Traditional Chinese medicine composition and traditional Chinese medicine preparation for treating skin toxic reaction of anti-angiogenesis medicine

Abstract

The invention discloses a traditional Chinese medicine composition for treating skin toxic reaction of an anti-angiogenesis medicine. The traditional Chinese medicine composition comprises the following components in parts by weight: 8-15 parts of angelica sinensis, 10-20 parts of radix polygoni multiflori preparata, 10-20 parts of wine-processed rhizoma polygonati, 8-15 parts of radix paeoniae rubra, 8-15 parts of cortex phellodendri, 10-20 parts of radix rehmanniae recen, 6-15 parts of tribulus terrestris, 6-15 parts of spina gleditsiae, 8-12 parts of cicada slough, 8-12 parts of schizonepeta, 8-12 parts of fructus kochiae and 4-8 parts of scorpio. And 8-15 parts of cortex dictamni. The traditional Chinese medicine composition for treating the skin toxic reaction of the anti-angiogenesis medicine can effectively control side effects generated by the anti-angiogenesis medicine, can resist the skin toxic reaction from the pathogenesis and quickly relieve symptoms, and is convenient to take, safe and reliable. The invention further provides a traditional Chinese medicine preparation for treating the skin toxic reaction of the anti-angiogenesis medicine.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine compositions, and particularly relates to a traditional Chinese medicine composition for treating skin toxicity reaction of anti-angiogenic drugs and a traditional Chinese medicine preparation. BACKGROUND

[0002] Anti-angiogenic drugs (such as VEGF inhibitors, tyrosine kinase inhibitors, etc.) inhibit tumor growth by targeting angiogenesis-related pathways, but also interfere with normal skin blood vessels and cell functions, causing various skin reactions. The principle mainly involves the following mechanisms:

[0003] 1. Direct effect of angiogenesis inhibition

[0004] VEGF signaling pathway blockage: VEGF is a key factor for maintaining skin microvascular structure and function. Inhibition of VEGF or its receptors (such as VEGFR) can lead to: skin microvascular degeneration, reduction of dermal capillary network, local ischemia and hypoxia; endothelial cell damage, increased vascular permeability, skin edema or hemorrhage (such as erythema and blisters in hand-foot syndrome);

[0005] Insufficient epidermal nutrition supply: impaired blood vessel function leads to metabolic disorders of keratinocytes, manifested as dry skin, desquamation or ulceration.

[0006] 2. Skin barrier destruction and inflammatory response

[0007] Impaired epidermal repair: VEGF is involved in wound healing, and its inhibition can delay epidermal regeneration (such as delayed wound healing).

[0008] Release of inflammatory factors: hypoxia-inducible factor (HIF-1α) activates pro-inflammatory pathways (such as TNF-α, IL-6), recruits neutrophils and macrophages, and aggravates inflammation (such as skin rash and itching).

[0009] Hand-foot syndrome (HFS): drugs accumulate in the palm / plantar apocrine gland area, directly damaging the vascular endothelium, causing local thrombotic microangiopathy and inflammation, damaging sweat glands, and causing dryness, peeling, and pain.

[0010] 3. Changes in immune microenvironment

[0011] Imbalance of pro-inflammatory cytokines: anti-angiogenic drugs may enhance Th1 / Th17 immune response, driving inflammatory skin diseases (such as psoriasis-like skin rash).

[0012] Autoimmune response: some patients have positive anti-nuclear antibody (ANA), which may induce lupus erythematosus-like skin rash or photosensitivity.

[0013] 4. Typical skin reactions and mechanisms

[0014] Hand-foot syndrome: microvascular thrombosis + direct cytotoxicity → ischemic necrosis, inflammatory acne-like rash: abnormal differentiation of hair follicle keratinocytes → hair follicle obstruction, inflammation psoriasis-like dermatitis, the mechanism is:

[0015] (1) Inflammation-related: intradermal T cells, abnormal activation, neutrophils, inflammatory cell infiltration; IFN-γ↑;

[0016] (2) Immune-related: activation of Th17 pathway, IL-17 produced by IL-17 is the key to the pathogenesis; activation of STAT-3 pathway, increased IL-22 production, promoting the occurrence of psoriasis;

[0017] (3) Keratinocytes overdivide;

[0018] (4) Increased tortuosity of dermal blood vessels and capillaries;

[0019] (5) Related to immune and keratinocyte metabolic reprogramming: inhibition of glucose metabolism, reduction of blood sugar, inhibition of fatty acid synthesis, can inhibit inflammatory response, can reduce glucose metabolism.

