Externally-applied traditional Chinese medicine ointment for treating radioactive skin injury and preparation method of externally-applied traditional Chinese medicine ointment

Abstract

The invention discloses an externally-applied traditional Chinese medicine ointment for treating radioactive skin injury and a preparation method thereof, and relates to the technical field of externally-applied traditional Chinese medicines. The externally-applied traditional Chinese medicine ointment is prepared from the following components in parts by weight: traditional Chinese medicine raw materials, targeted active ingredients and functional auxiliary materials, the traditional Chinese medicine raw materials comprise 30 parts of borneol, 30 parts of talc, 10 parts of radix sophorae flavescentis, 10 parts of fructus cnidii, 5 parts of frankincense, 5 parts of myrrh, 6 parts of fructus forsythiae, 10 parts of calamine, 10 parts of rheum officinale, 15 parts of mirabilite and 10 parts of cortex phellodendri. According to the external application traditional Chinese medicine ointment, classic traditional Chinese medicines such as borneol and talc are compatible and optimally proportioned, the effects of pungent and fragrant movement, heat clearing, pain relieving, inflammation resisting and itching relieving of the borneol are utilized, the effects of heat clearing, dampness astringing, sore astringing and skin barrier protecting of the talc are combined, intervention is achieved on core symptoms such as erythema, pruritus and erosion of acute radiodermatitis, and the traditional Chinese medicine ointment is safe and reliable. Different from an existing traditional Chinese medicine external preparation with a single effect, adverse reactions of western medicine hormones and growth factors are also avoided.

Description

Technical Field

[0001] This invention relates to the field of external application of traditional Chinese medicine, specifically to a traditional Chinese medicine external application ointment for treating radiation-induced skin damage and its preparation method. Background Technology

[0002] Radiation-induced skin injury is an acute or chronic injury caused by ionizing radiation (such as X-rays and V-rays) acting on the skin, commonly seen in tumor radiotherapy or occupational exposure. Typical manifestations include erythema, desquamation, ulceration, and pigmentation changes. Treatment depends on the severity of the injury, choosing between moisturizing, anti-infection, or surgical repair. Prevention focuses on protection and standardized procedures. This injury is divided into acute and chronic types. Acute injury is caused by short-term high-dose irradiation, while chronic injury is caused by long-term irradiation exceeding the dose limit or prolonged acute injury. Clinical manifestations are classified into grades 0-4 according to the RTOG grading standard, including typical symptoms such as erythema, desquamation, and ulceration.

[0003] Currently, topical medications for acute radiation dermatitis mostly focus on symptomatic treatment such as relieving dryness and desquamation and local anti-inflammatory measures. There is a lack of intervention methods that can simultaneously target and regulate the three core pathogenesis mechanisms of oxidative stress damage, cytokine storm, and tissue fibrosis. Furthermore, clinical practice only selects drugs based on the severity of skin lesions, without fully considering individual differences such as radiotherapy dose and skin type. Individualized treatment strategies have not been formed, and the disease progression cannot be curbed at its root. This results in limited improvement in ulceration and severe pain in moderate to severe dermatitis. Some patients experience poor efficacy due to insufficient drug compatibility, or adverse reactions such as skin atrophy and pigmentation caused by long-term use of some drugs, making it difficult to meet the needs of precise clinical treatment. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention provides a traditional Chinese medicine external ointment for treating radiation-induced skin damage and its preparation method, thus solving the problems mentioned in the background art.

[0005] To achieve the above objectives, the present invention provides the following technical solution: a traditional Chinese medicine external application ointment for treating radiation-induced skin damage, comprising, by weight, the following components: traditional Chinese medicine raw materials, targeted active ingredients, and functional excipients. The Chinese medicinal materials include: 30 parts borneol, 30 parts talc, 10 parts sophora flavescens, 10 parts cnidium monnieri, 5 parts frankincense, 5 parts myrrh, 6 parts forsythia, 10 parts calamine, 10 parts rhubarb, 15 parts mirabilite, and 10 parts phellodendron bark. The targeted active ingredients include: 2 parts of Solomon's seal exosomes, 3 parts of sea buckthorn flavonoids, and 4 parts of Tremella fuciformis polysaccharides; The functional excipients include: 5-10 parts poloxamer, 2 parts dipotassium glycyrrhizate, and 1 part vitamin E; The base of the herbal external ointment is a mixture of petrolatum and lanolin in a mass ratio of 2:1. The poloxamer in question is specifically poloxamer 407.

