A compound traditional Chinese medicine composition for treating dermatitis in tumor patients

Abstract

The application relates to a compound traditional Chinese medicine composition for treating dermatitis of tumor patients, which is prepared from the following raw materials in parts by weight: 20-40 parts by weight of Huangqi, 5-15 parts by weight of Wumei, 5-15 parts by weight of Baishao, 5-15 parts by weight of Dilong and 10-20 parts by weight of Danshen, and a preparation method thereof is disclosed. The application can obviously improve the clinical dermatitis score related to skin lesions, reduce the spleen coefficient index, and also has the functions of reducing the epidermal thickness and inflammatory infiltration such as mast cells in the dermis, and reducing the inflammatory factor level in the skin lesions, which shows that the application can treat dermatitis of tumor patients.

Description

Technical Field

[0001] This invention relates to a compound traditional Chinese medicine composition for treating dermatitis in cancer patients, belonging to the field of traditional Chinese medicine pharmaceuticals. Background Technology

[0002] Dermatitis (atopic dermatitis, contact dermatitis, traditional eczematous dermatitis, etc.) is a common skin condition in cancer patients. Cancer patients may develop dermatitis even without treatment, primarily due to the impact of the tumor itself and the patient's overall condition on the immune system and skin. The reasons for untreated dermatitis in cancer patients include: 1. Tumor cell secretion factors: Tumor cells produce immunosuppressive factors such as tumor necrosis factor (TNF) and transforming growth factor-β (TGF-β). These factors can inhibit the activity of immune cells, hindering the immune system's effective attack on the tumor and affecting the skin's immune response. These factors may affect skin health, leading to inflammatory reactions. 2. Tumor-related metabolic abnormalities: Certain tumors can cause metabolic abnormalities, such as abnormal hormone levels and malnutrition, all of which can affect skin health. 3. Immunosuppressive state: The tumor itself and its microenvironment may suppress the patient's immune system, making them more susceptible to skin infections and other skin problems. 4. Cancer Complications: Some cancer patients may have other diseases or complications, such as infection, anemia, malnutrition, etc., which may also lead to skin inflammation. 5. Psychological Factors: Cancer patients often face psychological stress, anxiety, depression, and other emotional problems, which may also affect skin health.

[0003] Dermatitis is a common inflammatory skin disease characterized by erythema, edema, papules, and lichenification at different stages, often accompanied by intense itching. Due to its long course, chronic, recurrent inflammation and scratching lead to thickened skin and lichenification, often trapping patients in a vicious cycle of itching and scratching, resulting in insomnia and sleep disorders, severely impacting and reducing their quality of life. Current treatments for dermatitis include the use of antihistamines such as antihistamines, corticosteroids, and antibiotics. However, these medications often cause adverse reactions with long-term use, cannot cure the condition, have high recurrence rates, and are poorly tolerated by patients. Therefore, there is an urgent need to find safer and more effective treatments. Summary of the Invention

[0004] The purpose of this invention is to provide a compound traditional Chinese medicine composition for treating dermatitis in cancer patients. Another purpose of this invention is to provide a method for preparing this compound traditional Chinese medicine composition.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] A compound traditional Chinese medicine composition for treating dermatitis in cancer patients is made from the following raw materials in parts by weight: 20-40 parts by weight of Scutellaria baicalensis, 5-15 parts by weight of Prunus mume, 5-15 parts by weight of Paeonia lactiflora, 5-15 parts by weight of Pheretima aspergillum, and 10-20 parts by weight of Salvia miltiorrhiza.

[0007] The compound traditional Chinese medicine composition for treating dermatitis in cancer patients is made from the following raw materials in parts by weight: 30 parts by weight of Scutellaria baicalensis, 10 parts by weight of Prunus mume, 10 parts by weight of Paeonia lactiflora, 10 parts by weight of Pheretima aspergillum, and 15 parts by weight of Salvia miltiorrhiza.

[0008] The compound traditional Chinese medicine composition for treating dermatitis in cancer patients is made from the following raw materials in parts by weight: 20 parts by weight of Scutellaria baicalensis, 15 parts by weight of Prunus mume, 5 parts by weight of Paeonia lactiflora, 15 parts by weight of Pheretima aspergillum, and 10 parts by weight of Salvia miltiorrhiza.

[0009] The compound traditional Chinese medicine composition for treating dermatitis in cancer patients is made from the following raw materials in parts by weight: 40 parts by weight of Scutellaria baicalensis, 5 parts by weight of Prunus mume, 15 parts by weight of Paeonia lactiflora, 5 parts by weight of Pheretima aspergillum, and 20 parts by weight of Salvia miltiorrhiza.

