A Chinese medicine composition for treating hand-foot syndrome and its preparation method and application

Abstract

The present invention provides a Chinese medicine composition for treating hand-foot syndrome and its preparation method and application. By weight, the Chinese medicine composition includes 5-50 parts of coptis root, 5-50 parts of phellodendron, 10-30 parts of ligusticum chuanxiong, 30-60 parts of bletilla striata, 10-30 parts of lithospermum officinale, 10-30 parts of quinquefolium, 5-10 parts of bee nest, 10-30 parts of geranium, and 10-30 parts of scutellaria baicalensis. The Chinese medicine composition provided by the present invention is screened for Chinese medicine prescriptions according to the theory of traditional Chinese medicine, and the formula is rigorous. For patients with hand-foot syndrome caused by chemotherapy or targeted therapy, it plays the effects of clearing away heat and detoxicating, alleviating pain, and improving the quality of life of patients, and its side effects are relatively small, simple to prepare, easy to use, simple to obtain materials, low price, and suitable for long-term external fumigation and washing of patients.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and specifically comprises a traditional Chinese medicine composition for treating hand-foot syndrome, and a preparation method and application thereof. Background Art

[0002] After anti-tumor treatment, the hands and feet are prone to blackening, ulceration, pus discharge, pain and other symptoms, which are called hand-foot syndrome (HFS) or hand-foot skin reaction (HFSR). The incidence rates are 6%-64% and 9%-62%, respectively. In most literatures, the two are not clearly distinguished and are collectively referred to as hand-foot syndrome. Although hand-foot syndrome does not endanger the patient's life, it seriously affects the patient's quality of life. Severe hand-foot syndrome makes it difficult for patients to take care of themselves. In addition, severe hand-foot syndrome may lead to a reduction in chemotherapy doses or even the need to stop treatment, which in turn affects the treatment of tumors. At present, there is no unified treatment plan. Western medicine uses large doses of vitamin B6, COX-2 inhibitor celecoxib, glucocorticoids, urea cream, etc. for treatment, but the effect is not good.

[0003] From ancient times to now, a large number of traditional Chinese medicines have been used for the diagnosis and treatment of hand and foot skin damage. Although it is different from modern diagnosis, its clinical manifestations are similar. The relevant diagnosis and treatment of hand and foot syndrome in classical books are summarized and applied in clinical treatment, and good results have been achieved. The adverse reactions of hand and foot skin are equivalent to "immersion sores", "finger carbuncle", "goose palm wind" and "scurvy" in traditional Chinese medicine. "Medical Mirror" records that "scurvy grows in the palms of the fingers, shaped like cornus officinalis, and grows on both hands. There are also clusters of yellow and white pustules, itching and pain at all times, breaking body fluids and yellow juice, sometimes good and sometimes bad, extremely tired and stubborn, caused by rheumatism invading the skin", "goose palm wind starts with purple and white spots, overlapping white skin, hard and thick, dry and cracked, extending to the whole hand". Traditional Chinese medicine believes that chemotherapy drugs are highly toxic, which not only damage the spleen and stomach, but also consume qi and blood. The defensive qi is not solid, and the exogenous wind, cold, dampness and other evil qi gather in the local area, causing qi and blood stagnation. Therefore, numbness of the hands and feet, dullness of sensation, and severe stasis can be seen in black skin. Stasis turns into heat and detoxification, and toxic heat and stasis are blocked. If it is not unblocked, it will cause pain, and even accompanied by pain, swelling, erythema, desquamation, cracking and other serious skin toxic reactions. Oral administration, external washing and soaking, ointment and other treatments can be used. Hands and feet are distal to the limbs, and external washing and soaking, ointment application and other methods can directly reach the diseased area, which can achieve better therapeutic effects. A large number of clinical cases have shown that Chinese medicine plays a positive role in treating hand-foot syndrome caused by chemotherapy or targeted therapy and improving the quality of life of patients.

[0004] In order to further expand the traditional Chinese medicine formula that can effectively treat hand-foot syndrome caused by chemotherapy or targeted therapy, the technical scheme of the present invention is specially proposed. Summary of the invention

[0005] In view of the above problems existing in the prior art, the first object of the present invention is to provide a Chinese medicine composition for treating hand-foot syndrome. The Chinese medicine composition can treat hand-foot syndrome caused by chemotherapy or targeted therapy, play the role of clearing away heat and detoxification, relieving pain, etc., and can effectively improve the quality of life of patients.

[0006] The second object of the present invention is to provide a method for preparing the above-mentioned Chinese medicine composition.

[0007] The third object of the present invention is to provide a Chinese medicine preparation for treating hand-foot syndrome.

[0008] The fourth object of the present invention is to provide a use of the above-mentioned Chinese medicine composition or Chinese medicine preparation in the preparation of a medicine for treating hand-foot syndrome.