[0006] A method for preparing a traditional Chinese medicine external ointment for treating radiation-induced skin damage includes the following steps: S1. The Chinese herbal raw materials are pulverized separately using a low-temperature individual pulverization process at a low temperature of -10℃ to 5℃. Nitrogen gas is introduced during the pulverization process to protect the volatile components. When borneol is pulverized separately, the temperature is controlled to be ≤0℃. When rhubarb and Glauber's salt are pulverized, the temperature is controlled to be ≤5℃. S2. The Polygonatum odoratum exosomes are prepared by homogenizing Polygonatum odoratum raw material and PBS buffer, multi-stage centrifugation and membrane purification. After filtration through a 0.22μm membrane, they are stored at low temperature for later use. The sea buckthorn flavonoids are extracted from sea buckthorn fruit by supercritical CO2 extraction. The purity of the sea buckthorn flavonoids is ≥83%. The Tremella fuciformis polysaccharide is prepared from Tremella fuciformis by water extraction and alcohol precipitation. After deproteinization, the Tremella fuciformis polysaccharide is dried and pulverized to 180 mesh. S3. The pulverized Chinese herbal raw material powder is first passed through a 100-mesh coarse sieve to remove impurities, and then through a 180-mesh fine sieve. Powder with a fine sieve passing rate of ≥95% is collected. The borneol and talc powder are premixed for 15 minutes, and then the remaining Chinese herbal raw material powder is added and mixed for 30 minutes. Then, the Solomon's seal exosome, the sea buckthorn flavonoids and the tremella polysaccharide are added and mixed for another 20 minutes. Finally, the dipotassium glycyrrhizate and vitamin E are added and mixed for 10 minutes to obtain a compound drug powder. S4. Mix the petrolatum and lanolin, heat to 60°C to melt and keep warm while stirring for 15 minutes. After mixing, cool down to 45°C and add the poloxamer 407 while stirring until completely dissolved. Then slowly add the compound drug powder and stir at high speed for 40 minutes at a constant temperature of 35°C to 40°C to form a uniform traditional Chinese medicine external ointment.

[0007] Preferably, after the traditional Chinese medicine external ointment is prepared, it is cooled to room temperature, and then the room temperature traditional Chinese medicine external ointment is dispensed into sterile light-proof ointment boxes, sealed, and stored in a refrigerated environment of 2℃~10℃. The sterile light-proof ointment box is made of medical grade polypropylene.

[0008] Preferably, the Solomon's seal exosomes, the sea buckthorn flavonoids, and the tremella polysaccharide are mixed in a weight ratio of 2:3:4.

[0009] Preferably, the herbal external ointment is classified into three levels of suitable dosage forms according to the radiotherapy dose, skin type, and stage of skin lesions; In the first-level dosage form, the mass ratio of the compound drug powder to the petrolatum and the lanolin is 1:3, the amount of poloxamer 407 added is 5 parts, corresponding to a radiotherapy dose ≤50Gy, a skin type of neutral or dry, and a skin lesion stage as a prevention period; In the second-level dosage form, the mass ratio of the compound drug powder to the petrolatum and the lanolin is 1:2.5, the amount of poloxamer 407 added is 7 parts, corresponding to a radiotherapy dose of 50-60 Gy, skin type of oily or sensitive skin, and skin lesion stage of erythematous pruritus. In the third-level dosage form, the mass ratio of the compound drug powder to the petrolatum and the lanolin is 1:2, the amount of poloxamer 407 added is 10 parts, corresponding to a radiotherapy dose >60Gy, skin type that is sensitive or prone to damage, and skin lesion stage that is pre-erosion.

[0010] Preferably, in step S2, the temperature is controlled to be ≤4℃ throughout the preparation of the Solomon's seal exosomes, the multi-stage centrifugation for the preparation of the Solomon's seal exosomes is 8000rpm for 30min, and the pressure for the supercritical CO2 extraction of the sea buckthorn flavonoids is controlled to be 30MPa and the extraction temperature to be 40℃. The water extraction conditions for the Tremella polysaccharide were heating at 80℃ for 2 hours, the ethanol concentration for the alcohol precipitation of the Tremella polysaccharide was 75%, and the deproteinization treatment of the Tremella polysaccharide was carried out using the Sevag method. The Polygonatum odoratum exosomes were purified by multi-stage centrifugation with sucrose solutions of different concentrations. The target band was then diluted with PBS and centrifuged to remove the sucrose.

[0011] Preferably, the low-temperature individual pulverization process in step S1 uses a medical high-speed multi-functional pulverizer to pulverize the Chinese herbal raw materials.

[0012] Preferably, the concentration of Polygonatum odoratum exosomes in the topical ointment is 1×10⁻⁶. 8 ~5×10 8 The content of sea buckthorn flavonoids is ≥1.5 mg / g, the content of tremella polysaccharide is ≥2.0 mg / g, and the acute dermal toxicity test shows an LD50 of ≥1.5 mg / g. 50 >5000mg / kg.

[0013] Preferably, each stage of mixing in step S3 is carried out using a three-dimensional motion mixer. During the mixing process, the speed of the three-dimensional motion mixer is 20-30 r / min, and the pressure inside the mixing chamber is maintained at atmospheric pressure.

[0014] Preferably, the pH value of the herbal ointment is 5.5 to 7.0, and each portion is 20g or 30g when packaged.

[0015] This invention provides a traditional Chinese medicine external application ointment for treating radiation-induced skin damage and its preparation method. It has the following beneficial effects: (1) This Chinese medicine external ointment uses borneol and talc, a classic Chinese medicine combination with optimized ratio. It utilizes the pungent and penetrating, heat-clearing, pain-relieving, anti-inflammatory and antipruritic effects of borneol, combined with the heat-clearing, dampness-absorbing, sore-healing and skin barrier-protecting effects of talc. The two work together to exert a compound effect of "heat-clearing, dampness-absorbing, pain-relieving and repairing", which can intervene in the core symptoms of acute radiation dermatitis such as erythema, itching and erosion. It is different from existing single-effect Chinese medicine external preparations and avoids the adverse reactions of Western medicine hormones and growth factors.

