Traditional Chinese medicine composition for treating skin toxic and side effects of chemotherapeutics as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating skin toxic and side effects of chemotherapeutics and a preparation method and application thereof. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 3-10 parts of liquorice, 0.5-8 parts of golden cypress, 0.5-8 parts of rheum officinale and 0.5-8 parts of turmeric. Compared with glucocorticoid, a COX-2 inhibitor and the like, the traditional Chinese medicine composition does not inhibit the immune function and increase cardiovascular side effects, has an excellent anti-inflammatory effect, also has a remarkable anti-oxidation effect and an anti-allergic effect, can effectively relieve the skin toxic and side effects of chemotherapy drugs, and can be used for preparing products for relieving the skin toxic and side effects of the chemotherapy drugs.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, and specifically relates to a traditional Chinese medicine composition for treating skin toxicity side effects of chemotherapy drugs, its preparation method, and its application. Background Technology

[0002] Currently, chemotherapy remains the primary treatment for cancer. However, while chemotherapy drugs kill tumor cells, they also have toxic effects on normal tissue cells. The skin, as the largest organ in the human body, is a common target for the toxic side effects of chemotherapy drugs. During chemotherapy, the skin experiences a variety of adverse reactions, including: stinging and burning sensations accompanied by erythema, numbness in the hands and feet, rough skin, desquamation, and even blisters and superficial ulcers; acne-like red papules and pustules; and dry, itchy skin. These skin damages not only significantly reduce patients' quality of life but may also lead to chemotherapy interruption or dosage adjustments, directly affecting the efficacy of anti-tumor treatment.

[0003] Currently, the main treatments for skin toxicity caused by chemotherapy include: topical corticosteroids such as triamcinolone to reduce skin inflammation, but long-term use can suppress immune function and increase the risk of infection; COX-2 inhibitors such as celecoxib, which can reduce inflammation, but have cardiovascular side effects; and moisturizers such as urea ointment, which can relieve dry skin, but have poor anti-inflammatory effects and cannot fundamentally relieve skin inflammation. Summary of the Invention

[0004] To address the above-mentioned technical problems, this invention provides a traditional Chinese medicine composition for treating the skin toxicity side effects of chemotherapy drugs, its preparation method, and its application. This traditional Chinese medicine composition uses relatively safe traditional Chinese medicines as its main raw materials, avoiding the immunosuppression and cardiovascular side effects caused by chemical drugs such as glucocorticoids and COX-2 inhibitors. It also possesses excellent anti-inflammatory, antioxidant, and anti-allergic effects, making it suitable for preparing medicines or special-purpose cosmetics that alleviate the skin toxicity side effects of chemotherapy drugs.

[0005] To achieve the above-mentioned objectives, the embodiments of the present invention employ the following technical solutions: On the one hand, the present invention provides a traditional Chinese medicine composition for treating skin toxicity side effects of chemotherapy drugs, wherein the raw materials include 3-10 parts of licorice, 0.5-8 parts of phellodendron bark, 0.5-8 parts of rhubarb and 0.5-8 parts of turmeric by mass ratio.

[0006] Licorice has a sweet and neutral flavor and functions to tonify the spleen and replenish qi, clear heat and detoxify, relieve pain and harmonize other medicines. It is mainly used for spleen and stomach weakness, fatigue, palpitations and shortness of breath, cough with phlegm, abdominal and limb spasms and pain, carbuncles and boils, and to alleviate the toxicity of other medicines.

[0007] Phellodendron bark is bitter and cold in nature, and has the functions of clearing heat and drying dampness, purging fire and eliminating steaming, detoxifying and healing sores. It is mainly used for damp-heat diarrhea, jaundice with red urine, leukorrhea and vulvar itching, painful and painful urination, beriberi with weakness and numbness, bone steaming fever, night sweats, seminal emission, sores and carbuncles, eczema and damp sores.

[0008] Rhubarb is bitter and cold in nature, and has the functions of purging and eliminating accumulations, clearing heat and purging fire, cooling blood and detoxifying, removing blood stasis and promoting menstruation, and promoting diuresis and relieving jaundice. It is mainly used for constipation due to heat accumulation, hematemesis and epistaxis due to blood heat, red eyes and sore throat, carbuncles and boils, intestinal pain and abdominal pain, amenorrhea due to blood stasis, postpartum blood stasis, traumatic injuries, damp-heat dysentery, jaundice and dark urine, urinary tract infection, edema, and external treatment for burns and scalds.

[0009] Turmeric is bitter, pungent, and warm in nature. It has the effects of breaking up blood stasis, promoting qi circulation, regulating menstruation, and relieving pain. It is mainly used for chest and rib pain, chest pain, dysmenorrhea, amenorrhea, emaciation, rheumatic shoulder and arm pain, and swelling and pain from falls.

[0010] The above-mentioned traditional Chinese medicine formula provided by this invention uses licorice as the principal ingredient, which plays a role in clearing heat and detoxifying, harmonizing the effects of other herbs, and relieving pain. Phellodendron bark and rhubarb are the assistant ingredients, which, when used in combination with licorice, enhance the effects of clearing heat and drying dampness, cooling blood and detoxifying. Turmeric is the adjuvant ingredient, which can invigorate blood and promote qi circulation, and also counteract the bitter and cold properties of phellodendron bark and rhubarb. This formula is mild in nature, with a balance of cold and warm properties. The principal ingredient, licorice, is sweet and neutral; the assistant ingredients, phellodendron bark and rhubarb, are very bitter and cold; and the adjuvant ingredient, turmeric, is pungent and warm. Overall, the formula focuses on clearing heat and cooling, while the warming properties of turmeric both aid in blood circulation and prevent excessive coldness. Licorice acts as a mediator, ensuring that the entire formula is neither too cold nor too warm. The four herbs, used in the above proportions, work together to achieve the effects of clearing heat and detoxifying, drying dampness and reducing swelling, invigorating blood and relieving pain.

