Traditional Chinese medicine ointment for treating hand-foot syndrome and preparation method thereof

Abstract

The present invention provides a traditional Chinese medicine ointment for treating hand-foot syndrome and a preparation method thereof. The ointment is made from the following ingredients: sesame oil, lithospermum erythrorhizon, angelica dahurica, bletilla striata, white mulberry, angelica sinensis, rhubarb, knotweed, honeysuckle, siler, raw rehmannia root, pearl powder, dragon's blood, borneol, radix trichosanthis, frankincense, myrrh, rosin, lard, beeswax, and quicklime. This ointment enhances the original Ziyun ointment by adding bletilla striata, rhubarb, knotweed, honeysuckle, pearl powder, dragon's blood, borneol, radix trichosanthis, frankincense, myrrh, and other ingredients, thereby enhancing its yin-nourishing, blood-cooling, and detoxifying effects. The ointment exhibits excellent effects in alleviating pain, removing rotten flesh, stopping bleeding, promoting tissue regeneration, and providing antibacterial and anti-inflammatory benefits, as well as promoting wound healing. The developed Yufu Jiedu ointment has demonstrated excellent initial efficacy in the clinical treatment of capecitabine-induced hand-foot syndrome, receiving unanimous praise from patients and addressing the shortcomings of the existing technology.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicine ointments, and in particular to a traditional Chinese medicine ointment for treating hand-foot syndrome and a preparation method thereof. Background Art

[0002] Hand-foot syndrome (HFS) is a skin toxicity induced by some anti-cancer drugs, including capecitabine, and is the most common dose-limiting toxicity. The main clinical manifestations include dryness and scaling of the hands and / or feet. In severe cases, ulcers, blisters, onycholysis, bleeding, numbness, hypoesthesia, or paresthesias in the hands and feet, such as tingling, burning, erythema, swelling, and hyperpigmentation, can occur. This reduces patients' quality of life, and severe cases may require prolonged chemotherapy, dose reduction, or even discontinuation of the drug.

[0003] Dose-limiting toxicities severely impact patients' treatment and quality of life, limiting the clinical application of capecitabine. Currently, there are no particularly effective treatments for capecitabine-related HFS, both domestically and internationally. Prevention, health education, and non-drug protection are the primary approaches. Topical urea ointment and oral vitamin B6 are currently standard treatments. For patients with significant pain and inflammation, celecoxib and corticosteroids are used to alleviate inflammation and pain. However, these measures have limited efficacy in preventing and treating HFS. Furthermore, COX-2 inhibitors and corticosteroids are associated with cardiovascular and gastrointestinal side effects, making long-term use unsuitable. While current medications and protective measures have limited efficacy, Traditional Chinese Medicine (TCM) has demonstrated promising results in the prevention and treatment of capecitabine-related HFS.

[0004] CN202110508472.8 discloses a traditional Chinese medicine composition for preventing and treating hand-foot syndrome and its preparation method. The traditional Chinese medicine composition is composed of the following components, by weight: 10-50 parts of raw astragalus, 15-40 parts of lithospermum, 8-25 parts of raw rhubarb, 20-38 parts of dandelion, 22-42 parts of radix schizonepetae, 15-35 parts of dense liquorice, 10-35 parts of angelica, 12-25 parts of phellodendron, 13-23 parts of white moss, 28-36 parts of angelica dahurica, 14-26 parts of kochia scoparia, and 20-33 parts of stir-fried white peony root. CN202210096750.8 discloses a traditional Chinese medicine compound ointment for external use for treating hand-foot syndrome and its preparation method. The ointment is composed of the following ingredients in parts by weight: 1-15 parts of frankincense, 1-15 parts of myrrh, 1-30 parts of viola yedoensis, 1-30 parts of bletilla striata, 1-30 parts of coptis chinensis, 1-20 parts of polygonum cuspidatum, 1-15 parts of lithospermum officinale, 1-40 parts of chrysanthemum notoginseng stem and leaf extract, 1-15 parts of notoginseng total saponins, 1-10 parts of baicalein, 1-10 parts of baicalin, 1-15 parts of emodin, 1-70 parts of vaseline, 1-15 parts of beta-sitosterol, 1-5 parts of zinc oxide powder, 1-5 parts of talc, 1-2 parts of lanolin, 1-2 parts of sodium stearate, and 1-20 parts of ethanol. CN202210315505.1 discloses a traditional Chinese medicine composition for treating hand-foot syndrome after targeted drug treatment, which is mainly prepared from the following components in parts by weight: 20-50 parts of Sophora flavescens, 20-50 parts of Taraxacum mongolicum, 20-50 parts of Chrysanthemum indica, 20-50 parts of Viola yedoensis, 20-50 parts of Smilax glabra, 30-60 parts of Astragalus, 10-35 parts of Kochia scoparia, 10-45 parts of Carthamus tinctorius, 15-45 parts of Dictamni, 5-15 parts of Ephedra, 5-25 parts of Angelica sinensis, 5-25 parts of Chuanxiong, 10-30 parts of Rehmannia glutinosa, 5-15 parts of Cassia twig, 10-30 parts of White Peony Root, 5-15 parts of Sinapis alba, 5-20 parts of Arisaema consanguineum, 5-20 parts of Raw Pinellia, and 10-40 parts of Raw Licorice. The above-mentioned Chinese medicine composition has a good effect of alleviating hand-foot syndrome, but cannot achieve the effects of removing dead tissue, stopping bleeding, promoting tissue regeneration, and promoting wound healing, and has shortcomings in clinical application. Summary of the Invention