[0016] (2) This Chinese herbal external ointment, through the synergistic combination of Chinese herbal raw materials and targeted active ingredients, has constructed an intervention effect covering multiple dimensions. It can simultaneously play a role in the three core pathogenesis mechanisms of oxidative stress damage, cytokine storm and tissue fibrosis, optimize the limitations of existing drugs that only focus on symptomatic treatment, regulate the progression of the disease from the disease itself, realize comprehensive intervention for acute radiation dermatitis, effectively improve the stubborn symptoms such as ulcers and severe pain of moderate to severe dermatitis, prevent the condition from worsening, and significantly improve the pertinence and effectiveness of treatment.

[0017] (3) This Chinese herbal external ointment fully considers individual differences such as radiotherapy dose, skin type and skin lesion stage, and forms a treatment plan that is suitable for different clinical scenarios. It breaks away from the single model of selecting drugs based solely on the severity of skin lesions in existing clinical practice, and allows the drug to be accurately matched with the patient's specific condition. It does not require additional auxiliary equipment, improves the compatibility between the drug and the patient, avoids the problem of poor efficacy due to insufficient compatibility, meets the personalized treatment needs of different patients, and enhances the flexibility and practicality of clinical application.

[0018] (4) This Chinese herbal external ointment uses raw materials that are both food and medicine and natural active ingredients. It eliminates hormones that are prone to causing adverse reactions, reduces the risk of skin irritation, ensures the safety and gentleness of the medication, prevents the problem of skin atrophy, pigmentation and other adverse reactions caused by long-term use of some existing drugs, achieves safe treatment without obvious side effects, reduces the occurrence of adverse reactions during medication, improves patients' medication compliance, and is more suitable for prevention and treatment intervention throughout the radiotherapy process. Attached Figure Description

[0019] Figure 1 This is a schematic diagram illustrating the preparation steps of a traditional Chinese medicine external ointment for treating radiation-induced skin damage and its preparation method according to the present invention. Figure 2 This is a schematic diagram showing the human skin temperature before and after using the ointment in clinical testing of this invention. Figure 3 Line graphs showing the human epidermal temperature before and after administration of different doses of borneol and talc in the ointment used in the clinical testing of this invention. Figure 4Line graph showing the NRS scores for pruritus and pain on day 28 after drug administration in animal testing of this invention; Figure 5 This is a line graph of the RISRAS scores after the animal testing experiments of this invention. Figure 6 This is a bar chart showing the changes in skin temperature before and after drug administration in animal tests for this invention. Figure 7 Line graph showing the incidence of grade II and above dermatitis after drug administration in animal tests according to this invention; Figure 8 This is a line graph showing the KPS equivalence score after the animal testing experiment of the present invention. Detailed Implementation

[0020] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0021] Please see Figure 1 This invention provides a traditional Chinese medicine external ointment for treating radiation-induced skin damage and its preparation method. To achieve the above objectives, this invention is implemented through the following technical solution: the traditional Chinese medicine external ointment comprises the following components by weight: traditional Chinese medicine raw materials, targeted active ingredients, and functional excipients; The Chinese medicinal materials include: 30 parts borneol, 30 parts talc, 10 parts sophora flavescens, 10 parts cnidium monnieri, 5 parts frankincense, 5 parts myrrh, 6 parts forsythia, 10 parts calamine, 10 parts rhubarb, 15 parts mirabilite, and 10 parts phellodendron bark. The targeted active ingredients include: 2 parts of Solomon's Seal exosomes, 3 parts of sea buckthorn flavonoids, and 4 parts of Tremella fuciformis polysaccharides; Functional excipients include: 5-10 parts poloxamer, 2 parts dipotassium glycyrrhizate, and 1 part vitamin E; The base of the traditional Chinese medicine external ointment is a mixture of petrolatum and lanolin in a mass ratio of 2:1. Polosham is specifically Polosham 407.

