CN111700982A

CN111700982A - Traditional Chinese medicine composition for treating rash caused by antitumor drugs

Info

Publication number: CN111700982A
Application number: CN202010716360.7A
Authority: CN
Inventors: 舒琦瑾; 陈舒怡; 寿柳梅; 陈赐慧
Original assignee: First Affiliated Hospital of ZCMU
Current assignee: First Affiliated Hospital of ZCMU
Priority date: 2020-07-23
Filing date: 2020-07-23
Publication date: 2020-09-25
Anticipated expiration: 2040-07-23
Also published as: CN111700982B

Abstract

The invention provides a traditional Chinese medicine composition for treating rash caused by antitumor drugs, which comprises the following components in parts by weight: 9-18 parts of taxus mairei, 10-30 parts of coix seeds, 10-30 parts of honeysuckle, 10-30 parts of reed stems, 10-20 parts of angelica sinensis, 9-15 parts of trichosanthes roots, 9-20 parts of figwort roots, 3-9 parts of angelica dahurica and 5-15 parts of liquorice. The invention can obviously improve and cure the rash caused by the anti-tumor drug in a short time, is safe to use, has definite curative effect, and obviously improves the survival quality of patients on the premise of not reducing the anti-tumor treatment intensity.

Description

Traditional Chinese medicine composition for treating rash caused by antitumor drugs

Technical Field

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating rash caused by antitumor drugs.

Background

Today, the rapid development of precise medicine is not rare, adverse skin reactions caused by antitumor drugs are not rare, wherein rash is a great problem which troubles treatment decisions of clinicians, about 2/3 patients have rash, and about 32 percent of patients have to reduce the dosage of the drugs or even stop taking the drugs due to serious rash. Therefore, it not only affects the quality of life of the patient, but also, more seriously, it weakens the anti-tumor treatment strength and reduces the curative effect until the life span of the patient is shortened, or even the life of the patient is directly threatened due to serious infection.

The antineoplastic drug-related rash is a characteristic skin toxicity reaction, which mostly occurs after 2-4 weeks of drug treatment, and the rash types are various, and mainly comprise acneiform rash, maculopapule, seborrheic dermatitis-like rash, dermatomyositis-like rash, scleroderma-like dermatitis, wiping-like rash and the like, and even rare and high-death-risk Stevens-Johnson syndrome/toxic epidermal necrolysis disease occurs. The rash is diverse in appearance, and may be manifested as papules, pustules, erythematous maculopathy, blisters, exfoliation of the epidermis, etc., accompanied by itching, pain, dry skin, etc.

Currently, the international authoritative multi-national Cancer treatment society (national Association of supported Care in Cancer, MASCC) recommends: for the patients with the skin rash of the I grade and the II grade, the original dose of anti-tumor treatment is continuously maintained, and hormone and/or antibiotic treatment is externally applied; for grade III patients, the dosage of the medicine should be adjusted according to the instruction, if necessary, bacteria/fungi/virus culture is carried out, and hormone and/or antibiotic treatment is carried out, and the medicine is stopped if the condition is not improved after 2 weeks of evaluation.

Although the international authoritative MASCC takes measures of drug reduction and even drug withdrawal, local or systemic medication, and the like to slightly alleviate the rash. However, it is also pointed out that there is currently a lack of adequate clinical data to support the effectiveness of drugs for treating skin rash, and many recommendations are based on expert opinions or consensus and lack of high quality research. The long-term use of hormones, antibiotics and the like easily causes flora imbalance and the reduction of the immune function of organisms to cause new infection, and the whole body hormone treatment scheme or the influence on the anti-tumor immune response level of a patient reduces the anti-tumor curative effect. More worried is that not only does the rash affect the psychological and self-care ability of the patient, but also it is easy to progress to a wide range of infections in various parts of the whole body, which seriously threatens life, and such patients cannot continue to tolerate the original dose of anti-tumor therapy, but have to take measures of reducing dose or even stopping drug, which undoubtedly weakens the treatment intensity, affects the anti-tumor therapy process, and threatens the long-term survival of the patient. Even after the medicine is stopped, the rash still needs about 4 weeks to completely disappear, so the rash is still suffered from the trouble in a long time and cannot be normally used. MASCC considers that the rash caused by the antitumor drug is one of the hot spots and difficulties in the rehabilitation and palliative treatment of the tumor at present or in future.

For the skin rash caused by the antitumor drugs at home and abroad, the clinical curative effect is not exact, the support of high-quality clinical research evidence is lacked, part of research is only stayed in clinical experience and preventive medication research, the antitumor treatment strength is lacked to be considered, and the overall life cycle of a patient is ignored. Therefore, it is urgent to find a safe and effective method for treating skin rash caused by anti-tumor drugs without reducing the anti-tumor treatment intensity so as to ensure that patients can complete the treatment.

Disclosure of Invention

The invention aims to provide a traditional Chinese medicine composition for treating rash caused by anti-tumor drugs aiming at the defects of the prior art, and achieves the aim of relieving and curing the rash caused by the anti-tumor drugs.

The purpose of the invention is realized by the following technical scheme: a traditional Chinese medicine composition for treating rash caused by antitumor drugs comprises the following raw material medicines: 9-18 parts of taxus mairei, 10-30 parts of semen coicis, 10-30 parts of honeysuckle, 10-30 parts of reed stem, 10-20 parts of angelica sinensis, 9-15 parts of trichosanthes root, 9-20 parts of figwort, 3-9 parts of angelica dahurica and 5-15 parts of liquorice.