[0020] Photosensitivity / erythema: drug phototoxicity + ultraviolet-induced oxidative stress. Common symptoms: itching, edema, pain, peeling, numbness of hands and feet.

[0021] For skin toxicity reactions of anti-angiogenic drugs, existing clinical management methods include:

[0022] Prevention: avoid sun exposure (reduce phototoxicity), moisturizing care (relieve dryness).

[0023] Symptomatic treatment:

[0024] Mild rash: topical glucocorticoids, antibiotic ointments;

[0025] Severe reactions (such as ulcers): suspend drug, systemically use anti-inflammatory or immunomodulatory agents;

[0026] Dose adjustment: reduce or stop drug according to skin toxicity grading (such as CTCAE standard).

[0027] At present, there is no clear and effective treatment for skin toxicity reactions of anti-angiogenic drugs, and prevention and symptomatic support treatment are mainly used, and the incidence rate is 30%-70%, many patients in clinical medication are seriously disturbed by it, and the quality of life is significantly decreased, at the same time, it leads to drug reduction and treatment interruption, ultimately affects the efficacy of tumor treatment, and skin toxicity reactions of anti-angiogenic drugs have become one of the side effects of drug restriction.

[0028] Chinese patent application (CN109745394A) discloses a traditional Chinese medicine composition for treating blood dryness, wind heat and skin itching, which contains angelica, peony, chuanqiong, tribulus terrestris, wind-preventing, rehmannia, radix polygoni multiflori, schizonepeta, astragalus, licorice and other components. According to the pathogenesis of blood dryness, wind heat and skin itching, the principle of clearing dryness and calming wind is used for dialectical prescription. However, the disease treated by this principle is blood deficiency, dryness, deficiency of healthy qi, the treatment method is mainly blood nourishing and yin nourishing, and wind relieving and pain relieving is auxiliary. The skin reaction caused by anti-angiogenic drugs is a combination of deficiency and excess, with wind, heat, dampness and stasis on the basis of qi and yin deficiency. Therefore, the traditional Chinese medicine composition in CN109745394A has little effect on the skin reaction caused by anti-angiogenic drugs.

[0029] Therefore, an effective drug is needed to control and resist the side effects of anti-angiogenic drugs, so as to resist skin toxicity reaction from the pathogenesis, quickly relieve symptoms, and conveniently administer. SUMMARY

[0030] The technical problem to be solved by the present application is to provide a traditional Chinese medicine composition for treating skin toxicity reaction of anti-angiogenic drugs, which can effectively control the side effects of anti-angiogenic drugs, resist skin toxicity reaction from the pathogenesis, quickly relieve symptoms, and conveniently administer.

[0031] The first aspect of the present application is to provide a traditional Chinese medicine composition for treating skin toxicity reaction of anti-angiogenic drugs, and the technical solution is:

[0032] A traditional Chinese medicine composition for treating skin toxicity reaction of anti-angiogenic drugs, comprising the following ingredients by weight fraction:

[0033] Angelica 8-15 parts, prepared radix polygoni multiflori 10-20 parts, wine yellow 10-20 parts, red peony 8-15 parts, huangbai 8-15 parts, raw rehmannia 10-20 parts, cistanche 6-15 parts, soapstick 6-15 parts, cicada exuviae 8-12 parts, schizonepeta 8-12 parts, kudzu 8-12 parts, scorpion 4-8 parts, white bark 8-15 parts.

[0034] Further, the traditional Chinese medicine composition for treating skin toxicity reaction of anti-angiogenic drugs comprises the following ingredients by weight fraction:

[0035] Angelica 10 parts, prepared radix polygoni multiflori 15 parts, wine yellow 15 parts, red peony 10 parts, huangbai 10 parts, raw rehmannia 15 parts, cistanche 10 parts, soapstick 10 parts, cicada exuviae 10 parts, schizonepeta 10 parts, kudzu 10 parts, scorpion 6 parts, white bark 10 parts.

[0036] The second aspect of the present application provides a traditional Chinese medicine preparation for treating the skin toxicity reaction of anti-angiogenic drugs, which is a water extract of the traditional Chinese medicine composition of the first aspect.

[0037] Further, the traditional Chinese medicine preparation is an external preparation.

