External heat-clearing traditional Chinese medicine ointment for improving targeted therapy skin tolerance

Abstract

The invention belongs to the field of traditional Chinese medicine external ointment, and discloses heat-clearing traditional Chinese medicine external ointment for improving targeted therapy skin tolerance, the ointment is composed of traditional Chinese medicine active components and a medicinal matrix, the traditional Chinese medicine active components comprise the following raw materials in parts by weight: 20-40 parts of scutellaria baicalensis, 15-35 parts of radix sophorae flavescentis, 15-30 parts of cortex dictamni, 25-45 parts of purslane, 10-25 parts of fructus kochiae, 10-25 parts of fructus cnidii, 12-28 parts of sanguisorba officinalis and 8-18 parts of mint; the medicinal matrix comprises an oil-phase matrix, a water-phase matrix, an emulsifier and a humectant, the traditional Chinese medicine active components account for 20-40% of the total mass of the ointment, the oil-phase matrix accounts for 25-45%, the water-phase matrix accounts for 15-30%, the emulsifier accounts for 3-8%, and the humectant accounts for 2-6%; according to the technical scheme, generation of EGFRIs related skin adverse reactions can be inhibited from the source, different types of skin symptoms can be relieved in a targeted mode, the tolerance of the skin of a patient to targeted therapy is comprehensively improved, and the traditional Chinese medicine composition is good in clinical use performance, convenient to use, free of adverse reactions and high in use safety.

Description

Technical Field

[0001] This invention relates to the field of topical ointments of traditional Chinese medicine, and more particularly to a topical ointment of traditional Chinese medicine for clearing heat that improves skin tolerance to targeted therapy. Background Technology

[0002] Epidermal growth factor receptor inhibitors (EGFRIs) are currently the core targeted drugs for the treatment of malignant tumors such as lung cancer, colon cancer, and pancreatic cancer. They inhibit tumor cell proliferation and metastasis by specifically blocking the epidermal growth factor receptor signaling pathway, significantly prolonging the survival of patients with malignant tumors. However, the incidence of skin adverse reactions of EGFRIs is as high as 40% to 90%, mainly manifested as acne-like rashes, dry skin, itching, pigmentation, abnormal hair, paronychia, and nail fissures. These adverse reactions not only seriously affect the quality of life of patients, but also force some patients to reduce the dosage or discontinue targeted therapy due to intolerance, which greatly limits the clinical application effect of EGFRIs.

[0003] Currently, clinical treatment for EGFRI-related skin adverse reactions mostly employs reactive therapy strategies. This involves applying topical clindamycin or hydrocortisone ointment or taking oral minocycline after symptoms appear to reduce skin adverse reactions caused by EGFRIs. However, these methods have limited preventative effects, and long-term use may lead to secondary adverse reactions such as drug resistance and skin atrophy. Traditional Chinese medicine (TCM) has unique advantages in preventing and treating skin diseases through "holistic conditioning and addressing both the symptoms and root cause," but currently, there is no highly effective topical ointment primarily composed of TCM ingredients that can improve skin tolerance to targeted therapy. Therefore, based on the theory of traditional Chinese medicine compatibility, this invention proposes a heat-clearing Chinese herbal external ointment to improve the skin tolerance to targeted therapy. While improving the skin tolerance to targeted therapy, it reduces secondary adverse reactions. Moreover, it is convenient to use, has a long-lasting effect, and provides more comprehensive efficacy when applied externally. Summary of the Invention

[0004] The present invention aims to provide a topical ointment of traditional Chinese medicine for clearing heat and improving skin tolerance to targeted therapy, so as to solve the problems mentioned in the background art.

[0005] To achieve the above objectives, the present invention provides the following technical solution: A topical ointment made from traditional Chinese medicine for clearing heat and improving skin tolerance to targeted therapy, the ointment being composed of active ingredients from traditional Chinese medicine and a medicinal matrix. The active ingredients from traditional Chinese medicine, by weight, include the following raw materials: 20-40 parts of Scutellaria baicalensis, 15-35 parts of Sophora flavescens, 15-30 parts of Dictamnus dasycarpus, 25-45 parts of Portulaca oleracea, 10-25 parts of Kochia scoparia, 10-25 parts of Cnidium monnieri, 12-28 parts of Sanguisorba officinalis, and 8-18 parts of Mentha haplocalyx. The medicinal matrix includes an oil phase matrix, an aqueous phase matrix, an emulsifier, and a moisturizer. The active ingredients from traditional Chinese medicine account for 20%-40% of the total mass of the ointment, the oil phase matrix accounts for 25%-45%, the aqueous phase matrix accounts for 15%-30%, the emulsifier accounts for 3%-8%, and the moisturizer accounts for 2%-6%.