Further, the raw material medicine composition of the traditional Chinese medicine composition is preferably as follows: 15 parts of taxus mairei, 20 parts of semen coicis, 20 parts of honeysuckle, 20 parts of reed stem, 15 parts of angelica, 12 parts of trichosanthes root, 15 parts of figwort, 6 parts of angelica dahurica and 12 parts of liquorice.

Further, the raw material medicine composition of the traditional Chinese medicine composition is preferably as follows: 18 parts of taxus mairei, 30 parts of semen coicis, 30 parts of honeysuckle, 30 parts of reed stem, 20 parts of angelica, 15 parts of trichosanthes root, 20 parts of figwort, 9 parts of angelica dahurica and 15 parts of liquorice.

Further, the raw material medicine composition of the traditional Chinese medicine composition is preferably as follows: 9 parts of taxus mairei, 10 parts of semen coicis, 10 parts of honeysuckle, 10 parts of reed stem, 10 parts of angelica, 9 parts of trichosanthes root, 9 parts of figwort, 3 parts of angelica dahurica and 5 parts of liquorice.

Further, the traditional Chinese medicine composition is prepared into an external preparation, and the external preparation comprises a liquid preparation, a gas preparation, a solid preparation and a semisolid preparation.

The invention has the advantages that the invention can obviously improve and cure the rash caused by the anti-tumor drug in a short time, is safe to use and definite in curative effect, and obviously improves the survival quality of patients on the premise of not reducing the anti-tumor treatment intensity.

Drawings

FIG. 1 is a graph showing comparison between the treatment of the present invention and the treatment of perilabial EGFR-TKIs-related skin rash (A: treatment day 0, B: treatment day 7, C: follow-up at 20 days after discharge) in typical case 1 of example 4.

FIG. 2 is a graph showing a comparison between the treatment of EGFR-TKIs-associated rash on the back of a typical case 1 of example 4 by the present invention (A: treatment day 0, B: treatment day 7, C: follow-up on post-discharge day 20).

FIG. 3 is a graph showing a comparison between the treatment of axillary EGFR-TKIs-associated skin rash according to the present invention and the treatment of axillary EGFR-TKIs of example 4 before and after the treatment (A: treatment day 0, B: treatment day 7, C: 20 days after discharge).

FIG. 4 is a graph comparing the facial MEK inhibitor-associated rash before and after treatment with the present invention (A: day 0 of treatment, B: day 3 of treatment, C: day 7 of treatment) for typical example 2 of example 4.

FIG. 5 is a comparison of MEK inhibitor-associated skin rash on the back before and after treatment according to the present invention for example 4, representative example 2 (A: day 0 of treatment, B: day 3 of treatment, C: day 7 of treatment).

FIG. 6 is a comparison of breast MEK inhibitor-associated rash before and after treatment with the present invention for typical case 2 of example 4 (A: day 0 of treatment, B: day 3 of treatment, C: day 7 of treatment).

FIG. 7 is a comparison of the treatment of EGFR inhibitor-associated rash before and after treatment according to the present invention in exemplary case 3 of example 4 (A: day 0 of treatment, B: day 3 of treatment, C: day 7 of treatment).

FIG. 8 is a comparison of perilip EGFR inhibitor-associated rash before and after treatment according to the present invention in typical case 3 of example 4 (A: day 0 of treatment, B: day 3 of treatment, C: day 7 of treatment).

FIG. 9 is a comparison of the postcervical EGFR inhibitor-associated rash before and after treatment with the present invention in typical case 3 of example 4 (A: day 0 of treatment, B: day 3 of treatment, C: day 7 of treatment).

FIG. 10 is a typical example 4 of example 4, in which scrub rash (right sole) was compared before and after treatment by the present invention (A: treatment day 0, B: treatment day 3, C: treatment day 7, D: follow-up on post-discharge day 23).

FIG. 11 is a comparison of breast PD-1 inhibitor associated rashes before and after treatment with the present invention for typical case 5 of example 4 (A: day 0 of treatment, B: day 3 of treatment, C: day 7 of treatment).

FIG. 12 is a comparison of Stevens-Johnson syndrome/toxic epidermal necrolysis (orolabial mucosa) of example 4 in Stevens-Johnson syndrome/toxic epidermal necrolysis (orolabial mucosa) before and after treatment with the present invention (A: day 0 of treatment, B: day 2 of treatment, C: day 5 of treatment, D: day 8 of treatment, E: day 9 of treatment).

FIG. 13 is a comparison of Stevens-Johnson syndrome/toxic epidermal necrolysis (hands) of example 4 before and after treatment with the present invention (A: day 0 of treatment, B: day 2 of treatment, C: day 5 of treatment, D: day 8 of treatment, E: day 9 of treatment).

FIG. 14 is a comparison of Stevens-Johnson syndrome/toxic epidermal necrolysis (foot) for example 4, compared to previous and subsequent treatment with the present invention (A: treatment day 0, B: treatment day 2, C: treatment day 5, D: treatment day 8, E: treatment day 9).

Detailed Description

And (3) taxus mairei: the traditional Chinese medicine is slightly bitter and pungent in taste and mild in nature, has the effects of detoxifying, resolving masses, activating blood, eliminating phlegm, reducing swelling and dredging channels, is used for treating symptoms such as carbuncle sore, pyogenic infection, traumatic injury and the like, and has the effects of relieving pain, resisting inflammation and improving the hemodynamics as shown by modern researches.