[0010] The preparation method of the compound traditional Chinese medicine composition for treating dermatitis in cancer patients includes the following steps: extracting and filtering the raw Chinese medicine, and cooling it to obtain a drug extract; mixing an appropriate amount of sweet almond oil and beeswax, heating it in a hot water bath to 65°C until all the beeswax melts and dissolves in the sweet almond oil to form an oil solution; slowly adding the above hot oil solution to the drug extract while stirring vigorously during the addition process to form an oil-in-water emulsion cream.

[0011] The compound traditional Chinese medicine composition for treating dermatitis in cancer patients is prepared by the following method: weigh five kinds of traditional Chinese medicine raw materials, add 10 times the weight of the traditional Chinese medicine in water and soak for 1 hour, boil, keep boiling for 2 hours, filter, and obtain the extract. The extraction is repeated twice and the extracts are combined to obtain the drug extract.

[0012] The application of the compound traditional Chinese medicine composition for treating dermatitis in cancer patients in the preparation of drugs for treating dermatitis in cancer patients.

[0013] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0014] 1. Traditional Chinese medicine (TCM) is a treasure of our national culture, characterized by its diverse sources and low toxicity, and it has a unique effect in the external treatment of dermatitis. Modern clinical research has found that TCM preparations have good effects in treating dermatitis, and their dosage forms are mainly ointments and compound preparations. The compound composition of this invention consists of earthworm, salvia miltiorrhiza, scutellaria baicalensis, white peony root, and dried plum. The colors of these five herbs are green, red, yellow, white, and black, respectively, corresponding to the "wood, fire, earth, metal, and water" in the TCM Five Elements theory, hence the name Five Elements Ointment. Dermatitis in tumor patients is characterized by erythema, edema, papules, and lichenification, and its etiology is mostly due to a combination of internal and external factors. External pathogens such as wind, dampness, and heat invade the skin, and the combination of internal and external pathogens causes disease. Internal factors are primarily due to spleen deficiency, insufficient endowment, and the generation of dampness and heat; or due to impaired lung function, resulting in insufficient nourishment of the skin and hair; or due to deficiency of the liver and kidneys, leading to deficiency of qi, blood, yin, and yang. This disease is recurrent and difficult to cure, eventually depleting qi and blood, leading to dryness and wind. Treatment focuses on cooling the blood, moisturizing dryness, eliminating dampness, and relieving itching. This invention's Five Elements Ointment is primarily used clinically for skin conditions such as eczema, sores, and itching in cancer patients, showing good improvement effects on erythema, itching, epidermal peeling, and lichenified skin.

[0015] 2. The Five Elements Ointment of this invention has a reasonable formula, in which each component is indispensable: Scutellaria baicalensis, the principal ingredient, is the rhizome of Scutellaria baicalensis, a plant of the Lamiaceae family. It is bitter and cold in nature and enters the liver and gallbladder meridians. It has the effects of clearing heat and detoxifying, cooling blood and stopping bleeding, suppressing fire and calming the mind, and promoting bile secretion and relieving jaundice. It is mainly used to treat symptoms such as damp-heat jaundice, itchy skin, and skin sores; Prunus mume, the assistant ingredient, is the fruit of Prunus mume, a plant of the Rosaceae family. It is sour and astringent in nature and enters the liver, stomach, and kidney meridians. It has the effects of astringing the intestines and stopping diarrhea, clearing heat and detoxifying, astringing and stopping bleeding, and moisturizing and beautifying the skin. It is mainly used to treat symptoms such as damp-heat diarrhea, skin bleeding, and boils. White peony root, an assistant herb, is the root of the white peony plant in the Ranunculaceae family. Its taste is bitter and sweet, and it enters the liver and spleen meridians. It has the effects of promoting blood circulation and relieving pain, regulating menstruation and relieving itching, and clearing heat and detoxifying. It is mainly used to treat symptoms such as pain, urticaria and itching, and damp-heat skin diseases. Earthworm, an adjuvant herb, is the earthworm of the family Lepidodendron in the order Oligochaeta of the class Oligochaeta. Its taste is pungent and warm, and it enters the liver, heart, and spleen meridians. It has the effects of dispelling wind and relieving itching, promoting blood circulation and removing blood stasis, and reducing swelling and dissipating nodules. It is mainly used to treat symptoms such as itching, blood stasis, eczema, and boils. Salvia miltiorrhiza, an adjuvant herb, is the rhizome of the plant Salvia miltiorrhiza in the Lamiaceae family. Its taste is bitter and slightly cold, and it enters the heart, liver, and stomach meridians. It has the effects of promoting blood circulation, removing blood stasis, relaxing muscles and tendons, and is mainly used to treat symptoms such as bleeding due to blood stasis, boils and carbuncles, and erysipelas. In terms of treatment, the Five Elements Ointment of this invention first treats the symptoms, and after the damp-heat subsides, it strengthens the spleen and promotes digestion to treat the root cause, enhancing its anti-inflammatory and antipruritic abilities. Clinical efficacy observations show that the Five Elements Ointment of this invention can effectively relieve skin inflammation, regulate skin immune function, and has significant therapeutic effects on dermatitis in cancer patients. It has no adverse reactions, no toxic side effects, and does not irritate the patient's skin. It can enhance the skin's resistance and achieve both symptomatic and root-cause treatment.