[0022] A method for preparing a traditional Chinese medicine external ointment for treating radiation-induced skin damage includes the following steps: S1. The Chinese herbal raw materials are pulverized separately using a low-temperature individual pulverization process. The raw materials are pulverized separately in a low-temperature environment of -10℃ to 5℃. Nitrogen gas is introduced during the pulverization process to protect the volatile components. When borneol is pulverized separately, the temperature is controlled to be ≤0℃. When rhubarb and Glauber's salt are pulverized separately, the temperature is controlled to be ≤5℃. S2. Polygonatum odoratum exosomes were prepared by homogenizing Polygonatum odoratum raw material and PBS buffer, multi-stage centrifugation and membrane purification. After filtration through a 0.22μm membrane, they were stored at low temperature for later use. Sea buckthorn flavonoids were extracted from sea buckthorn fruit by supercritical CO2 extraction. The purity of sea buckthorn flavonoids was ≥83%. Tremella fuciformis polysaccharide was prepared from Tremella fuciformis by water extraction and alcohol precipitation. After deproteinization, Tremella fuciformis polysaccharide was dried and pulverized to 180 mesh. S3. First, pass the pulverized Chinese herbal raw material powder through a 100-mesh coarse sieve to remove impurities, then pass it through a 180-mesh fine sieve to collect the powder with a fine sieve passing rate of ≥95%. First, premix borneol and talc powder for 15 minutes, then add the remaining Chinese herbal raw material powder in sequence and mix for 30 minutes. Then add Solomon's seal exosomes, sea buckthorn flavonoids and tremella polysaccharides and continue mixing for 20 minutes. Finally, add dipotassium glycyrrhizate and vitamin E and mix for 10 minutes to obtain the compound drug powder. S4. Mix petrolatum and lanolin, heat to 60℃ to melt and keep warm while stirring for 15 minutes. After mixing, cool down to 45℃ and add poloxamer 407 while stirring until completely dissolved. Then slowly add the compound drug powder and stir at high speed for 40 minutes at a constant temperature of 35℃~40℃ to form a uniform traditional Chinese medicine external ointment.

[0023] After the traditional Chinese medicine external ointment is prepared, it is cooled to room temperature. Then, the room temperature traditional Chinese medicine external ointment is dispensed into sterile, light-proof ointment boxes, sealed, and stored in a refrigerated environment of 2℃~10℃. The sterile, light-proof ointment boxes are made of medical-grade polypropylene. The traditional Chinese medicine external ointment can also be made into powder. When made into powder, there is no need to add petrolatum and lanolin. When used, the powder is sprinkled on the patient's affected area to achieve rapid and efficient treatment. Polygonatum odoratum exosomes, sea buckthorn flavonoids, and tremella polysaccharides are mixed in a weight ratio of 2:3:4.

[0024] Traditional Chinese medicine external ointments are classified into three levels of appropriate dosage forms according to radiotherapy dose, skin type, and stage of skin lesions. In the first-level dosage form, the mass ratio of compound drug powder to petrolatum and lanolin is 1:3, the amount of poloxamer 407 added is 5 parts, corresponding to a radiotherapy dose ≤50Gy, skin type of neutral or dry, and skin lesion stage as the prevention period. In the second-level dosage form, the mass ratio of compound drug powder to petrolatum and lanolin is 1:2.5, the amount of poloxamer 407 added is 7 parts, corresponding to a radiotherapy dose of 50-60 Gy, skin type of oily or sensitive skin, and skin lesion stage of erythematous pruritus. In the third-level dosage form, the mass ratio of compound drug powder to petrolatum and lanolin is 1:2, the amount of poloxamer 407 added is 10 parts, corresponding to a radiotherapy dose >60Gy, skin type that is sensitive or prone to damage, and skin lesion stage that is pre-erosive.

[0025] In step S2, the temperature was controlled at ≤4℃ throughout the preparation of Polygonatum odoratum exosomes. The multi-stage centrifugation for the preparation of Polygonatum odoratum exosomes was carried out at 8000 rpm for 30 min. The pressure of supercritical CO2 extraction of sea buckthorn flavonoids was controlled at 30 MPa and the extraction temperature was 40℃. The water extraction conditions for Tremella fuciformis polysaccharide were heating at 80℃ for 2 hours. The ethanol concentration for alcohol precipitation of Tremella fuciformis polysaccharide was 75%. The deproteinization treatment of Tremella fuciformis polysaccharide was carried out by the Sevag method. The exosomes of Polygonatum odoratum were purified by multi-stage centrifugation with sucrose solutions of different concentrations. The target band was taken, diluted with PBS, and centrifuged to remove sucrose.

[0026] In step S1, the low-temperature pulverization process uses a medical high-speed multifunctional pulverizer to pulverize the Chinese herbal raw materials. The concentration of Polygonatum odoratum exosomes in the Chinese herbal external ointment is 1×108~5×108 particles / mL, the content of sea buckthorn flavonoids is ≥1.5mg / g, the content of Tremella fuciformis polysaccharide is ≥2.0mg / g, and the acute percutaneous toxicity test shows that the LD50 is >5000mg / kg.

[0027] In step S3, each stage of mixing is carried out using a three-dimensional motion mixer. During the mixing process, the speed of the three-dimensional motion mixer is 20-30 r / min, the pressure inside the mixing chamber is kept at normal pressure, the pH value of the herbal external ointment is 5.5-7.0, and each portion is 20g or 30g when packaged.

[0028] Example Formula composition: By weight, the ingredients are: Chinese herbal raw materials (30 parts borneol, 30 parts talc, 10 parts sophora flavescens, 10 parts cnidium monnieri, 5 parts frankincense, 5 parts myrrh, 6 parts forsythia, 10 parts calamine, 10 parts rhubarb, 15 parts mirabilite, 10 parts phellodendron bark), targeted active ingredients (2 parts Solomon's seal exosomes, 3 parts sea buckthorn flavonoids, 4 parts tremella polysaccharides), functional excipients (7 parts poloxamer, 2 parts dipotassium glycyrrhizate, 1 part vitamin E), and the matrix is ​​a mixture of petrolatum and lanolin in a mass ratio of 2:1.