[0011] This invention, through classical model validation, demonstrates that, in the LPS-induced RAW264.7 macrophage inflammation model, the above-mentioned traditional Chinese medicine composition provided by this invention can significantly reduce the content of the inflammatory mediator NO and the levels of inflammatory factors such as TNF-α, IL-1β, and IL-6; in 5-Fu-induced HaCaT cells, the above-mentioned traditional Chinese medicine composition provided by this invention can significantly reduce the levels of inflammatory factors TNF-α, IL-1β, and IL-6 and improve antioxidant indicators SOD, GSH-Px, and MDA; and in mouse mast cells MC / 9 cells induced by PMA combined with calcium iontophoresis agent A23187, the above-mentioned traditional Chinese medicine composition provided by this invention can significantly inhibit histamine production.

[0012] Preferably, the raw materials of the traditional Chinese medicine composition include 5-9 parts licorice, 1-6 parts phellodendron bark, 1-6 parts rhubarb, and 1-6 parts turmeric by mass ratio.

[0013] Preferably, the raw materials of the traditional Chinese medicine composition include 7 parts licorice, 3 parts phellodendron bark, 3 parts rhubarb, and 3 parts turmeric in the indicated mass ratios.

[0014] Secondly, the present invention also provides a method for preparing the above-mentioned traditional Chinese medicine composition, specifically including the following steps: S1. Crush the raw material to obtain raw material powder; S2. The raw material powder is soaked in an oily solvent and then subjected to ultrasonic extraction, and the resulting extract is collected. S3. Filter the extract until the filtrate is clear to obtain the final product.

[0015] This preparation method uses oil as the extraction solvent and ultrasonic extraction to make the anti-inflammatory, antioxidant, and anti-allergic effects of the obtained traditional Chinese medicine composition more significant, thus enabling it to be better applied to external products.

[0016] The clarified filtrate obtained from S3 can be used directly, or it can be combined with common additives found in topical pharmaceutical preparations or special-purpose cosmetics to produce corresponding products according to actual needs using conventional methods.

[0017] Preferably, in step S1, the raw material is pulverized to a particle size of less than 4 mm.

[0018] More preferably, the raw material is pulverized to a particle size of less than 0.9 mm.

[0019] Preferably, the nonpolar oily solvent in S2 is selected from at least one of the following: caprylic / capric triglyceride, coconut oil alcohol-caprylate / capric acid ester, propyl heptyl caprylate, phytosterol / octyldodecyl lauroyl glutamate, triolein, meadowfoam seed oil, squalane, coconut oil, olive oil, sweet almond oil, grape seed oil, jojoba oil, rosehip oil, sesame oil, wheat germ oil, and camellia seed oil.

[0020] Preferably, the temperature of the ultrasonic extraction is 40~80℃ and the ultrasonic power is 400~800W.

[0021] More preferably, when soaking in the oily solvent, the material-to-liquid ratio is 1:2~5, and the soaking time is 2~48 hours.

[0022] Further preferably, the ultrasonic extraction method comprises: ultrasonically extracting the raw material powder with the oily solvent that has been soaked for 30-90 minutes, filtering to obtain a first filtrate; adding the same amount of the oily solvent, equivalent to 2-5 times the mass of the raw material powder, to the obtained filter residue for ultrasonic extraction again for 60-120 minutes, filtering to obtain a second filtrate; combining the first filtrate and the second filtrate to obtain the extract. The second oily solvent added is an oily solvent that has not soaked the raw material powder.

[0023] Preferably, in step S3, the extract is filtered using a filter plate with a pore size of 2μm to 10μm.

[0024] Thirdly, the present invention also provides the application of the above-mentioned traditional Chinese medicine composition or the traditional Chinese medicine composition prepared by the above-mentioned preparation method in the preparation of products that reduce the skin toxicity side effects of chemotherapy drugs.

[0025] Preferably, the product is a product used to reduce inflammatory responses.

[0026] Preferably, the product is a product that alleviates the skin oxidative stress imbalance caused by chemotherapy drugs. More preferably, the skin oxidative stress imbalance includes dry skin, erythema, and inflammatory responses stimulated by oxidative products.

[0027] Preferably, the product is a product for relieving skin itching. More preferably, the product is a product for inhibiting histamine production.

[0028] Preferably, the products include pharmaceuticals and special-purpose cosmetics.

[0029] More preferably, the product also includes additives acceptable for topical pharmaceutical preparations or special-purpose cosmetics.

[0030] More preferably, the amount of the above-mentioned traditional Chinese medicine composition or the traditional Chinese medicine composition prepared by the above preparation method added to the product is 0.5%~50%wt.

[0031] The beneficial effects of the present invention are as follows: The traditional Chinese medicine composition provided by the present invention uses licorice, phellodendron bark, rhubarb and turmeric as raw materials. Compared with glucocorticoids, COX-2 inhibitors, etc., it does not inhibit immune function or increase cardiovascular side effects, and has excellent anti-inflammatory effects. At the same time, it also has significant antioxidant and anti-allergic effects, which can effectively reduce the skin toxic side effects of chemotherapy drugs. It can be used to make products that reduce the skin toxic side effects of chemotherapy drugs. Detailed Implementation

[0032] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to specific embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. All other embodiments obtained by those skilled in the art based on the implementation methods of this invention without inventive effort fall within the protection scope of this invention.

[0033] The skin is a common target for the toxic side effects of chemotherapy drugs. During chemotherapy for tumors, various toxic side effects can occur on the skin, significantly reducing patients' quality of life and potentially leading to chemotherapy interruption or dosage adjustments, directly affecting the efficacy of anti-tumor treatment. Current drug treatments for chemotherapy-induced skin toxicity have limitations, such as immunosuppression or cardiovascular side effects, or poor anti-inflammatory effects.