[0038] Compared with the prior art, the traditional Chinese medicine composition for treating the skin toxicity reaction of anti-angiogenic drugs provided by the present application has the beneficial effect that:

[0039] Firstly, the traditional Chinese medicine composition provided by the present application has the functions of tonifying qi and nourishing yin, strengthening the body resistance, clearing heat and removing dampness, cooling blood and removing blood stasis, and dredging the meridians and removing wind. The composition combines the effects of attack and supplementation, and treats the primary and secondary symptoms at the same time, so that the internal drug toxicity is released, the external evil is dispersed, the blood is sufficient, the wind is removed, the heat is cleared, the blood stasis is removed, the itching is stopped, the rash is disappeared, and the skin lesions are smoothed. The traditional Chinese medicine composition is used as an external preparation after being decocted with water, and is applied to the affected area, which can effectively control the side effects caused by anti-angiogenic drugs, can resist the skin toxicity reaction from the pathogenesis, can quickly relieve symptoms, and is convenient, safe and reliable. BRIEF DESCRIPTION OF DRAWINGS

[0040] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings needed in the embodiment description will be briefly introduced. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor.

[0041] Figure 1 is a state diagram of the patient after using anlotinib treatment to appear systemic rash;

[0042] Figure 2 is a state diagram of the patient after using the traditional Chinese medicine composition of the present application for treatment.

[0043] DETAILED EMBODIMENT

[0044] In order to make the person skilled in the art better understand the technical solutions in the embodiments of the present application, and make the above-mentioned purposes, features and advantages of the present application more obvious and easy to understand, the specific embodiment of the present application will be further described.

[0045] The endpoints of the ranges and any values in the present disclosure are not limited to the precise values stated. The endpoints of the ranges and the values are approximate values and should be understood to include values approximately near these ranges and values within these ranges. For ranges of values, the endpoints of the ranges are combined with the individual points to form new ranges. These new ranges are to be considered as disclosed herein.

[0046] The traditional Chinese medicine composition provided by the application is used for treating drug eruption caused by chemotherapy / targeting anti-tumor drugs. Drug toxicity invades internally, first damaging qi and blood, burning yin fluid, causing deficiency of both qi and yin, and blood deficiency and dryness; the drug has a strong nature, brewing dampness, heat and toxic evil, and forming a complex pathogenesis of deficiency in root and excess in branch, wind, dampness, heat and toxic evil stagnation, with symptoms of dry skin, desquamation, erythema, papules, severe itching, and even induration and pain.

[0047] The traditional Chinese medicine composition for treating skin toxicity reaction of anti-angiogenic drugs provided by the application has the following composition idea from the pharmacological point of view:

[0048] The composition idea is as follows according to the pathogenesis:

[0049] (1) Anti-inflammation

[0050] Angelica sinensis: inhibits the expression of TNF-α and IL-6 through regulating STAT6 signal pathway, and has anti-inflammatory effect;

[0051] Radix Rehmanniae: reduces TNF-α and has anti-inflammatory effect;

[0052] Periostracum Cicadae: inhibits JAK1-STAT3 pathway, reduces the levels of IL-4, IL-17, IL-22 and INF-γ, and improves skin inflammation;

[0053] Schizonepeta: reduces the contents of IgE, TNF-α and IL-6 in serum of specific dermatitis model mice, and has anti-inflammatory effect;

[0054] Dictamnus dasycarpus Turcz: inhibits STAT6 signal pathway, reduces IL-4 and IL-31, and has anti-inflammatory effect;

[0055] Phellodendri Cortex: reduces IL-1β and IL-6, and has anti-inflammatory effect.

[0056] (2) For vascular endothelial cells

[0057] Radix Polygoni Multiflori + Radix Paeoniae Rubra: improves vascular endothelial function, makes the vascular intima relatively complete, and reduces the degree of vascular endothelial injury;

[0058] Rhizoma Polygonati Nudifontis: reduces blood pressure and reduces vascular endothelial injury through polysaccharide in Rhizoma Polygonati Nudifontis;

[0059] Fructus Tribuli: reduces blood pressure and further reduces vascular endothelial injury.

[0060] (3) Promoting angiogenesis

[0061] Scorpion: promotes angiogenesis through P38 / MKI pathway.

[0062] (4) Regulating immune microenvironment

[0063] Angelica sinensis: regulates Th17 cell function, balances Th17 / Treg cells, and regulates immune microenvironment.