[0016] 3. Traditional Chinese medicine ointments have the advantages of convenient use, fast absorption, local effect, high bioavailability and wide range of indications. They are one of the important preparation forms of traditional Chinese medicine and have good application prospects in some skin diseases, trauma, pain and other aspects. This invention organically combines traditional Chinese medicine extraction technology with water-in-oil emulsion cream preparation process, etc., and has the effects of cooling blood and moisturizing dryness, removing dampness and relieving itching. It overcomes the disadvantages of Western medicine such as large side effects, patients are not suitable for large-scale long-term use, and easy relapse after discontinuation. The Five Elements Ointment of this invention is a semi-solid or solid ointment in the storage state at room temperature. When used, it can be spread on the affected area through the skin. Its advantages are as follows: (1) The Five Elements Ointment has good bioadhesion and is suitable for the patient's skin. It can be administered through skin application, and the dosage is accurate. It prolongs the retention time of the drug at the site of action and achieves the purpose of slow release of inflammatory skin diseases. It not only avoids the first-pass effect of oral administration in the gastrointestinal tract, but also reduces the adverse reactions of the drug. (2) It can accommodate the extracts of traditional Chinese medicine compound, etc. The process conditions are not harsh, which is suitable for the current production status of traditional Chinese medicine compound ointments and facilitates promotion and application. (3) The oil phase in the water-in-oil emulsion cream base can form a protective film, which helps to enhance the skin barrier function and prevent external irritants from damaging the skin. It can isolate the drug application site from the external environment, provide a moist environment for wound healing, and avoid infection. (4) The water phase in the water-in-oil emulsion cream base has a high water content, which can effectively provide the skin with the moisture it needs. At the same time, the oil phase can lock in moisture and enhance the skin's moisturizing ability. (5) The Five Elements Cream has a wide range of applications and is suitable for people with different skin types. It has a good skin feel and is gentle. (6) It is convenient to carry and easy to use.

[0017] 4. This invention discloses for the first time the application of the compound traditional Chinese medicine composition Wuxing Ointment in improving dermatitis. The Wuxing Ointment of this invention can be demonstrated in the skin lesions of mice with tumor-bearing 2,4-dinitrochlorobenzene (DNCB) induced dermatitis. The Wuxing Ointment of this invention can significantly improve the clinical dermatitis score related to the skin lesions, reduce the spleen coefficient index, and also has the functions of reducing epidermal thickness and inflammatory infiltration such as mast cells in the dermis, and reducing the level of inflammatory factors in the skin lesions, indicating the potential of the Wuxing Ointment of this invention in improving inflammatory skin diseases in cancer patients. Attached Figure Description

[0018] Figure 1 This is a schematic diagram illustrating the effect of the compound composition of the present invention on skin lesions in mice with tumor-bearing dermatitis.

[0019] Figure 2 This is a schematic diagram showing the HE staining results of the compound composition of the present invention on the dorsal skin lesions of mice with tumor-bearing dermatitis;

[0020] Figure 3 This is a schematic diagram showing the results of toluidine blue staining of mast cells on the back lesions of mice bearing tumor dermatitis using the compound composition of the present invention;

[0021] Figure 4 This is a schematic diagram illustrating the effect of the compound composition of the present invention on the expression of serum inflammatory factors in mice bearing tumor dermatitis;

[0022] Figure 5 This is a schematic diagram showing the spleen coefficient results of the compound composition of the present invention on mice with tumor-bearing dermatitis;

[0023] Figure 6 This is a schematic diagram showing the effect of the compound composition of the present invention on the degree of ear swelling and the quality of the right ear flap in mice with tumor-bearing dermatitis.