[0005] Through extensive research into ancient and modern literature and accumulated clinical experience, the inventors of this application observed that hand-foot syndrome is closely related to dampness and toxic heat, qi and yin deficiency, and meridian stasis, often with complex pathogenesis, consistent with the pathological mechanism of yin deficiency, dry skin, and toxic stagnation in the meridians in Traditional Chinese Medicine (TCM). In response to the clinical characteristics of capecitabine-induced hand-foot syndrome, the inventors developed the "Yufu Jiedu Recipe," which nourishes the skin, detoxifies, and promotes blood circulation, for the treatment of capecitabine-induced hand-foot syndrome. This ointment, derived from the famous Ming Dynasty TCM surgical formula Ziyun Ointment, documented in the "Yue Ke Mi Ling," is composed of angelica sinensis, lithospermum officinale, sesame oil, yellow wax, and lard. It has excellent effects in clearing heat and toxicity, removing dead tissue, and promoting tissue regeneration. Clinical experience shows that Ziyun Ointment is effective for palmar keratosis, burns, bedsores, dry tinea pedis, plantar pustulosis, ulcers, erosions, and various skin diseases. Modern research also shows that Ziyun ointment has a wide range of pharmacological effects, including moisturizing dryness, relieving pain, reducing inflammation and fever, stopping bleeding and sterilizing, strengthening the body, promoting granulation formation, and eliminating the foul odor of wounds. The Yufu Jiedu ointment developed by the inventors of this application builds on the original Ziyun ointment by adding ingredients such as white mulberry, rhubarb, knotweed, honeysuckle, pearl powder, dragon's blood, borneol, radix trichosanthis, frankincense, and myrrh. This enhances the effects of nourishing yin, cooling blood, and detoxifying. It has excellent effects in relieving pain, removing rotten flesh, stopping bleeding, promoting tissue regeneration, and promoting antibacterial and anti-inflammatory effects, as well as promoting wound healing. This Yufu Jiedu ointment has demonstrated excellent initial efficacy in the clinical treatment of capecitabine-induced hand-foot syndrome, receiving unanimous praise from patients and addressing the shortcomings of existing technologies.

[0006] The present invention adopts the following technical solutions:

[0007] On the one hand, the present invention provides a traditional Chinese medicine ointment (also known as: Yufu Jiedu ointment) for treating hand-foot syndrome, which is made from the following components: sesame oil, lithospermum erythrorhizon, angelica dahurica, bletilla striata, white peony root, angelica sinensis, rhubarb, knotweed, honeysuckle, siler, raw rehmannia, pearl powder, dragon's blood, borneol, radix trichosanthis, frankincense, myrrh, rosin, lard, beeswax, and quicklime.

[0008] Furthermore, the Chinese medicinal ointment is prepared from the following components by weight: 1000-2000 parts of sesame oil, 50-100 parts of lithospermum erythrorhizon, 50-100 parts of angelica dahurica, 50-100 parts of bletilla striata, 50-100 parts of white ampelopsis, 50-100 parts of angelica sinensis, 50-100 parts of rhubarb, 50-100 parts of knotweed, 10-50 parts of honeysuckle, 50-100 parts of siler, 50-100 parts of rehmannia root, 10-50 parts of pearl powder, 10-50 parts of dragon's blood, 10-50 parts of borneol, 50-100 parts of trichosanthes, 10-50 parts of frankincense, 10-50 parts of myrrh, 10-50 parts of rosin, 10-50 parts of quicklime, 500-1000 parts of lard and 150-360 parts of beeswax.

[0009] Furthermore, the Chinese medicinal ointment is made of the following components in parts by weight: 2000 parts of sesame oil, 100 parts of lithospermum erythrorhizon, 60 parts of angelica dahurica, 50 parts of bletilla striata, 60 parts of white ampelopsis, 100 parts of angelica sinensis, 50 parts of rhubarb, 50 parts of knotweed, 50 parts of trichosanthes, 50 parts of siler, 60 parts of rehmannia glutinosa, 10 parts of honeysuckle, 10 parts of pearl powder, 20 parts of dragon's blood, 10 parts of borneol, 15 parts of frankincense, 15 parts of myrrh, 15 parts of rosin, 50 parts of quicklime, 1000 parts of lard and 300-360 parts of beeswax.