[0034] This invention provides a traditional Chinese medicine composition for treating the skin toxicity of chemotherapy drugs. The raw materials, in the following mass proportions, include: 3-10 parts licorice root, 0.5-8 parts phellodendron bark, 0.5-8 parts rhubarb, and 0.5-8 parts turmeric. This traditional Chinese medicine composition, through rational formulation, exhibits excellent anti-inflammatory, antioxidant, and anti-allergic effects, and can be used to alleviate the skin toxicity of chemotherapy drugs. Furthermore, the raw materials in this composition are relatively safe traditional Chinese medicines, avoiding the immunosuppression and cardiovascular side effects caused by chemical drugs such as glucocorticoids and COX-2 inhibitors.

[0035] This invention also provides a method for preparing the traditional Chinese medicine composition, specifically including the following steps: S1. Crush the raw material to obtain raw material powder; S2. The raw material powder is soaked in an oily solvent and then subjected to ultrasonic extraction, and the resulting extract is collected. S3. Filter the extract until the filtrate is clear to obtain the final product.

[0036] The present invention will be described below through specific embodiments.

[0037] Unless otherwise specified, all reagents, pharmaceuticals, and instruments used in the following examples were obtained commercially.

[0038] The licorice, phellodendron bark, rhubarb, and turmeric used in the following examples all comply with the relevant provisions of the Chinese Pharmacopoeia (2020 edition) under the various medicinal materials section.

[0039] Example 1 This invention provides a traditional Chinese medicine composition for treating skin toxicity side effects of chemotherapy drugs, wherein the raw materials are: 7 parts licorice, 3 parts phellodendron bark, 3 parts rhubarb, and 3 parts turmeric.

[0040] The preparation method is as follows: Weigh out each Chinese medicinal material according to the mass ratio of 7 parts licorice, 3 parts phellodendron bark, 3 parts rhubarb, and 3 parts turmeric. Mix them, pulverize them, and pass them through a 20-mesh sieve to obtain raw material powder. Caprylic / capric triglycerides were added to the raw material powder at a material-to-liquid ratio of 1:3. After soaking at room temperature for 24 hours, ultrasonic extraction was performed directly under the following conditions: ultrasonic temperature 60℃, ultrasonic power 600W, and ultrasonic time 60 minutes. The mixture was filtered to obtain the first filtrate. Three times the mass of the raw material powder was added to the filter residue, and ultrasonic extraction was performed again under the following conditions: ultrasonic temperature 60℃, ultrasonic power 600W, and ultrasonic time 90 minutes. The mixture was filtered to obtain the second filtrate. The first and second filtrates were combined and filtered through a 5μm filter plate to obtain a clear filtrate, which is the final product.

[0041] Example 2 This invention provides a traditional Chinese medicine composition for treating skin toxicity side effects of chemotherapy drugs, wherein the raw materials are: 5 parts licorice, 1 part phellodendron bark, 1 part rhubarb, and 1 part turmeric.

[0042] The preparation method is the same as in Example 1.

[0043] Example 3 This invention provides a traditional Chinese medicine composition for treating skin toxicity side effects of chemotherapy drugs, wherein the raw materials are: 9 parts licorice, 6 parts phellodendron bark, 6 parts rhubarb, and 6 parts turmeric.

[0044] The preparation method is the same as in Example 1.

[0045] Example 4 This invention provides a traditional Chinese medicine composition for treating skin toxicity side effects of chemotherapy drugs, wherein the raw materials are: 6 parts licorice, 3 parts phellodendron bark, 2 parts rhubarb, and 2.5 parts turmeric.

[0046] The preparation method is as follows: Weigh out each Chinese medicinal material according to the mass ratio of 6 parts licorice, 3 parts phellodendron bark, 2 parts rhubarb, and 2.5 parts turmeric. Mix them, pulverize them, and pass them through a 16-mesh sieve to obtain raw material powder. Coconut oil alcohol-caprylate / capric acid ester was added to the raw material powder at a material-to-liquid ratio of 1:4. After soaking at room temperature for 36 hours, ultrasonic extraction was performed directly under the following conditions: ultrasonic temperature 70℃, ultrasonic power 700W, and ultrasonic time 75 minutes. The mixture was filtered to obtain the first filtrate. Four times the mass of the raw material powder was added to the filter residue, and ultrasonic extraction was performed again under the following conditions: ultrasonic temperature 70℃, ultrasonic power 700W, and ultrasonic time 90 minutes. The mixture was filtered to obtain the second filtrate. The first and second filtrates were combined and filtered through a 5μm filter plate to obtain a clear filtrate, which is the final product.

[0047] Example 5 This invention provides a traditional Chinese medicine composition for treating skin toxicity side effects of chemotherapy drugs, wherein the raw materials are: 8 parts licorice, 3 parts phellodendron bark, 4 parts rhubarb, and 3.5 parts turmeric.

[0048] The preparation method is as follows: Weigh out each Chinese medicinal material according to the mass ratio of 8 parts licorice, 3 parts phellodendron bark, 4 parts rhubarb, and 3.5 parts turmeric. Mix them, pulverize them, and pass them through a 10-mesh sieve to obtain raw material powder. Add propylheptaethyl octanoate to the raw material powder at a material-to-liquid ratio of 1:3.5 by mass. After soaking at room temperature for 18 hours, perform direct ultrasonic extraction under the following conditions: ultrasonic temperature 50℃, ultrasonic power 600W, and ultrasonic time 80 minutes. Filter to obtain the first filtrate. Add propylheptaethyl octanoate at a mass ratio of 3.5 times the raw material powder to the filter residue and perform ultrasonic extraction again under the following conditions: ultrasonic temperature 50℃, ultrasonic power 600W, and ultrasonic time 100 minutes. Filter to obtain the second filtrate. Combine the first and second filtrates and filter through a 5μm filter plate to obtain a clear filtrate, which is the final product.