Coix seed: the coix seed wine is sweet and light in taste and cool in nature, enters spleen, stomach and lung channels, has the functions of promoting diuresis and strengthening spleen, removing arthralgia, expelling pus, detoxifying and removing stasis, is mainly used for treating edema, rheumatic arthralgia, flat wart and the like, and has the functions of resisting bacteria, resisting viruses, calming and easing pain, resisting inflammation, inhibiting histamine release of mast cells and the like as proved by modern pharmacology.

Honeysuckle flower: the honeysuckle flower tea is sweet in taste and cold in flavor, enters lung, heart and stomach channels, has the effects of clearing heat and removing toxicity, cooling and dispersing wind heat, is mainly used for treating carbuncle and furuncle, and modern pharmacological studies show that the honeysuckle flower tea has the effects of resisting bacteria and viruses, resisting inflammation and relieving pain, reducing specific IgE, inhibiting histamine release of mast cells and the like.

And (3) reed stems: the traditional Chinese medicine composition has sweet taste and cold nature, enters heart and lung channels, has the efficacy of clearing heat and removing toxicity, is mainly used for treating carbuncle, and has the effects of clearing heat, resisting bacteria, relieving pain and the like according to modern pharmacology.

Chinese angelica: the angelica sinensis is sweet and pungent in taste and warm in nature, enters liver, heart and spleen channels, has the effects of nourishing blood, promoting blood circulation and relieving pain, treats the diseases of blood and blood circulation, and is mainly used for treating carbuncle-abscess sores and skin numbness and the like, and modern pharmacological studies show that the angelica sinensis can reduce capillary permeability, inhibit synthesis and release of PGE2, promote blood circulation, regulate immunity, and has the effects of resisting inflammation, relieving pain and the like.

Trichosanthes root: the traditional Chinese medicine is sweet in taste, slightly bitter and slightly cold in nature, enters lung and stomach channels, has the effects of clearing heat, promoting fluid production, reducing swelling and expelling pus, and is mainly used for treating pyocutaneous disease and pyogenic infection.

Figwort root: the traditional Chinese medicine composition is sweet, bitter, salty and slightly cold in nature, enters lung, stomach and kidney channels, has the effects of cooling blood, nourishing yin, purging fire and detoxifying, is mainly used for treating carbuncle swelling and sore toxin, and is shown by modern pharmacology to be capable of resisting bacteria and inhibiting the generation of inflammation media.

Radix angelicae: the traditional Chinese medicine composition has pungent taste and warm nature, enters stomach, large intestine and lung channels, has the effects of dispelling wind and eliminating dampness, and reducing swelling and relieving pain, is mainly used for treating carbuncle ulcer, skin dryness and itching and mange, and has the effects of relieving fever, easing pain, resisting inflammation, inhibiting pathogenic microorganisms, whitening and removing freckles, maintaining and protecting skin, improving hemorheology and the like according to modern pharmacology.

Licorice root: the liquorice has sweet taste and neutral nature, enters heart, lung, spleen and stomach channels, has the functions of tonifying spleen and qi, clearing away heat and toxic materials, relieving spasm and pain and harmonizing the drugs, is mainly used for treating carbuncle swelling and sore toxicity, and modern pharmacology proves that the liquorice can resist inflammation, allergy and histamine release, is applied to rash and pruritus and has remarkable effect.

The source of the traditional Chinese medicine is not particularly limited, and the traditional Chinese medicine can be prepared from conventional commercially available traditional Chinese medicines which are well known to those skilled in the art.