[0009] To achieve the above first object, the technical solution adopted by the present invention includes:

[0010] The invention discloses a traditional Chinese medicine composition for treating hand-foot syndrome. The traditional Chinese medicine composition comprises 5-50 parts of coptis root, 5-50 parts of phellodendron, 10-30 parts of chuanxiong, 30-60 parts of bletilla striata, 10-30 parts of lithospermum officinale, 10-30 parts of quinquefolius, 5-10 parts of honeycomb, 10-30 parts of geranium and 10-30 parts of scutellaria baicalensis.

[0011] The Chinese medicine composition provided by the present invention is screened for Chinese medicine formula according to the theory of traditional Chinese medicine, has a rigorous formula, and has the effects of clearing away heat and detoxifying, relieving pain, etc. for patients with hand-foot syndrome caused by chemotherapy or targeted therapy, and can effectively improve the quality of life of patients. It has fewer side effects, is simple to prepare, easy to use, has simple materials, and is low in price, so it is suitable for long-term external fumigation and washing for patients.

[0012] The sources and functions of the medicinal materials used in the formula of the present invention are as follows:

[0013] Coptis chinensis: It is a perennial herb with a bitter taste and cold nature. It enters the heart, liver, stomach, and large intestine meridians, clears away heat and purges fire, dries dampness, and detoxifies. It is mainly used to treat high fever, irritability, delirium caused by febrile evil entering the heart meridian, or vomiting blood due to excessive heat forcing blood to flow, and chest fullness caused by damp heat.

[0014] Phellodendron chinense Schneid. is a dried bark of the Rutaceae plant. It is bitter and cold in nature. It enters the kidney and bladder meridians, clears away heat and purges fire, dries dampness and detoxifies. It is mainly used to treat heat dysentery, diarrhea, thirst, jaundice, etc.

[0015] Chuanxiong: Spicy and warm in nature, it enters the liver, gallbladder and pericardium meridians. It promotes blood circulation and removes blood stasis, promotes qi and relieves depression, dispels wind and relieves pain, and is mainly used to treat irregular menstruation, amenorrhea and dysmenorrhea.

[0016] Bletilla striata: It is a terrestrial herbaceous plant of the Orchidaceae family and the genus Bletilla. It tastes bitter and sweet, is cool, and enters the lung meridian. It nourishes the lungs, stops bleeding, reduces swelling, promotes tissue regeneration, and heals sores. It is used to treat lung injury, coughing up blood, epistaxis, bleeding from wounds, carbuncle swelling, ulcer pain, burns from hot water or fire, and chapped hands and feet.

[0017] Lithospermum: It is a perennial herbaceous plant of the genus Lithospermum of the Boraginaceae family. It tastes bitter and cold. It enters the pericardium and liver meridians. It cools the blood, activates blood circulation, clears away heat, and detoxifies. It is used to treat warm-heat macules, damp-heat jaundice, purpura, vomiting, epistaxis, hematuria, stranguria, heat-stagnation constipation, burns, eczema, erysipelas, and carbuncle.

[0018] Wulingzhi: It is the dried excrement of the orange-footed flying squirrel and flying squirrel of the family Sciuridae. It is sweet and warm in taste and enters the liver and spleen meridians. It can be used raw to promote blood circulation and relieve pain. It can treat various pains caused by blood and qi in the heart and abdomen, amenorrhea in women, and pain caused by blood stasis after childbirth. It can also be used externally to treat bites by snakes, scorpions, and centipedes. It can be used when stir-fried to stop bleeding. It can treat metrorrhagia, excessive menstruation, and continuous red discharge in women.

[0019] Wasp nest: It is the nest of the yellow-star long-legged wasp or a variety of closely related insects of the Vespidae family. It tastes sweet, flat, and poisonous. It enters the lung and liver meridians. It dispels wind, attacks poison, and kills insects. It can treat epilepsy, rheumatism, itching caused by eczema, breast abscess, furuncle, scrofula, hemorrhoid fistula, toothache caused by wind and fire, tinea capitis, and swelling and pain caused by bee stings.

[0020] Geranium: The whole herb with fruits of Erodium stephanianum Willd., Geranium wilfordii Maxim., Geranium sibiricum L., Geranium nepalense Sweet and Geranium dahuricum DC. of the Geranaceae family; it has the effects of dispelling wind and dredging meridians, activating blood circulation, clearing away heat and removing dampness; it is commonly used for rheumatism, numbness of the skin, soreness of muscles and bones, bruises, diarrhea, dysentery, sores, etc.

[0021] Herba pedunculatae: It is a perennial herb with a pungent and warm taste. It enters the lung and liver meridians. It dispels wind and dampness, relaxes muscles and activates blood circulation, disperses blood stasis and reduces swelling, and detoxifies and relieves eye pain. It is used to treat rheumatic arthralgia, muscle and bone contracture, cold and damp athlete's foot, waist sprain, paralysis, amenorrhea, scrotal eczema, sores, boils, and swelling.

