CN115590812A

CN115590812A - Traditional Chinese medicine ointment for treating hand-foot syndrome and preparation method thereof

Info

Publication number: CN115590812A
Application number: CN202211247199.9A
Authority: CN
Inventors: 梁慧; 李宁; 王莹雪; 刘赳
Original assignee: Hunan Cancer Hospital
Current assignee: Hunan Cancer Hospital
Priority date: 2022-10-12
Filing date: 2022-10-12
Publication date: 2023-01-13

Abstract

The invention provides a traditional Chinese medicine ointment for treating hand-foot syndrome and a preparation method thereof, wherein the traditional Chinese medicine ointment is prepared from the following components: sesame oil, lithospermum, angelica dahurica, bletilla striata, ampelopsis japonica, angelica sinensis, rheum officinale, polygonum cuspidatum, honeysuckle, saposhnikovia divaricata, radix rehmanniae, pearl powder, dragon's blood, borneol, trichosanthes root, frankincense, myrrh, rosin, lard, beeswax and quicklime. The invention adds ampelopsis japonica, rheum officinale, polygonum cuspidatum, honeysuckle, pearl powder, dragon's blood, borneol, trichosanthes root, frankincense, myrrh and the like on the basis of the original ziyun ointment, increases the effects of nourishing yin, cooling blood, detoxifying and the like, and has good effects of relieving spasm, relieving pain, removing necrotic tissue, stopping bleeding, promoting granulation, resisting bacteria, diminishing inflammation, promoting wound healing and the like. The developed jade skin detoxification paste shows good early-stage curative effect in clinical application of treating hand-foot syndrome caused by capecitabine, obtains consistent favorable comment of patients, and makes up for the defects of the prior art.

Description

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

Technical Field

The invention relates to the technical field of traditional Chinese medicine ointment, and particularly relates to traditional Chinese medicine ointment for treating hand-foot syndrome and a preparation method thereof.

Background

Hand-foot syndrome (HFS) is a skin toxic response induced by some antineoplastic drugs, represented by capecitabine, and is the most common dose-limiting toxic response. The main clinical manifestations are dryness of hands and/or feet, desquamation, ulcer, blister, demethylation, hemorrhage, etc. in severe cases, and numbness of hands and feet, dysesthesia or paresthesia, such as acupuncture, burning, swelling of erythema, pigmentation, etc. This reduces the quality of life of the patient and the critically ill needs to prolong the duration of chemotherapy, reduce the dose and even stop the drug.

Dose-limiting toxic reactions seriously affect the treatment and the life quality of patients, limit the clinical application of capecitabine, and no particularly effective method for treating capecitabine-related HFS exists at home and abroad at present. Mainly takes prevention as a main part, health promotion and education, non-drug protection and the like. The urea ointment for external use and the vitamin B6 for oral administration are conventional treatment methods at present, celecoxib and cortisol medicaments are used for relieving inflammatory reaction and pain for patients with obvious pain and inflammatory reaction, but the measures have limited prevention and treatment capacity on HFS, COX-2 inhibitors and cortisol medicaments also have cardiovascular and gastrointestinal side effects and the like, and are not suitable for long-term use. At present, the prevention and treatment capacity of medicines and protective measures is limited, and the traditional Chinese medicine shows good curative effect in the aspect of preventing and treating capecitabine related HFS.

CN202110508472.8 discloses a traditional Chinese medicine composition with the effect of preventing and treating hand-foot syndrome and a preparation method thereof, wherein the traditional Chinese medicine composition comprises the following components in parts by weight: 10 to 50 parts of raw astragalus root, 15 to 40 parts of lithospermum, 8 to 25 parts of raw rhubarb, 20 to 38 parts of dandelion, 22 to 42 parts of paniculate swallowwort root, 15 to 35 parts of honey-fried licorice root, 10 to 35 parts of angelica, 12 to 25 parts of phellodendron, 13 to 23 parts of dittany bark, 28 to 36 parts of angelica dahurica, 14 to 26 parts of broom cypress fruit and 20 to 33 parts of fried white paeony root. CN202210096750.8 discloses an external traditional Chinese medicine compound ointment for treating hand-foot syndrome and a preparation method thereof. The ointment comprises the following components in parts by weight: 1 to 15 parts of frankincense, 1 to 15 parts of myrrh, 1 to 30 parts of Chinese violet, 1 to 30 parts of bletilla striata, 1 to 30 parts of coptis chinensis, 1 to 20 parts of giant knotweed, 1 to 15 parts of lithospermum, 1 to 40 parts of gynura segetum stem and leaf extract, 1 to 15 parts of panax notoginseng saponins, 1 to 10 parts of baicalein, 1 to 10 parts of baicalin, 1 to 15 parts of emodin, 1 to 70 parts of vaseline, 1 to 15 parts of beta-sitosterol, 1 to 5 parts of zinc oxide powder, 1 to 5 parts of talcum powder, 1 to 2 parts of wool fat, 1 to 2 parts of sodium stearate and 1 to 20 parts of ethanol. CN202210315505.1 discloses a traditional Chinese medicine composition for treating hand-foot syndrome after targeted drug therapy, which is mainly prepared from the following components in parts by weight: 20 to 50 parts of lightyellow sophora root, 20 to 50 parts of dandelion, 20 to 50 parts of wild chrysanthemum flower, 20 to 50 parts of Chinese violet, 20 to 50 parts of glabrous greenbrier rhizome, 30 to 60 parts of astragalus root, 10 to 35 parts of belvedere fruit, 10 to 45 parts of safflower, 15 to 45 parts of densefruit pittany root-bark, 5 to 15 parts of ephedra herb, 5 to 25 parts of angelica, 5 to 25 parts of szechuan lovage rhizome, 10 to 30 parts of rehmannia root, 5 to 15 parts of cassia twig, 10 to 30 parts of white paeony root, 5 to 15 parts of white mustard seed, 5 to 20 parts of raw arisaema tuber, 5 to 20 parts of raw pinellia tuber and 10 to 40 parts of raw liquoric root. The traditional Chinese medicine composition has a good effect of relieving hand-foot syndrome, but cannot realize the effects of removing the necrotic tissue, stopping bleeding, promoting granulation, promoting wound healing and the like, and has defects in the clinical application process.