[0064] (5) Regulating glucose and lipid metabolism disorder

[0065] Phellodendri Chinensis Cortex: Regulating glucose and lipid metabolism disorder, returning lipid metabolism to balance, inhibiting inflammatory response, reducing IL-1β and IL-6 levels;

[0066] Kochia Scopariae Fructus: Reducing blood glucose, regulating abnormal glucose metabolism;

[0067] Tribulus terrestris: Reducing blood glucose, regulating abnormal glucose metabolism.

[0068] (6) Activating blood

[0069] Angelica sinensis + Red Peony Root: Activating blood and resolving stasis;

[0070] Gleditsia sinensis + Red Peony Root: Activating blood and resolving stasis;

[0071] Schizonepeta: Promoting blood circulation;

[0072] (7) Anti-oxidative stress

[0073] Angelica sinensis: Reducing oxidative stress level;

[0074] Schizonepeta: Anti-oxidative, reducing oxidative stress level.

[0075] According to symptoms, the composition is conceived as follows:

[0076] (1) Relieving itching

[0077] Dictamnus dasycarpus Turcz: Anti-inflammatory and relieving itching;

[0078] Schizonepeta: Improving pain threshold of mice, relieving itching;

[0079] (2) Anti-edema

[0080] Schizonepeta: Reducing IgE, TNF-α and IL-6 contents in serum of specific dermatitis model mice, improving blood circulation and reducing edema;

[0081] Tribulus terrestris: Reducing vascular injury, anti-oxidative and reducing edema.

[0082] (3) Relieving pain

[0083] Schizonepeta: Improving pain threshold of mice, having peripheral and central analgesic effects.

[0084] (4) Complete skin barrier, anti-peeling

[0085] Scorpion: Promoting ulcer wound healing through P38 / MKI pathway, complete skin barrier, anti-peeling;

[0086] Cicada slough: inhibit JAK1-STAT3 pathway, reduce the expression level of skin barrier decomposition enzyme and kallikrein related peptidase, restore skin barrier function.

[0087] (5) Anti numbness of hands and feet

[0088] Catnip: improve the pain threshold of mice, and resist numbness;

[0089] Trichosanthin: restore acetylcholine activity, has good neuroprotective effect, and reduce numbness caused by nerve injury.

[0090] From the perspective of traditional Chinese medicine, the compatibility principle is as follows:

[0091] The traditional Chinese medicine composition of the present application, in the prescription, angelica nourishes blood and promotes blood circulation, and the prepared rehmannia nourishes liver and kidney and benefits essence and blood, the wine yellow ginseng tonifies qi and nourishes yin, and the spleen and dryness. The three drugs work together to drastically supplement qi, blood, yin and fluid, and consolidate the root of healthy qi, to solve the source of drug toxicity and injury to the healthy, and to be the monarch drug. Rehmannia glutinosa tonifies yin and cools blood, red peony root clears heat and cools blood, and disperses blood stasis and relieves pain. The two drugs are used together to directly clear the blood stasis and heat caused by drug toxicity, and to stop the transmission and change of the disease. Trichosanthin soothes the liver and dispels wind, catnip disperses and penetrates the surface, opens the pores to give the evil a way out, and scorpion searches the meridians, expels wind and relieves itching, and deeply enters the disease, and relieves the stasis of collaterals and the accumulation of wind caused by drug toxicity. The two groups of ministers treat the symptoms caused by drug toxicity. Semen euryales, bai xian pi clear heat, benefit wind and relieve itching, and attack the damp heat drug toxicity accumulated in the skin; huang bai clears heat and dries dampness, and purges fire and detoxifies, and is especially good at clearing the damp heat and fire in the lower jiao, and is matched with the monarch drug of tonifying, which not only clears virtual heat, but also prevents the accumulation of evil. Soap nut is pungent and warm, and is good at attacking hard, dredging collaterals and resolving knots, and is aimed at the hard knot skin lesions caused by drug toxicity and blood stasis, and promotes the dispersion of the lesions. These are all auxiliary drugs for treating symptoms. Cicada slough is light in quality and good in dispersing wind and heat to relieve itching, and can also guide the drugs to the skin lesions, and govern the whole prescription, and harmonize the drugs. It is the ministerial drug in the prescription. The drugs are matched together to achieve the effects of benefiting qi and nourishing yin, supporting healthy and supplementing deficiency, clearing heat and removing dampness, cooling blood and removing stasis, and searching for wind and dredging collaterals. The attack is combined with the supplement, the symptoms and the root are treated, the drug toxicity is solved, and the evil qi is dispersed, so that the blood is sufficient, the wind is eliminated, the heat is cleared, the stasis is removed, the itching is stopped, the rash is disappeared, and the skin lesions are self-leveling.