[0022] Adverse reactions to the skin of hands and feet are equivalent to "immersion sores", "fingers boils", "goose palm wind" and "malaria" in traditional Chinese medicine. "Medical Mirror" records that "malaria grows in the palms of the fingers, shaped like dogwood, and grows on both hands facing each other. There are also clusters of yellow and white pustules, itching and pain at all times, breaking the body fluids and yellow juice, sometimes getting better and sometimes getting worse, extremely tired and stubborn, caused by rheumatism invading the skin", "goose palm wind starts with purple and white spots, overlapping white skin, hard and thick, dry and cracked, and extending to the whole hand". It can be treated by oral administration, external washing and soaking, ointment, etc. Hands and feet are the distal parts of the limbs, and external washing and soaking, ointment application and other methods can directly reach the diseased area and have a better therapeutic effect.

[0023] Chemotherapy drugs belong to the category of "drug poison". They are highly toxic, consume qi and blood, damage the spleen and stomach, and cause insufficient qi and blood biochemistry. Hands and feet are the ends of the limbs, with relatively less microcirculation and blood circulation. Drug poisons gather locally, or chemotherapy drugs damage qi and blood, qi deficiency and blood stasis, and eventually lead to qi stagnation and blood stasis, and blood cannot nourish the body. In the early stage, the skin of the hands and feet can be seen to be dark purple, dull and numb. In the late stage, skin cracking and desquamation can be seen. Drug poisons gather locally, and if they are not unblocked, pain will occur. Over time, they will turn into heat and poison, and damage the skin. Skin erythema and pain can be seen. In severe cases, skin ruptures and obvious exudation may occur.

[0024] During chemotherapy, patients experience redness, erythema, edema, pain, ulceration, and obvious exudation on the skin of hands and feet, which are signs of damp-heat and heat toxicity. Medicinal Coptis chinensis and Phellodendron chinense are used to clear away heat and dampness, detoxify, or in the early or late stages of chemotherapy, dryness, roughness, chapped skin, desquamation, dullness, and numbness on the skin of hands and feet are signs of blood deficiency and wind dryness. Medicinal Bletilla striata is used to astringe and promote tissue regeneration, and is the main drug. Chuanxiong promotes qi and blood circulation, and is combined with Wulingzhi to promote blood circulation, which can promote blood circulation and relieve pain, and is the minister drug. Erythema, pain, swelling, and hyperkeratosis of the skin of hands and feet may be accompanied by chapped skin, desquamation, or abnormal sensation, tingling, and burning sensation, which are signs of blood stasis and toxicity stagnation. Medicinal Herba Tougucao and Geranium are used as adjuvants, and together with Chuanxiong and Wulingzhi, they can promote blood circulation, dredge the meridians, and relieve pain. Beehive nourishes blood and dispels wind, while combined with lithospermum officinale to clear away heat, cool blood and detoxify. Together they are guiding herbs that can nourish blood and moisturize the skin, as well as cool blood and detoxify.

[0025] Furthermore, in parts by weight, the Chinese medicine composition includes 5-30 parts of Coptis chinensis, 5-30 parts of Phellodendron chinense, 10-30 parts of Chuanxiong, 30-60 parts of Bletilla striata, 10-30 parts of Lithospermum officinale, 10-30 parts of Aconiti Lateralis Preparata, 5-10 parts of Beehive, 10-30 parts of Geranium sibiricum, and 10-30 parts of Herba Scutellariae Sinensis.

[0026] Furthermore, in parts by weight, the Chinese medicine composition includes 10 parts of Coptis chinensis, 10 parts of Phellodendron chinense, 20 parts of Ligusticum chuanxiong, 30 parts of Bletilla striata, 30 parts of Lithospermum officinale, 30 parts of Aconiti Lateralis Preparata, 5 parts of Beehive, 30 parts of Geranium sibiricum and 30 parts of Herba Scutellariae Sinensis.

[0027] Furthermore, in terms of weight, the Chinese medicine composition includes 5 parts of Coptis chinensis, 5 parts of Phellodendron amurense, 30 parts of Chuanxiong, 30 parts of Bletilla striata, 30 parts of Lithospermum officinale, 10 parts of Aconiti Lateralis Preparata, 30 parts of Geranium sibiricum, 10 parts of Beehive, and 30 parts of Herba Scutellariae Sinensis.

[0028] Furthermore, in parts by weight, the Chinese medicine composition includes 50 parts of Phellodendron chinense, 30 parts of Geranium sibiricum, 50 parts of Coptis chinensis, 10 parts of Beehive, 10 parts of Aconiti Lateralis Preparata, 30 parts of Lithospermum erythrorhizon, 30 parts of Chuanxiong, 30 parts of Bletilla striata, and 10 parts of Herba Scutellariae Torr.