Disclosure of Invention

Through a large amount of ancient and modern literature researches and clinical experience accumulation in the early period, the inventor observes that hand-foot syndrome is closely related to damp toxin, heat toxin, deficiency of both qi and yin and channel stasis, mostly has complicated pathogenesis and is matched with the pathological mechanism of yin deficiency and skin dryness and toxic stagnation and collateral obstruction in traditional Chinese medicine. Aiming at the clinical characteristics of the hand-foot syndrome caused by capecitabine, a 'jade skin detoxification prescription' with the effects of nourishing skin, moisturizing skin, detoxifying and activating blood is formulated and used for treating the hand-foot syndrome caused by capecitabine. The paste is prepared from famous prescription of traditional Chinese medicine surgery in Ming dynasty, is recorded in Yinyun paste of ulcer department, consists of angelica, lithospermum, linseed oil, yellow wax and lard, and has good effects of clearing away heat and toxic materials, removing necrotic tissue and promoting granulation. According to clinical experience, the ointment has curative effects on palm keratosis, burn, bedsore, dry tinea pedis, plantar pyosis, ulcer, erosion and various skin diseases. Modern researches also show that the rhododendron paste has extremely wide drug effect effects of moistening and drying, relieving pain, diminishing inflammation and relieving fever, stopping bleeding and sterilizing, strengthening, promoting granulation, eliminating putrefaction and malodor of wound defects and the like. The jade skin detoxification ointment developed by the inventor of the application is added with Japanese ampelopsis root, rhubarb, giant knotweed rhizome, honeysuckle flower, pearl powder, dragon's blood, borneol, mongolian snakegourd root, frankincense, myrrh and the like on the basis of the original ziyun ointment, has the effects of nourishing yin, cooling blood, detoxifying and the like, and has good effects of relieving spasm, relieving pain, removing putrefaction, stopping bleeding, promoting granulation, resisting bacteria, diminishing inflammation, promoting wound healing and the like. The developed jade skin detoxification paste shows good early-stage curative effect in clinical application of treating hand-foot syndrome caused by capecitabine, obtains consistent favorable comment of patients, and makes up for the defects of the prior art.

The invention adopts the following technical scheme:

on one hand, the invention provides a traditional Chinese medicine ointment (also called as jade skin detoxification ointment) for treating hand-foot syndrome, which is prepared from the following components: sesame oil, lithospermum, angelica dahurica, bletilla striata, ampelopsis japonica, angelica sinensis, rheum officinale, polygonum cuspidatum, honeysuckle, saposhnikovia divaricata, radix rehmanniae, pearl powder, dragon's blood, borneol, trichosanthes root, frankincense, myrrh, rosin, lard, beeswax and quicklime.

Further, the traditional Chinese medicine ointment is prepared from the following components in parts by weight: 1000-2000 parts of sesame oil, 50-100 parts of lithospermum, 50-100 parts of angelica dahurica, 50-100 parts of bletilla striata, 50-100 parts of ampelopsis japonica, 50-100 parts of angelica, 50-100 parts of rheum officinale, 50-100 parts of polygonum cuspidatum, 10-50 parts of honeysuckle, 50-100 parts of divaricate saposhnikovia root, 50-100 parts of radix rehmanniae, 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 and 150-360 parts of beeswax.