[0006] Preferably, the active components of the traditional Chinese medicine are as follows by weight: 30 parts of Scutellaria baicalensis, 25 parts of Sophora flavescens, 20 parts of Dictamnus dasycarpus, 35 parts of Portulaca oleracea, 18 parts of Kochia scoparia, 18 parts of Cnidium monnieri, 20 parts of Sanguisorba officinalis, and 12 parts of Mentha haplocalyx.

[0007] Preferably, the oil phase matrix is ​​selected from one or more of petrolatum, lanolin, and stearic acid, and the aqueous phase matrix is ​​purified water.

[0008] Preferably, the emulsifier is one or both of Tween-80 and Span-60.

[0009] Preferably, the moisturizer is selected from one or both of glycerin and propylene glycol.

[0010] Preferably, the ointment is prepared according to the following steps: S1. Extraction of active components from traditional Chinese medicine: Weigh the raw materials of active components from traditional Chinese medicine, pulverize the raw materials separately and pass them through a 40-60 mesh sieve, weigh the corresponding raw materials according to the set weight parts, and then add purified water. The mass of the purified water added is 8-12 times the total mass of the raw materials. After soaking for 30-60 minutes, perform two heating and reflux extractions. The heating and reflux extraction time is 1.5-2 hours each time. Mix the extracts from the two heating and reflux extractions, and then filter and concentrate under reduced pressure to obtain a clear extract. The relative density of the clear extract at 60℃ is 1.1-1.2.

[0011] S2. Prepare the oil phase matrix: Weigh the oil phase matrix according to the mass percentage, heat the oil phase matrix to 75-85℃, and maintain the temperature of 75-85℃ until the oil phase matrix is ​​completely melted. Keep the melted oil phase matrix warm for later use. S3. Preparation of aqueous phase: Add the clear paste obtained in step S1 to the aqueous phase matrix, then add a humectant, heat to 75-85℃, so that the clear paste and the aqueous phase matrix are mixed evenly to obtain a mixture, and keep it warm for later use. S4. Emulsification: Add the emulsifier to the oil phase matrix or the mixture prepared in step S3, stir to make the emulsifier and the oil phase matrix or the mixture evenly mixed, and then slowly add the mixture to the oil phase matrix. During the addition process, keep the temperature at 75-85℃ and stir while adding. After the mixture is added, keep the temperature at 75-85℃ and continue stirring for 20-30 minutes to obtain the primary emulsion. S5. Cooling and shaping: After obtaining the colostrum, the colostrum is no longer kept warm. It is allowed to cool naturally to room temperature while being stirred. Then, stirring is continued for 10-15 minutes. After homogenization, it is packaged to obtain a heat-clearing Chinese herbal external ointment.

[0012] Preferably, in step S1, the pressure during vacuum concentration is -0.06 to -0.08 MPa, and the concentration temperature is 55 to 65°C.

[0013] Preferably, the stirring speed in step S4 is 300-500 r / min.

[0014] Preferably, the ointment is used to improve skin tolerance to targeted therapy, wherein the targeted therapy is an epidermal growth factor receptor inhibitor.