[0024] In the above figures, Control represents the normal feeding blank group, Model represents the model group, Dex represents the compound dexamethasone acetate cream group, WXG-H represents the high-dose group of the present invention, and WXG-L represents the low-dose group of the present invention. Detailed Implementation

[0025] The present invention will be further described in detail below through specific embodiments. Unless otherwise specified, the raw materials, reagents, or apparatus used in the embodiments can be obtained from conventional commercial sources or by existing technical methods. Unless otherwise specified, the experimental or testing methods are conventional methods in the art.

[0026] Example 1: Take 30g of Scutellaria baicalensis, 10g of Prunus mume, 10g of Paeonia lactiflora, 10g of Pheretima aspergillum, and 15g of Salvia miltiorrhiza. The preparation method is as follows:

[0027] Step (1) Weigh the five Chinese medicinal materials, add 10 times the weight of the Chinese medicinal materials to water and soak for 1 hour, boil, keep boiling for 2 hours, filter, and obtain the extract. Extract twice in total, combine the extracts to obtain the drug extract.

[0028] Step (2) Cool the drug extract to room temperature;

[0029] Step (3) Mix an appropriate amount of sweet almond oil and beeswax, and heat in a hot water bath to 65°C until all the beeswax melts and dissolves in the sweet almond oil to form an oil solution;

[0030] Step (4) Slowly add the hot oil solution to the drug extract while stirring vigorously to form an oil-in-water emulsion cream.

[0031] Example 2: Take 20g of Scutellaria baicalensis, 15g of Prunus mume, 5g of Paeonia lactiflora, 15g of Pheretima aspergillum, and 10g of Salvia miltiorrhiza. The preparation method is as follows:

[0032] Step (1) Weigh the five Chinese medicinal materials, add 10 times the weight of the Chinese medicinal materials to water and soak for 1 hour, boil, keep boiling for 2 hours, filter, and obtain the extract. Extract twice in total, combine the extracts to obtain the drug extract.

[0033] Step (2) Cool the drug extract to room temperature;

[0034] Step (3): Mix an appropriate amount of sweet almond oil and beeswax, and heat them in a water bath to 65 °C until all the beeswax melts and dissolves in the sweet almond oil to form an oil solution.

[0035] Step (4): Slowly add the above-mentioned hot oil solution to the drug extract, and stir vigorously during the addition process to form an oil-in-water emulsion cream.

[0036] Example 3: Take 40 g of Scutellaria baicalensis, 5 g of Prunus mume, 15 g of Paeonia lactiflora, 5 g of Pheretima aspergillum, and 20 g of Salvia miltiorrhiza. The preparation method steps are as follows:

[0037] Step (1): Weigh the five traditional Chinese medicine raw materials, soak them in 10 times the weight of water for 1 hour, boil, keep boiling for 2 hours, filter to obtain the extract, extract twice in total, and combine to obtain the drug extract.

[0038] Step (2): Cool the drug extract to room temperature.

[0039] Step (3): Mix an appropriate amount of sweet almond oil and beeswax, and heat them in a water bath to 65 °C until all the beeswax melts and dissolves in the sweet almond oil to form an oil solution.

[0040] Step (4): Slowly add the above-mentioned hot oil solution to the drug extract, and stir vigorously during the addition process to form an oil-in-water emulsion cream.

[0041] Example 4: The effect of the present invention on 2,4-dinitrochlorobenzene (DNCB)-induced dermatitis in tumor-bearing mice

[0042] 1) Experimental method:

[0043] (1) Experimental animal grouping: SPF-grade BALB / c mice, 30 males, provided by Beijing Spearf Bio-Technology Co., Ltd. (Production License No.: SCXK (Beijing)-2019-0010), 6 mice in each group, raised in an environment of 23 ± 2 °C, relative humidity of 55 ± 5%, 12-hour day-night cycle light, housed separately in cages, and free to eat and drink.

[0044] Normal feeding blank group: Stimulate the back skin of mice with a blank matrix solution, and give normal saline during treatment.

[0045] Model group: Adjust the concentration of S-180 cell suspension to 1 × 10⁶ per milliliter with PBS, inoculate 0.2 ml per mouse under the left forelimb of the mouse, and then stimulate the back skin and right ear of the mouse with 2%, 1% or 0.5% DNCB, and give normal saline during treatment.