[0092] The traditional Chinese medicine composition for treating the skin toxicity reaction of anti-angiogenic drugs is described in detail through the specific embodiments.

[0093] Example 1

[0094] A traditional Chinese medicine composition for treating the skin toxicity reaction of anti-angiogenic drugs, comprising the following ingredients by weight fraction:

[0095] Angelica 10 parts, prepared rehmannia 15 parts, wine yellow ginseng 15 parts, red peony root 10 parts, huang bai 10 parts, rehmannia glutinosa 15 parts, trichosanthin 10 parts, soap nut 10 parts, cicada slough 10 parts, catnip 10 parts, semen euryales 10 parts, scorpion 6 parts, bai xian pi 10 parts.

[0096] Example 2

[0097] A traditional Chinese medicine composition for treating skin toxicity reaction of anti-angiogenic drugs, comprising the following ingredients in parts by weight:

[0098] Angelica 8 parts, prepared rehmannia 10 parts, rhizome of polygonatum 10 parts, red peony root 8 parts, golden cypress 8 parts, rehmannia 10 parts, tribulus terrestris 6 parts, soapberry 6 parts, periostracum cypraea 8 parts, schizonepeta 8 parts, semen eurycoma 8 parts, scorpion 4 parts, and dictamnus 8 parts.

[0099] Example 3

[0100] A traditional Chinese medicine composition for treating skin toxicity reaction of anti-angiogenic drugs, comprising the following ingredients in parts by weight:

[0101] Angelica 15 parts, prepared rehmannia 20 parts, rhizome of polygonatum 20 parts, red peony root 15 parts, golden cypress 15 parts, rehmannia 20 parts, tribulus terrestris 15 parts, soapberry 15 parts, periostracum cypraea 12 parts, schizonepeta 12 parts, semen eurycoma 12 parts, scorpion 8 parts, and dictamnus 15 parts.

[0102] The traditional Chinese medicine composition for treating skin toxicity reaction of anti-angiogenic drugs of the present application, the use method comprising the following steps:

[0103] (1) The traditional Chinese medicine composition is weighed according to the proportion, and a proper amount of water is added for decoction;

[0104] (2) The decocted medicinal liquid is applied.

[0105] Example 4 Animal toxicity experiment of traditional Chinese medicine composition

[0106] ICR mice with a body weight of (20±2) g, half male and half female, are selected. The above animals are provided by Shanghai Xipu-Bike Experimental Animal Co., Ltd.

[0107] The back of the test group mice is shaved on both sides of the spine, and the depilated area is about 4×3 cm.

[0108] The traditional Chinese medicine composition of Example 1 is decocted and applied to the depilated area of the test group mice, and the mice are applied every 3 hours for 3 consecutive days. Whether the mice have erythema and edema is observed. The control group is normally fed. The test results are shown in Table 1.

[0109] Table 1: Toxicity test results

[0110] Group n Erythema (only) Edema (only) Test group 8 0 0 Control group 8 0 0

[0111] As can be seen from Table 1, the traditional Chinese medicine composition of the present application has no toxicity reaction on mice, and the skin of mice has no obvious irritation.

[0112] Example 5 Animal effectiveness experiment of traditional Chinese medicine composition

[0113] Establishment of animal model of skin toxicity reaction of anti-angiogenic drugs (such as VEGF inhibitors, tyrosine kinase inhibitors, etc.):