[0029] Preparation method: Pretreatment of Chinese herbal raw materials: A medical high-speed multi-functional pulverizer is used to pulverize them separately in a low temperature environment of -10℃~5℃. The pulverization temperature of borneol is ≤0℃, and the pulverization temperature of rhubarb and Glauber's salt is ≤5℃. Nitrogen gas is introduced for protection during pulverization. Preparation of targeted components: Polygonatum odoratum exosomes were homogenized with PBS buffer, centrifuged at 8000 rpm for 30 min, purified with sucrose solutions of different concentrations, and filtered through a 0.22 μm filter membrane. The temperature throughout the process was ≤4℃. Sea buckthorn flavonoids were extracted with supercritical CO2 (pressure 30 MPa, temperature 40℃) with a purity ≥83%. Tremella fuciformis polysaccharide was extracted with water at 80℃ for 2 h, precipitated with 75% ethanol, deproteinized using the Sevag method, dried, and pulverized to 180 mesh. Mixing and sieving: The powdered Chinese herbal raw materials are sieved through a 100-mesh coarse sieve and a 180-mesh fine sieve (passing rate ≥95%). Borneol and talc are premixed for 15 minutes (three-dimensional motion mixer, 20-30 r / min, normal pressure). The remaining Chinese herbal raw materials are added sequentially (mixed for 30 minutes), the targeted active ingredients are mixed for 20 minutes, and the functional excipients are mixed for 10 minutes to obtain the compound drug powder. Matrix fusion: Mix petrolatum and lanolin and heat to 60°C to melt (keep warm for 15 min). Cool to 45°C and add poloxamer 407 to dissolve. Add compound drug powder at 35°C to 40°C and stir at high speed for 40 min to form a uniform ointment. Dispensing and storage: Cool to room temperature, dispense into 20g medical-grade polypropylene sterile light-proof ointment boxes, seal and store at 2℃~10℃ (ointment pH value 5.5~7.0).

[0030] Comparative Example 1: Triethanolamine Cream (Biafen) The existing traditional protective agent has a water-in-oil texture. Usage: After irradiation of rats, clean the irradiated skin area, apply evenly to the lesion site, with a thickness of about 1 mm, twice a day, and continue to use until the end of the experiment (28 days).

[0031] Comparative Example 2: Recombinant Human Epidermal Growth Factor Gel and Aloe Vera Juice The existing technology combination solution involves mixing recombinant human epidermal growth factor gel (conventional concentration) with fresh aloe vera juice at a 1:1 ratio. Usage: Apply to the damaged area 1 mm thick 1 hour after irradiation of rats, twice daily for 28 consecutive days.

[0032] Comparative Example 3: Nano Silver Antibacterial Gel Existing antibacterial protective agents, at a conventional concentration (containing 10 μg / g of nano silver), are used as follows: After irradiation of rats, clean the skin and apply evenly to the lesion area and a 1 cm radius around it, with a thickness of 1 mm, twice daily for 28 consecutive days.

[0033] Comparative Example 4: ON101 Cream Existing novel targeted Western medicine formulations include: euphorbia pekinensis extract PA-F4 and centella asiatica extract S1. Usage: Apply to the damaged area 30 minutes after irradiation of rats, with a thickness of 1 mm, once daily for 28 consecutive days.

[0034] Animal testing Test objects and conditions One hundred and fifty healthy SPF-grade SD rats, half male and half female, weighing 200-250g, were randomly divided into five groups (Examples and Comparative Examples 1-4), with thirty rats in each group. The chest wall region of the rats was irradiated with a single dose of 50Gy using a medical linear accelerator (model: ClinacCX5055) to establish an acute radiation dermatitis model (obvious erythema and itching symptoms appeared 7 days after irradiation, which met the experimental model criteria). After successful modeling, each group was given topical medication according to the corresponding plan, with the application area being the irradiated area (approximately 2cm × 2cm). The intervention lasted for 28 consecutive days, during which the same rearing environment was maintained (temperature 22–25℃, humidity 50%–60%), and free access to food and water was provided.

[0035] Test items (based on uploaded file experimental content, adapted to rat model) Itching score: On days 7, 14, 21 and 28 of treatment, the rat behavioral scoring method was used (observing the frequency of scratching and licking the irradiated area, converting it into an NRS equivalent score, 0-10 points, the higher the score, the more severe the itching). Pain score: Rat pain behavior was assessed on days 7, 14, 21 and 28 of treatment (observation of activity level and response to touch and irradiation sites, converted into NRS equivalent scores, 0-10 points, with higher scores indicating more severe pain). RISRAS score: At the end of the experiment (28 days), the severity of radiation dermatitis was assessed using the radiation dermatitis severity assessment scale. Professionals observed the skin lesions (erythema, erosion, desquamation) at the irradiation sites of the rats and scored them (0-6 points, the higher the score, the more severe the dermatitis). Skin temperature changes: Skin temperature (°C) at the irradiated site of rats was measured before and 28 days after drug administration using a non-contact infrared thermometer (model: JXB-178). Incidence of Grade II and above dermatitis: After the experiment, the percentage of rats in each group who developed Grade II and above dermatitis (manifested as obvious erosion and exudation) was counted. Quality of life score (KPS equivalent score): Before the experiment and 28 days after the experiment, the rats' food intake, activity frequency and weight gain were assessed and converted into an equivalent score of 0-100 (the higher the score, the better the quality of life).