[0046] Dex group: The concentration of S-180 cell suspension was adjusted to 1×10⁶ cells per ml with PBS. 0.2 ml of the suspension was inoculated into the left forelimb of each mouse. The skin on the back and right ear of the mice were stimulated with 2%, 1% or 0.5% DNCB. During treatment, 200 mg of compound dexamethasone acetate cream was applied evenly to the test area on the back once a day.

[0047] The high-dose group of this invention: The concentration of S-180 cell suspension was adjusted to 1×10⁶ cells per milliliter with PBS. 0.2 ml of the suspension was inoculated into the left forelimb of each mouse. The skin on the back and right ear of the mouse was stimulated with 2%, 1%, or 0.5% DNCB. During treatment, 200 mg of the emulsion cream prepared by the method in Example 1 was applied evenly to the test area on the back once a day.

[0048] The low-dose group of this invention: The concentration of S-180 cell suspension was adjusted to 1×10⁶ cells per milliliter with PBS. 0.2 ml of the suspension was inoculated into the left forelimb of each mouse. The skin on the back and right ear of the mouse was stimulated with 2%, 1%, or 0.5% DNCB. During treatment, 100 mg of the emulsion cream prepared by the method in Example 1 was applied evenly to the test area on the back once a day.

[0049] (2) Drug preparation:

[0050] Matrix solution: Prepare acetone and olive oil in a 3:1 ratio; 2% DNCB solution: Weigh 160 mg of solid DNCB using an analytical balance and dissolve in 80 mL of matrix solution; 1% DNCB solution: Weigh 80 mg of solid DNCB using an analytical balance and dissolve in 80 mL of matrix solution; 0.5% DNCB solution: Weigh 40 mg of solid DNCB using an analytical balance and dissolve in 80 mL of matrix solution.

[0051] (3) Modeling method and medication regimen:

[0052] A. Skin preparation and tumor implantation: One day before the experiment, mice in each group were anesthetized with isoflurane (4%, 300-500 ml / min). Longer hair was initially trimmed using a special experimental shaver, followed by removal of vellus hair with Veet Mild Depilatory Cream, covering an area of ​​3 × 3 cm². On the first day of the experiment, 24 mice were randomly selected for S-180 solid tumor modeling. The concentration of the S-180 cell suspension was adjusted to 1 × 10⁶ cells per ml using PBS, and 0.2 ml was inoculated into the left forelimb of each mouse.

[0053] B. Initial sensitization: For the first 3 days after the start of the experiment (week 0), except for the control group, mice in the other groups were sensitized daily with 100 μl of 2.0% DNCB solution on the skin of the mouse's back and 10 μl of 1.0% DNCB solution on the right ear.

[0054] C. Second challenge: Four days later (starting from week 1), except for the control group, the skin on the back and right ear of mice in the other groups were sensitized every 2 days with 100 μl of 1.0% DNCB solution and 10 μl of 0.5% DNCB solution for a total of 3 weeks;

[0055] D. Medication regimen: Starting in week 4, patients will be treated in groups daily during the modeling period.

[0056] 2) Observation indicators:

[0057] (1) The scoring criteria and standards for back skin lesions include:

[0058] A. Skin erythema / bleeding: 4 points for area greater than 75% of exposed skin area; 3 points for area between 40% and 75%; 2 points for area between 10% and 40%; 1 point for area less than 10%; 0 points for no bleeding or erythema.

[0059] B. Skin scratches / erosions: 4 points for areas greater than 75% of the exposed skin area; 3 points for areas between 40% and 75%; 2 points for areas between 10% and 40%; 1 point for areas less than 10%; 0 points for no bleeding or erythema.

[0060] C. Skin edema: Deep red skin, moist surface, obvious swelling, and no new hair growth: 4 points; Light red skin, slightly dry surface, reduced edema, and no new hair growth: 3 points; Pink skin, slightly darker than normal mouse skin, uneven surface, and new hair growth: 2 points; Skin color close to normal mouse skin color, abundant new hair growth, and smooth skin: 1 point; No of the above characteristics: 0 points.

[0061] D. Skin with scaling or lichenification: 4 points for areas greater than 75% of the exposed skin area; 3 points for areas between 40% and 75%; 2 points for areas between 10% and 40%; 1 point for areas less than 10%; 0 points for no bleeding or erythema.

[0062] (2) Material sourcing method:

[0063] A. On the last day of the experiment, the bare skin was assessed and the body weight was measured.

[0064] B. After respiratory anesthesia with (4% isoflurane, 300-500 ml / min), 0.5-1 mL of blood is collected from the retroocular venous plexus of mice. The blood is allowed to stand at room temperature for 1 hour, then centrifuged at 3000 rpm / min for 15 minutes at 4°C to separate the serum. The serum is then frozen and stored at -80°C for later use.