[0029] To achieve the above second purpose, the technical solution adopted by the present invention includes:

[0030] The present invention discloses a method for preparing the above-mentioned traditional Chinese medicine composition, comprising the following steps:

[0031] Weigh each raw material by mass, add water to cover it, soak for 30-40 minutes, and boil twice;

[0032] Among them, after the first frying is boiled over high heat, it is simmered over low heat for 30-50 minutes; after the second frying is boiled over high heat, it is simmered over low heat for 20-40 minutes. After decocting, the residue is removed and the juice is taken.

[0033] To achieve the third objective above, the technical solution adopted by the present invention includes:

[0034] The invention discloses a traditional Chinese medicine preparation for treating hand-foot syndrome. The traditional Chinese medicine composition as mentioned above is prepared into an external medicine.

[0035] Furthermore, the dosage form of the topical drug includes but is not limited to ointment, liniment, lotion, patch, paste, gel, coating or papule.

[0036] To achieve the fourth objective above, the technical solution adopted by the present invention includes:

[0037] The present invention discloses an application of the above-mentioned traditional Chinese medicine composition or the above-mentioned traditional Chinese medicine preparation in preparing a medicine for treating hand-foot syndrome.

[0038] In one specific embodiment, a lotion is prepared for fumigation treatment of hand-foot syndrome, and the specific steps are:

[0039] Weigh each raw material by mass, add water to cover it, soak for 30-40 minutes, and boil twice;

[0040] Among them, after the first decoction is boiled over high heat, simmer for 40 minutes over low heat; after the second decoction is boiled over high heat, simmer for 30 minutes over low heat. After decocting and removing the residue and taking the juice, fumigate at an appropriate distance first. When the temperature of the medicine liquid drops to the tolerable level of the patient (the water temperature is about 35-40℃), immerse the affected area in the medicine liquid for soaking and washing. Fumigation and washing should be 30 minutes each time, once a day.

[0041] Furthermore, the hand-foot syndrome is a hand-foot syndrome caused by chemotherapy drugs or targeted drugs.

[0042] Furthermore, the chemotherapy drug is selected from pyrimidine analogs such as capecitabine, 5-fluorouracil, etc., or anthracycline drugs such as doxorubicin, etc.

[0043] Furthermore, the targeted drugs include but are not limited to apatinib, sorafenib or sunitinib.

[0044] Beneficial effects of the present invention:

[0045] The present invention discloses a Chinese medicine composition for treating hand-foot syndrome, which has the following advantages over the prescription disclosed in the prior art:

[0046] 1. The Chinese medicine composition disclosed in the present invention can play the role of clearing away heat and detoxifying, relieving pain, etc. for patients with hand-foot syndrome caused by chemotherapy or targeted therapy, and can effectively improve the quality of life of patients. It has small side effects, is simple to prepare, is convenient for external fumigation and washing, has simple materials to obtain, and is low in price, so it is suitable for long-term external fumigation and washing of patients.

[0047] 2. The present invention screens Chinese medicine prescriptions based on the theory of traditional Chinese medicine, and the ratio of the Chinese medicine composition for treating hand-foot syndrome provided by the present invention is scientific and reasonable. The Chinese medicine composition provided by the present invention has the effects of detoxifying heat, alleviating discomfort such as pain, and improving the quality of life of patients. Long-term clinical experimental studies have shown that the Chinese medicine composition for treating hand-foot syndrome provided by the present invention has high safety and low toxic and side effects.

[0048] 3. The Chinese medicine composition for treating hand-foot syndrome provided by the present invention can be conveniently prepared into a decoction with a pharmaceutical carrier for external fumigation and washing, and is convenient for clinical use. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] Figure 1 Shown are comparison pictures of typical case 1 before and after treatment.

[0050] Figure 2 Shown are comparison pictures of typical case 2 before and after treatment. DETAILED DESCRIPTION

[0051] In order to explain the present invention more clearly, the present invention is further described below in conjunction with preferred embodiments. It should be clear that the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0052] Example 1

[0053] The formula is as follows by weight: 10 parts of coptis root, 10 parts of phellodendron, 20 parts of chuanxiong, 30 parts of bletilla striata, 30 parts of lithospermum officinale, 30 parts of aconiti lobata, 5 parts of honeycomb, 30 parts of geranium, and 30 parts of scutellaria baicalensis.

[0054] Weigh all the raw materials according to the prescription, add water to cover them, soak for 30-40 minutes, and boil twice; the first time, boil over high heat, then simmer for 40 minutes over low heat; the second time, boil over high heat, then simmer for 30 minutes over low heat. After boiling, remove the residue and take the juice, you can get a decoction for external fumigation and washing.

[0055] Example 2

[0056] The formula is as follows by weight: 5 parts of coptis root, 5 parts of phellodendron, 30 parts of chuanxiong, 30 parts of bletilla striata, 30 parts of lithospermum officinale, 10 parts of truncatum officinale, 30 parts of geranium, 10 parts of honeycomb, and 30 parts of scutellaria baicalensis.