[0010] On the other hand, the present invention provides a method for preparing a traditional Chinese medicine ointment for treating hand-foot syndrome, the specific steps of which are as follows:

[0011] Step 1: Soak comfrey in 1 / 2 sesame oil for one week, stirring once a day until the sesame oil turns dark purple-red; heat the sesame oil and fry the comfrey until crispy;

[0012] Step 2: Take 1 / 2 of sesame oil, add angelica root, white striata root, white peony root, angelica root, rhubarb, knotweed, radix trichosanthis, siler, radix rehmanniae, and honeysuckle, and soak for a week; heat the sesame oil and fry each component until brown;

[0013] Step 3: Remove and discard the fried lithospermum erythrorhizon, angelica dahurica, bletilla striata, white peony root, angelica sinensis, rhubarb, knotweed, radix trichosanthis, saposhnikovia divaricata, radix rehmanniae, and honeysuckle; add beeswax and lard to the two groups of heated sesame oil, stir and melt, and let stand until warm;

[0014] Step 4: Add ground frankincense, myrrh, dragon's blood, borneol, rosin, pearl powder and ethyl hydroxybenzoate solution, stir to mix, add quicklime water and cool to obtain.

[0015] Furthermore, in step 3, the temperature of the sesame oil placed to be warmed is 45-55°C.

[0016] Furthermore, the ethylparaben ethanol solution refers to ethylparaben completely dissolved in ethanol. Furthermore, the ethanol is ethanol with a concentration of 60% to 99.9%. Furthermore, the ethanol is ethanol with a concentration of 75%.

[0017] Furthermore, in step 4, the weight ratio of the sesame oil obtained in step 3 to the ethyl paraben solution is 100:0.25.

[0018] Furthermore, the quicklime water refers to a clear liquid obtained by dissolving quicklime in water, wherein the weight ratio of quicklime to water is 1:2.

[0019] Furthermore, in step 4, the particle size of the frankincense, myrrh, dragon's blood, borneol, rosin, and pearl powder after grinding is 200 mesh.

[0020] On the other hand, the present invention provides a use of the traditional Chinese medicine ointment of the present invention in preparing a medicine for treating hand-foot syndrome.

[0021] Beneficial effects:

[0022] Yufu Jiedu Paste is a Ming Dynasty TCM surgical formula based on the famous Ziyun Paste, enhanced with herbs such as white peony root, dragon's blood, and borneol. It nourishes yin and moisturizes the skin, detoxifies and activates blood circulation, relieves acute pain, and removes dead tissue and promotes tissue regeneration. This paste features Lithospermum officinale as the main ingredient, cooling blood and activating blood circulation, detoxifying and clearing rashes. Other ingredients include angelica sinensis, sesame oil, white peony root, white peony root, white angelica root, bletilla striata, frankincense, and myrrh, which tonify blood and activate blood circulation, heal sores and stop bleeding, and clear away heat and detoxify. Additional ingredients include dragon's blood, borneol, rhubarb, knotweed, honeysuckle, and pearl powder, which nourish yin and cool blood, remove dead tissue and promote tissue regeneration, reduce swelling and relieve pain. Finally, beeswax and lard nourish yin and moisturize the skin. Modern research has also shown that the various herbs in this formula have antibacterial and anti-inflammatory effects, antioxidant properties, reduced swelling and pain, promoted wound healing, and improved microcirculation.

[0023] This Chinese medicine ointment is a dark red, slightly viscous topical ointment. Apply evenly to the affected area and gently massage until absorbed. Apply 2-3 times daily for 1-2 hours. Because it contains ingredients such as sesame oil and has a slightly oily texture, use plastic gloves or wrap your hands and feet. If you forget to apply the ointment, reapply it promptly.

[0024] This ointment is derived from the classic Ming Dynasty TCM surgical formula, Ziyun Ointment. It is effective for palmar keratosis, burns, bedsores, dry tinea pedis, plantar pustulosis, ulcers, erosions, and various skin diseases. Through clinical observation and research, this ointment is modified with herbs such as Atractylodes macrocephala, Draconis dasyphylla, and Borneol. This, combined with the clinical characteristics of hand-foot syndrome caused by the chemotherapy drug capecitabine, is treated through TCM dialectical analysis. While leveraging the benefits of this ancient formula, this ointment incorporates modern clinical practice with the addition of herbs. This represents a new use of an ancient formula, resulting in a formula that nourishes yin and cools blood, clears heat and detoxifies, and removes necrosis and promotes tissue regeneration, representing a significant technological innovation.

[0025] The clinical treatment and application of this traditional Chinese medicine ointment demonstrate superior efficacy compared to urea ointment. Yufu Jiedu Cream has demonstrated promising results in clinical treatment, alleviating symptoms such as pain and dryness in patients' hands and feet, promoting wound healing, enhancing capecitabine tolerance, improving patient quality of life, and enhancing treatment compliance, thereby maximizing the therapeutic potential of capecitabine in tumors. This ointment also lays the foundation for the development of new traditional Chinese medicines for the treatment of capecitabine-induced hand-foot syndrome, demonstrating significant clinical significance and potential for generating positive socioeconomic benefits. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 Comparison chart of patient Cheng Moumou's treatment results before and after treatment

[0027] Figure 2Comparison chart of patient Wang's treatment results before and after

[0028] Figure 3 The Chinese medicinal ointment prepared in Example 1.