[0065] C. After blood collection, the mouse spleen was bluntly dissected and weighed.

[0066] D. Take two portions of back skin tissue: one portion is fixed by immersing in 4% paraformaldehyde, and the other portion is frozen at -80℃ for later use.

[0067] (3) Spleen and thymus index analysis: The spleen index was calculated using the spleen weight and mouse body weight recorded on the day of sampling, according to the following formula, and the changes in spleen weight were compared between the groups: Spleen index = Spleen weight (g) / Mouse body weight (g) * 10. Thymus index: Thymus weight (mg) / Mouse body weight (g) * 10.

[0068] (4) Preparation of skin pathology sections:

[0069] A. Dehydration, clearing, and paraffin impregnation: Take an appropriate size of skin tissue that has been soaked in 4% paraformaldehyde for more than 24 hours, place it in an embedding cassette, and perform routine dehydration, clearing, and paraffin impregnation in sequence with 75% ethanol for 4 hours, 85% ethanol for 2 hours, 95% ethanol I for 2 hours, 95% ethanol II for 1 hour, 100% ethanol I for 1 hour, 100% ethanol II for 1 hour, xylene I for 40 minutes, xylene II for 40 minutes, paraffin I for 1 hour, and paraffin II for 1.5 hours.

[0070] B. Embedding: Turn on the tissue embedding machine in advance to completely melt the solid paraffin. First, place the paraffin mold on the hot table for preheating. Then, use tweezers to hold the mold horizontally and drip in a small amount of paraffin. Place the skin tissue that has been soaked in paraffin into the paraffin and cover it with the tissue embedding box. After the paraffin has solidified slightly, continue to drip paraffin until the mold is full. Then place it on a cold surface to solidify. After 10-15 minutes, remove the wax block from the mold.

[0071] C. Sectioning, Spreading, and Drying: ① Trimming the Paraffin Block: Depending on the size of the tissue block, remove excess paraffin around the block; ② Preparing the Sectioning Tools: Microtome, ophthalmic forceps, 2B pencil, slide spreader, slide dryer; ③ Installing the Paraffin Block: Turn on the microtome, secure the paraffin holder, and install the paraffin block onto it; ④ Installing the Microtome: Install the microtome on the blade holder and tighten the screw to ensure it is secure and does not wobble; ⑤ Correcting the Section Surface: Adjust the section thickness of the microtome to 20μm, and adjust the distance and height between the paraffin block and the microtome, so that they are about to touch the paraffin block. Begin by slowly rotating the microtome rollers to correct the cut surface of the paraffin block, making it smooth and flat and exposing the tissue surface; ⑥ Slicing: After correcting the cut surface of the tissue block, adjust the slice thickness to 4μm, slice at a uniform speed, and gently pick up the cut paraffin slice with ophthalmic forceps in your left hand and gently place it into the preheated warm water of the slide spreader. The surface tension and temperature of the water will naturally flatten the slightly wrinkled paraffin slice; ⑦ After the slice has been fully flattened on the constant temperature water surface, remove the paraffin slice to the middle of the slide, drain the excess water, mark it with a pencil, place it on the slide warmer and warm it for 15 minutes, then insert it into the slide holder and continue to warm it in a 60℃ constant temperature oven for 4-5 hours.

[0072] (5) HE staining of tissue: Dewaxing paraffin sections to water using routine methods: Paraffin sections were sequentially dewaxed in xylene I for 10 min, xylene II for 10 min, xylene III for 10 min, anhydrous ethanol I for 5 min, anhydrous ethanol II for 5 min, 90% ethanol for 5 min, 80% ethanol for 5 min, and 70% ethanol for 5 min, followed by rinsing with tap water for 2 min. Hematoxylin staining was applied for 5 min, followed by rinsing with distilled water, differentiation in differentiation solution for 30 s, rinsing twice with distilled water for 2 min each time, adding eosin staining solution for 60 s, discarding excess staining solution, and then rapidly dehydrating. Rapid dehydration was performed with 95% ethanol for 3 s, followed by anhydrous ethanol for 2 min, and clearing twice with xylene for 1 min each time. The sections were then mounted with neutral resin.

[0073] (6) Toluidine blue staining of mast cells: After routine dewaxing to water, wash with tap water for 2 min, immerse in mast cell staining solution for 12 min, wash with tap water for 2 min, and blot dry with filter paper; separate the color with 95% ethanol until the mast cells are blue-purple and the background is light blue, repeat with anhydrous ethanol twice, 2 min each time, clear with xylene, and mount with neutral resin.