[0049] Example 6 This invention provides a traditional Chinese medicine composition for treating skin toxicity side effects of chemotherapy drugs, wherein the raw materials are: 7 parts licorice, 2.5 parts phellodendron bark, 3.5 parts rhubarb, and 3 parts turmeric.

[0050] The preparation method is as follows: Weigh out each Chinese medicinal material according to the mass ratio of 7 parts licorice, 2.5 parts phellodendron bark, 3.5 parts rhubarb, and 3 parts turmeric. Mix them, pulverize them, and pass them through a 20-mesh sieve to obtain raw material powder. A mixture of phytosterol / octyldodecyl lauroyl glutamate and triolein at a mass ratio of 1:1 was added to the raw material powder at a material-to-liquid ratio of 1:2.5. After soaking at room temperature for 36 hours, ultrasonic extraction was performed directly under the following conditions: ultrasonic temperature 60℃, ultrasonic power 600W, and ultrasonic time 60 minutes. The mixture was filtered to obtain the first filtrate. A mixture of phytosterol / octyldodecyl lauroyl glutamate and triolein at a mass ratio of 1:1 (2.5 times the mass of the raw material powder) was added to the filter residue, and ultrasonic extraction was performed again under the following conditions: ultrasonic temperature 60℃, ultrasonic power 600W, and ultrasonic time 90 minutes. The mixture was filtered to obtain the second filtrate. The first and second filtrates were combined and filtered through a 5μm filter plate to obtain a clear filtrate, which is the final product.

[0051] Example 7 This invention provides a traditional Chinese medicine composition for treating skin toxicity side effects of chemotherapy drugs, wherein the raw materials are: 4 parts licorice, 2.2 parts phellodendron bark, 1.8 parts rhubarb, and 2.5 parts turmeric.

[0052] The preparation method is as follows: Weigh out each Chinese medicinal material according to the mass ratio of 4 parts licorice, 2.2 parts phellodendron bark, 1.8 parts rhubarb, and 2.5 parts turmeric. Mix them, pulverize them, and pass them through a 20-mesh sieve to obtain raw material powder. A mixture of meadowfoam seed oil, squalane, and coconut oil in a 3:1:2 mass ratio was added to the raw material powder at a material-to-liquid ratio of 1:4. After soaking at room temperature for 36 hours, ultrasonic extraction was performed directly under the following conditions: ultrasonic temperature 70℃, ultrasonic power 600W, and ultrasonic time 70 minutes. The mixture was then filtered to obtain the first filtrate. Four times the mass of the raw material powder was added to the filter residue, along with another mixture of meadowfoam seed oil, squalane, and coconut oil in a 3:1:2 mass ratio, and ultrasonic extraction was performed again under the following conditions: ultrasonic temperature 70℃, ultrasonic power 600W, and ultrasonic time 100 minutes. The mixture was then filtered to obtain the second filtrate. The first and second filtrates were combined and filtered through a 5μm filter plate to obtain a clear filtrate, which is the final product.

[0053] Example 8 This invention provides a traditional Chinese medicine composition for treating skin toxicity side effects of chemotherapy drugs, wherein the raw materials are: 7 parts licorice, 3 parts phellodendron bark, 3 parts rhubarb, and 3 parts turmeric.

[0054] The preparation method is as follows: Weigh out each Chinese medicinal material according to the mass ratio of 7 parts licorice, 3 parts phellodendron bark, 3 parts rhubarb, and 3 parts turmeric. Mix them, pulverize them, and pass them through a 20-mesh sieve to obtain raw material powder. A mixture of olive oil, sweet almond oil, and grapeseed oil in a 5:2:1 mass ratio was added to the raw material powder at a material-to-liquid ratio of 1:3. After soaking at room temperature for 36 hours, ultrasonic extraction was performed directly under the following conditions: ultrasonic temperature 60℃, ultrasonic power 600W, and ultrasonic time 60 minutes. The mixture was then filtered to obtain the first filtrate. A mixture of meadowfoam seed oil, squalane, and coconut oil in a 3:1:2 mass ratio (3 times the mass of the raw material powder) was added to the filter residue, and ultrasonic extraction was performed again under the following conditions: ultrasonic temperature 60℃, ultrasonic power 600W, and ultrasonic time 90 minutes. The mixture was then filtered to obtain the second filtrate. The first and second filtrates were combined and filtered through a 5μm filter plate to obtain a clear filtrate, which is the final product.

[0055] Example 9 This invention provides a traditional Chinese medicine composition for treating skin toxicity side effects of chemotherapy drugs, wherein the raw materials are: 7 parts licorice, 3 parts phellodendron bark, 3 parts rhubarb, and 3 parts turmeric.

[0056] The preparation method is as follows: Weigh out each Chinese medicinal material according to the mass ratio of 7 parts licorice, 3 parts phellodendron bark, 3 parts rhubarb, and 3 parts turmeric. Mix them, pulverize them, and pass them through a 20-mesh sieve to obtain raw material powder. A mixture of jojoba oil and rosehip oil in a 3:1 mass ratio was added to the raw material powder at a material-to-liquid ratio of 1:3. After soaking at room temperature for 36 hours, ultrasonic extraction was performed directly under the following conditions: ultrasonic temperature 50℃, ultrasonic power 400W, and ultrasonic time 60 minutes. The mixture was then filtered to obtain the first filtrate. A mixture of jojoba oil and rosehip oil in a 3:1 mass ratio (3 times the mass of the raw material powder) was added to the filter residue, and ultrasonic extraction was performed again under the following conditions: ultrasonic temperature 50℃, ultrasonic power 400W, and ultrasonic time 90 minutes. The mixture was then filtered to obtain the second filtrate. The first and second filtrates were combined and filtered through a 5μm filter plate to obtain a clear filtrate, which is the final product.

[0057] Example 10 This invention provides a traditional Chinese medicine composition for treating skin toxicity side effects of chemotherapy drugs, wherein the raw materials are: 3 parts licorice, 0.5 parts phellodendron bark, 0.5 parts rhubarb, and 0.5 parts turmeric.