[0015] The beneficial effects of this technical solution compared to existing technologies are as follows: (1) The traditional Chinese medicine external ointment provided by this technical solution is composed of multiple groups of traditional Chinese medicine raw materials. The multiple traditional Chinese medicine raw materials form a multi-component synergistic system, which can cool the blood and moisten dryness, enhance the effects of clearing heat and relieving itching, and relieve the burning sensation. It plays a comprehensive role in preventing and relieving various adverse skin reactions caused by EGFRIs targeted drugs. It can not only inhibit the occurrence of EGFRIs-related adverse skin reactions from the root, but also specifically relieve different types of skin symptoms, and comprehensively improve the patient's skin tolerance to targeted therapy. The medicine is prepared as an external ointment, which is convenient to apply. The optimization of raw materials makes the ointment easy to adhere to the skin. The ointment is not easily lost from the skin surface. Combined with the sustained-release and water-locking effects of the oil-phase matrix and moisturizer, it prolongs the duration of action of the drug, allowing it to exert its efficacy for a longer period of time and improving patient compliance. Furthermore, the ointment is made from highly safe traditional Chinese medicine ingredients, making the drug itself relatively safe. When used in conjunction with topical application, it avoids the effects of oral medications on the gastrointestinal tract and liver and kidney function. Clinical trials have confirmed that it has no adverse effects on patients' blood routine tests, liver and kidney function, and there are no obvious drug-related adverse reactions. Long-term use has not resulted in secondary adverse reactions such as skin atrophy, greatly improving the safety of use.

[0016] (2) This technical solution optimizes the preparation process of the proposed ointment. It adopts a heated water extraction process to extract the effective components from the Chinese herbal raw materials, avoids organic solvent residue, and greatly improves the safety of the final product. By optimizing the extraction time, temperature and concentration conditions, the active ingredients of each Chinese herbal raw material are preserved to the maximum extent, thereby improving the therapeutic effect. Emulsification and homogenization ensure the stability and uniformity of the preparation. The addition of moisturizer further enhances the effect of the preparation on dry skin. The overall preparation process is simple, requires no complicated equipment, has low production cost, and is easy to industrialize. Attached Figure Description

[0017] Figure 1 A schematic diagram of the preparation steps of the heat-clearing traditional Chinese medicine external ointment provided by the present invention; Detailed Implementation

[0018] The following is a reference to the accompanying drawings in the instruction manual. Figure 1 The present invention will be further described in detail below with reference to the embodiments: A topical ointment made from traditional Chinese medicine for clearing heat and improving skin tolerance to targeted therapy. The ointment is composed of active ingredients from traditional Chinese medicine and a medicinal matrix. The active ingredients from traditional Chinese medicine include the following raw materials by weight: 20-40 parts of Scutellaria baicalensis, 15-35 parts of Sophora flavescens, 15-30 parts of Dictamnus dasycarpus, 25-45 parts of Portulaca oleracea, 10-25 parts of Kochia scoparia, 10-25 parts of Cnidium monnieri, 12-28 parts of Sanguisorba officinalis, and 8-18 parts of Mentha haplocalyx. The medicinal matrix includes an oil phase matrix, an aqueous phase matrix, an emulsifier, and a moisturizer. The active ingredients from traditional Chinese medicine account for 20%-40% of the total mass of the ointment, the oil phase matrix accounts for 25%-45%, the aqueous phase matrix accounts for 15%-30%, the emulsifier accounts for 3%-8%, and the moisturizer accounts for 2%-6%.

[0019] The oil phase matrix is ​​selected from one or more of petrolatum, lanolin, and stearic acid; the aqueous phase matrix is ​​purified water; the emulsifier is selected from one or two of Tween-80 and Span-60; and the humectant is selected from one or two of glycerin and propylene glycol. The ointment is prepared by following these steps: S1. Extraction of active components from traditional Chinese medicine: Weigh the raw materials of active components from traditional Chinese medicine, pulverize them separately and pass them through a 40-60 mesh sieve. Weigh the corresponding raw materials according to the set weight parts, then add purified water. The mass of purified water added should be 8-12 times the total mass of the raw materials. Soak for 30-60 minutes, then perform two heating and reflux extractions. Each heating and reflux extraction time is 1.5-2 hours. Mix the extracts from the two heating and reflux extractions, then filter and concentrate under reduced pressure to obtain a clear extract. The pressure during reduced pressure concentration is -0.06 to -0.08 MPa, and the concentration temperature is 55-65℃. Finally, the relative density of the clear extract at 60℃ should be 1.1-1.2.