Further, the traditional Chinese medicine ointment is prepared from the following components in parts by weight: 2000 parts of sesame oil, 100 parts of lithospermum, 60 parts of angelica dahurica, 50 parts of bletilla striata, 60 parts of ampelopsis japonica, 100 parts of angelica, 50 parts of rheum officinale, 50 parts of polygonum cuspidatum, 50 parts of trichosanthes root, 50 parts of divaricate saposhnikovia root, 60 parts of radix rehmanniae, 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.

On the other hand, the invention provides a preparation method of a traditional Chinese medicine ointment for treating hand-foot syndrome, which comprises the following specific steps:

step one, soaking lithospermum in 1/2 of sesame oil, continuously stirring once a day for a week until the sesame oil is dark purple red; heating oleum Sesami, and frying radix Arnebiae to brown and crisp;

step two, adding 1/2 of sesame oil into radix angelicae, bletilla striata, radix ampelopsis, angelica sinensis, rheum officinale, polygonum cuspidatum, trichosanthes root, radix sileris, radix rehmanniae and honeysuckle, and soaking for one week; heating oleum Sesami, and frying the above materials to brown;

step three, fishing out the fried lithospermum, angelica dahurica, bletilla striata, ampelopsis japonica, angelica sinensis, rheum officinale, polygonum cuspidatum, trichosanthes root, divaricate saposhnikovia root, radix rehmanniae and honeysuckle respectively, and discarding; respectively adding Cera flava and adeps Phocae vitulinae into the two groups of oleum Sesami, stirring to melt, and standing to warm;

step four: adding the ground solution of Olibanum, myrrha, sanguis Draxonis, borneolum Syntheticum, colophonium, margarita powder and ethylparaben, stirring, adding calx water, and cooling.

Further, in the third step, the temperature of the sesame oil which is placed to be warmed is 45-55 ℃.

Further, the ethylparaben ethanol solution means that ethylparaben is completely dissolved in ethanol. Further, the ethanol is ethanol with the concentration of 60-99.9%. Further, the ethanol is ethanol with a concentration of 75%.

Further, in the fourth step, the weight ratio of the sesame oil obtained in the third step to the ethylparaben solution is 100.

Further, the quicklime water is clear liquid obtained by dissolving quicklime in water and clarifying, wherein the weight ratio of quicklime to water is 1:2.

further, in the fourth step, the particle size of the ground frankincense, myrrh, dragon's blood, borneol, rosin and pearl powder is 200 meshes.

On the other hand, the invention provides application of the traditional Chinese medicine ointment in preparing a medicine for treating hand-foot syndrome.

Has the advantages that:

the jade skin detoxification paste is prepared by adding traditional Chinese medicines such as Japanese ampelopsis, dragon's blood, borneol and the like on the basis of Ming dynasty traditional Chinese medicine surgical famous prescription ZIYUN paste, and has the effects of nourishing yin and moisturizing the muscles, detoxifying and activating blood, relieving spasm and pain, removing putrefaction and promoting granulation and the like. The ointment formula takes the lithospermum as a monarch drug, and can cool blood, activate blood, detoxify and promote eruption; the ministerial drugs comprise angelica, sesame oil, japanese ampelopsis root, angelica dahurica, bletilla striata, frankincense, myrrh and the like, and can enrich blood, promote blood circulation, heal sores, stop bleeding, clear heat and remove toxicity; the Chinese medicinal composition is supplemented with dragon's blood, borneol, rhubarb, giant knotweed, honeysuckle, pearl powder and the like, and can nourish yin, cool blood, remove putrefaction, promote tissue regeneration, relieve swelling and alleviate pain; the beeswax, the lard and the like can nourish yin and moisten skin and the like. Modern researches have also shown that various medicaments of the recipe have the pharmacological effects of inhibiting bacteria, resisting inflammation, resisting oxidation, relieving swelling and pain, promoting wound healing, improving microcirculation of the organism and the like.

The Chinese medicinal ointment is dark red slightly viscous topical ointment, and is applied to affected part uniformly and gently kneaded until the medicine is absorbed, 2-3 times per day, and 1-2 hr for each time. Because the product contains sesame oil, etc., and has slightly oily texture, the hands and feet can be wrapped by plastic gloves or plastic films. If the medicine is forgotten to be applied in time, the medicine needs to be applied.

The paste is prepared from the Ming dynasty traditional Chinese medicine surgery classic famous prescription of ZIYUN paste, which has curative effects on palm keratosis, burn, bedsore, tinea pedis, plantar impetigo, ulcer, erosion and various skin diseases. Through clinical observation and research, drugs such as white astringing, dragon's blood, borneol and the like are added on the basis of the Ziyun ointment, the clinical pathogenic characteristics of hand-foot syndrome caused by chemotherapeutic drug capecitabine are combined, the ancient prescription is improved by the dialectical treatment of the traditional Chinese medicine and combining modern clinical practical additional traditional Chinese medicines on the basis of exerting the effect of the ancient famous prescription, and the traditional Chinese medicine belongs to a new ancient prescription.