[0058] The preparation method is as follows: Weigh out each Chinese herbal raw material according to the mass ratio of 3 parts licorice, 0.5 parts phellodendron bark, 0.5 parts rhubarb, and 0.5 parts turmeric. Mix them, pulverize them, and pass them through a 5-mesh sieve to obtain raw material powder. A mixture of sesame oil and wheat germ oil in a 1:2 mass ratio was added to the raw material powder at a material-to-liquid ratio of 1:2. After soaking at room temperature for 48 hours, ultrasonic extraction was performed directly under the following conditions: ultrasonic temperature 40℃, ultrasonic power 800W, and ultrasonic time 30 minutes. The mixture was then filtered to obtain the first filtrate. A mixture of sesame oil and wheat germ oil in a 1:2 mass ratio, twice the mass of the raw material powder, was added to the filter residue, and ultrasonic extraction was performed again under the following conditions: ultrasonic temperature 40℃, ultrasonic power 800W, and ultrasonic time 120 minutes. The mixture was then filtered to obtain the second filtrate. The first and second filtrates were combined and filtered through a 2μm filter plate to obtain a clear filtrate, which is the final product.

[0059] Example 11 This invention provides a traditional Chinese medicine composition for treating skin toxicity side effects of chemotherapy drugs, wherein the raw materials are: 10 parts licorice, 8 parts phellodendron bark, 8 parts rhubarb, and 8 parts turmeric.

[0060] The preparation method is as follows: Weigh out each Chinese medicinal material according to the mass ratio of 10 parts licorice, 8 parts phellodendron bark, 8 parts rhubarb, and 8 parts turmeric. Mix them, pulverize them, and pass them through a 20-mesh sieve to obtain raw material powder. Camellia seed oil was added to the raw material powder at a material-to-liquid ratio of 1:5 by mass. After soaking at room temperature for 2 hours, ultrasonic extraction was performed directly under the following conditions: ultrasonic temperature 80℃, ultrasonic power 400W, and ultrasonic time 90 minutes. The mixture was then filtered to obtain the first filtrate. Five times the mass of the raw material powder (e.g., camellia seed oil) was added to the filter residue, and ultrasonic extraction was performed again under the following conditions: ultrasonic temperature 80℃, ultrasonic power 400W, and ultrasonic time 60 minutes. The mixture was then filtered to obtain the second filtrate. The first and second filtrates were combined and filtered through a 10μm filter plate to obtain a clear filtrate, which is the final product.

[0061] Comparative Example 1 This comparative example provides a topical product made solely from licorice, in which the medicinal raw material is licorice, and its preparation method is the same as in Example 1.

[0062] Comparative Example 2 This comparative example provides a topical product made solely from Phellodendron bark, in which the medicinal raw material is only Phellodendron bark, and its preparation method is the same as in Example 1.

[0063] Comparative Example 3 This comparative example provides a topical product made solely from rhubarb, in which the only medicinal ingredient is rhubarb, and its preparation method is the same as in Example 1.

[0064] Comparative Example 4 This comparative example provides a topical product made solely from turmeric, in which the medicinal raw material is only turmeric, and its preparation method is the same as in Example 1.

[0065] Comparative Example 5 This comparative example provides a traditional Chinese medicine composition, in which the raw materials are licorice and phellodendron bark in a mass ratio of 7:3, and the preparation method is the same as in Example 1.

[0066] Comparative Example 6 This comparative example provides a traditional Chinese medicine composition, in which the raw materials are licorice and rhubarb in a mass ratio of 7:3, and the preparation method is the same as in Example 1.

[0067] Comparative Example 7 This comparative example provides a traditional Chinese medicine composition in which the raw materials are licorice and turmeric in a mass ratio of 7:3, and the preparation method is the same as in Example 1.

[0068] Comparative Example 8 This comparative example provides a traditional Chinese medicine composition, in which the raw materials are Phellodendron bark and rhubarb in a mass ratio of 3:3, and the preparation method is the same as in Example 1.

[0069] Comparative Example 9 This comparative example provides a traditional Chinese medicine composition, in which the raw materials are Phellodendron bark and turmeric in a mass ratio of 3:3, and the preparation method is the same as in Example 1.

[0070] Comparative Example 10 This comparative example provides a traditional Chinese medicine composition in which the raw materials are rhubarb and turmeric in a mass ratio of 3:3, and the preparation method is the same as in Example 1.

[0071] Comparative Example 11 This comparative example provides a traditional Chinese medicine composition in which the raw materials are licorice, phellodendron bark and rhubarb in a mass ratio of 7:3:3, and the preparation method is the same as in Example 1.

[0072] Comparative Example 12 This comparative example provides a traditional Chinese medicine composition in which the raw materials are licorice, phellodendron bark, and turmeric in a mass ratio of 7:3:3, and the preparation method is the same as in Example 1.

[0073] Comparative Example 13 This comparative example provides a traditional Chinese medicine composition in which the raw materials are licorice, rhubarb and turmeric in a mass ratio of 7:3:3, and the preparation method is the same as in Example 1.

[0074] Comparative Example 14 This comparative example provides a traditional Chinese medicine composition in which the raw materials are Phellodendron bark, rhubarb, and turmeric in a mass ratio of 3:3:3, and the preparation method is the same as in Example 1.

[0075] Comparative Example 15 This comparative example provides a traditional Chinese medicine composition, in which the raw materials are the same as in Example 1, and the preparation method is as follows: Weigh out each Chinese medicinal material according to the mass ratio of 7 parts licorice, 3 parts phellodendron bark, 3 parts rhubarb, and 3 parts turmeric. Mix them, pulverize them, and pass them through a 20-mesh sieve to obtain raw material powder. Caprylic / capric triglycerides were added to the raw material powder at a material-to-liquid ratio of 1:3. After soaking at room temperature for 24 hours, the mixture was soaked at 60°C for 60 minutes, and then filtered to obtain the first filtrate. Three times the mass of the raw material powder was added to the filter residue, and the mixture was soaked at 60°C for 90 minutes, and then filtered to obtain the second filtrate. The first and second filtrates were combined and filtered through a 5μm filter plate to obtain a clear filtrate, which is the final product.