[0029] Figure 4 The packaging style of the Chinese medicinal ointment prepared in Example 1. DETAILED DESCRIPTION

[0030] The present invention will be further described below with reference to specific examples. These examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention.

[0031] Example 1

[0032] A traditional Chinese medicine ointment for treating hand-foot syndrome is prepared from the following components by weight: 2000 parts of sesame oil, 100 parts of lithospermum erythrorhizon, 60 parts of angelica dahurica, 50 parts of bletilla striata, 60 parts of white ampelopsis, 100 parts of angelica sinensis, 50 parts of rhubarb, 50 parts of knotweed, 50 parts of trichosanthes root, 50 parts of siler, 60 parts of rehmannia root, 10 parts of honeysuckle, 10 parts of pearl powder, 20 parts of dragon's blood, 10 parts of borneol, 15 parts of frankincense, 15 parts of myrrh, 15 parts of rosin, 50 parts of quicklime, 1000 parts of lard and 300 parts of beeswax.

[0033] The preparation method comprises the following specific steps:

[0034] Step 1: Soak comfrey in 1 / 2 sesame oil for one week, stirring once a day until the sesame oil turns dark purple-red; heat the sesame oil and fry the comfrey until crispy;

[0035] Step 2: Take 1 / 2 of sesame oil, add angelica root, white striata root, white peony root, angelica root, rhubarb, knotweed, radix trichosanthis, siler, radix rehmanniae, and honeysuckle, and soak for a week; heat the sesame oil and fry each component until brown;

[0036] Step 3: Remove the fried lithospermum erythrorhizon, angelica dahurica, bletilla striata, white peony root, angelica sinensis, rhubarb, knotweed, radix trichosanthis, saposhnikovia divaricata, radix rehmanniae, and honeysuckle respectively; add beeswax and lard to the two groups of heated sesame oil respectively, stir to melt, and let stand until the temperature reaches about 50°C;

[0037] Step 4: Add ground 200-mesh frankincense, myrrh, dragon's blood, borneol, rosin, pearl powder and ethyl hydroxybenzoate solution (the weight ratio of sesame oil obtained in step 3 to ethyl hydroxybenzoate solution is 100:0.25), stir to mix, and then add quicklime water to obtain the product.

[0038] The quicklime water refers to the clear liquid obtained by dissolving quicklime in water, wherein the weight ratio of quicklime to water is 1:2.

[0039] Example 2

[0040] A traditional Chinese medicine ointment for treating hand-foot syndrome is prepared from the following components: 1000 parts of sesame oil, 50 parts of lithospermum erythrorhizon, 50-100 parts of angelica dahurica, 50 parts of bletilla striata, 100 parts of white ampelopsis, 50 parts of angelica sinensis, 100 parts of rhubarb, 100 parts of knotweed, 50 parts of honeysuckle, 100 parts of siler, 50 parts of raw rehmannia, 50 parts of pearl powder, 10 parts of dragon's blood, 50 parts of borneol, 100 parts of trichosanthes, 10 parts of frankincense, 10 parts of myrrh, 10 parts of rosin, 10 parts of quicklime, 500 parts of lard and 150 parts of beeswax.

[0041] The preparation process is the same as that in Example 1.

[0042] Example 3

[0043] A traditional Chinese medicine ointment for treating hand-foot syndrome is prepared from the following components: 1500 parts of sesame oil, 60 parts of lithospermum erythrorhizon, 100 parts of angelica dahurica, 60 parts of bletilla striata, 100 parts of white ampelopsis, 60 parts of angelica sinensis, 60 parts of rhubarb, 60 parts of knotweed, 30 parts of honeysuckle, 70 parts of siler, 100 parts of rehmannia root, 30 parts of pearl powder, 50 parts of dragon's blood, 30 parts of borneol, 70 parts of trichosanthes, 50 parts of frankincense, 50 parts of myrrh, 50 parts of rosin, 20 parts of quicklime, 800 parts of lard and 360 parts of beeswax.

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

[0045] Clinical data on the treatment of chemotherapy-induced hand-foot syndrome using the traditional Chinese medicine ointment prepared in Example 1 of the present invention

[0046] 1. Clinical data:

[0047] 1.1 Research subjects

[0048] Sixty patients diagnosed with colorectal cancer who developed hand-foot syndrome and received capecitabine-containing chemotherapy from the outpatient or inpatient departments of the Department of Integrated Traditional Chinese and Western Medicine and the Department of Gastroenterology at Hunan Cancer Hospital from January 1, 2021 to May 30, 2022 were selected. After the hand-foot syndrome was graded, the patients were divided into a Yufu cream group and a control group using a random number table method, with 30 cases in each group. Among them, there were 15 males and 15 females in the Yufu cream group with an average age of (52.37±10.04) years; 21 of them had colon cancer and 9 had rectal cancer. There were 15 males and 15 females in the control group with an average age of (51.77±11.72) years; 18 of them had colon cancer and 12 had rectal cancer. There was no statistically significant difference in the general information of the two groups of patients (P>0.05), and they were comparable.