The traditional Chinese medicine composition for treating the skin rash caused by the antitumor drugs comprises taxus mairei, semen coicis, honeysuckle, reed stems, angelica sinensis, trichosanthes kirilowii maxim, radix scrophulariae, radix angelicae and liquorice. The rash caused by the antitumor drugs is usually manifested by red and swollen rash around the body, exudation, pruritus, pain, yellow urine, dry and hard stool, red tongue with yellow and greasy coating, and wiry pulse. Under the guidance of the theory of traditional Chinese medicine, by combining the common expression of the skin rash caused by the anti-tumor drugs and the clinical experience of the inventor, the inventor thinks that the pathogenesis of the skin rash caused by the anti-tumor drugs is as follows: the anti-tumor medicine damages the body, is easy to be infected by wind evil, has endogenous damp toxin pathogenic heat, has insufficient source of qi and blood biochemistry, can not nourish nutrient blood and dredge the exterior of the skin, accumulates the long-term anti-tumor medicine and metabolites thereof to form tangible pathogenic factors, has internal drug toxicity, internally stagnates and transforms into heat, has heat to hurt yin, has damp-heat to accumulate and evaporate, and has blood stasis to stagnate blood vessels to be stagnated in the skin to cause skin rash. The external preparation belongs to one of transdermal drug delivery systems, and the externally-applied medicine is delivered and absorbed through skin or mucous membrane and the like to directly reach the focus, thereby avoiding the first pass effect of the liver and the damage of gastrointestinal tract, ensuring the local drug concentration and not influencing anti-tumor drugs; on the other hand, because the medicine acts on local parts for a long time, the blood concentration is lower, and the medicine is safe and reliable when being metabolized and excreted by the liver and the kidney. The inventor uses the principles of clearing away heat and toxic material, promoting diuresis and activating blood circulation, and dispelling wind and arresting itching as treatment rules, repeatedly knocks and screens medicines, and invents the traditional Chinese medicine composition. The invention takes the taxus mairei as a monarch drug, compared with other traditional Chinese medicines with the effects of clearing heat and removing toxicity, the taxus mairei has the effects of removing toxicity and dissipating stagnation, activating blood and eliminating phlegm, and reducing swelling and stimulating menstrual flow, and can dredge blood vessels and eliminate rash by eliminating pathogenic heat and toxicity. The coix seeds have the effects of promoting diuresis, tonifying spleen, relaxing muscles and tendons, eliminating arthralgia, clearing heat and expelling pus, and can dispel damp evil, poison and heat and relieve rash exudation; honeysuckle flower has the effects of clearing heat and removing toxicity, and cooling and dispersing wind heat, is good at treating carbuncle and furuncle, strengthens the effects of clearing heat and removing toxicity of monarch drugs, and can cool and disperse wind heat at the same time, so that pathogenic factors go out; the reed stem has the effects of clearing heat, detoxifying and expelling pus, is good at treating carbuncle and cellulitis, and can strengthen the effects of relieving swelling and removing rash; the three medicines are compatible and are used as ministerial medicines, which not only helps the monarch medicines clear heat and detoxify, but also has the effects of promoting diuresis and dispelling wind, and enables the toxic and pathogenic heat of the medicines to be released from the outside. The angelica sinensis has the effects of nourishing blood, promoting blood circulation and relieving pain, the angelica dahurica has the effects of dispelling wind, eliminating dampness and relieving swelling and pain, the drug toxicity eruption is formed by the struggle of three pathogenic factors of wind, dampness and heat, and the monarch and minister drugs attack the patent to remove dampness and heat and have the effects of dispelling wind and dredging channels, so the angelica sinensis and the angelica dahurica are used together to strengthen the effects of dispelling wind and nourishing blood, the blood is treated when the wind is treated, the wind in the blood circulation is automatically eliminated, and the pruritus and the; the radix scrophulariae has the effects of cooling blood, nourishing yin, purging pathogenic fire and detoxifying, not only assists the monarch and minister drugs in detoxifying and dissipating stagnation, but also can nourish yin and generate body fluid, so that the yin is not lingering to the pathogen, and the blood is cooled without damaging the body resistance; the angelica, the angelica dahurica, the radix trichosanthis and the radix scrophulariae are used as adjuvant drugs, so that the effects of fire purging and detoxification of monarch and minister drugs are enhanced, wind dispelling, blood nourishing, yin nourishing and body fluid production are achieved, the body resistance is strengthened without attaching to evil, the body resistance is eliminated without damaging the body resistance, and the repair of the rash is promoted. Licorice root, radix Glycyrrhizae coordinates the effects of the other drugs in the recipe, and has the effects of clearing away heat and toxic materials. The whole formula has the effects of monarch, minister, assistant and guide, has the effects of clearing heat and removing toxicity, promoting diuresis and activating blood, dispelling wind and arresting itching, and is good at treating rash caused by anti-tumor drugs.

The invention takes the raw materials according to the proportion, and can be prepared into the external preparation according to the conventional preparation process after being extracted by water or organic solvent according to the conventional extraction method.

The conventional extraction method comprises any one of reflux extraction, immersion extraction, decoction extraction, ultrasonic extraction or percolation extraction, or combination of different extraction methods; the organic solvent is selected from methanol, ethanol solution with volume concentration of 20-95% and acetone; the external dosage forms comprise liquid dosage forms, gas dosage forms, solid dosage forms and semisolid dosage forms. To more clearly show the technical solutions, objects and advantages of the present invention, the present invention will be further clearly and specifically explained below with reference to specific embodiments and the accompanying drawings. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

Prescription: 15g of taxus mairei, 20g of coix seeds, 20g of honeysuckle, 20g of reed stems, 15g of angelica sinensis, 12g of trichosanthes root, 15g of figwort, 6g of angelica dahurica and 12g of liquorice;

the preparation method comprises the following steps: the raw material medicines are taken according to the proportion, 10 times of water by mass is added, the decoction is carried out twice, the filtrate is obtained by filtration, the concentration and the filtration are carried out, and the package with 100 ml/bottle is packed.

The use method comprises the following steps: it can be directly applied to the rash part.

Example 2

Prescription: 18 parts of taxus mairei, 30 parts of semen coicis, 30 parts of honeysuckle, 30 parts of reed stems, 20 parts of angelica sinensis, 15 parts of trichosanthes root, 20 parts of figwort, 9 parts of angelica dahurica and 15 parts of liquorice;

the preparation method comprises the following steps: taking the raw materials according to a certain proportion, carrying out reflux extraction twice by 50% ethanol, combining the extracting solutions, filtering, recovering ethanol, adding water for dissolution, carrying out reduced pressure concentration until the density is 1.10(60 ℃), carrying out high-speed centrifugation, taking the supernatant, adding conventional auxiliary materials, and preparing the external preparation.

Example 3

Prescription: 9g of taxus mairei, 10g of coix seeds, 10g of honeysuckle, 10g of reed stems, 10g of angelica sinensis, 9g of trichosanthes root, 9g of figwort, 3g of angelica dahurica and 5g of liquorice;

the preparation method comprises the following steps: the preparation method is the same as that of example 1.