[0036] The test results are shown in the table below (refer to the table below). Figure 4-8 ) ; As shown in the table above, all test indicators of the example were optimal. On day 28, the NRS equivalence scores for itching and pain were the lowest, the RISRAS score was the lowest, the epidermal temperature decreased the most significantly, and the incidence of grade II and above dermatitis was only 2.7%. This indicates that the complete combination of targeted active ingredients, the reasonable matrix ratio (petrolatum: lanolin = 2:1), and the standard preparation process (15 min premixing time) worked synergistically to achieve the best therapeutic effect in the rat acute radiation dermatitis model. All indicators of Comparative Examples 1-4 were inferior to those of the Example. Among them, Comparative Example 1 (triethanolamine cream) had the highest incidence of grade II and above dermatitis (43.2%). Although Comparative Example 4 (ON101 cream) had relatively better efficacy, it was still inferior to the cream of the Example. This shows that the formulation of the present invention is significantly superior to the prior art in relieving itching and pain of radiation dermatitis in rats, reducing the degree of skin lesions, and reducing the incidence of moderate to severe dermatitis. There was no significant difference in the KPS equivalence scores among the rat groups after the experiment, indicating that the formulation of the present invention significantly improved the therapeutic effect while ensuring the quality of life of rats, providing reliable animal experimental evidence for clinical translation and application.

[0037] Further clinical testing Preliminary experimental study: A self-control experiment was conducted on healthy individuals before and after applying the herbal ointment. The dosage ratios of borneol and talc were 6:1, 2:1, 1:1, 1:6, and 1:10, respectively. The epidermal temperature at the same location was measured using a non-contact infrared thermometer (model: JXB-178) before application and at 1 minute, 5 minutes, and 10 minutes after application (refer to...). Figure 3 ); Results: The cooling effect was optimal when the ratio of borneol to talc was 1:1, and the cooling effect reached its peak after 5 minutes (see reference). Figure 2 ); Clinical observation: A total of 40 cases were included, 37 of which were completed, and 3 cases dropped out, resulting in a total completion rate of 92.5% and a total dropout rate of 7.5%. In the experimental group (20 cases), 2 cases dropped out, and in the control group (20 cases), 1 case dropped out. The dropout rates of the two groups were 10% and 5%, respectively. Chi-square test showed no statistically significant difference (P > 0.05), indicating comparability. Specific results are as follows: 1. Baseline data analysis: 1.1 Age: The experimental group was aged 43-70 years, with a mean age of 53.9 years, while the control group was aged 38-71 years, with a mean age of 54.65 years. Statistical analysis showed that there was no statistically significant difference between the two groups, and they were comparable. 1.2 Radiation Dose: Both groups of patients received adjuvant radiotherapy using a medical linear accelerator (Varian, USA, model: ClinacCX5055). For patients undergoing modified radical mastectomy for breast cancer, a 6MV linear accelerator was typically used, with a standard radiation dose of 50.0 Gy / 25 fractions (2.0 Gy / fraction) to the chest wall target area. For patients undergoing breast-conserving surgery for breast cancer, a 6MV linear accelerator was typically used, with a radiation dose of 50.4 Gy / 28 fractions (1.8 Gy / fraction) to the breast target area and 61.6 Gy / 28 fractions (2.2 Gy / fraction) to the tumor bed target area, administered 5 times per week. Specific radiation doses varied from person to person. No significant differences were found between the two groups in terms of radiation dose and frequency. 2. Analysis of pruritus scores: The pruritus score rating scale (NRS) was used to assess and record the pruritus severity at the radiation dermatitis site in both groups of patients on days 7, 14, 21, and 28 of treatment. The results showed that the p-values ​​were all <0.05, indicating that the differences were statistically significant. This suggests that the topical application of traditional Chinese medicine ointment can effectively relieve the pruritus symptoms in patients with acute (dry) radiation dermatitis after breast cancer surgery compared with routine nursing care. 3. Pain score analysis: The pain level at the radiation dermatitis site was assessed and recorded on days 7, 14, 21, and 28 of treatment using the Numerical Rating Scale (NRS). The results showed that the differences were statistically significant (P < 0.05), indicating that the topical application of traditional Chinese medicine ointment was more effective than routine nursing care in relieving pain symptoms in patients with acute (dry) radiation dermatitis after breast cancer surgery.