[0020] S2. Prepare the oil phase matrix: Weigh the oil phase matrix according to the mass percentage, heat the oil phase matrix to 75-85℃, and maintain the temperature of 75-85℃ until the oil phase matrix is ​​completely melted. Keep the melted oil phase matrix warm for later use. S3. Preparation of aqueous phase: Add the clear paste obtained in step S1 to the aqueous phase matrix, then add a humectant, heat to 75-85℃, so that the clear paste and the aqueous phase matrix are mixed evenly to obtain a mixture, and keep it warm for later use. S4. Emulsification: Add the emulsifier to the oil phase matrix or the mixture prepared in step S3, and stir to make the emulsifier and the oil phase matrix or the mixture evenly mixed. Then, slowly add the mixture to the oil phase matrix while maintaining the temperature at 75-85°C and stirring continuously. After the mixture is added, maintain the temperature at 75-85°C and continue stirring for 20-30 minutes at a stirring speed of 300-500 r / min. After stirring is complete, the primary emulsion is obtained. S5. Cooling and shaping: After obtaining the colostrum, the colostrum is no longer kept warm. It is allowed to cool naturally to room temperature while being stirred. Then, stirring is continued for 10-15 minutes. After homogenization, it is packaged to obtain a heat-clearing Chinese herbal external ointment.

[0021] The ointment is used to improve skin tolerance to targeted therapy, which is epidermal growth factor receptor inhibitor (EGFR) drugs. Improved skin tolerance is manifested in delaying the onset of adverse skin reactions related to EGFR inhibitors and reducing their severity.

[0022] Example 1, A topical ointment of traditional Chinese medicine for clearing heat and improving skin tolerance to targeted therapy. The ointment is composed of active ingredients of traditional Chinese medicine and a medicinal matrix. The active ingredients of traditional Chinese medicine include the following raw materials by weight: 30g of Scutellaria baicalensis, 25g of Sophora flavescens, 20g of Dictamnus dasycarpus, 35g of Portulaca oleracea, 18g of Kochia scoparia, 18g of Cnidium monnieri, 20g of Sanguisorba officinalis, and 12g of Mentha haplocalyx. The oil phase matrix is ​​a mixture of petrolatum, lanolin, and stearic acid. In this example, 25g of petrolatum, 8g of lanolin, and 5g of stearic acid are used. The emulsifier is Tween-80, with a mass of 5g. The humectant is glycerin, with a mass of 4g. 20g of purified water (aqueous phase matrix) is used. The ointment is prepared by following these steps: S1. Extraction of active components from traditional Chinese medicine: Weigh the raw materials of active components from traditional Chinese medicine, pulverize them separately and pass them through a 50-mesh sieve. Weigh the corresponding powder of the filtered traditional Chinese medicine raw materials according to the above-mentioned usage mass, then add purified water. The mass of purified water added is 10 times the total mass of the traditional Chinese medicine raw materials. After soaking for 45 minutes, perform two heating and reflux extractions, each heating and reflux extraction time is 1.5 hours. Mix the extracts from the two heating and reflux extractions, then filter and concentrate under reduced pressure to obtain a clear extract. The pressure during the reduced pressure concentration is controlled at -0.07MPa and the concentration temperature is 60℃. Finally, the relative density of the clear extract at 60℃ is 1.1. The clear extract is then ready for use. S2. Prepare the oil phase matrix: Weigh out the petrolatum, lanolin and stearic acid according to the above mass, put them into a jacketed kettle, heat the oil phase matrix to 80°C, and keep the temperature at 80°C until the oil phase matrix is ​​completely melted. During this period, you can help stir to make the petrolatum, lanolin and stearic acid evenly mixed. Keep the melted oil phase matrix warm for later use. S3. Preparation of aqueous phase: Add the clear paste obtained in step S1 to the aqueous phase matrix (pure water), then add the humectant (glycerin), heat to 80°C, and mix the clear paste and aqueous phase matrix evenly to obtain a mixture. Keep it warm for later use. S4. Emulsification: Add the emulsifier (Tween-80) to the oil phase matrix prepared in step S2 and stir to make the emulsifier and oil phase matrix evenly mixed. Then slowly add the mixture to the oil phase matrix while maintaining the temperature at 80°C and stirring continuously. After the mixture is added, maintain the temperature at 80°C and continue stirring for 25 minutes at a stirring speed of 400 r / min. After stirring is complete, the primary emulsion is obtained. S5. Cooling and molding: After obtaining the colostrum, the colostrum is no longer kept warm. It is allowed to cool naturally to room temperature while being stirred. Then, stirring is continued for 12 minutes. Then, it is homogenized under a pressure of 20 MPa. Then, it is packaged into storage containers to obtain a heat-clearing traditional Chinese medicine external ointment.