Example 4

Typical case 1: yang Yi in a male age of 63 years

As shown in fig. 1-fig. 3, 2018-7 confirmed diagnosis of EGFR 19 exon deletion mutation at stage IV of lung adenocarcinoma, and 7-25 oral iressa 250mg qd treatment. 8-27 appear a plurality of skin rashes of the whole body, distribute in the perioral, axillary, chest back, scrotum, etc., the skin rashes are red, the local swelling, some visible purulent secretion, accompanied with severe pruritus, pain, influence sleep, have not been relieved all the time, 9-4 income I treatment, the area of the skin rashes is 31%, diagnose: EGFR-TKIs associated rash grade III. After the patient is hospitalized, the patient 1 is ordered to continue taking the oral Iressa in the original dosage, the traditional Chinese medicine composition of the invention example 1 is used for external treatment, the skin rash on the whole body obviously fades after 7 days of treatment without pruritus, the area of the skin rash is 5%, the skin rash is graded and reduced to the I grade, and the patient is discharged. After discharge, case 1 was treated with the original dose of orally administered iressa, and the traditional Chinese medicine composition of the invention example 1 was not used again, and 9-27 had no recurrence of rash with follow-up visits.

Typical case 2: somesome hair, male, age 62

As shown in fig. 4-6, 2018-6 shows red rash on face and back, some rashes can be seen as purulent secretion with pruritus and pain due to the confirmed malignant melanoma oral administration of semetinib 100mg bid treatment, and the area of the rash is 33%, and the diagnosis is as follows: MEK inhibitor-associated rash grade iii. After hospitalization, case 2 is ordered to continue to take oral administration of the same dosage of semetinib, and the external treatment of the traditional Chinese medicine composition of the invention example 1 is given, case 2 obviously relieves pruritus and pain on the 3 rd day of treatment, the systemic rash obviously subsides, the rash further subsides on the 7 th day of treatment, the area of the rash is 8%, and the level of the rash is graded to be I.

Typical case 3: yang Yi in a male age of 57

As shown in fig. 7-9, when cetuximab is applied to treat colon cancer in stage iv, red rashes of head and neck and chest and back appear in 2019-9-11 days, pustules can be seen on part of rashes, pruritus is accompanied, no improvement and reverse aggravation are seen on the rashes in the intermittent period of cetuximab application, the area of the rashes is 31%, and the diagnosis is as follows: grade iii EGFR inhibitor-associated rash. After hospitalization, case 3 was treated with cetuximab continuously according to the schedule, and the external treatment of the traditional Chinese medicine composition of the invention example 1 was given, so that on the 3 rd day of treatment, case 3 had obviously relieved pruritus, the rash of the head, neck, chest and back was partially resolved, and on the 7 th day of treatment, the original rash was basically scabbed, the area of the rash was 13%, and the rash was graded down to the II grade.

Typical case 4: wu Yi in Wu Dynasty, female, age 57

As shown in figure 10, due to the confirmed diagnosis of the stage IV of the right lung adenocarcinoma, 2019-6 had been treated with afatinib 40mg qd orally, and 2019-8 had skin folds and ulceration at the right sole, ankle, hip, vulva and the like, accompanied by pruritus and pain, affecting sleep, and the application of mupirocin ointment to the outside hospital was ineffective. 2019-9 pustules at the foot bottom ulcer part are increased and are self-broken, the rash is light red, granulation tissues can be seen in the middle, the pain is difficult to endure and is stabbing pain, the foot bottom ulcer part cannot walk and is accompanied by numbness and burning sensation, and the diagnosis is that: the rash was observed intermittently. After admission, case 4 was ordered to continue the original dose of oral afatinib, and the external treatment of the traditional Chinese medicine composition of the invention example 1 was given, on the 3 rd day of treatment, case 4 had significantly relieved pain, on the 7 th day of treatment, case 4 had no pain and was able to walk freely and was given for discharge. Case 4 after discharge continued the original dose of oral afatinib treatment and no further use of the traditional Chinese medicine composition of the invention example 1, the 10-23 followed rash had healed and no recurrence.

Typical case 5: wang somebody, man, 63 years old

As shown in fig. 11, when liver cancer is diagnosed at iv stage, 2019-10-02, 10-30 and 11-27 are treated by regorafenib + terepril monoclonal antibody in the external hospital, maculopapule appears in whole body at 11-29, both forearms, both hands, both shanks and both feet are affected, the color is bright red, the itch is obvious, the sleep is affected, no pain is caused, the terepril monoclonal antibody is not improved and is aggravated in a reverse way in the intermittent period, the area of the rash is 66%, and the diagnosis is as follows: PD-1 inhibitor-associated rash grade iii. After the patient is admitted, the traditional Chinese medicine composition of the invention in the embodiment 1 is used for treatment, the systemic maculopapule of the patient on the treatment day 3 basically fades away, a little mark remains, and the pruritus is obviously relieved. On the 7 th day of treatment, the maculopapule of the whole body of the patient disappears, no itch exists, the area of the rash is 0%, the rash area is graded to 0 level, and the treatment of the regorafenib and the terepril monoclonal antibody is continuously used according to the period after the patient is healed and discharged.

Typical case 6: wu Yi in Wu, Man, 62 years old

As shown in FIGS. 12-14, the FOLFIRINOX regimen was applied for 4 cycles at 2020-02-04 to 2020-03-17 during the IV phase of pancreatic cancer followed by immunotherapy with Terepril mab in the last two cycles. 4-9 red rash, pruritus and swelling of hands and feet, and 4-12 blisters, swelling and pain, oral ulcer, food intake influence, ulcer at vulva mucosa, and about 14% of body surface area are affected, so that the traditional Chinese medicine is admitted to hospital, and the diagnosis is combined with skin biopsy pathology: Stevens-Johnson syndrome/toxic epidermal necrolysis. After the patient is admitted, the traditional Chinese medicine composition disclosed in the embodiment 1 of the invention is used for external treatment, and on the 2 nd day of treatment, hand blisters are shrunken, skin swelling is relieved, and ulcers and scabs on the oral lip part are generated. On the 5 th day of treatment, hand swelling subsided, skin wrinkles increased, foot swelling alleviated, and ulcer of the lips basically scabbed. On the 8 th day of treatment, the eschar skin of the mouth and lips fell off, the neogenetic mucous membrane was intact, the hand and foot parts were molted, and the neogenetic skin was intact. On the 9 th day of treatment, the lips and hands and feet were substantially healed, and the new skin and mucous membrane were intact.