[0074] 3) Experimental results:

[0075] (1) A schematic diagram of the effect of the compound composition of the present invention on the skin lesions of mice bearing tumor dermatitis is shown below. Figure 1 Where Control is the normal feeding blank group, Model is the model group, Dex group is the compound dexamethasone acetate cream group, WXG-H is the high-dose group of the present invention, WXG-L is the low-dose group of the present invention, and so on. Figure 1 The diagram shows the changes in DNCB-induced dermatitis in BALB / c mice over time. Compared with the control group, the model group mice showed more severe edema, erythema, scaling, and epidermal erosion on their backs during the first week of drug administration. From the second week after drug administration to the final sampling stage, the model group mice showed obvious inflammatory manifestations such as skin erythema, edema, scaling, erosion, and epidermal shedding. Compared with the model group, in the first week after drug administration, the above symptoms were significantly improved in all treatment groups with different doses of the drug, the area of ​​erythema crusting was significantly reduced, and the new hair growth was significantly increased. In the second week after drug administration, the skin of the mice in the traditional Chinese medicine treatment group showed significant recovery.

[0076] (2) The skin lesion scores of mice in each treatment group are shown in Table 1. Control is the normal feeding blank group, Model is the model group, Dex group is the compound dexamethasone acetate cream group, WXG-H is the high-dose group of the present invention, and WXG-L is the low-dose group of the present invention. The same applies below.

[0077] Table 1. Dorsal skin lesion scores of mice in each group (Mean±SD, n=6)

[0078]

[0079] Note: Compared with the NC group, #P<0.05, ##P<0.01; compared with the Model group, *P<0.05, **P<0.01.

[0080] Table 1 shows the skin lesion scores of mice in each treatment group. Compared with the blank group, the skin lesion score of mice in the model group was significantly increased (P<0.01); compared with the model group, the skin lesion score of mice in the traditional Chinese medicine treatment group was significantly improved, which was statistically significant.

[0081] (3) The levels of serum IgE, TNF-α, IL-17, and IL-4 in mice in each treatment group are shown in the figure. Figure 4 And Table 2.

[0082] Table 2. Serum Inflammatory Factor Levels in Groups of Mice (Mean±SD, n=6)

[0083]

[0084] like Figure 4 As shown in Table 2, the effects of each treatment group on the serum IgE, TNF-α, IL-17, and IL-4 levels in mice were investigated. Compared with the control group, the serum IgE, TNF-α, IL-17, and IL-4 levels in the model group were significantly increased (P<0.01). Compared with the model group, the serum IgE, TNF-α, IL-17, and IL-4 levels in the traditional Chinese medicine treatment groups were all decreased to varying degrees, showing statistically significant differences.

[0085] (4) The effects of each drug administration group on the spleen coefficient of mice are shown in the figure. Figure 5 And Table 3.

[0086] Table 3. Spleen coefficients for each group of mice (Mean±SD, n=6)

[0087]

[0088] like Figure 5 As shown in Table 3, the effects of each drug administration group on the spleen index of mice were investigated. After continuous stimulation with DNCB, the spleen index of mice in the model group increased significantly, showing a significant difference compared with the blank group (P<0.01); compared with the model group, the spleen index of mice in each Chinese medicine administration group decreased (P<0.01).

[0089] (5) The effects of each treatment group on the ear swelling degree and swelling inhibition rate in mice are shown in the figure. Figure 6 And Table 4.

[0090] Table 4. Swelling degree and swelling inhibition rate of mouse ear in each group (Mean±SD, n=6)

[0091]

[0092] like Figure 6 Table 4 shows the effects of each drug administration group on ear swelling and swelling inhibition rate in mice. After continuous DNCB stimulation, the ear swelling and right ear tissue mass of mice in the model group increased significantly, showing a significant difference compared with the blank group (P<0.01). Compared with the model group, the ear swelling and right ear tissue mass of mice in the Chinese medicine administration group were significantly reduced, which was statistically significant, and the ear swelling inhibition rate also increased with the dosage.