[0023] Example 2, A topical ointment of traditional Chinese medicine for clearing heat and improving skin tolerance to targeted therapy. The ointment is composed of active ingredients of traditional Chinese medicine and a medicinal matrix. The active ingredients of traditional Chinese medicine include the following raw materials by weight: 25g of Scutellaria baicalensis, 20g of Sophora flavescens, 25g of Dictamnus dasycarpus, 40g of Portulaca oleracea, 15g of Kochia scoparia, 22g of Cnidium monnieri, 16g of Sanguisorba officinalis, and 15g of Mentha haplocalyx. The oil phase matrix is ​​a mixture of petrolatum, lanolin, and stearic acid. In this example, 22g of petrolatum, 10g of lanolin, and 6g of stearic acid are used. The emulsifier is Span-60, with a mass of 4g. The humectant is propylene glycol, with a mass of 5g. 21g of purified water (aqueous phase matrix) is used. The ointment is prepared by following these steps: S1. Extraction of active components from traditional Chinese medicine: Weigh the raw materials of active components from traditional Chinese medicine, pulverize them separately and pass them through a 50-mesh sieve. Weigh the corresponding powder of the filtered traditional Chinese medicine raw materials according to the above-mentioned usage mass, then add purified water. The mass of purified water added is 11 times the total mass of the traditional Chinese medicine raw materials. After soaking for 50 minutes, perform two heating and reflux extractions, each heating and reflux extraction time is 1.5 hours. Mix the extracts from the two heating and reflux extractions, then filter and concentrate under reduced pressure to obtain a clear extract. The pressure during the reduced pressure concentration is controlled at -0.06MPa and the concentration temperature is 60℃. Finally, the relative density of the clear extract at 60℃ is 1.1. The clear extract is then ready for use. S2. Prepare the oil phase matrix: Weigh out the petrolatum, lanolin and stearic acid according to the above mass, put them into a jacketed kettle, heat the oil phase matrix to 80°C, and keep the temperature at 80°C until the oil phase matrix is ​​completely melted. During this period, you can help stir to make the petrolatum, lanolin and stearic acid evenly mixed. Keep the melted oil phase matrix warm for later use. S3. Preparation of aqueous phase: Add the clear paste obtained in step S1 to the aqueous phase matrix (pure water), then add the humectant (propylene glycol), heat to 80°C, and mix the clear paste and aqueous phase matrix evenly to obtain a mixture. Keep it warm for later use. S4. Emulsification: Add the emulsifier (Span-60) to the oil phase matrix prepared in step S2 and stir to make the emulsifier and oil phase matrix evenly mixed. Then slowly add the mixture to the oil phase matrix while maintaining the temperature at 80°C and stirring continuously. After the mixture is added, maintain the temperature at 80°C and continue stirring for 28 minutes at a stirring speed of 450 r / min. After stirring is complete, the primary emulsion is obtained. S5. Cooling and molding: After obtaining the colostrum, the colostrum is no longer kept warm. It is allowed to cool naturally to room temperature while being stirred. Then, stirring is continued for 14 minutes. Then, it is homogenized under a pressure of 22 MPa. Then, it is packaged into storage containers to obtain a heat-clearing traditional Chinese medicine external ointment.

[0024] Clinical application trial of heat-clearing Chinese herbal external ointment; First, select test subjects. Test subjects must meet the following criteria; Selection criteria: Lung cancer patients with a clear pathological diagnosis; gene testing results indicating EGFR gene mutation; planned treatment with the EGFRI drug gefitinib; no serious impairment of heart, liver and kidney function; age range of 18-85 years; no intellectual or mental impairment, with normal language expression ability; understanding and accepting the treatment and signing an informed consent form; Exclusion criteria: Patients with other skin diseases; patients with allergies; patients with poor compliance; Dropout criteria: Patients who failed to take medication as required during the trial, or who took medication for less than 14 days; or patients who discontinued EGFRIs within 14 days.