Example 5

The invention relates to small sample clinical observation of a traditional Chinese medicine composition for treating rash caused by antitumor drugs

Clinical data: 33 patients with grade III rash caused by 2018-6 to 2020-5 treated with antitumor drugs in our hospital have the average age of 59.21 years, the minimum person is 36 years and the maximum person is 72 years, wherein the number of the patients is 20 in males and 13 in females. The types of malignant tumors include: 19 non-small cell lung cancer, 1 malignant melanoma, 9 colorectal cancers, 1 gastric cancer, 1 pancreatic cancer and 2 liver cancers. The anti-tumor drugs include: gefitinib 9 human, erlotinib 2 human, erlotinib 3 human, afatinib 3 human, ocitinib 2 human, cetuximab 9 human, semetinib 1 human, caprolizumab 2 human, teriepril mab 1 human, palbociclizumab 1 human (table 1).

Table 1: study population characterization

Inclusion criteria were: (1) the age is more than 18 years old, and the nature is not limited; (2) receiving an anti-tumor drug to treat the patient; (3) the kit meets the NCI-CTCAE vs5.0 grade III skin rash diagnosis standard; (4) the general situation is good, KPS is more than 60 minutes, and the predicted life cycle is more than 3 months; (5) the major organ levels met the following criteria: the blood routine examination standard needs to meet the following requirements: ANC is more than or equal to 1.5 multiplied by 109/L, PLT is more than or equal to 75 multiplied by 109/L, Hb is more than or equal to 80 g/L; the biochemical inspection needs to meet the following standards: TBIL < 1.5 × ULN, ALT, AST < 2.5 × ULN with liver metastasis the subject can be < 5 × ULN, BUN and Cr are less than or equal to 1 × ULN or endogenous creatinine clearance is more than or equal to 50ml/min (Cockcroft-Gault formula); (6) subjects voluntarily added the study, signed an informed consent, with good compliance, in coordination with follow-up visits.

Exclusion criteria: (1) there were skin lesions or skin diseases that the investigator considered to affect the study, or had a history of other drug exposure allergies; (2) study treatment received hormones or antibiotics or any other drug that may affect skin rash within 1 week before initiation of treatment, including Chinese patent drugs and herbs; (3) there are serious or uncontrollable systemic diseases (e.g. unstable or uncompensated respiratory, circulatory, digestive, urinary, hematologic, etc. diseases); (4) the existing history of definite neurological or mental disorders, including epilepsy, dementia and the like; (5) patients in gestation or lactation; (6) the investigator believes that the subject is unlikely to be able to complete the study or to comply with the requirements of the study (for regulatory or other reasons);

diagnostic criteria for rash: with reference to the national cancer institute adverse event terminology standard version 5.0(NCI-ctcaevs5.0), in conjunction with a rash-associated clinical study, rashes were graded as follows (tables 2-4):

table 2: standard for grading acneiform rash

Table 3: maculopapular grading Standard

Table 4: bullous dermatitis/Stevens-Johnson syndrome (SJS)/Toxic Epidermal Necrolysis (TEN)

The research method comprises the following steps: a prospective, open, one-armed clinical study approach was adopted.

The treatment scheme comprises the following steps: continuing to receive the anti-tumor medicament treatment in the original dose, and simultaneously using the traditional Chinese medicine composition (prepared by the method of the example 1); the administration mode of the invention is as follows: the medical non-woven fabric is soaked in the liquid medicine and externally applied to the rash part for 20 minutes 2 times a day until any one of the following conditions occurs: (1) the endothelial rash declined to grade 0 in 7 days; (2) the patient cannot tolerate the symptom without relieving within 7 days; (3) until day 7 was complete.

Observation indexes are as follows: comparing the symptoms and signs of the rash at 3 rd and 7 th days before and after treatment, referring to the standard edition of adverse event terminology of national cancer institute of America Standard 5.0(NCI-CTCAE vs5.0), grading the rash by combining with the related clinical research of the rash, evaluating the total effective rate, the recovery rate and the remission rate, and simultaneously evaluating the safety of the invention.

And (4) judging the standard: and (3) healing: the rash is graded and reduced to 0 grade after the drug is taken, and no accompanying symptoms or infection symptoms exist; and (3) relieving: after the medicine is taken, the grade of the rash is reduced by 1 grade or more, but the grade is not reached to 0 grade; and (4) invalidation: the grade of rash after administration is unchanged or increased by 1 grade or more. Therefore, the total effective rate, cure rate and remission rate are calculated as follows: the cure rate is 100% of the number of people reaching the cure standard/total number of people; the remission rate is 100% of the number of people who meet the remission criteria/total number of people; the total effective rate is the cure rate plus the remission rate.

The statistical method comprises the following steps: statistical analysis was performed using SPSS 24.0 software. The interclass comparison adopts independent sample t test, the intraclass comparison before and after treatment adopts paired sample t test, and the measurement data meeting normal distribution adopts mean plus or minus standard deviation

Expressed as the data usage (%) in counts, the data were analyzed by chi-square test. The treatment effect is considered as p less than 0.05, and statistical difference exists.