[0114] Model one

[0115] 26 male 6-week ICR mice were randomly divided into a control group (6 mice) and an experimental group (20 mice). The experimental group was continuously administered sorafenib (140 mg / kg, once a day) by gavage for 10 days, and the control group was administered solvent normal saline (4 ml / kg, once a day). When the mice developed skin toxicity reactions (itching, hair loss, skin rash, edema, etc.), the modeling was considered successful. After the modeling was successful, 5 successfully modeled mice in each group were divided into an experimental group A and an experimental group B. The control group was rubbed with normal saline on the back skin of the mice, the experimental group B was rubbed with the traditional Chinese medicine composition of Example 1 on the skin tissue of the skin toxicity reaction site of the mice, and the experimental group A was rubbed with normal saline on the skin tissue of the skin toxicity reaction site of the mice. All were rubbed three times a day. After one week, the mice were sacrificed, and the treated skin tissue was quickly collected and placed in pre-cooled PBS to wash away the blood, dried, and removed from the excess subcutaneous fat and fascia. Then, the skin tissue was weighed, homogenized, lysed, centrifuged, and the supernatant was collected. The IL-6, IL-17, and TNF-α were detected by ELISA, and the detection results are shown in Table 2.

[0116] Table 2: IL-6, IL-17, and TNF-α detection results of each research object in model one

[0117] (pg / mg tissue protein, n=5, mean ± SD)

[0118] IL-6 (pg / mg) TNF-α (pg / mg) IL-17 (pg / mg) P value Control group 52±7 38±5 15.2±2.4 Experimental group A 135±12 114±3 68.7±10.5 <0.001 Experimental group B 75±2 45±4 17.0±2.1 >0.05

[0119] Model two

[0120] 26 male 6-week ICR mice were randomly divided into a control group (6 mice) and an experimental group (20 mice). The experimental group was continuously administered anlotinib (1.3 mg / kg, once a day) by gavage for 6 weeks, and the control group was administered solvent normal saline (4 ml / kg, once a day). After the modeling was successful, 5 successfully modeled mice in each group were divided into an experimental group C and an experimental group D. The control group was rubbed with normal saline on the back skin of the mice, the experimental group D was rubbed with the traditional Chinese medicine composition of Example 1 on the skin tissue of the skin toxicity reaction site of the mice, and the experimental group C was rubbed with normal saline on the skin tissue of the skin toxicity reaction site of the mice. All were rubbed three times a day. Then, the treatment method was the same as above. The detection results are shown in Table 3.

[0121] Table 3: IL-6, IL-17, and TNF-α detection results of each research object in model two

[0122] (pg / mg tissue protein, n=5, mean ± SD)

[0123] IL-6 (pg / mg) TNF-α (pg / mg) IL-17 (pg / mg) P value Control group 60±4 45±8 15.2±2.4 Experimental group C 218±30 156±21 68.7±10.5 <0.001 Experimental group D 80±10 70±6 17.0±2.1 >0.05

[0124] It can be seen from Tables 2 and 3 that the IL-6, IL-17 and TNF-α levels of the experimental group treated with the traditional Chinese medicine composition of the present application are lower than those of the normal saline treated experimental group, and close to those of the control group, indicating that the traditional Chinese medicine composition of the present application can effectively inhibit inflammation.

[0125] Example 6 Clinical trial

[0126] 1. Research object

[0127] Select 40 cases of patients with malignant tumors who visited the clinic from September 2020 to January 2022, and were diagnosed with skin toxicity after using anti-angiogenic drugs, including 18 male cases and 22 female cases. There were 24 patients over 65 years old and 16 patients under or equal to 65 years old. The patients were randomly divided into a control group and a treatment group, with 20 cases in the control group and 20 cases in the treatment group. The control and treatment groups were compared in terms of disease severity and disease duration, and there was no significant difference (P>0.05), which was comparable.

[0128] 2. Diagnostic criteria

[0129] (1) There is a history of malignant tumor diagnosed by pathological diagnosis;

[0130] (2) There is a history of using anti-angiogenic drugs;

[0131] (3) The following symptoms appear: itching, rash, dry skin on hands and feet, numbness, chapped skin, skin pigmentation, etc.;

[0132] (4) Skin toxicity grading:

[0133] Referring to the WHO standard targeted drug skin toxicity grading standard and CTCAE, the skin toxicity is divided into three levels:

[0134] Mild: covering <10% of the body surface area (BSA), head, face and upper torso, with or without symptoms such as itching, burning, tightness, tenderness, and no impact on daily life;

[0135] Moderate: covering 10%-30% of the body surface area (BSA), with a wide range, with or without itching and tenderness, but affecting mental health, limiting social daily activities. No signs of secondary infection, such as redness, fever, etc.

[0136] Severe: covering >30% of the body surface area (BSA), with or without symptoms, with the possibility of secondary infection, limiting self-care daily activities, and requiring oral antibiotic treatment for local secondary infection.