[0025] During the trial, a randomization table was set up, and a third party coded the drugs according to the randomization table and sealed the data in a blind.

[0026] 120 patients who met the trial criteria were selected and divided into three groups of 40 each: Trial Group 1, Trial Group 2, and Control Group. Trial Group 1 was treated with the ointment prepared according to Example 1, Trial Group 2 was treated with the ointment prepared according to Example 2, and the Control Group received conventional reactive therapy.

[0027] Treatment plan: In Experiment 1, the heat-clearing traditional Chinese medicine ointment prepared in Example 1 of this invention was applied topically twice daily for 14 consecutive days as a preventative treatment when gefitinib treatment began in Kashgar; Experiment 2 used the heat-clearing traditional Chinese medicine ointment prepared in Example 2 of this invention in the same way. In the control group, patients received gefitinib treatment and received reactive treatment for any adverse skin reactions, specifically: Grade 1 rash: observation or topical application of 2% clindamycin and 1% hydrocortisone ointment twice daily; Grade 2a rash: topical application of 2% clindamycin and 1% hydrocortisone ointment twice daily until the rash disappears or decreases to Grade 1; Grade 2b rash: topical application of 2% clindamycin and 1% hydrocortisone ointment twice daily, along with oral minocycline 100 mg twice daily for 4 weeks until the rash disappears or decreases to Grade 1; Grade 3 rash: gefitinib was discontinued for 1 week, and the same treatment as for Grade 2b was applied.

[0028] Observation methods: Before treatment, a detailed physical examination and medical history were conducted. Patients' faces, chests, and backs were photographed (at fixed locations, with consistent lighting and angles) while protecting their privacy. During treatment, patients were assessed every 4 weeks for the first 3 months, and then observed every 2 months thereafter. Patient follow-up records were distributed, noting the time of rash onset and informing patients to seek medical attention if the rash became intolerable. During these visits, doctors photographed the rash areas (face, chest, back, etc.) and recorded accompanying symptoms. Survival was monitored every 12 weeks. Quality of life questionnaires were administered at baseline, at rash diagnosis, at each outpatient visit, and at the time of disease progression. Accompanying medications and adverse events during the study period were recorded.

[0029] Evaluation indicators: 1. Onset time and duration of EGFRI-related rashes; 2. Grading of EGFRIs-related rashes at their most severe stage (according to NCI-CTCAE 4.0 criteria). 3. Grading of other symptoms of EGFRIs-related adverse skin reactions (dry skin, itching, pigmentation, abnormal hair growth, paronychia and nail cracking, hypersensitivity reactions); 4. Dynamic changes in interleukin-6 (IL-6) levels before and after treatment; 5. Gefitinib dosage reduction or discontinuation status; 6. Patient's quality of life score (KPS score); 7. Median survival time (PFS) of patients; 8. Blood routine test, liver function test, and kidney function test results; 9. Evaluation of itching severity: The Visual Analog Scale (VAS) method was used to measure the patient's pruritus score (IS). IS was measured periodically to compare changes in pruritus severity during treatment.

[0030] Data Analysis: SPSS 20.0 statistical software was used for statistical analysis. All statistical tests were two-tailed, and a p-value < 0.05 was considered statistically significant. Basic demographic data and underlying diseases of the enrolled cases were described; the dosage and duration of EGFRIs were described; the occurrence of EGFRI-related rashes (onset time, duration, severity, etc.) were described; and the quality of life scores, gefitinib dosage reduction and discontinuation, and median survival time were described for the three groups. For comparisons between groups, for continuous variables, one-way ANOVA or rank-sum test was used depending on the homogeneity of variance test results; pairwise comparisons were performed using the LSD or SNK method; χ² test was used for categorical data, and Ridit analysis was used for ordinal data.