[0049] 1.2 Medical Record Standards

[0050] 1.2.1 Diagnostic criteria:

[0051] 1) Western medicine diagnostic criteria:

[0052] ① Diagnostic criteria for colorectal cancer: According to the relevant standards of the "Chinese Common Malignant Tumor Diagnosis and Treatment Standards" compiled by the Medical Administration Department of the Ministry of Health of the People's Republic of China, colorectal cancer is confirmed by pathology.

[0053] ②Hand-foot syndrome grading standard: Chemotherapy-related hand-foot syndrome is graded using the chemotherapy-related standards developed by the National Cancer Institute (NCI) of the United States, which are divided into grades I-III. Grade I clinical manifestations include pigmentation and redness of the hands and feet, without pain, and no functional impact on daily life; Grade II clinical manifestations include erythema, swelling, and pain on the skin of the hands and feet, which affects daily life; Grade III clinical manifestations include desquamation, blisters, and ulcers on the skin of the hands and feet, accompanied by severe pain, and inability to lead a normal life.

[0054] 2) Traditional Chinese Medicine Syndrome Diagnostic Criteria: "Yin Deficiency, Dry Skin, and Toxic Stagnation in the Meridians" is based on Section 11, "Drug Toxicity," of the fourth edition of Traditional Chinese Medicine Surgery (New Century Edition): Primary Symptoms: Localized pain in the hands and feet, rough, dry skin, thickened stratum corneum, erythema, purpura, erosions, and exudate, numbness, and paresthesia in the hands and feet; Secondary Symptoms: Dry mouth, dry stool, and scanty or yellowish-red urine; Tongue: Red, with scant fluid and minimal coating; Pulse: Thready, rapid, or wiry. Symptoms meeting these criteria include two primary symptoms and one secondary symptom.

[0055] 1.2.2 Inclusion criteria

[0056] 1. Pathologically confirmed colorectal cancer; 2. Expected survival of at least 3 months; 3. Meet NCI diagnostic criteria for hand-foot syndrome; 4. Use of a chemotherapy regimen containing capecitabine; 5. Age 18-73 years; 6. Clear consciousness and good patient compliance; 7. Meet Traditional Chinese Medicine (TCM) diagnostic criteria; 8. Subjects fully understand the study's medication regimen and the possibility of randomization to different groups, voluntarily participate in this study, and sign the informed consent form.

[0057] 1.2.3 Exclusion criteria

[0058] 1) Severe primary neurological diseases, such as Alzheimer's disease, epilepsy, Parkinson's disease, etc. 2) Uncontrolled infections and metabolic diseases. 3) Serious heart, lung, liver, kidney, or other major diseases. 5) Preexisting neurological diseases, such as numbness or hypoesthesia in the hands and feet. 6) Other skin diseases of the hands and feet. 7) Allergies to experimental drug ingredients. 8) Patients whose efficacy cannot be evaluated.

[0059] 1.2.4 Elimination criteria

[0060] 1) Those who did not meet the inclusion criteria and were mistakenly included; 2) Those who dropped out or were lost to follow-up during the medication intervention period; 3) Those who had poor compliance and were unable to cooperate with the treatment; 4) Patients who voluntarily withdrew from treatment.

[0061] 1.2.5 Exit (fall-off) criteria

[0062] 1) Patients who develop severe toxicity and side effects during the observation period and need to withdraw from the study; 2) Patients who need to stop treatment and / or switch to other treatments due to their condition; 3) Patients with poor compliance, which affects the observation of efficacy; 4) Patients who request to withdraw from the study.

[0063] 1.3 Treatment methods:

[0064] 1.3.1 Drugs:

[0065] The Chinese medicinal ointment prepared in Example 1 (also known as Yufu Jiedu ointment) is prepared by a preparation room that meets GMP standards.

[0066] 1.3.2 Dosage method:

[0067] The control group was treated with symptomatic treatment of urea ointment topically, while the Yufu ointment group was treated with Yufu detoxification ointment applied topically to the wound surface. It was used three times a day (once in the morning, noon and evening). If the patient was washed within half an hour (bathing or washing hands), the ointment could be applied a second time. The ointment was used continuously for 21 days.

[0068] 1.4 Observation indicators

[0069] 1.4.1 Hand-foot syndrome severity grading criteria: The hand-foot syndrome grade of patients before and after treatment was recorded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. Cured: Complete symptom relief or reduction to grade 0; Effective: Hand-foot syndrome grade reduced by 1 or more grades compared to the previous treatment, but not to grade 0; Ineffective: No change or even worsening of hand-foot syndrome grade. Total effective rate = (cured + effective) / total number of cases × 100%.

[0070] 1.4.2 Pain VAS Score: The visual analogue scale (VAS) was used to assess the patient's pain intensity, with 0 representing no pain and 10 representing unbearable pain. Higher scores indicate greater pain intensity. VAS scores were recorded before and after treatment.

[0071] 1.4.3 Quality of life: The Chinese version of the Hand-Foot Skin Reaction Quality of Life Scale (HF-QoL) was used, and the scores before and after treatment were recorded.