Compared with the urea ointment, the traditional Chinese medicine ointment has better curative effect through clinical treatment and application. The Jade skin detoxification ointment shows a certain treatment effect in the clinical treatment process at present, relieves the symptoms of ulceration pain, chapping and the like of hands and feet of patients, promotes wound healing, enhances the drug tolerance of capecitabine, improves the life quality of the patients, improves the treatment compliance of the patients, and is beneficial to fully playing the treatment effect of the capecitabine in tumors. Meanwhile, the method lays a foundation for developing a new traditional Chinese medicine for treating the hand-foot syndrome caused by capecitabine, has important clinical significance, and can create good social and economic benefits.

Drawings

FIG. 1 is a graph showing the comparison of the effect of a patient before and after a certain treatment

FIG. 2 is a graph showing the comparison of the effect of a patient before and after a certain treatment

Fig. 3 the traditional Chinese medicine ointment prepared in example 1.

Fig. 4 a pattern of the Chinese medicinal ointment prepared in example 1 after packaging.

Detailed Description

The invention will be further illustrated with reference to the following specific examples. These examples are intended to illustrate the invention and are not intended to limit the scope of the invention.

Example 1

A traditional Chinese medicine ointment for treating hand-foot syndrome is prepared from the following components in parts by weight: 2000 parts of sesame oil, 100 parts of lithospermum, 60 parts of angelica dahurica, 50 parts of bletilla striata, 60 parts of ampelopsis japonica, 100 parts of angelica, 50 parts of rheum officinale, 50 parts of polygonum cuspidatum, 50 parts of trichosanthes root, 50 parts of divaricate saposhnikovia root, 60 parts of radix rehmanniae, 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.

The preparation method comprises the following specific steps:

step one, soaking lithospermum in 1/2 of sesame oil, and stirring once a day for a week continuously until the sesame oil is dark purple red; heating oleum Sesami, and frying radix Arnebiae to brown and crisp;

step three, fishing out the fried lithospermum, angelica dahurica, bletilla striata, ampelopsis japonica, angelica, rheum officinale, polygonum cuspidatum, trichosanthes root, divaricate saposhnikovia root, radix rehmanniae and honeysuckle respectively; respectively adding Cera flava and adeps Phocae vitulinae into the two groups of oleum Sesami, stirring to melt, and standing at about 50 deg.C;

step four: adding 200 meshes of the ground frankincense, myrrh, dragon's blood, borneol, rosin, pearl powder and ethylparaben solution (the weight ratio of the sesame oil to the ethylparaben solution obtained in the third step is 100: 0.25), stirring uniformly, and adding quicklime water to obtain the ointment.

The quicklime water is clear liquid obtained by dissolving quicklime in water and clarifying, wherein the weight ratio of quicklime to water is 1:2.

example 2

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, 50-100 parts of angelica dahurica, 50 parts of bletilla striata, 100 parts of ampelopsis japonica, 50 parts of angelica, 100 parts of rheum officinale, 100 parts of polygonum cuspidatum, 50 parts of honeysuckle, 100 parts of saposhnikovia divaricata, 50 parts of radix rehmanniae, 50 parts of pearl powder, 10 parts of dragon's blood, 50 parts of borneol, 100 parts of trichosanthes root, 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.

The procedure was as in example 1.

Example 3

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, 100 parts of angelica dahurica, 60 parts of bletilla striata, 100 parts of ampelopsis japonica, 60 parts of angelica, 60 parts of rheum officinale, 60 parts of polygonum cuspidatum, 30 parts of honeysuckle, 70 parts of divaricate saposhnikovia root, 100 parts of radix rehmanniae, 30 parts of pearl powder, 50 parts of dragon's blood, 30 parts of borneol, 70 parts of trichosanthes root, 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.

The procedure was as in example 1.

Clinical data of traditional Chinese medicine ointment prepared in embodiment 1 of the invention for treating chemotherapeutic hand-foot syndrome

1. Clinical data:

1.1 study object

The outpatient service from the department of integration of traditional Chinese medicine and western medicine and the department of digestive medicine in tumor hospital of Hunan province or 60 cases of the patients who are diagnosed as colorectal cancer and who have developed hand-foot syndrome by capecitabine-containing regimen chemotherapy from 2021, 1 month, 1 day to 2022, 5 months, 30 days in the department of living. After the patients are classified into the hand-foot syndrome, the patients are divided into 30 cases of jade skin ointment groups and control groups by a random digital table method. Wherein the jade skin cream group comprises 15 male cases and 15 female cases; mean age (52.37 ± 10.04) years; among them 21 cases of colon cancer and 9 cases of rectal cancer. 15 male and 15 female control groups; mean age (51.77 ± 11.72) years; among them, there are 18 cases of colon cancer and 12 cases of rectal cancer. The general data comparison of two groups of patients has no statistical significance (P > 0.05) and is comparable.