[0057] Weigh all the raw materials according to the prescription, add water to cover them, soak for 30-40 minutes, and boil twice; the first time, boil over high heat, then simmer for 40 minutes over low heat; the second time, boil over high heat, then simmer for 30 minutes over low heat. After boiling, remove the residue and take the juice, you can get a decoction for external fumigation and washing.

[0058] Example 3

[0059] The formula is as follows by weight: 50 parts of Phellodendron amurense, 30 parts of Geranium sibiricum, 50 parts of Coptis chinensis, 10 parts of Beehive, 10 parts of Ophiopogon japonicus, 30 parts of Lithospermum officinale, 30 parts of Chuanxiong, 30 parts of Bletilla striata, and 10 parts of Herba scutellariae;

[0060] Weigh all the raw materials according to the prescription, add water to cover them, soak for 30-40 minutes, and boil twice; the first time, boil over high heat, then simmer for 40 minutes over low heat; the second time, boil over high heat, then simmer for 30 minutes over low heat. After boiling, remove the residue and take the juice, you can get a decoction for external fumigation and washing.

[0061] Typical Cases

[0062] Case 1: Xu, female, 60 years old, underwent hysteroscopic endometrial curettage at Beijing Obstetrics and Gynecology Hospital in March 2021. Pathology showed: (intrauterine mass, base of intrauterine mass) adenocarcinoma, moderately-poorly differentiated, considered endometrioid carcinoma, IHC: ER(+)PR(-)Ki-67(+70%)MLH(+)MSH(+)MSH6(+), serous carcinoma is considered likely. On May 18, 2021, she underwent total hysterectomy with bilateral salpingo-oophorectomy, and the postoperative pathology was unknown. After surgery, she received paclitaxel combined with carboplatin chemotherapy once, and was changed to doxorubicin combined with oxaliplatin for numbness of the hands and feet. On July 27, 2021, the initial diagnosis was immediate: numbness and pain in the hands and feet, poor vitality, severe pain in the left foot, skin ulceration on the left foot, pus discharge, bitter taste in the mouth, dry mouth, fatigue, poor appetite, good sleep, dry stool, and regular urine.

[0063] The following prescription was used for treatment: 50g of Phellodendron chinense, 30g of Geranium sibiricum, 50g of Coptis chinensis, 10g of Beehive, 10g of Aconiti Lateralis Preparata, 30g of Lithospermum erythrorhizon, 30g of Lithospermum chuanxiong, 30g of Bletilla striata, and 10g of Herba Scutellariae.

[0064] Usage: Prepare according to the decoction method of Example 1, add water to decoct the medicine to 1000 ml, fumigate at a suitable distance, and when the temperature of the medicine drops to the patient's tolerance level (water temperature is about 35-40°C), immerse the limbs in the medicine for washing, fumigate for 30 minutes each time, once a day, and 14 days as a course of treatment. Figure 1, indicating that this prescription can effectively improve the hand-foot syndrome caused by chemotherapy drugs.

[0065] Case 2: Ms. Pan, female, 52 years old, had breast tumor puncture in Beijing Aerospace General Hospital in September 2013. Pathology showed: invasive ductal carcinoma of the left breast, some of which were invasive lobular carcinoma, IHC: ER(+++)PR(+++)Ki-67(<5%)Her-2(+), and TAC chemotherapy was performed 4 times. In December 2013, she underwent modified radical mastectomy on the left breast. Postoperative pathology showed invasive ductal carcinoma, involving the skin and nipple, lymph node metastasis (2 / 2), and TAC chemotherapy was performed 2 times after surgery. After the end of chemotherapy, she took oral letrozole treatment, and then changed to exemestane due to joint pain. In June 2017, the left axillary lymph nodes and thoracic vertebrae metastasis were re-examined for possible metastasis, and lymph node puncture was performed: ER(+++)PR(-)Ki-67(+20%)Her-2(++), FISH(-), and epirubicin chemotherapy was given 4 times, and oral anastrozole was taken after the end of chemotherapy. In March 2018, bone metastasis was poorly controlled, and endocrine therapy was changed to fulvestrant. In January 2019, CT showed: multiple small nodules in the lungs, and metastasis was not excluded. Pathology consultation at Beijing Cancer Hospital: (left breast puncture) Infiltrating ductal carcinoma, grade II, IHC: ER (+90%) PR (+80%) Her-2 (0) Ki-67 (+10%), lymph node puncture: ER (+90%) PR (-) Her-2 (2+) Ki-67 (+20%), 8 cycles of docetaxel chemotherapy, lesions shrank. Endocrine drugs were changed to oral toremifene. In June 2020, albumin-paclitaxel chemotherapy was given for 3 cycles due to the appearance of pleural effusion, but the tumor was poorly controlled. In September 2020, anlotinib combined with capecitabine treatment was started. Symptoms at the first visit on November 23, 2021: numbness of both hands, dry and cracked skin, desquamation, pain, stomach bloating, good sleep, and regular bowel movements.