[0072] 1.4.4 Traditional Chinese Medicine (TCM) Syndrome Scores: Based on the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines" (2002 edition), four primary symptoms were selected: dry skin, numbness, rash, and pain; and secondary symptoms such as dry mouth, bowel movements, tongue condition, and pulse condition were selected. Both primary and secondary symptoms were categorized into four levels: none, mild, moderate, and severe. Primary symptom scores were assigned 0, 2, 4, and 6 points, respectively, and secondary symptom scores were assigned 0, 1, 2, and 3 points, respectively, depending on the severity. TCM syndrome scores were recorded before and after treatment.

[0073] 1.4.5 Anxiety Status: The Self-Rating Anxiety Scale (SAS), developed by Chinese-American professor Zung in 1971, was used. It consists of 20 items, 15 of which are positively scored and 5 of which are negatively scored. Each item is scored on a four-point scale. Scores are compared with norms or control groups for analysis. The SAS is primarily used to assess the patient's subjective experience of anxiety. The primary statistical indicator is the total score. The scores for each of the 20 items are summed to obtain a crude score. The crude score is then multiplied by 1.25, rounded to the nearest integer, to obtain the standard score. The patient's self-rating anxiety scale scores were recorded before and after treatment.

[0074] 1.5 Statistical methods: SPSS 25.0 statistical software was used. Statistical data were expressed as % or greater. The independent sample t-test was used to compare measurement data between groups that conformed to a normal distribution, and the nonparametric Mann-Whitney U test was used to compare measurement data that did not conform to a normal distribution. The nonparametric Willcoxon rank-sum test was used to compare paired measurement data that did not conform to a normal distribution. Enumeration data were expressed as frequencies and constituent ratios, and the chi-square test was used for comparison between groups. Rank data were compared using the rank-sum test. P < 0.05 was considered statistically significant.

[0075] 2. Research Results

[0076] 2.1 Comparison of HFS grades before and after treatment between the two groups: The two groups were comparable before treatment (P>0.05);

[0077] Table 1 Changes in HFS grades before and after treatment in the two groups (%)

[0078]

[0079]

[0080] Table 1 shows that after treatment, 17 (56.7%) grade 0 cases were reported in the Yufu Cream group, while 11 (36.7%) grade 0 cases were reported in the control group. This suggests that the Yufu Cream group was superior to the control group in reducing HFS grade. After treatment, two grade 3 cases in the Yufu Cream group had healed hand and foot wounds, while two grade 3 cases in the control group showed no significant improvement. This suggests that Yufu Detoxification Cream has potential advantages in promoting wound healing and warrants further study.

[0081] 2.2 Comparison of efficacy between the two groups before and after treatment: The efficacy was determined based on the hand-foot syndrome grading before and after treatment.

[0082] Table 2 The efficacy of hand-foot syndrome in the two groups after treatment (%)

[0083]

[0084] Note: Total effective rate = (number of cured cases + number of effective cases) / total number of cases × 100%. Compared with the control group, *P < 0.05

[0085] Conclusion: As shown in Table 2, there were 22 effective cases in the Yufu ointment group (17 cured and 5 effective), 8 ineffective cases, and the total effective rate was 73.3%; there were 14 effective cases in the control group (11 cured and 3 effective), 16 ineffective cases, and the total effective rate was 46.7%.

[0086] 2.3 Comparison of VAS scores of pain between the two groups before and after treatment: There was no significant difference between the two groups before treatment (P>0.05).

[0087] Table 3 Pain VAS scores of the two groups of patients before and after treatment

[0088] Group n Before treatment After treatment Jade Skin Cream Set 30 3.17±1.46 <![CDATA[1.97±1.32 **# ]]> control group 30 3.13±1.45 <![CDATA[2.80±1.52 ** ]]>

[0089] Note: Compared with before treatment, **P<0.01; compared with control group, #P<0.05.

[0090] As shown in Table 3, within-group comparison, the VAS score of the Yufu cream group was lower after treatment than before treatment, and the pain was significantly improved (P < 0.001); the VAS score of the control group was lower after treatment than before treatment, and the pain was improved (P < 0.01); after treatment, the VAS score of the Yufu cream group was lower than that of the control group, and the pain relief effect was better than that of the control group (P < 0.05).

[0091] 2.4 Comparison of hand-foot skin reaction quality of life scale (HF-QoL) between the two groups before and after treatment: There was no significant difference between the two groups before treatment (P>0.05). Note: Compared with the Yufu cream group before treatment, **P<0.01; compared with the control group before treatment, *P<0.05; compared with the control group, #P<0.05.

[0092] Table 4 HF-QoL scores of the two groups of patients before and after treatment

[0093] Group n Before treatment After treatment Jade Skin Cream Set 30 39.50±9.12 <![CDATA[31.70±7.25 **# ]]> control group 30 39.37±8.96 <![CDATA[37.60±10.02 * ]]>

[0094] Conclusion: Intra-group comparison showed that the HF-QoL scores of the two groups were lower after treatment than before treatment (p < 0.05), but the decrease was more significant in the Yufu cream group (p < 0.05), indicating that the Yufu cream group can better improve the quality of life of patients.