[0076] Comparative Example 16 This comparative example provides a traditional Chinese medicine composition, in which the raw materials are the same as in Example 1, and the preparation method is basically the same as in Example 1, except that caprylic / capric triglyceride is replaced with deionized water.

[0077] Comparative Example 17 This comparative example provides a traditional Chinese medicine composition in which the raw materials are based on Example 1, with Scutellaria baicalensis, which has heat-clearing and detoxifying effects, replacing licorice. Specifically, the mass ratio of Scutellaria baicalensis, Phellodendron chinense, Rheum palmatum, and Curcuma longa is 7:3:3:3. The preparation method is the same as in Example 1.

[0078] Comparative Example 18 This comparative example provides a traditional Chinese medicine composition in which the raw materials are based on Example 1, with Coptis chinensis (Huanglian) replacing Phellodendron chinense (Huangbai) due to its heat-clearing and dampness-drying effects. Specifically, the composition consists of licorice, Coptis chinensis, rhubarb, and turmeric in a mass ratio of 7:3:3:3. The preparation method is the same as in Example 1.

[0079] Comparative Example 19 This comparative example provides a traditional Chinese medicine composition in which the raw materials are based on Example 1, with gardenia, which has the effect of clearing heat and cooling blood, replacing rhubarb. That is, the mass ratio of licorice, phellodendron bark, gardenia, and turmeric is 7:3:3:3. The preparation method is the same as in Example 1.

[0080] Comparative Example 20 This comparative example provides a traditional Chinese medicine composition in which the raw materials are based on Example 1, with safflower (which has the effect of promoting blood circulation and removing blood stasis) replacing turmeric. Specifically, the mass ratio of licorice, phellodendron bark, rhubarb, and safflower is 7:3:3:3. The preparation method is the same as in Example 1.

[0081] Example 1 Inflammation is the core reaction of skin toxicity caused by chemotherapy drugs. Chemotherapy drugs or their metabolites, acting as "foreign substances," can activate Langerhans cells in the skin, releasing pro-inflammatory cytokines (such as TNF-α, IL-6, and IL-1β), recruiting neutrophils and macrophages to infiltrate, manifesting as erythema, pain, swelling, and itching. Traditional Chinese medicine contains various active ingredients, some of which possess anti-inflammatory activity. However, due to the complexity of the components in traditional Chinese medicine, interactions between these components may exist, making it difficult to accurately determine the overall pharmacological activity of traditional Chinese medicine extracts through theoretical analysis.

[0082] Therefore, this efficacy example uses the classic in vitro screening model of LPS-induced RAW264.7 macrophage inflammation to test the traditional Chinese medicine composition samples and topical products prepared in Example 1 and Comparative Examples 1-20 of this invention and evaluate their respective anti-inflammatory effects.

[0083] 1. Establishment of cell models and drug administration RAW264.7 cell line (purchased from Wuhan Pronosei Biotechnology Co., Ltd.) was seeded in DMEM medium containing 10% FBS and 1% penicillin / streptomycin antibiotics and cultured in a cell culture incubator at 37°C and 5% CO2. Cells in the logarithmic growth phase were used for experiments. Cells were seeded in 24-well plates at a seeding density of 1×10⁶ cells / well. 5 Cells were cultured at a concentration of 10 cells / mL for 12 hours. Then, they were pre-treated and protected for 12 hours with DMSO solution (800 μg / mL, based on crude drug) of the sample from Example 1, comparative examples 1-20, and a dexamethasone positive control (50 μg / mL). RAW264.7 cells were then induced with LPS for 24 hours. After induction, cells were collected, and measurements were performed according to the instructions of the detection kits.

[0084] 2. Indicator Testing 2.1 Determination of NO content by Griess method The cell supernatant was collected and the NO content was determined using the Griess method to evaluate the anti-inflammatory effect of each sample.

[0085] 2.2 ELISA method for determining the levels of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 The cell supernatant was collected and the contents of TNF-α, IL-1β, and IL-6 were measured according to the ELISA kit instructions to evaluate the anti-inflammatory effects of each sample.

[0086] 3. Experimental Results The results of the levels of inflammatory mediator NO and pro-inflammatory cytokines TNF-α, IL-1β and IL-6 are shown in Table 1.

[0087] Table 1. Results of anti-inflammatory assays using the RAW264.7 cell model (n=9)

[0088] Note: Compared with the blank group, ## P <0.01. Compared with the model group, * P <0.05, ** P <0.01. Compared with Example 1, Δ P <0.05, ΔΔ P <0.01.

[0089] As shown in Table 1, the levels of the inflammatory mediator NO and inflammatory factors such as TNF-α, IL-1β, and IL-6 in the cell supernatant of the LPS model group were significantly increased compared with the blank group, which was statistically significant. P <0.01). In each sample group, after cell treatment, the levels of inflammatory mediator NO and inflammatory factors such as TNF-α, IL-1β, and IL-6 in the sample of Example 1 and comparative examples 1-20 were significantly reduced, showing significant differences compared with the model group. P <0.05, P <0.01). Based on the combined results of the determination of inflammatory mediators and inflammatory factors in the cell supernatant, the sample of Example 1 showed the most significant improvement in the above indicators, and the effect was better than that of other groups of samples, which was statistically significant. P <0.05, P <0.01).