[0066] The following prescription was used for treatment: 5 parts of Coptis chinensis, 5 parts of Phellodendron chinense, 30g of Chuanxiong, 30g of Bletilla striata, 30g of Lithospermum officinale, 10g of Aconiti Lateralis Preparata, 30g of Geranium sibiricum, 10g of Beehive, and 30g of Herba Scutellariae.

[0067] Usage: Prepare according to the decoction method of Example 1, add water to decoct the medicine to 1000 ml, fumigate at a suitable distance, and when the temperature of the medicine drops to the patient's tolerance level (water temperature is about 35-40°C), immerse the limbs in the medicine for washing, fumigate for 30 minutes each time, once a day, and 14 days as a course of treatment. Figure 2 , indicating that this prescription can effectively improve the hand-foot syndrome caused by chemotherapy drugs.

[0068] Clinical trials

[0069] 1 Research subjects

[0070] 1.1 Case source

[0071] The cases were from outpatients and inpatients who visited the Oncology Department of Guang'anmen Hospital from September 2020 to March 2022. They were diagnosed with hand-foot syndrome in accordance with Western medicine diagnostic criteria. The total sample size of this study was 60 cases, including 30 cases in the experimental group and 30 cases in the control group. The random number table method was used to put the random numbers and corresponding intervention plans in a sealed, opaque envelope with a number affixed to the outside of the envelope. The researcher opened the envelope in the order of the numbers and randomly divided the patients into the experimental group and the control group.

[0072] 1.2 Diagnostic criteria

[0073] 1.2.1 Clinical manifestations of adverse reactions on the hands and feet

[0074] Hand-foot skin adverse reactions include hand-foot syndrome and hand-foot skin reaction. Hand-foot syndrome initially manifests as insensitivity and numbness in the palms and soles, which may then progress to tingling and burning pain, with local erythema and edema, and the lesions are mostly on the outside of the distal fat pad of the fingers, or accompanied by nail changes. Local erythema may develop into blisters, followed by desquamation, erosion, and ulceration. Recurrent hand-foot syndrome can lead to hypertrophy of the palmoplantar stratum corneum similar to keratosis. Characteristics of hand-foot skin reaction: erythema with or without blisters, followed by excessive keratotic damage to the palms and soles, accompanied by paresthesia or insensitivity, which often occur in the bent, weight-bearing or pressured parts of the hands and feet. Loss of gloss and fingerprints is rare, and the incidence is higher in Asians.

[0075] 1.2.1 Grading criteria for hand-foot syndrome

[0076] The grading standard refers to the NCI standard: ① Grade 0: no clinical manifestations; ② Grade 1: mild skin changes or dermatitis (such as erythema, desquamation) accompanied by abnormal sensation (such as numbness, tingling, burning sensation), but not affecting daily activities; ③ Grade 2: skin changes as before accompanied by pain, slightly affecting daily activities, and the skin surface is intact; ④ Grade 3: ulcerative dermatitis or skin changes accompanied by severe pain, seriously affecting daily life, and obvious tissue destruction (such as desquamation, blisters, bleeding, edema).

[0077] 1.3 Inclusion criteria

[0078] ① Hand-foot syndrome occurs after chemotherapy such as capecitabine or targeted therapy such as apatinib; ② KPS score ≥ 60 points; ③ Age 18-75 years old; ④ No intellectual or mental disorders, normal language expression ability, ability to judge their own pain and general condition, and able to cooperate in evaluating pain and quality of life; ⑤ Understand and agree to accept the treatment and sign the informed consent form.

[0079] 1.4 Exclusion criteria

[0080] ① Critically ill patients with severe pain in other parts of the body; ② Patients with skin allergic diseases; ③ Patients who are unable to cooperate with clinical trials.

[0081] 2 Treatment options

[0082] Patients who meet the criteria for inclusion and exclusion are randomly divided into a test group and a control group. The test group is treated with Chinese medicine fumigation. The formula of Example 2 is selected, and water is added and boiled to 1000mL according to the preparation steps. The appropriate distance is taken for fumigation first. When the temperature of the medicine liquid drops to the patient's tolerable level (water temperature is about 35-40°C), the limbs are immersed in the medicine liquid for soaking and washing. Each fumigation and washing lasts 30 minutes, once a day, and 14 days is an observation period. The control group is coated with vaseline. The above test drugs are provided by the preparation room of the Department of Pharmacy, Guang'anmen Hospital, China Academy of Chinese Medical Sciences.

