3.3 of the acute tolerated dose. The medium and low doses were 1 / 2 and 1 / 4 of the high dose, respectively. This dose range adequately assessed the potential toxicity of long-term drug administration without exceeding the clinical safety window. Each group received the drug once daily via gavage for 12 consecutive weeks. After drug withdrawal, the rats were observed for another 4 weeks, with 10 rats from each group retained to observe the recovery period. At the end of the 12th week of administration and the end of the 4th week of drug withdrawal, 10 rats from each group were sacrificed, and the following indicators were measured:

[0129] General condition: weight, behavior, food intake, physical appearance.

[0130] Hematological parameters: red blood cell count, white blood cell count, hemoglobin, platelet count.

[0131] Blood biochemical indicators: alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (CRE).

[0132] Organ coefficient: Weigh the wet weight of the heart, liver, spleen, lungs, kidneys, adrenal glands, thymus, and testes / ovaries, and calculate the organ coefficient (organ weight / body weight × 100%).

[0133] Histopathological examination: The above-mentioned organs and skin tissues were taken, fixed in 10% formalin, embedded in paraffin, stained with hematoxylin and eosin (HE), and observed under a light microscope for structural changes.

[0134] 3. Test Results

[0135] (1) Effects on liver and kidney function (data after 12 weeks of drug administration)

[0136] Table 6 Long-term toxicity of liver and kidney function

[0137] Group Dosage (g / kg) ALT (U / L) AST (U / L) BUN (mmol / L) CRE (μmol / L) control group - 32.5±4.1 38.6±5.2 5.8±0.7 45.2±5.6 low-dose group 1.0 33.1±4.3 39.2±5.4 5.9±0.8 45.8±5.7 medium dose group 2.0 32.8±4.2 38.9±5.3 5.7±0.7 44.9±5.5 High-dose group 4.0 33.0±4.2 39.1±5.4 5.8±0.7 45.1±5.6

[0138] After 12 weeks of continuous administration, compared with the control group, there were no statistically significant differences in ALT, AST, BUN, and CRE levels in rats of each dose group of the water pills (P>0.05), and all levels were within the normal physiological range. Follow-up examinations 4 weeks after drug withdrawal showed no significant differences between the above indicators and the control group. These results indicate that long-term use of the water pills has no damaging effect on liver and kidney function in rats.

[0139] (2) Effects on organ coefficients and histopathology

[0140] There were no significant differences in organ coefficients (heart, liver, spleen, lung, kidney, adrenal gland, thymus, etc.) between the drug-treated groups and the control group (P>0.05). Histopathological examination showed no obvious pathological changes in the heart, liver, spleen, lung, kidney, stomach, intestine, and skin of rats in both the control and drug-treated groups. In the high-dose group, a few rats showed slight hepatocyte swelling, but no obvious toxic lesions such as necrosis or fibrosis were observed. These changes returned to normal 4 weeks after drug withdrawal, considered a reversible adaptive change. The skin epidermis remained intact, without hyperkeratosis or inflammatory infiltration.

[0141] Long-term toxicity tests showed that no obvious toxic reactions were observed during 12 weeks of continuous administration of the water pills. It had no significant effect on liver and kidney function, the structure of important organs and tissues, or organ coefficients, and there were no delayed toxic reactions, indicating that it is safe at the clinically intended dose.

[0142] The foregoing has only described certain exemplary embodiments of the present invention by way of illustration. Undoubtedly, those skilled in the art can modify the described embodiments in various ways without departing from the spirit and scope of the present invention. Therefore, the above description is illustrative in nature and should not be construed as limiting the scope of protection of the claims of the present invention.

Claims

1. A method for preparing a traditional Chinese medicine composition for treating skin diseases of the damp-heat accumulation and wind-toxin stagnation type, characterized in that, Includes the following steps: S1. Weigh the following raw materials according to the following parts by weight: Rehmannia glutinosa 25-35 parts, Gentiana scabra 8-12 parts, Dictamnus dasycarpus 15-25 parts, Sophora flavescens 15-25 parts, Hedyotis diffusa 25-35 parts, Phellodendron chinense 15-25 parts, Cicadae periostracum 8-12 parts, Kochia scoparia 15-25 parts, Citrus reticulata 8-12 parts, Lonicera japonica 15-25 parts, Forsythia suspensa 15-25 parts, Saposhnikovia divaricata 8-12 parts, Gypsum fibrosum 25-35 parts, Schizonepeta tenuifolia 8-12 parts, Anemarrhena asphodeloides (salted) 12-18 parts, Tribulus terrestris (salted) 15-25 parts, Portulaca oleracea 25-35 parts, Glycyrrhiza uralensis 8-12 parts. S2. Mix the weighed raw materials and decoct them with water; S3. Filter, combine the filtrates to obtain the decoction.

2. The method for preparing a traditional Chinese medicine composition for treating skin diseases of the damp-heat and wind-toxin stagnation type according to claim 1, characterized in that, The specific steps for adding water and decocting are as follows: add 1000-1400mL of water and soak for 20-40 minutes, bring to a boil over high heat and then simmer over low heat for 20-40 minutes, then filter the liquid; add 600-1000mL of water to the dregs and simmer for 15-25 minutes, then filter the liquid; combine the two filtrates.

3. The method for preparing a traditional Chinese medicine composition for treating skin diseases of the damp-heat and wind-toxin stagnation type according to claim 1, characterized in that, It also includes concentrating the combined filtrate under reduced pressure to a thick paste with a relative density of 1.15-1.25 at 60°C, drying it to obtain a dry extract powder, and adding excipients to make capsules or pills.

4. The method for preparing a traditional Chinese medicine composition for treating skin diseases of the damp-heat and wind-toxin stagnation type according to claim 3, characterized in that, The pills are prepared by adding 10%-20% glutinous rice flour by weight of the raw materials.

5. The method for preparing a traditional Chinese medicine composition for treating skin diseases of the damp-heat accumulation and wind-toxin stagnation type according to claim 3, characterized in that, The capsules are prepared by mixing dry extract powder with microcrystalline cellulose and magnesium stearate and then filling the capsule shell.

6. The method for preparing a traditional Chinese medicine composition for treating skin diseases of the damp-heat accumulation and wind-toxin stagnation type according to claim 1, characterized in that, The dregs of the decoction are used for external washing or wet compresses on the affected area.

7. The use of the traditional Chinese medicine composition according to any one of claims 1-6 in the preparation of a medicament for treating skin diseases of the damp-heat and wind-toxin stagnation type.

8. The application according to claim 7, characterized in that, The skin condition is eczema, dermatitis, urticaria, or pruritus.

9. The use of the traditional Chinese medicine composition according to any one of claims 1-6 in the preparation of a medicament for anti-inflammatory, antipruritic, astringent, or reduction of skin inflammation recurrence.