[0090] Example 2 5-Fu (5-fluorouracil)-induced HaCaT cell models are effective for screening chemotherapy drugs causing dermatotoxic side effects. The core basis for this model is its ability to mimic the key cellular and molecular mechanisms of skin damage caused by chemotherapy drugs such as 5-Fu, while also possessing the advantages of in vitro model operability and mechanism relevance. HaCaT cells exhibit biological characteristics highly similar to normal keratinocytes, which are the core target cells for chemotherapy-induced dermatotoxic side effects. Stimulation of HaCaT cells with 5-Fu induces the production of excessive reactive oxygen species (ROS), triggering oxidative stress. This is consistent with the mechanism of oxidative stress imbalance in the skin caused by chemotherapy drugs (manifested as dry skin, erythema, and inflammatory responses stimulated by oxidative products). Therefore, the antioxidant effect of samples can be determined by detecting corresponding oxidative stress indicators.

[0091] In addition, 5-Fu-induced HaCaT cells can release pro-inflammatory cytokines, mimicking local skin inflammation in vivo: this directly corresponds to the pathological mechanism of skin erythema and swelling caused by chemotherapy drugs in vivo, and can be used to determine the anti-inflammatory effect of the sample.

[0092] This example demonstrates the anti-inflammatory and antioxidant effects of the traditional Chinese medicine composition samples and topical products prepared in Example 1 and Comparative Examples 1-20 of this invention on 5-Fu-induced HaCaT cells.

[0093] 1. Establishment of cell models and drug administration HaCaT cell lines (purchased from Wuhan Pronosai Life Sciences Co., Ltd.) were seeded in DMEM medium containing 10% FBS and 1% penicillin / streptomycin antibiotics and cultured in a cell culture incubator at 37°C and 5% CO2. Cells in the logarithmic growth phase were used for experiments. Cells were then cultured at a rate of 1×10⁻⁶ cells / year. 5 HaCaT cells were seeded at a density of 1 cell / mL in 24-well plates and cultured for 24 h. They were then pre-treated and protected for 24 h with DMSO solution (800 μg / mL, based on crude drug) of the sample from Example 1, comparative examples 1–20, and a dexamethasone positive control (50 μg / mL). HaCaT cells were then induced with 5-Fu for 24 h. After induction, cells were collected, and measurements were performed according to the instructions of the detection kits.

[0094] 2. Indicator Testing 2.1 ELISA method for determining the levels of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 The cell supernatant was collected and the contents of TNF-α, IL-1β, and IL-6 were measured according to the ELISA kit instructions to evaluate the anti-inflammatory effects of each sample.

[0095] 2.2 Determination of oxidative stress markers SOD, MDA, and GSH-Px using kit-based methods The cell lysates were collected, and the levels of SOD, MDA, and GSH-Px were measured according to the kit instructions to evaluate the antioxidant activity of each sample.

[0096] 3. Experimental Results 3.1 Results of the levels of inflammatory factors TNF-α, IL-1β, and IL-6 The results of the levels of inflammatory factors TNF-α, IL-1β, and IL-6 are shown in Table 2.

[0097] Table 25 Results of inflammatory factor indices measurement in the Fu-induced HaCaT cell model (n=9)

[0098] Note: Compared with the blank group, ## P <0.01. Compared with the model group, * P <0.05, ** P <0.01. Compared with Example 1, Δ P <0.05, ΔΔ P <0.01.

[0099] As shown in Table 2, the levels of inflammatory factors such as TNF-α, IL-1β, and IL-6 in the cell supernatant of the 5-Fu model group were significantly increased compared with those of the blank group, which was statistically significant. P <0.01). In each sample group, after cell treatment, the levels of inflammatory factors such as TNF-α, IL-1β, and IL-6 in the sample of Example 1 and the comparative examples 1-20 were significantly reduced, showing a significant difference compared with the model group. P <0.05, P <0.01). Regarding inflammatory markers in the 5-Fu-induced HaCaT cell model, the sample from Example 1 showed the most significant improvement in inflammatory factors, outperforming all other groups and demonstrating statistical significance. P <0.05, P <0.01).

[0100] 3.2 Results of level measurement of oxidative stress indicators SOD, MDA, and GSH-Px The results of the determination of oxidative stress indicators SOD, MDA, and GSH-Px levels are shown in Table 3.

[0101] Table 35 shows the results of oxidative stress index measurement in the 5-Fu-induced HaCaT cell model (n=9).

[0102] Note: Compared with the blank group, ## P <0.01. Compared with the model group, * P <0.05, ** P <0.01. Compared with Example 1, Δ P <0.05, ΔΔ P <0.01.

[0103] Table 3 shows that oxidative stress response was abnormally activated in the 5-Fu model group cells, with decreased SOD and GSH-Px levels and increased MDA levels, which were significantly different from the control group. P <0.01). After administration of each sample to the cell model, the abnormal oxidative stress response was inhibited, and the contents of SOD and GSH-Px increased to varying degrees, while the contents of MDA decreased accordingly. Compared with the model group, there were significant differences. P <0.05, P <0.01). Among all sample groups, the sample of Example 1 showed the most significant antioxidant effect, with substantial improvements in antioxidant indicators such as SOD, GSH-Px, and MDA, outperforming all other groups and demonstrating statistical significance. P <0.05, P <0.01).

[0104] The experimental results of this example show that the sample of Example 1 of the present invention can significantly improve the inflammatory and oxidative stress response of the HaCaT cell model, and its effect is better than that of other comparative samples. This indicates that the traditional Chinese medicine composition provided by the present invention has significant preventive and therapeutic effects on the skin toxic side effects of chemotherapy drugs and can be applied to clinical patients.