[0083] 3 Observation indicators

[0084] 3.1 Observation and analysis of the therapeutic efficacy of the two groups: Efficacy evaluation criteria: Cure (CR): After treatment, the patient's erythema, pain, redness and swelling of the hands and feet and other clinical symptoms and signs were completely eliminated, and the grade was reduced to 0; Effective (PR): After treatment, the patient's erythema, pain, redness and swelling of the hands and feet and other clinical symptoms and signs were relieved to a certain extent, and the grade was reduced by 1 grade or more; Ineffective (NP): After treatment, the patient's erythema, pain, redness and swelling of the hands and feet and other clinical symptoms and signs did not change at all, and the grade did not decrease. Among them, the total effective rate = cure rate + effective rate.

[0085] 3.2 Quality of life evaluation: The quality of life of breast cancer patients was evaluated using the Functional Assessment of Cancer Therapy breast cancer-specific (FACT-B). FACT is a functional evaluation system for cancer therapy developed by Cell et al. It consists of a general scale (common module FACI-G) that measures the common parts of the quality of life of cancer patients and a specific scale (specific module) for specific cancer types. FACT-G consists of 27 items and is divided into four parts, namely physical well-being, emotional well-being, social / family well-being, and functional well-being. FACT-B is composed of FACT-G and a breast cancer-specific module, and each item is set up in a hierarchical manner (0-4). The higher the score, the better the quality of life.

[0086] 3.3 TCM syndrome scoring: Refer to the "Guidelines for Clinical Research of New Chinese Medicines" to evaluate the patient's skin sensation, limb involvement, skin changes, pain and other symptoms before and after treatment. The lower the score, the better the improvement of the patient's symptoms. TCM syndrome scoring is divided into primary and secondary symptoms. Primary symptoms include skin and nail discoloration, skin rash morphology, numbness of hands and feet, paresthesia, and pain. Secondary symptoms include complexion, dizziness, fatigue, tongue coating, and pulse.

[0087] 3.4 Safety indicators: routine blood tests, liver and kidney function tests, urine routine tests, stool routine tests, and electrocardiograms before and after treatment.

[0088] 4 Statistical methods

[0089] SPSS26.0 statistical software was used to analyze and organize clinical data, and descriptive statistics were used to analyze all data, including demographic data, baseline, and various efficacy evaluation indicators. For measurement data, a normal distribution test was performed, and the data that met the normal distribution were tested with an independent sample t test to describe their mean, standard deviation, median, maximum, and minimum values; the data that did not meet the normal distribution were tested with a nonparametric rank sum test. For count data, the chi-square test was used to describe their frequencies and percentages, and P < 0.05 was considered statistically significant.

[0090] 5 Results

[0091] 5.1 Enrolled cases

[0092] A total of 60 cases were enrolled, including 30 cases in the experimental group and 30 cases in the control group. The age of the experimental group was (50.30±1.586) years old; the age of the control group was (49.80±1.774) years old. The age of the two groups of cases was not statistically significant by independent sample t test. The general data such as tumor size, histological grade, and tumor stage were not statistically significant by chi-square test and independent sample t test (P>0.05), and they were comparable.

[0093] 5.2 HFS grading changes and efficacy analysis

[0094] At the time of enrollment, there were 1 case of HFS grade 1, 17 cases of grade 2, and 12 cases of grade 3 in the experimental group, and 2 cases of grade 1, 15 cases of grade 2, and 13 cases of grade 3 in the control group. The chi-square test showed no significant difference between the two groups (Table 1). After treatment, there were 16 cases of grade 0, 9 cases of grade 1, 3 cases of grade 2, and 2 cases of grade 3 in the experimental group; after treatment, there were 8 cases of grade 0, 7 cases of grade 1, 7 cases of grade 2, and 8 cases of grade 3 in the control group. The chi-square test showed a significant difference between the two groups (P = 0.044) (Table 2).

[0095] Table 1 Comparison of HFS grades between the two groups before treatment (cases)

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[0098] Table 2 Comparison of HFS grades between the two groups after treatment (cases)

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[0100] Analysis of HFS efficacy: In the experimental group, 16 cases were cured (53.33%), 12 cases were effective (40%), and 2 cases were ineffective (6.67%), with a total effective rate of 93.33%; in the control group, 8 cases were cured (26.67%), 14 cases were effective (46.67%), and 8 cases were ineffective (26.66%), with a total effective rate of 73.34%. The chi-square test showed that the difference between the groups was statistically significant (P<0.05).

[0101] 5.3 Comparison of quality of life scores before and after

[0102] There was no difference in the scores of physiological status, social and family status, emotional status, functional status, and additional attention between the two groups before treatment (P>0.05). After treatment, compared with the control group, the scores of physiological status, social and family status, emotional status, functional status, and additional attention in FACT-B were all increased, and the difference was statistically significant (P<0.05), as shown in Table 3-4.

[0103] Table 3 Comparison of FACT-B scores before treatment (points)

[0104]

[0105] Note: Physiological status, social / family status, emotional status, functional status, additional concerns, after examination, compared with before treatment, * P>0.05, not statistically significant.