As a result: on the premise of not changing the anti-tumor treatment intensity, the total effective rate is 60.61% on the 3 rd day of treatment; on the 7 th day of treatment, the total effective rate is 90.91%, the cure rate is 18.18%, and the remission rate is 72.73% (tables 5 and 6). During the treatment process, adverse events related to the invention do not occur, and indexes such as blood routine, liver and kidney functions and the like of patients before and after treatment have no obvious statistical difference, so that the invention is safe to use and has no obvious toxic or side effect (Table 7).

Table 5: the classification and distribution of the rash of the patients on 0, 3 and 7 days

Table 6: effective rate distribution of the invention on days 0, 3 and 7

Table 7: the invention can be used for treating the change of the blood routine, the liver and the kidney functions of patients before and after the administration

Item	Before treatment	After treatment	P value
				White blood cells (× 10)⁹/L)	5.78±1.76	6.09±1.58	0.63
Hemoglobin (g/L)	105.4±11.66	105±11.09	0.60
				Platelets (× 10)⁹/L)	146.9±42.15	147.4±42.05	0.07
Glutamic-pyruvic transaminase (U/L)	35.15±5.51	35.36±4.75	0.50
				Glutamic-oxalacetic transaminase (U/L)	35.73±4.51	36.12±4.44	0.24
Blood creatinine (mu mol/L)	64.70±12.12	64.91±11.83	0.21

Example 6: comparison of clinical efficacy of different formulations on skin rash

The first prescription is as follows: 15g of taxus mairei, 20g of coix seeds, 20g of honeysuckle, 20g of reed stems, 15g of angelica sinensis, 12g of trichosanthes root, 15g of figwort, 6g of angelica dahurica and 12g of liquorice;

and a second prescription: 20g of honeysuckle, 15g of angelica, 15g of figwort and 12g of liquorice;

and a third prescription: 20g of caulis spatholobi, 20g of honeysuckle stem, 15g of angelica, 15g of figwort root and 12g of liquorice;

Clinical data: 74 patients with grade III skin rash caused by antitumor drugs in the hospital from 2015-8 to 2018-5 are collected.

The research method comprises the following steps: using a retrospective case control study, patients were divided into A, B, C groups with three groups of basic data as shown in Table 8.

Table 8: A. b, C three groups of basic data of patients

The treatment scheme comprises the following steps: group A: giving an intervention to the prescription; group B: intervention is given to the prescription II; group C: giving prescription three interventions; the intervention mode is as follows: the medical non-woven fabric is soaked in the liquid medicine and is externally applied to the rash part for 20 minutes for 2 times a day, and the medicine is continuously applied for 1 week.

Follow-up index: with reference to national cancer institute adverse event terminology standard version 5.0 (NCI-ctcaevss 5.0), statistical analysis of classification of rash before and after administration of drugs was performed on each group of patients in combination with clinical studies related to rash, and total effective rate, recovery rate, and remission rate were evaluated (see tables 2, 3, and 4 for criteria of rash classification).

Expressed as the data usage (%) in counts, the data were analyzed by chi-square test. The treatment effect is considered as that p is less than 0.05In the statistical case.

As a result: A. b, C Classification of rash before and after three groups of medicines, and its total effective rate, cure rate and remission rate are shown in tables 9-12

Table 9: grading of rash before and after group A administration

Table 10: grading of rash before and after group B administration

Table 11: grading of rash before and after group C administration

Table 12: A. b, C comparison of total effective rate, cure rate and remission rate

	Total effective rate (%)	Recovery rate (%)	Remission rate (%)
				Group A	91.67	20.83	70.84
Group B	65.22	13.04	52.18
				Group C	74.07	14.81	59.26

The results show that: the total effective rate of the group A is obviously higher than that of the group B, C, p is less than 0.05, and statistical difference exists, which shows that the curative effect of the group A is better than that of the group B, C, so that the effect of the formula I (namely the invention) is better.

Example 7 comparison of clinical efficacy and safety of different drug combinations for skin rash

Proportioning one: 15g of taxus mairei, 20g of coix seeds, 20g of honeysuckle, 20g of reed stems, 15g of angelica sinensis, 12g of trichosanthes root, 15g of figwort, 6g of angelica dahurica and 12g of liquorice;

proportioning two: 18g of taxus mairei, 30g of coix seeds, 30g of honeysuckle, 30g of reed stems, 20g of angelica sinensis, 15g of trichosanthes root, 20g of figwort, 9g of angelica dahurica and 15g of liquorice;

proportioning three: 9g of taxus mairei, 10g of coix seeds, 10g of honeysuckle, 10g of reed stems, 10g of angelica sinensis, 9g of trichosanthes root, 9g of figwort, 3g of angelica dahurica and 5g of liquorice;

Clinical data: the total number of the drug is 50 patients with grade III rash caused by the treatment of antitumor drugs in the hospital from 2015-8 to 2017-12.

The research method comprises the following steps: patients were divided into three groups a, b, and c using a retrospective case control study, and the basic data of the three groups are shown in Table 13.

Table 13: a. b, c three groups of basic data of patients

The treatment scheme comprises the following steps: a group: pre-proportioning a prescription for intervention; b group: intervention of the two prescriptions is performed; and c, group: intervention of three prescriptions is performed; the intervention mode is as follows: the medical non-woven fabric is soaked in the liquid medicine and is externally applied to the rash part for 20 minutes for 2 times a day, and the medicine is continuously applied for 1 week.