[0095] 2.5 Comparison of Self-Rating Anxiety Scale (SAS) scores between the two groups before and after treatment: There was no significant difference between the two groups before treatment (P>0.05). Intra-group comparison showed that the scores of both groups were lower after treatment than before treatment (P<0.01). After treatment, the SAS score of the Yufu cream group was lower than that of the control group (P<0.01).

[0096] Table 5 Self-Rating Anxiety Scale (SAS) scores of the two groups of patients before and after treatment

[0097] Group n Before treatment After treatment Jade Skin Cream Set 30 58.53±5.10 <![CDATA[49.53±5.10 **## ]]> control group 30 58.47±4.96 <![CDATA[53.03±4.61 ** ]]>

[0098] Note: Compared with before treatment, **P<0.01; compared with control group, ##P<0.01.

[0099] Conclusion: Table 5 shows that the Yufu ointment group can improve the anxiety of patients.

[0100] 2.6 Comparison of TCM syndrome scores between the two groups before and after treatment: There was no significant difference between the two groups before treatment (P>0.05). Intra-group comparison showed that the TCM syndrome scores of the two groups were lower after treatment than those before treatment (P<0.01). After treatment, the TCM syndrome score of the Yufu cream group was lower than that of the control group (P<0.001).

[0101] Table 6 TCM syndrome scores of the two groups of patients before and after treatment

[0102] Group n Before treatment After treatment Jade Skin Cream Set 30 17.73±4.98 <![CDATA[6.23±3.21 **## ]]> control group 30 17.60±5.20 <![CDATA[12.30±3.25 ** ]]>

[0103] Note: Compared with before treatment, **P<0.01; compared with control group, #P<0.05.

[0104] As can be seen from Table 6, the Yufu ointment group can reduce the patients' TCM syndrome scores and improve the patients' related symptoms.

[0105] 3. Typical cases:

[0106] 1. Patient Cheng, male, 48 years old, stage IV rectal cancer, took oral capecitabine, and developed desquamation, ulcers, ulcers and pigmentation on the feet, numbness and dullness, which seriously affected daily walking and life. The hand-foot syndrome was graded as 3. After 14 days of medication (applying this ointment to the affected area, 2-3 times a day until the end of treatment), the patient's hand-foot syndrome symptoms improved significantly, the ulcers and cracks healed, and there was no obvious pain or numbness. The therapeutic effect was good. (such as Figure 1 shown).

[0107] 2. Patient Wang, male, 69 years old, stage IV colon cancer, took oral capecitabine and experienced scaling, dryness and pigmentation on the feet, pain accompanied by numbness and dullness, which affected his daily life. After 14 days of medication (applying this ointment to the affected area 2-3 times a day until the end of treatment), the patient's hand-foot syndrome symptoms improved significantly, the skin regained its moisture and elasticity, and there was no obvious pain or numbness. The treatment effect was good. (such as Figure 2 shown).

[0108] 4. Analysis and explanation of research results

[0109] Yufu Detoxification Paste is based on Ziyun Paste and contains Baizhi, Xuejie, and borneol. The lithospermum erythrorhizon in this paste has the effects of cooling blood and activating blood circulation, detoxifying and clearing rashes, and exhibits multiple pharmacological activities in terms of antibacterial, anti-inflammatory, and antioxidant properties. Angelica sinensis has the effects of nourishing blood and activating blood circulation, and modern research shows that it has pharmacological effects such as antibacterial, anti-inflammatory, immune function regulation, and antioxidant properties. External use of borneol has the effects of clearing heat, reducing swelling, and relieving pain. Modern pharmacological research shows that borneol has the effects of reducing swelling, relieving pain, anti-inflammatory, and promoting wound healing, and is commonly used clinically to treat burns and scalds. Xuejie has the effects of activating blood circulation and relieving pain, removing blood stasis and reducing swelling, and astringing sores and stopping bleeding. Pharmacology has confirmed that it has multiple physiological activities such as antioxidant, blood circulation activation and hemostasis, and improving the body's microcirculation. Bletilla striata has the effects of clearing heat and detoxifying, astringing sores and promoting tissue regeneration, and is used to treat carbuncles, back ulcers, sores, burns and scalds. In summary, the analysis of the composition and mechanism of traditional Chinese medicine, and according to the research results, Yufu Jiedu Paste can reduce the patient's pain VAS score better than urea ointment and relieve their pain symptoms. This may be because this prescription contains traditional Chinese medicines such as borneol, angelica, and dragon's blood, which have the effects of promoting blood circulation and removing blood stasis, reducing swelling and relieving pain, while the main mechanism of action of urea ointment is to dissolve keratin, increase protein hydration, thereby softening and dissolving keratin, and its analgesic effect is inferior to Yufu Jiedu Paste; at the same time, its TCM syndrome score is lower than that of urea ointment, but it is better than urea ointment in improving dry and cracked skin, numbness and pain, and promoting wound healing. This may be because this ointment contains drugs such as lithospermum officinale, white mulberry, dragon's blood, phellodendron, and knotweed, which can nourish yin and cool blood, clear away heat and detoxify, stop bleeding and promote tissue regeneration, and can better relieve the TCM-related symptoms of hand-foot syndrome; and compared with urea ointment, it can significantly improve related symptoms, reduce the patient's HFS clinical grade, improve the patient's quality of life, and thus relieve their anxiety.