[0031] The results of the trial conducted on the subjects based on the above standards and treatment protocols are as follows: The table below shows the time of rash appearance and severity in the three groups of patients with ringworm: Both the F-value and the χ² value are statistical test statistics. Their core function is to determine whether the differences between groups are accidental. Both the F-value and the χ² value are quantitative indicators of the significance of the differences. The larger the value, the more obvious the differences between groups. The F-value corresponds to continuous variables (such as the time of rash appearance) and is used in ANOVA to reflect the ratio of variation between groups to variation within groups. A larger F-value indicates a significant difference between groups and a lower probability that the difference is accidental. The P-value (usually P < 0.05) is used to determine whether the difference is statistically significant. As shown in the table above, the rash appearance times of the three groups are continuous values: 28.6 days, 27.8 days, and 14.3 days. The F-value calculated using ANOVA is 89.762, P < 0.001, indicating that the difference in rash appearance time among the three groups is real and not accidental. The χ² value corresponds to categorical data (such as rash grading and incidence of adverse skin reactions) and is used in the chi-square test to reflect the deviation between the actual observed frequency and the theoretical expected frequency. The larger the χ² value, the greater the deviation between the actual results and the theoretical assumption of no difference between groups. Combined with the P value (usually P < 0.05 as the standard), we judge whether the difference is statistically significant. As can be seen from the data in the table above, for the overall test of rash grading, the total χ² value is 38.521, P < 0.001, indicating that there is a significant difference in the distribution of rash severity (the proportion of people with grades 1-4) among the three groups of patients. The data in the table above show that the onset of EGFRIs-related rashes in patients in experimental groups 1 and 2 was significantly later than that in the control group, and the severity of the rashes was significantly lower in the experimental groups. Most patients in experimental groups 1 and 2 had a severity grade of 1 at the time of the most severe rashes, while most patients in the control group had a severity grade of 2 or 3, and some had a severity grade of 4. This proves that the traditional Chinese medicine ointment proposed in this technical solution does have preventive and therapeutic effects.

[0032] The data on other adverse skin reactions in the three groups of patients are shown in the table below: The data in the table above show that the incidence of adverse skin reactions such as dryness, itching, and peeling was significantly lower in groups 1 and 2 than in the control group. The following table shows the gefitinib dosage reduction / discontinuation rate and KPS score data for the three groups of patients: The data in the table above show that the gefitinib reduction and discontinuation rates in experimental groups 1 and 2 were significantly lower than those in the control group, and the KPS scores for quality of life were significantly higher in experimental groups than in the control group, further demonstrating that the ointment proposed in this technical solution has a good therapeutic effect. According to the tests and observations, the blood routine and liver and kidney function indicators of the three groups of patients were within the normal range before and after treatment, with no significant differences. No obvious drug-related adverse reactions occurred in experimental group 1 and experimental group 2. Three patients in the control group experienced adverse reactions of Western medicine such as skin atrophy and telangiectasia.

[0033] According to clinical trials, the heat-clearing traditional Chinese medicine external ointment prepared according to the technical solution proposed in this invention can effectively prevent the occurrence of skin adverse reactions related to EGFRIs targeted drugs, significantly improve the patient's skin tolerance to targeted therapy, ensure the smooth progress of targeted therapy, and has good safety.

[0034] The above descriptions are merely embodiments of the present invention, and common knowledge such as specific technical solutions and / or characteristics are not described in detail here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the technical solutions of the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the implementation of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A topical ointment made from traditional Chinese medicine for clearing heat and improving skin tolerance to targeted therapy, characterized in that, The ointment is composed of active traditional Chinese medicine components and a medicinal matrix. The active traditional Chinese medicine components, by weight, include the following raw materials: 20-40 parts of Scutellaria baicalensis, 15-35 parts of Sophora flavescens, 15-30 parts of Dictamnus dasycarpus, 25-45 parts of Portulaca oleracea, 10-25 parts of Kochia scoparia, 10-25 parts of Cnidium monnieri, 12-28 parts of Sanguisorba officinalis, and 8-18 parts of Mentha haplocalyx. The medicinal matrix includes an oil phase matrix, an aqueous phase matrix, an emulsifier, and a humectant. The active traditional Chinese medicine components account for 20%-40% of the total mass of the ointment, the oil phase matrix accounts for 25%-45%, the aqueous phase matrix accounts for 15%-30%, the emulsifier accounts for 3%-8%, and the humectant accounts for 2%-6%.