1.2 medical record Standard

1.2.1 diagnostic criteria:

1) Western diagnostic criteria:

(1) diagnosis standard of colorectal cancer: according to the relevant standard of 'standard for diagnosing and treating common malignant tumor' in China 'written by the ministry of health of the people's republic of China, the colorectal cancer is proved by pathology.

(2) Grading standard of hand-foot syndrome: the chemotherapy-related hand-foot syndrome is classified into I-III grades by adopting the chemotherapy-related standard established by the National Cancer Institute (NCI), wherein the I-grade clinical manifestations are hand-foot pigmentation, redness and no pain, and the daily life is not influenced functionally; the II-grade clinical manifestations are erythema, swelling and pain of the skin of hands and feet, which affect daily life; the clinical manifestations of grade III are desquamation, blister, ulcer of hands and feet skin, accompanied by severe pain, and unable to live normally.

2) The traditional Chinese medicine syndrome diagnosis standard is as follows: the syndrome of yin deficiency and skin dryness, toxin Yu Lao obstruction is formulated according to the eleventh section of the TCM surgery of the fourth edition of the New century: the main symptoms are: local pain of hands and feet, rough and dry skin, thickening cuticle, erythema, purpura, erosion effusion, numbness of hands and feet and abnormal sensation; the secondary symptoms are as follows: dry mouth, dry stool, short or yellow-red urine; tongue manifestation: red tongue with little fluid and coating. The pulse condition: the pulse is thready, rapid or astringent. Symptoms that meet the above criteria are 2 primary symptoms and 1 secondary symptom.

1.2.2 inclusion criteria

1) Pathologically diagnosing colorectal cancer; 2) The expected life span is more than 3 months; 3) Meets the diagnostic standard of NCI hand-foot syndrome. 4) Using a capecitabine-containing chemotherapy regimen; 5) Age 18-73 years; 6) The Shenqing is cooperated, and the compliance of patients is good; 7) The traditional Chinese medicine syndrome diagnosis standard is met; 8) Subjects were fully informed of the study dosing regimen and possibly randomized to different groups, voluntarily participated in the study, and signed informed consent.

1.2.3 exclusion criteria

1) Serious primary nervous system diseases, such as senile dementia, epilepsy, parkinson's disease, etc. 2) With uncontrollable infections and metabolic diseases. 3) Serious diseases such as severe center of gravity, lung, liver and kidney; 5) The existing nervous system diseases such as numbness of hands and feet and dysesthesia. 6) Hands and feet are accompanied by other skin diseases. 7) Allergic to experimental drug components. 8) Those who cannot evaluate the therapeutic effect.

1.2.4 rejection Standard

1) Those who fail to meet the inclusion criteria and are mistakenly included; 2) Shed or lost visits during drug intervention; 3) Poor compliance and incapability of being matched with a therapist; 4) The patient voluntarily withdraws from treatment.

1.2.5 Exit (drop) criteria

1) Serious toxic and side effects appear during observation, and people need to quit; 2) Patients who require cessation and/or diversion of other treatments due to their condition; 3) Poor compliance, affecting the efficacy observers; 4) The patient is asked to withdraw from the experiment.

1.3 methods of treatment:

1.3.1 drugs:

the traditional Chinese medicine ointment (also called jade skin detoxification ointment) prepared in example 1 is prepared in a preparation room meeting GMP standards.

1.3.2 methods of administration:

the control group is topically applied with urea ointment for symptomatic treatment, and the skin ointment group is applied with skin detoxicating ointment for topical application on wound surface for treatment, 3 times per day (once every morning, noon and evening), and if there is washing (bathing and washing hands) within half an hour, the ointment can be applied twice for 21 days.

1.4 Observation index

1.4.1 grading evaluation standard of the degree of hand-foot syndrome: the grading of hand-foot syndrome in patients before and after treatment was recorded with reference to the national cancer institute general terminology for adverse events standard (NCI-CTCAE) version 4.0. And (3) curing: complete remission or grade reduction to grade 0; the method has the following advantages: the grade of the hand-foot syndrome is reduced by more than or equal to grade 1 but not to grade 0; and (4) invalidation: the grading of the hand-foot syndrome is unchanged or even worsened. Total effective rate = (cure + effective)/total number of cases × 100%.

1.4.2 pain VAS score: the patients were assessed for pain using a pain Visual Analogue Score (VAS), with 0 points representing no pain and 10 points representing intolerable severe pain, with higher scores indicating greater intensity of pain. VAS scores were recorded before and after treatment.

1.4.3 quality of life: the Chinese version of the hand and foot skin reaction quality of life scale (HF-QoL) was used to record the scale scores before and after treatment.