[0110] This prospective, open-label, randomized, controlled trial enrolled 60 patients with colorectal cancer and HFS induced by capecitabine alone or in combination with chemotherapy. Preliminary results confirmed that Yufu Jiedu Paste effectively reduced the clinical grade of capecitabine-related HFS, alleviated pain symptoms, promoted wound healing, reduced Traditional Chinese Medicine (TCM) syndrome scores, improved quality of life, and alleviated anxiety. These findings suggest that Yufu Jiedu Paste is effective and safe for the treatment of capecitabine-related HFS. Therefore, this study preliminarily confirms the clinical efficacy of Yufu Jiedu Paste in treating capecitabine-related HFS and warrants further promotion and application.

[0111] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art will be able to modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein with equivalents. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. A Chinese medicinal ointment for treating hand-foot syndrome, characterized in that: The Chinese medicinal ointment is prepared from the following components by weight: 1000-2000 parts of sesame oil, 50-100 parts of lithospermum erythrorhizon, 50-100 parts of angelica dahurica, 50-100 parts of bletilla striata, 50-100 parts of white ampelopsis, 50-100 parts of angelica sinensis, 50-100 parts of rhubarb, 50-100 parts of knotweed, 10-50 parts of honeysuckle, 50-100 parts of siler, 50-100 parts of rehmannia root, 10-50 parts of pearl powder, 10-50 parts of dragon's blood, 10-50 parts of borneol, 50-100 parts of trichosanthes root, 10-50 parts of frankincense, 10-50 parts of myrrh, 10-50 parts of rosin, 10-50 parts of quicklime, 500-1000 parts of lard, 150-360 parts of beeswax and ethyl hydroxybenzoate solution.

2. The Chinese medicinal ointment according to claim 1, wherein The invention is prepared from the following components by weight: 2000 parts of sesame oil, 100 parts of lithospermum erythrorhizon, 60 parts of angelica dahurica, 50 parts of bletilla striata, 60 parts of white ampelopsis, 100 parts of angelica sinensis, 50 parts of rhubarb, 50 parts of knotweed, 50 parts of trichosanthes root, 50 parts of siler, 60 parts of rehmannia root, 10 parts of honeysuckle, 10 parts of pearl powder, 20 parts of dragon's blood, 10 parts of borneol, 15 parts of frankincense, 15 parts of myrrh, 15 parts of rosin, 50 parts of quicklime, 1000 parts of lard, 300-360 parts of beeswax and ethyl hydroxybenzoate solution.

3. A method for preparing the traditional Chinese medicine ointment for treating hand-foot syndrome according to any one of claims 1-2, characterized in that: The specific steps are as follows: Step 1: Soak comfrey in 1 / 2 sesame oil for one week, stirring once a day until the sesame oil turns dark purple-red; heat the sesame oil and fry the comfrey until crispy; Step 2: Take 1 / 2 of sesame oil, add angelica root, white striata root, white peony root, Chinese angelica root, rhubarb, knotweed, radix trichosanthis, siler, radix rehmanniae and honeysuckle, and soak for a week; heat sesame oil and deep-fry each component until brown; Step 3: Remove and discard the fried lithospermum erythrorhizon, angelica dahurica, white striata, white peony root, angelica sinensis, rhubarb, knotweed, radix trichosanthis, siler, honeysuckle and radix rehmanniae; add beeswax and lard to the sesame oil mixed after heating in steps 1 and 2, stir and melt, and let stand until warm; Step 4: Add ground frankincense, myrrh, dragon's blood, borneol, rosin, pearl powder and ethyl hydroxybenzoate solution, stir to mix, add quicklime water and cool to obtain.

4. The preparation method according to claim 3, characterized in that In step 3, the temperature of the sesame oil placed to be warmed is 45-55°C.

5. The preparation method according to claim 3, characterized in that: The ethylparaben solution refers to ethylparaben completely dissolved in ethanol.

6. The preparation method according to claim 5, characterized in that: The ethanol concentration is 60% to 99.9%.

7. The preparation method according to claim 3, characterized in that: The quicklime water refers to the clear liquid obtained by dissolving quicklime in water, wherein the weight ratio of quicklime to water is 1:

2.

8. The preparation method according to claim 3, characterized in that: In step 4, the particle size of the frankincense, myrrh, dragon's blood, borneol, rosin, and pearl powder after grinding is 200 mesh; the weight ratio of the sesame oil obtained in step 3 to the ethyl paraben solution is 100:0.

25.

9. Use of the traditional Chinese medicine ointment according to claim 1 in preparing a medicine for treating hand-foot syndrome.

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