2. The topical ointment of traditional Chinese medicine for clearing heat and improving skin tolerance to targeted therapy as described in claim 1, characterized in that, The active components of the traditional Chinese medicine are as follows by weight: 30 parts of Scutellaria baicalensis, 25 parts of Sophora flavescens, 20 parts of Dictamnus dasycarpus, 35 parts of Portulaca oleracea, 18 parts of Kochia scoparia, 18 parts of Cnidium monnieri, 20 parts of Sanguisorba officinalis, and 12 parts of Mentha haplocalyx.

3. The topical ointment of traditional Chinese medicine for clearing heat and improving skin tolerance to targeted therapy as described in claim 1, characterized in that, The oil phase matrix is ​​selected from one or more of petrolatum, lanolin, and stearic acid, and the aqueous phase matrix is ​​purified water.

4. The topical ointment of traditional Chinese medicine for clearing heat and improving skin tolerance to targeted therapy as described in claim 1, characterized in that, The emulsifier is selected from one or both of Tween-80 and Span-60.

5. The topical ointment of traditional Chinese medicine for clearing heat and improving skin tolerance to targeted therapy as described in claim 1, characterized in that, The moisturizer is selected from one or both of glycerin and propylene glycol.

6. The topical ointment of traditional Chinese medicine for clearing heat and improving skin tolerance to targeted therapy as described in claim 1, characterized in that, The ointment is prepared according to the following steps: S1. Extraction of active components from traditional Chinese medicine: Weigh the raw materials of active components from traditional Chinese medicine, pulverize the raw materials separately and pass them through a 40-60 mesh sieve, weigh the corresponding raw materials according to the set weight parts, and then add purified water. The mass of the purified water added is 8-12 times the total mass of the raw materials. After soaking for 30-60 minutes, perform two heating and reflux extractions. The heating and reflux extraction time is 1.5-2 hours each time. Mix the extracts from the two heating and reflux extractions, and then filter and concentrate under reduced pressure to obtain a clear extract. The relative density of the clear extract at 60℃ is 1.1-1.

2. S2. Prepare the oil phase matrix: Weigh the oil phase matrix according to the mass percentage, heat the oil phase matrix to 75-85℃, and maintain the temperature of 75-85℃ until the oil phase matrix is ​​completely melted. Keep the melted oil phase matrix warm for later use. S3. Preparation of aqueous phase: Add the clear paste obtained in step S1 to the aqueous phase matrix, then add a humectant, heat to 75-85℃, so that the clear paste and the aqueous phase matrix are mixed evenly to obtain a mixture, and keep it warm for later use. S4. Emulsification: Add the emulsifier to the oil phase matrix or the mixture prepared in step S3, stir to make the emulsifier and the oil phase matrix or the mixture evenly mixed, and then slowly add the mixture to the oil phase matrix. During the addition process, keep the temperature at 75-85℃ and stir while adding. After the mixture is added, keep the temperature at 75-85℃ and continue stirring for 20-30 minutes to obtain the primary emulsion. S5. Cooling and shaping: After obtaining the colostrum, the colostrum is no longer kept warm. It is allowed to cool naturally to room temperature while being stirred. Then, stirring is continued for 10-15 minutes. After homogenization, it is packaged to obtain a heat-clearing Chinese herbal external ointment.

7. The topical ointment of traditional Chinese medicine for clearing heat and improving skin tolerance to targeted therapy as described in claim 6, characterized in that, In step S1, the pressure during vacuum concentration is -0.06 to -0.08 MPa, and the concentration temperature is 55 to 65°C.

8. The topical ointment of traditional Chinese medicine for clearing heat and improving skin tolerance to targeted therapy as described in claim 1, characterized in that, The stirring speed in step S4 is 300-500 r / min.

9. The topical ointment of traditional Chinese medicine for clearing heat and improving skin tolerance to targeted therapy as described in claim 1, characterized in that, The ointment is used to improve skin tolerance to targeted therapy, which is epidermal growth factor receptor inhibitor therapy.

10. A topical ointment of traditional Chinese medicine for clearing heat and improving skin tolerance to targeted therapy as described in claim 9, characterized in that, The improved skin tolerance manifests as a delay in the onset of adverse skin reactions related to epidermal growth factor receptor inhibitors and a reduction in their severity.

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