[0093] (6) The effects of each drug administration group on HE staining and mast cell infiltration of dorsal skin lesions in mice are shown in the figure. Figure 2 , 3 .like Figure 2 , 3 The effects of each treatment group on HE staining and mast cell infiltration of dorsal skin lesions in mice were shown: The results indicated that the epidermis of the control group was smooth, the dermal collagen was regular, and there was no inflammatory infiltration. Compared with the control group, the model group showed significant thickening of the epidermis and dermis, hyperkeratosis, and significant inflammatory cell infiltration in the dermis. Compared with the model group, the Dex treatment group and each traditional Chinese medicine treatment group showed significantly reduced epidermal and dermal thickness, and reduced inflammatory cell infiltration in the dermis. Toluidine blue staining was used to count mast cell infiltration in the dermis. Compared with the control group, the model group showed an abnormally increased number of mast cells and significant infiltration. Compared with the model group, the traditional Chinese medicine treatment groups showed a significant reduction in mast cell infiltration, demonstrating that the traditional Chinese medicine composition of this invention can, to a certain extent, improve the pathological thickening of the skin and the occurrence of inflammatory cell infiltration, thus playing a role in improving dermatitis.

[0094] In summary, the Five Elements Ointment of this invention has been demonstrated in mice with tumor-bearing 2,4-dinitrochlorobenzene (DNCB)-induced dermatitis to significantly improve clinical dermatitis scores associated with the skin lesions, reduce the spleen index, and also reduce epidermal thickness and inflammatory infiltration such as mast cells in the dermis, as well as reduce the level of inflammatory factors in the skin lesions, indicating the potential of the Five Elements Ointment in improving inflammatory skin diseases in cancer patients.

[0095] The Five Elements Ointment of this invention has a significant effect on improving dermatitis. As a traditional Chinese medicine compound composition, it has fewer toxic side effects than Western medicine. Developing the Five Elements Ointment into a new drug for treating dermatitis and applying it in clinical practice has broad prospects.

[0096] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the described embodiments. Those skilled in the art can make various equivalent modifications or substitutions without departing from the spirit of the present invention, and these equivalent modifications or substitutions are all included within the scope defined by the claims of this application.

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

Claims

1. A compound traditional Chinese medicine composition for treating dermatitis in cancer patients, characterized in that, It is made from the following raw materials in parts by weight: Scutellaria baicalensis 20-40 parts by weight, Prunus mume 5-15 parts by weight, Paeonia lactiflora 5-15 parts by weight, Pheretima aspergillum 5-15 parts by weight, and Salvia miltiorrhiza 10-20 parts by weight.

2. The compound traditional Chinese medicine composition for treating dermatitis in cancer patients as described in claim 1, characterized in that, It is made from the following raw materials in parts by weight: Scutellaria baicalensis 30 parts by weight, Prunus mume 10 parts by weight, Paeonia lactiflora 10 parts by weight, Pheretima aspergillum 10 parts by weight, and Salvia miltiorrhiza 15 parts by weight.

3. The compound traditional Chinese medicine composition for treating dermatitis in cancer patients as described in claim 1, characterized in that, It is made from the following raw materials in parts by weight: 20 parts by weight of Scutellaria baicalensis, 15 parts by weight of Prunus mume, 5 parts by weight of Paeonia lactiflora, 15 parts by weight of Pheretima aspergillum, and 10 parts by weight of Salvia miltiorrhiza.

4. The compound traditional Chinese medicine composition for treating dermatitis in cancer patients as described in claim 1, characterized in that, It is made from the following raw materials in parts by weight: Scutellaria baicalensis 40 parts by weight, Prunus mume 5 parts by weight, Paeonia lactiflora 15 parts by weight, Pheretima aspergillum 5 parts by weight, and Salvia miltiorrhiza 20 parts by weight.

5. The compound traditional Chinese medicine composition for treating dermatitis in cancer patients as described in claim 1, characterized in that, The preparation method includes the following steps: extracting and filtering the Chinese herbal medicine raw materials, and cooling to obtain a drug extract; mixing an appropriate amount of sweet almond oil and beeswax, heating in a hot water bath to 65°C until all the beeswax melts and dissolves in the sweet almond oil to form an oil solution; slowly adding the above hot oil solution to the drug extract while stirring vigorously during the addition process to form an oil-in-water emulsion cream.

6. The compound traditional Chinese medicine composition for treating dermatitis in cancer patients as described in claim 5, characterized in that, The preparation method of the drug extract is as follows: weigh five kinds of Chinese herbal raw materials, add 10 times the weight of Chinese herbal medicines in water and soak for 1 hour, boil, keep boiling for 2 hours, filter, and obtain the extract. Extract twice in total, and combine the extracts to obtain the drug extract.

7. The use of the compound traditional Chinese medicine composition for treating dermatitis in cancer patients as described in claim 1 in the preparation of a drug for treating dermatitis in cancer patients.

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