[0106] Table 4 Comparison of FACT-B scores after treatment (points)

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[0108] Note: Physiological status, social / family status, emotional status, functional status, additional concerns, compared with before treatment, by non-parametric test, * P<0.05, statistically significant.

[0109] 5.4 Comparison of TCM syndrome scores before and after

[0110] After normality test, the main symptoms, secondary symptoms and total scores of TCM syndromes did not conform to normal distribution. After non-parametric test, there was no statistical difference in the main symptoms, secondary symptoms and total scores between the experimental group and the control group before treatment (P>0.05); after treatment, there was a statistical difference in the main symptoms, secondary symptoms and total scores between the experimental group and the control group after treatment (P=0.011) (Table 5).

[0111] Table 5 Comparison of TCM syndrome scores before and after treatment (points) ([M(P 25 ,P 75 )])

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[0113]

[0114] 5.5 Security Analysis

[0115] Adverse Events

[0116] During the trial, no adverse events occurred in the experimental group or the control group, and no serious adverse events occurred in both groups.

[0117] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not limitations on the implementation methods of the present invention. For ordinary technicians in the relevant field, other different forms of changes or modifications can be made based on the above description. It is impossible to list all the implementation methods here. All obvious changes or modifications derived from the technical solution of the present invention are still within the protection scope of the present invention.

Claims

1. A Chinese medicine composition for treating hand-foot syndrome, characterized in that: The invention is prepared from 5-50 parts of coptis root, 5-50 parts of phellodendron, 10-30 parts of ligusticum chuanxiong, 30-60 parts of bletilla striata, 10-30 parts of lithospermum officinale, 10-30 parts of aconiti lobata, 5-10 parts of honeycomb, 10-30 parts of geranium and 10-30 parts of scutellaria baicalensis.

2. The Chinese medicine composition according to claim 1, characterized in that: The invention is prepared from 5-30 parts of coptis root, 5-30 parts of phellodendron, 10-30 parts of ligusticum chuanxiong, 30-60 parts of bletilla striata, 10-30 parts of lithospermum officinale, 10-30 parts of aconiti lobata, 5-10 parts of honeycomb, 10-30 parts of geranium and 10-30 parts of scutellaria baicalensis.

3. The Chinese medicine composition according to claim 1, characterized in that The preparation method is made from 10 parts of coptis root, 10 parts of phellodendron, 20 parts of ligusticum chuanxiong, 30 parts of bletilla striata, 30 parts of lithospermum officinale, 30 parts of aconiti lobata, 5 parts of honeycomb, 30 parts of geranium and 30 parts of scutellaria baicalensis.

4. The Chinese medicine composition according to claim 1, characterized in that: The preparation method is made from 5 parts of coptis root, 5 parts of phellodendron, 30 parts of ligusticum chuanxiong, 30 parts of bletilla striata, 30 parts of lithospermum officinale, 10 parts of aconiti lobata, 30 parts of geranium, 10 parts of honeycomb and 30 parts of scutellaria baicalensis by weight.

5. The Chinese medicine composition according to claim 1, characterized in that: The invention is prepared by weight from 50 parts of Phellodendron amurense, 30 parts of Geranium sibiricum, 50 parts of Coptis chinensis, 10 parts of Honeycomb, 10 parts of Aconiti Lateralis Preparata, 30 parts of Lithospermum officinale, 30 parts of Chuanxiong, 30 parts of Bletilla striata and 10 parts of Herba Scutellariae.

6. The method for preparing the Chinese medicine composition according to any one of claims 1 to 5, characterized in that: The steps include: Weigh each raw material by weight, add water to cover it, soak for 30-40 minutes, and boil twice; Among them, after the first frying is boiled over high heat, it is simmered over low heat for 30-50 minutes; after the second frying is boiled over high heat, it is simmered over low heat for 20-40 minutes. After decocting, the residue is removed and the juice is taken.

7. A Chinese medicine preparation for treating hand-foot syndrome, characterized in that: The Chinese medicine composition according to any one of claims 1 to 5 is prepared into an external medicine.

8. The Chinese medicine preparation according to claim 7, characterized in that: The dosage form of the external medicine is ointment, liniment, lotion, patch, paste, gel, coating or papule.

9. Use of the Chinese medicine composition according to any one of claims 1 to 5 or the Chinese medicine preparation according to claim 7 or 8 in the preparation of a medicament for treating hand-foot syndrome.

10. The use according to claim 9, characterized in that: The hand-foot syndrome is a hand-foot syndrome caused by chemotherapy drugs or targeted drugs.

11. The use according to claim 10, characterized in that: The chemotherapy drug is selected from capecitabine, 5-fluorouracil or doxorubicin.

12. The use according to claim 10, characterized in that: The targeted drug is selected from apatinib, sorafenib or sunitinib.

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