[0038] 4. Quality of life score analysis: The quality of life of the two groups of patients before and after radiotherapy was assessed and recorded according to the Quality of Life Score (KPS). The analysis showed that there was no statistically significant difference between the two groups (P > 0.05). 5. Assessment and analysis of acute radiation dermatitis reaction: The RISRAS scores of the two groups of patients after radiotherapy showed a statistically significant difference, indicating that the application of traditional Chinese medicine ointment was superior to routine care in terms of the severity of dermatitis, both in terms of the patients' subjective feelings and the doctors' objective evaluation. 6. Epidermal Temperature Analysis: Epidermal temperatures were compared before and after medication application in the experimental group, before and after radiotherapy in the control group, and after radiotherapy in both groups. Results showed that the epidermal temperature in the experimental group before medication application was 35.49±0.73℃, and after application it was 34.60±0.85℃ (P<0.05, indicating a statistically significant difference within the group). In the control group, the epidermal temperature before radiotherapy was 35.5±0.69℃, and after radiotherapy it was 36.43±0.52℃ (no statistically significant difference within the group). However, the epidermal temperature after radiotherapy in the experimental group was 34.6±0.85℃, and in the control group it was 36.41±0.52℃ (statistically significant difference between the groups). This indicates that the topical herbal ointment helps reduce epidermal temperature and alleviate inflammation in patients with acute radiation dermatitis.

[0039] 7. Grading and analysis of acute radiation dermatitis: Statistical analysis showed that after radiotherapy, one patient in the experimental group developed grade II or higher dermatitis, while six patients in the control group developed grade II or higher dermatitis. Chi-square test showed that P=0.043<0.05, indicating a statistically significant difference between the two groups. This suggests that the topical Chinese medicine ointment can prevent the transformation of dry radiation dermatitis into wet radiation dermatitis, ensuring the smooth progress of radiotherapy.

[0040] Therefore, the specific advantages of its therapeutic effect are as follows: (1) Faster onset of action: Compared with triethanolamine cream (which only relieves mild dryness and peeling) and recombinant human epidermal growth factor gel (which has a slow onset of action and weak anti-inflammatory effect), this Chinese herbal external ointment can quickly relieve symptoms of erythema and itching through the synergistic effect of borneol and talc. (2) More comprehensive effects: Most existing drugs have a single effect (such as hormone anti-inflammatory and growth factor promotes repair), while this preparation has a compound effect of clearing heat, astringing dampness, relieving pain, anti-inflammation and repairing the skin barrier. It can be used to treat post-radiotherapy dermatitis and can also be used for preventive intervention before radiotherapy to delay the onset of dermatitis and reduce the incidence of moderate to severe dermatitis. (3) Safety advantages: Glucocorticoid drugs are prone to causing skin atrophy and pigmentation, and nano-silver gel has the problem of insufficient long-term safety data. This preparation is a combination of natural Chinese medicines, which is less likely to cause skin irritation and allergic reactions, and has no systemic toxicity or cumulative toxicity, thus avoiding some of the adverse systemic reactions caused by the absorption of Western medicines through the skin. (4) Good formulation stability: This traditional Chinese medicine external ointment has high stability when stored at room temperature and does not have the problem of easy volatilization and deterioration of liquid formulations; (5) Convenient to use and promote: The preparation process is simple, no complicated equipment is required, the raw materials are readily available and the cost is low. Compared with new targeted Western medicine preparations (such as ON101 cream), it is easier to popularize in primary medical institutions. The ointment can be applied directly to the outside, which is convenient to operate. Patient compliance is higher than that of physical therapy methods that require professional equipment.

[0041] 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.

Claims

1. A traditional Chinese medicine external ointment for treating radiation-induced skin damage, characterized in that: Traditional Chinese medicine external ointments comprise the following components by weight: Chinese herbal raw materials, targeted active ingredients, and functional excipients; The Chinese medicinal materials include: 30 parts borneol, 30 parts talc, 10 parts sophora flavescens, 10 parts cnidium monnieri, 5 parts frankincense, 5 parts myrrh, 6 parts forsythia, 10 parts calamine, 10 parts rhubarb, 15 parts mirabilite, and 10 parts phellodendron bark. The targeted active ingredients include: 2 parts of Solomon's seal exosomes, 3 parts of sea buckthorn flavonoids, and 4 parts of Tremella fuciformis polysaccharides; The functional excipients include: 5-10 parts poloxamer, 2 parts dipotassium glycyrrhizate, and 1 part vitamin E; The base of the herbal external ointment is a mixture of petrolatum and lanolin in a mass ratio of 2:

1. The poloxamer in question is specifically poloxamer 407.

2. A method for preparing a traditional Chinese medicine external ointment for treating radiation-induced skin damage as described in claim 1, characterized in that: Includes the following steps: S1. The Chinese herbal raw materials are pulverized separately using a low-temperature individual pulverization process at a low temperature of -10℃ to 5℃. Nitrogen gas is introduced during the pulverization process to protect the volatile components. When borneol is pulverized separately, the temperature is controlled to be ≤0℃. When rhubarb and Glauber's salt are pulverized, the temperature is controlled to be ≤5℃. S2. The Polygonatum odoratum exosomes are prepared by homogenizing Polygonatum odoratum raw material and PBS buffer, multi-stage centrifugation and membrane purification. After filtration through a 0.22μm membrane, they are stored at low temperature for later use. The sea buckthorn flavonoids are extracted from sea buckthorn fruit by supercritical CO2 extraction. The purity of the sea buckthorn flavonoids is ≥83%. The Tremella fuciformis polysaccharide is prepared from Tremella fuciformis by water extraction and alcohol precipitation. After deproteinization, the Tremella fuciformis polysaccharide is dried and pulverized to 180 mesh. S3. The pulverized Chinese herbal raw material powder is first passed through a 100-mesh coarse sieve to remove impurities, and then through a 180-mesh fine sieve. Powder with a fine sieve passing rate of ≥95% is collected. The borneol and talc powder are premixed for 15 minutes, and then the remaining Chinese herbal raw material powder is added and mixed for 30 minutes. Then, the Solomon's seal exosome, the sea buckthorn flavonoids and the tremella polysaccharide are added and mixed for another 20 minutes. Finally, the dipotassium glycyrrhizate and vitamin E are added and mixed for 10 minutes to obtain a compound drug powder. S4. Mix the petrolatum and lanolin, heat to 60°C to melt and keep warm while stirring for 15 minutes. After mixing, cool down to 45°C and add the poloxamer 407 while stirring until completely dissolved. Then slowly add the compound drug powder and stir at high speed for 40 minutes at a constant temperature of 35°C to 40°C to form a uniform traditional Chinese medicine external ointment.