1.4.4 Chinese medicine syndrome integration: according to the guideline of clinical research on new drugs in Chinese medicine (2002), four main symptoms of dry skin, numbness, rash and pain, and secondary symptoms of dry mouth, stool and urine, tongue condition, pulse condition, etc. are selected. The major symptoms and the minor symptoms are divided into four grades according to the degree of absence, lightness, middle and weight, the integral of the major symptoms is respectively divided into 0, 2, 4 and 6 according to the degree, and the integral of the minor symptoms is respectively divided into 0, 1, 2 and 3 according to the degree. The traditional Chinese medicine syndrome integrals of the patients before and after treatment are recorded.

1.4.5 anxiety conditions: the anxiety self-rating scale (SAS) compiled in 1971 by History professor Zung, which comprises 20 items including 15 forward-rating items and 5 backward-rating items, wherein each item is graded by 4 grades, and the grades are analyzed by comparing with a norm or a control group and are mainly used for evaluating the subjective feeling of anxiety patients. The main statistical indicator of SAS is the total score. Adding the scores of the 20 items to obtain a rough score; and multiplying the rough score by 1.25 to obtain an integer part which is used as a standard score. The patients were scored on the anxiety self-rating scale before and after the recorded treatment.

1.5 statistical methods: the SPSS 25.0 statistical software was used. Metering dataBy using

To indicate. The measurement data comparison between two groups which are in accordance with normal distribution adopts independent sample t test, and the measurement data comparison between two groups which are not in accordance with normal distribution adopts nonparametric Mann-Whitney U test; adopting nonparametric Willcoxon rank sum test when the difference value of the pairing design measurement data does not conform to normal distribution; counting data is expressed by frequency count and composition ratio, comparison between groups is checked by chi-square, and grade data is checked by rank sum. P < 0.05 is statistically significant.

2. Results of the study

2.1 two groups of pre-and post-treatment HFS grading comparisons: between groups, the drug was comparable before treatment (P > 0.05);

TABLE 1 two groups of examples of HFS fractionation (%)

As can be seen from Table 1: after treatment, 17 cases of the jade skin ointment group 0 account for 56.7 percent; after treatment, 11 cases account for 0 grade cases in the control group, accounting for 36.7 percent; the jade skin cream group was suggested to be superior to the control group in reducing HFS grading. The wound surfaces of the hands and the feet of 2 cases and 3 cases in the jade skin ointment group after treatment are healed, while the wound surfaces of the hands and the feet of 2 cases and 3 cases in the control group are not obviously improved, so that the jade skin detoxification ointment has potential advantages in promoting wound surface healing and is worthy of further research.

2.2 the curative effect before and after the two groups of treatments is compared: and (4) carrying out treatment judgment according to the classification of the hand-foot syndrome before and after treatment.

Table 2 two therapeutic examples of treating hind paw syndrome (%)

Note: total effective rate = (number of cure cases + number of effective cases)/total number of cases × 100%. P < 0.05 compared to control group

And (4) conclusion: as can be seen from table 2, the effective rate of the skin care ointment group is 22 cases (17 cases are cured, 5 cases are effective), the ineffective rate is 8 cases, and the total effective rate is 73.3%; the control group has 14 effective cases (11 cured cases and 3 effective cases) and 16 ineffective cases, and the total effective rate is 46.7 percent.

2.3 comparison of pain VAS scores before and after treatment in two groups: the comparison of the two groups before treatment has no significant difference (P is more than 0.05),

TABLE 4 pain VAS score before and after treatment in two groups of patients

Group of	n	Before treatment	After treatment
				Jade skin cream group	30	3.17±1.46	1.97±1.32 ^**#
Control group	30	3.13±1.45	2.80±1.52 ^**

Note: p < 0.01 compared to pre-treatment; compared with the control group, # P < 0.05.

As can be seen from Table 4, in-group comparison, the VAS score after the jade skin ointment group treatment is reduced compared with that before the treatment, and the pain is obviously improved (P is less than 0.001) compared with that before the treatment; the VAS score after the treatment of the control group is reduced compared with that before the treatment, and the pain is improved (P is less than 0.01); the VAS score of the jade skin ointment group after treatment is lower than that of the control group, and the pain relieving effect is better than that of the control group (P is less than 0.05).

2.4 comparison of the hands and feet skin reaction quality of life scale (HF-QoL) before and after two groups of treatment: the two groups compared without significant difference before treatment (P > 0.05), note: p < 0.01 compared to the group of jade skin creams before treatment; p < 0.05 compared to control group before treatment; compared with the control group, # P < 0.05.