[0137] 3. Treatment methods

[0138] The treatment group used the traditional Chinese medicine preparation made from the traditional Chinese medicine composition of the present invention. Before using the medicine, the lesion was first cleaned with warm water, and then the traditional Chinese medicine preparation of the present invention was applied. It was used 3-5 times a day for 7 days as one course of treatment.

[0139] The control group received Western medicine treatment, including aloe vera gel and urea ointment, which were applied evenly to the wound twice a day.

[0140] 4. Criteria for Evaluating Therapeutic Effect

[0141] Recovery: The skin toxicity reaction has completely disappeared, and the patient can work and live normally.

[0142] Improvement: The skin toxicity reaction grade decreases by 1 level or more;

[0143] Ineffective: No change or even worsening of skin toxicity reaction, with the grade rising by 1 level or above.

[0144] 5. Clinical efficacy

[0145] Table 4: Comparison of therapeutic effects between the treatment group and the control group

[0146] Group Number of cases Cure Improvement Ineffective Effective rate Treatment group 20 12 7 1 95% Control group 20 3 9 8 60%

[0147] As shown in Table 4, the effective rate in the treatment group was significantly higher than that in the control group (P<0.05). Therefore, the traditional Chinese medicine composition of this invention has significant therapeutic effects on patients diagnosed with skin toxicity after using anti-angiogenic drugs.

[0148] Example 7 Typical Case

[0149] Patient 1, male, 50 years old, lung cancer, undergoing anlotinib targeted therapy. He developed a generalized rash after the first cycle of anlotinib treatment, as shown in the image. Figure 1 As shown.

[0150] After 7 days of treatment with the traditional Chinese medicine composition of Example 1, the symptoms significantly disappeared. Figure 2 As shown.

[0151] The traditional Chinese medicine composition provided by this invention, through the combined effects of various herbs, works synergistically to invigorate qi and nourish yin, strengthen the body's resistance, clear heat and eliminate dampness, cool the blood and remove blood stasis, and dispel wind and unblock the meridians. It combines attack with tonification, treating both the root cause and the symptoms, thereby detoxifying internal drug toxicity and dispersing external pathogenic factors. This results in sufficient blood to eliminate wind, clearing heat and resolving blood stasis, stopping itching and rashes, and healing skin lesions. When decocted and applied topically to the affected area, this traditional Chinese medicine composition effectively controls the side effects of anti-angiogenic drugs, counteracting skin toxicity at the pathogenesis level and rapidly relieving symptoms, resulting in significant therapeutic effects.

[0152] The above detailed description of the embodiments of the present application is not intended to limit the present application to the described embodiments. Various changes, modifications, substitutions and alterations to the described embodiments will be apparent to those skilled in the art without departing from the principles and spirit of the present application.

Claims

1. A traditional Chinese medicine composition for treating the skin toxicity reaction of anti-angiogenic drugs, characterized in that, It comprises the following ingredients by weight fraction: Angelica 8-15 parts, prepared rehmannia 10-20 parts, rhizome of polygonatum 10-20 parts, red peony root 8-15 parts, golden cypress 8-15 parts, raw rehmannia 10-20 parts, tribulus terrestris 6-15 parts, saponaria 6-15 parts, periostracum cicadae 8-12 parts, schizonepeta 8-12 parts, semen eurycoma 8-12 parts, scorpion 4-8 parts, cortex dictamni 8-15 parts.

2. The traditional Chinese medicine composition for treating the skin toxicity reaction of anti-angiogenic drugs according to claim 1, characterized in that, It comprises the following ingredients by weight fraction: Angelica 10 parts, prepared rehmannia 15 parts, rhizome of polygonatum 15 parts, red peony root 10 parts, golden cypress 10 parts, raw rehmannia 15 parts, tribulus terrestris 10 parts, saponaria 10 parts, periostracum cicadae 10 parts, schizonepeta 10 parts, semen eurycoma 10 parts, scorpion 6 parts, cortex dictamni 10 parts.

3. A traditional Chinese medicine preparation for treating the skin toxicity reaction of anti-angiogenic drugs, characterized in that, The water extract of the traditional Chinese medicine composition of claim 1 or 2.

4. The traditional Chinese medicine preparation for treating the skin toxicity reaction of anti-angiogenic drugs according to claim 3, characterized in that, The traditional Chinese medicine preparation is an external preparation.

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