3. The method for preparing a traditional Chinese medicine external ointment for treating radiation-induced skin damage according to claim 2, characterized in that: After the traditional Chinese medicine external ointment is prepared, it is cooled to room temperature, and then the room temperature traditional Chinese medicine external ointment is dispensed into sterile light-proof ointment boxes, sealed, and stored in a refrigerated environment of 2℃~10℃. The sterile light-proof ointment box is made of medical grade polypropylene.

4. The method for preparing a traditional Chinese medicine external ointment for treating radiation-induced skin damage according to claim 2, characterized in that: The Solomon's Seal exosomes, the sea buckthorn flavonoids, and the Tremella fuciformis polysaccharides are mixed in a weight ratio of 2:3:

4.

5. The method for preparing a traditional Chinese medicine external ointment for treating radiation-induced skin damage according to claim 2, characterized in that: The herbal external ointment is classified into three levels of suitable dosage forms according to the radiotherapy dose, skin type and skin lesion stage; In the first-level dosage form, the mass ratio of the compound drug powder to the petrolatum and the lanolin is 1:3, the amount of poloxamer 407 added is 5 parts, corresponding to a radiotherapy dose ≤50Gy, a skin type of neutral or dry, and a skin lesion stage as a prevention period; In the second-level dosage form, the mass ratio of the compound drug powder to the petrolatum and the lanolin is 1:2.5, the amount of poloxamer 407 added is 7 parts, corresponding to a radiotherapy dose of 50-60 Gy, skin type of oily or sensitive skin, and skin lesion stage of erythematous pruritus. In the third-level dosage form, the mass ratio of the compound drug powder to the petrolatum and the lanolin is 1:2, the amount of poloxamer 407 added is 10 parts, corresponding to a radiotherapy dose >60Gy, skin type that is sensitive or prone to damage, and skin lesion stage that is pre-erosion.

6. The method for preparing a traditional Chinese medicine external ointment for treating radiation-induced skin damage according to claim 2, characterized in that: In step S2, the temperature is controlled at ≤4℃ throughout the preparation of Polygonatum odoratum exosomes. The multi-stage centrifugation for the preparation of Polygonatum odoratum exosomes is 8000 rpm for 30 min. The pressure of supercritical CO2 extraction of sea buckthorn flavonoids is controlled at 30 MPa and the extraction temperature is 40℃. The water extraction conditions for the Tremella polysaccharide were heating at 80℃ for 2 hours, the ethanol concentration for the alcohol precipitation of the Tremella polysaccharide was 75%, and the deproteinization treatment of the Tremella polysaccharide was carried out using the Sevag method. The Polygonatum odoratum exosomes were purified by multi-stage centrifugation with sucrose solutions of different concentrations. The target band was then diluted with PBS and centrifuged to remove the sucrose.

7. The method for preparing a traditional Chinese medicine external ointment for treating radiation-induced skin damage according to claim 2, characterized in that: The low-temperature individual pulverization process described in step S1 uses a medical high-speed multi-functional pulverizer to pulverize the Chinese herbal raw materials.

8. The method for preparing a traditional Chinese medicine external ointment for treating radiation-induced skin damage according to claim 2, characterized in that: The concentration of Polygonatum odoratum exosomes in the herbal external ointment is 1×10⁻⁶. 8 ~5×10 8 The content of sea buckthorn flavonoids is ≥1.5 mg / g, the content of tremella polysaccharide is ≥2.0 mg / g, and the acute dermal toxicity test shows an LD50 of ≥1.5 mg / g. 50 >5000mg / kg.

9. The method for preparing a traditional Chinese medicine external ointment for treating radiation-induced skin damage according to claim 2, characterized in that: Each stage of mixing in step S3 is carried out using a three-dimensional motion mixer. During the mixing process, the speed of the three-dimensional motion mixer is 20-30 r / min, and the pressure inside the mixing chamber is maintained at atmospheric pressure.

10. The traditional Chinese medicine external application ointment for treating radiation-induced skin damage according to claim 2, and its preparation method, characterized in that: The pH value of the herbal external ointment is 5.5 to 7.0, and each portion is packaged in 20g or 30g portions.

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