TABLE 5 HF-QoL score before and after treatment in two groups of patients

Group of	n	Before treatment	After treatment
				Jade skin cream group	30	39.50±9.12	31.70±7.25 ^**#
Control group	30	39.37±8.96	37.60±10.02 ^*

And (4) conclusion: compared with the group, the HF-QoL score after the treatment of the two groups is reduced (p is less than 0.05) compared with that before the treatment, but the reduction of the jade skin ointment group is more obvious (p is less than 0.05), which indicates that the jade skin ointment group can improve the life quality of patients.

2.5 comparison of anxiety self-rating scale (SAS) scores before and after treatment in two groups: the two groups before treatment have no significant difference (P is more than 0.05), the two groups in the group after treatment have reduced anxiety (P is less than 0.01) compared with the two groups before treatment, and the anxiety self-rating scale score of the jade skin ointment group after treatment is lower than that of the control group (P is less than 0.01).

TABLE 6 Pre-and post-treatment anxiety self-rating Scale (SAS) scores in two groups of patients

Group of	n	Before treatment	After treatment
				Jade skin cream group	30	58.53±5.10	49.53±5.10 ^**##
Control group	30	58.47±4.96	53.03±4.61 ^**

Note: p < 0.01 compared to pre-treatment; compared with the control group, # # P < 0.01.

And (4) conclusion: as can be seen from table 6, the group of skin creams improved the anxiety state of the patients.

2.6 the integral comparison of the traditional Chinese medicine syndrome before and after two groups of treatments: the two groups have no significant difference before treatment (P is more than 0.05), the traditional Chinese medicine syndrome integrals after the two groups are compared in the group are reduced compared with the traditional Chinese medicine syndrome integrals before treatment (P is less than 0.01), and the traditional Chinese medicine syndrome integrals after the treatment are lower than the control group (P is less than 0.001).

TABLE 7 integration of Chinese medical condition before and after treatment of two groups of patients

Group of	n	Before treatment	After treatment
				Jade skin cream group	30	17.73±4.98	6.23±3.21 ^**##
Control group	30	17.60±5.20	12.30±3.25 ^**

As can be seen from Table 7, the Yufu ointment composition can reduce the traditional Chinese medicine syndrome integral of the patients and improve the relevant symptoms of the patients.

3. Typical cases are as follows:

1. after a patient becomes a certain adult, male and a patient is 48 years old, and has rectal cancer stage IV, capecitabine is orally taken, foot desquamation, ulcer, ulceration and pigmentation occur, numbness and dullness are felt, daily walking and life are seriously affected, the grading of the hand-foot syndrome belongs to grade 3, the hand-foot syndrome symptoms of the patient are obviously improved after the ointment is applied to an affected part for 2-3 times every day until the treatment is finished, the ulceration and the gap are healed, no obvious pain and numbness exist, and the curative effect is good. (as shown in fig. 1).

2. When a patient takes capecitabine orally in the stage IV of colon cancer, the male patient has the symptoms of foot desquamation, dryness and pigmentation, feels pain with numbness and dullness and affects daily life, and after the ointment is used for being applied to an affected part for 2-3 times every day until treatment is finished, the hand-foot syndrome symptoms of the patient are obviously improved, the skin recovers moist and elasticity, no obvious pain and numbness exist, and the curative effect is good. (as shown in fig. 2).

4. Analysis of the results of the study shows

The jade skin detoxicating ointment is prepared with Chinese medicinal materials including white peony root, dragon's blood, borneol, etc. The lithospermum in the ointment has the effects of cooling blood, activating blood, detoxifying, promoting eruption and the like, and shows various pharmacological activities in the aspects of bacteriostasis, anti-inflammation and antioxidation. The angelica has the efficacies of enriching blood, promoting blood circulation and the like, and modern researches show that the angelica has the pharmacological effects of resisting bacteria and inflammation, regulating the immunologic function, resisting oxidation and the like. Borneol has the effects of clearing heat, relieving swelling and pain and the like for external use, and modern pharmacological studies show that the borneol has the effects of relieving swelling and pain, resisting inflammation, promoting wound healing and the like, and is clinically used for treating burns and scalds and the like. The dragon's blood has the effects of promoting blood circulation, relieving pain, removing blood stasis, relieving swelling, healing sore, stopping bleeding and the like, and has various physiological activities of resisting oxidation, promoting blood circulation, stopping bleeding, improving microcirculation of organisms and the like which are proved by pharmacology. The ampelopsis japonica has the effects of clearing away heat and toxic materials, healing sore and promoting granulation, and is used for treating carbuncle, cellulitis, back, sore, burn and scald and the like. In conclusion of the composition and mechanism analysis of the traditional Chinese medicines, according to research results, compared with urea ointment, the jade skin detoxification ointment can reduce VAS (pain-relieving by-products) scores of patients and relieve pain symptoms of the patients, probably because the formula contains traditional Chinese medicines such as borneol, angelica, dragon's blood and the like, the formula has the effects of promoting blood circulation to remove blood stasis, relieving swelling and pain and the like, and the urea ointment mainly has the action mechanism of dissolving keratin and increasing the hydration of protein, so that cutin is softened and dissolved, and the pain relieving effect is inferior to that of the jade skin detoxification ointment; meanwhile, the traditional Chinese medicine syndrome score is lower than that of the urea ointment, the effects on improving dry and chapped skin, numbness and pain and promoting wound healing are better than those of the urea ointment, and probably because the ointment contains the medicines of lithospermum, japanese ampelopsis root, dragon's blood, golden cypress, giant knotweed and the like, the ointment can nourish yin, cool blood, clear away heat and toxic materials, stop bleeding, promote tissue regeneration and the like, and can further relieve the relevant symptoms of hand-foot syndrome in traditional Chinese medicine; compared with urea ointment, the ointment can obviously improve related symptoms, lower the clinical grade of HFS of patients, improve the quality of life of the patients and further relieve the anxiety condition of the patients.