Follow-up index: with reference to national cancer institute adverse event terminology standard version 5.0 (NCI-ctcaevss 5.0), combined with rash-related clinical studies, the grading conditions of rashes before and after administration of drugs in each group of patients were compared to evaluate the total effective rate, recovery rate, and remission rate (the grading criteria of rashes refer to tables 2, 3, and 4); the occurrence of adverse events after the administration of the drugs in each group of patients is compared, the adverse events mainly comprise allergic reactions, the grading standards of the adverse events are shown in a table 14, and the incidence rate of the allergic reactions after the administration of the drugs in each group is counted.

Table 14: criteria for grading allergy

The judgment standard of the curative effect of the medicine is as follows: the same criteria as in example 6 were evaluated.

Drug safety evaluation record: all adverse events occurred during the medication process are counted according to name, severity, number of occurrence cases and the like, and the occurrence rate of each adverse event is counted.

The statistical method comprises the following steps: the statistical method is the same as in example 6.

As a result: a. the classification condition of the rash before and after the three groups of medicines b and c, the total effective rate, the cure rate, the remission rate and the incidence rate of adverse events are shown in tables 15-19.

Table 15: grading of rash before and after group a application

Table 16: grading of rash before and after b groups of drugs

Table 17: grading of rash before and after c groups of drugs

Table 18: a. b, c comparing the total effective rate, cure rate and remission rate

	Total effective rate (%)	Recovery rate (%)	Remission rate (%)
				Group a	87.50	25.00	62.50
Group b	94.44	44.44	50.00
				Group c	81.25	12.50	68.75

Table 19: a. distribution and incidence of three groups of allergic reactions

And (4) analyzing results: a. the effective rates of the three groups b and c are respectively 87.50%, 94.44% and 81.25%, and compared with each other, p is more than 0.05, no statistical difference exists, and the three proportioning modes are effective on the skin rash; the cure rate of the group c is obviously reduced compared with that of the group b, p is less than 0.05, the statistical difference exists, the c group has the smallest dosage of the medicine, the remission rate is higher than that of the group a and the group b, but the cure rate is lower than that of the group a and the group b, the smaller the dosage of the medicine is, the slower the rash is cured, and if the dosage is reduced continuously, the phenomenon of poor curative effect of the medicine can occur, so the dosage of the medicine of the group c is determined to be the lower limit of the dosage of the medicine; a. no patient in group c has allergy, group b has grade I allergy 2, the incidence rate is 11.11%, the dosage of group b is maximum, although the total effective rate and cure rate are higher than those of group a and group c, the probability of adverse events (allergy) is correspondingly increased, but no serious adverse events of grade III or above are generated, the dosage belongs to a controllable range, and if the dosage is continuously increased, the risk of serious adverse reactions is greatly increased, so the dosage of group b is determined to be the upper limit of the dosage of the invention.

And (4) conclusion: in summary, the mixture ratio of the invention is determined as follows: 9-18 parts of taxus mairei, 10-30 parts of coix seeds, 10-30 parts of honeysuckle, 10-30 parts of reed stems, 10-20 parts of angelica sinensis, 9-15 parts of trichosanthes roots, 9-20 parts of figwort roots, 3-9 parts of angelica dahurica and 5-15 parts of liquorice.

The above-described embodiments are merely illustrative of several embodiments of the present invention, which are described in more detail, but are not to be construed as limiting the present invention. It should be noted that various changes and modifications can be made by those skilled in the art without departing from the principle of the present invention, and these changes and modifications are within the scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating rash caused by antitumor drugs is characterized by comprising the following raw material medicines: 9-18 parts of taxus mairei, 10-30 parts of semen coicis, 10-30 parts of honeysuckle, 10-30 parts of reed stem, 10-20 parts of angelica sinensis, 9-15 parts of trichosanthes root, 9-20 parts of figwort, 3-9 parts of angelica dahurica and 5-15 parts of liquorice.

2. The traditional Chinese medicine composition according to claim 1, wherein the composition of the raw material medicines of the traditional Chinese medicine composition is preferably as follows: 15 parts of taxus mairei, 20 parts of semen coicis, 20 parts of honeysuckle, 20 parts of reed stem, 15 parts of angelica, 12 parts of trichosanthes root, 15 parts of figwort, 6 parts of angelica dahurica and 12 parts of liquorice.

3. The traditional Chinese medicine composition according to claim 1, wherein the composition of the raw material medicines of the traditional Chinese medicine composition is preferably as follows: 18 parts of taxus mairei, 30 parts of semen coicis, 30 parts of honeysuckle, 30 parts of reed stem, 20 parts of angelica, 15 parts of trichosanthes root, 20 parts of figwort, 9 parts of angelica dahurica and 15 parts of liquorice.

4. The traditional Chinese medicine composition according to claim 1, wherein the composition of the raw material medicines of the traditional Chinese medicine composition is preferably as follows: 9 parts of taxus mairei, 10 parts of semen coicis, 10 parts of honeysuckle, 10 parts of reed stem, 10 parts of angelica, 9 parts of trichosanthes root, 9 parts of figwort, 3 parts of angelica dahurica and 5 parts of liquorice.

5. The traditional Chinese medicine composition according to any one of claims 1 to 4, wherein the traditional Chinese medicine composition is prepared into an external preparation, and the external preparation comprises a liquid preparation, a gas preparation, a solid preparation, a semisolid preparation and the like.