[0105] Example 3 Skin itching caused by chemotherapy drugs is one of the common skin toxic side effects of chemotherapy. It is often paroxysmal or persistent, varying in severity, and can occur systemically or locally on the hands and feet. Repeated scratching can lead to skin damage and bleeding, easily causing secondary bacterial or fungal infections and worsening skin damage. Furthermore, itching often worsens at night, severely affecting sleep quality, leading to insomnia, fatigue, and further weakening the immune system. Therefore, the antipruritic effect is one of the key indicators to be evaluated in treating the skin toxic side effects of chemotherapy drugs. The mechanism of chemotherapy drug-induced skin itching: Most chemotherapy drugs can act as "haptens," binding to skin proteins to form "complete antigens," triggering an immune response and releasing histamine and other mediators, stimulating nerve endings in the skin and causing itching. Therefore, inhibiting histamine production is crucial for relieving itching. This study uses a classic model of mouse mast cell MC / 9 cells induced by PMA combined with calcium iontophoresis agent A23187 to evaluate the effect of the sample of this invention in inhibiting histamine release.

[0106] This example provides the antipruritic effect (evaluation of the effect of inhibiting histamine production) of the traditional Chinese medicine composition samples and external products prepared in Example 1 and Comparative Examples 1-20 of the present invention.

[0107] 1. Establishment of cell models and drug administration Mouse mast cell line MC / 9 was seeded in IMEM medium containing 10% FBS and 1% penicillin / streptomycin antibiotics. Cells were cultured in a 37°C, 5% CO2 incubator, and cells in the logarithmic growth phase were used for experiments. In the histamine production assay, cells were seeded in 24-well plates at a density of 1 × 10⁶ cells / well. 5 Cells were cultured at a concentration of 1 cell / mL for 24 hours. Then, they were pre-treated and protected for 24 hours with DMSO solution (800 μg / mL, based on crude drug) of the sample from Example 1 of this invention, comparative examples 1-20, and a sodium cromoglycate positive control (30 μg / mL). MC / 9 cells were then induced for 24 hours with propylene glycol methyl ether acetate (PMA, 50 nM) and calcium iontophoresis agent A23187 (1 μM). After induction, the cell culture supernatant was collected.

[0108] 2. Indicator Testing Cell culture supernatant was collected, and the histamine content was detected using an ELISA kit. The antipruritic effect of each sample was evaluated. The results are shown in Table 4.

[0109] Table 4. Results of experiments on inhibiting histamine production (n=9)

[0110] Note: Compared with the blank group, ## P <0.01. Compared with the model group, *P <0.05, ** P <0.01. Compared with Example 1, Δ P <0.05, ΔΔ P <0.01.

[0111] Table 4 shows that the release of histamine from MC / 9 cells was significantly increased after induction with PMA combined with A23187, showing a significant difference compared with the control group. P <0.01). The results of the measurements for each sample group showed that after administration of each sample, the production of histamine in cells was inhibited, and there were significant differences compared with the model group. P <0.05, P <0.01). Among them, the sample in Example 1 showed the most significant inhibitory effect on histamine production, and its effect was significantly better than that of other groups of samples, showing statistical significance ( P <0.05, P <0.01).

[0112] 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 or improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating skin toxicity side effects of chemotherapy drugs, characterized in that, The raw materials of the traditional Chinese medicine composition include, by mass fraction, 3-10 parts licorice, 0.5-8 parts phellodendron bark, 0.5-8 parts rhubarb, and 0.5-8 parts turmeric.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The raw materials of the traditional Chinese medicine composition include 5-9 parts licorice, 1-6 parts phellodendron bark, 1-6 parts rhubarb, and 1-6 parts turmeric by mass fraction.

3. The traditional Chinese medicine composition according to claim 2, characterized in that, The raw materials of the traditional Chinese medicine composition include 7 parts licorice, 3 parts phellodendron bark, 3 parts rhubarb, and 3 parts turmeric by mass fraction.

4. The method for preparing the traditional Chinese medicine composition according to any one of claims 1 to 3, characterized in that, Specifically, the following steps are included: S1. Crush the raw material to obtain raw material powder; S2. The raw material powder is soaked in an oily solvent and then subjected to ultrasonic extraction, and the resulting extract is collected. S3. Filter the extract until the filtrate is clear to obtain the final product.

5. The preparation method according to claim 4, characterized in that, In S1, the raw material is pulverized to a particle size of less than 4 mm; and / or In step S3, the extract is filtered using a filter plate with a pore size of 2μm to 10μm.

6. The preparation method according to claim 4, characterized in that, The nonpolar oily solvent described in S2 is selected from at least one of the following: caprylic / capric triglyceride, coconut oil-caprylate / capric acid ester, propylheptaethyl caprylate, phytosterol / octyl-dodecanol lauroyl glutamate, triolein, meadowfoam seed oil, squalane, coconut oil, olive oil, sweet almond oil, grapeseed oil, jojoba oil, rosehip oil, sesame oil, wheat germ oil, and camellia seed oil; and / or The ultrasonic extraction temperature is 40~80℃, and the ultrasonic power is 400~800W.

7. The preparation method according to claim 6, characterized in that, When soaking in the oily solvent, the material-to-liquid ratio is 1:2~5, and the soaking time is 2~48 hours; and / or The ultrasonic extraction method is as follows: ultrasonic extraction is performed for 30-90 minutes with the oily solvent in which the raw material powder is soaked, followed by filtration to obtain a first filtrate; the same amount of oily solvent, equivalent to 2-5 times the mass of the raw material powder, is added to the obtained filter residue for ultrasonic extraction again for 60-120 minutes, followed by filtration to obtain a second filtrate; the first filtrate and the second filtrate are combined to obtain the extract.

8. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3 or the traditional Chinese medicine composition prepared by the preparation method according to any one of claims 4 to 7 in the preparation of products that reduce the skin toxicity side effects of chemotherapy drugs.

9. The application according to claim 8, characterized in that, The product is used to reduce inflammatory responses; and / or The product is designed to alleviate skin oxidative stress imbalance caused by chemotherapy drugs; and / or The product described is for relieving itchy skin.

10. The application according to claim 8 or 9, characterized in that, The products include pharmaceuticals and special-purpose cosmetics.

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