The study adopts a prospective open random control test design, and 60 cases of colorectal cancer patients with HFS (HFS-induced by capecitabine single drug or combined chemotherapy are collected for clinical study. The research preliminarily proves that the jade skin detoxification paste can effectively reduce the clinical grading of the capecitabine related HFS, relieve the pain symptom of a patient, promote the healing of a wound surface, reduce the traditional Chinese medicine syndrome score, improve the life quality of the patient, improve the anxiety condition of the patient and the like, and the jade skin detoxification paste has good curative effect and safety on the capecitabine related HFS. Therefore, the research preliminarily proves that the Jade skin detoxification ointment has definite clinical curative effect on capecitabine related HFS, and is worthy of further popularization and application.

Although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that changes may be made in the embodiments and/or equivalents thereof without departing from the spirit and scope of the invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. The traditional Chinese medicine ointment for treating hand-foot syndrome is characterized by being prepared from the following components: sesame oil, lithospermum, angelica dahurica, bletilla striata, ampelopsis japonica, angelica sinensis, rheum officinale, polygonum cuspidatum, honeysuckle, saposhnikovia divaricata, radix rehmanniae, pearl powder, dragon's blood, borneol, trichosanthes root, frankincense, myrrh, rosin, lard, beeswax and quicklime.

2. The traditional Chinese medicine ointment of claim 1, which is prepared from the following components in parts by weight: 1000-2000 parts of sesame oil, 50-100 parts of lithospermum, 50-100 parts of angelica dahurica, 50-100 parts of bletilla striata, 50-100 parts of ampelopsis japonica, 50-100 parts of angelica, 50-100 parts of rheum officinale, 50-100 parts of polygonum cuspidatum, 10-50 parts of honeysuckle, 50-100 parts of divaricate saposhnikovia root, 50-100 parts of radix rehmanniae, 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 and 150-360 parts of beeswax.

3. The traditional Chinese medicine ointment of claim 1, which is prepared from the following components in parts by weight: 2000 parts of sesame oil, 100 parts of lithospermum, 60 parts of angelica dahurica, 50 parts of bletilla striata, 60 parts of ampelopsis japonica, 100 parts of angelica, 50 parts of rheum officinale, 50 parts of polygonum cuspidatum, 50 parts of trichosanthes root, 50 parts of divaricate saposhnikovia root, 60 parts of radix rehmanniae, 10 parts of honeysuckle flower, 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.

4. A preparation method of the traditional Chinese medicine ointment for treating hand-foot syndrome according to any one of claims 1 to 3, which is characterized by comprising the following specific steps:

step three, fishing out the fried lithospermum, angelica dahurica, bletilla striata, ampelopsis japonica, angelica, rheum officinale, polygonum cuspidatum, trichosanthes root, divaricate saposhnikovia root, honeysuckle and radix rehmanniae respectively, and discarding; respectively adding beeswax and lard into the sesame oil heated and mixed in the first step and the second step, stirring and melting, and standing for warming;

5. The method of claim 4, wherein the temperature of the sesame oil left to warm in step three is 45-55 ℃.

6. The method of claim 4, wherein the ethylparaben solution is obtained by completely dissolving ethylparaben in ethanol.

7. The method according to claim 6, wherein the ethanol concentration is 60 to 99.9%.

8. The preparation method of claim 4, wherein the quicklime water is clear liquid obtained by dissolving quicklime in water and clarifying, wherein the weight ratio of quicklime to water is 1:2.

9. the preparation method according to claim 4, wherein in the fourth step, the particle size of the ground frankincense, myrrh, dragon's blood, borneol, rosin and pearl powder is 200 meshes; the weight ratio of the sesame oil obtained in the third step to the ethylparaben solution is 100.

10. Use of the traditional Chinese medicine ointment of claim 1 in the preparation of a medicament for treating hand-foot syndrome.