Traditional Chinese medicine composition for treating skin diseases

Abstract

The invention belongs to the field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating skin diseases and application thereof. The traditional Chinese medicine composition for treating skin diseases is further optimized on the basis of water nourishing and heart-fire clearing drink, takes kidney nourishing, heart-fire clearing, food retention removing and stagnation removing as a core treatment rule, and is prepared from radix rehmanniae, fructus gardeniae, hawthorn, medicated leaven, scutellaria baicalensis, lophatherum gracile, fructus aurantii, uncaria rhynchophylla, purslane, honeysuckle, cortex dictamni and areca catechu. The traditional Chinese medicine composition is few in medicine flavor, good in taste, fast in effect taking, high in safety and better in curative effect, and a treatment scheme is provided for patients with atopic dermatitis.

Description

Technical Field

[0001] The invention belongs to the field of traditional Chinese medicine, and specifically relates to a traditional Chinese medicine composition for treating skin diseases and application thereof. Background Art

[0002] Skin diseases are common diseases in dermatology, with high incidence and complex pathogenesis. The interaction and close connection between internal and external factors lead to diverse manifestations of skin diseases. Among them, dermatitis and eczema are the most common. After the onset of the disease, it not only affects the patient's physical health, but also changes the patient's mind due to the disease, seriously affecting the patient's quality of life and physical and mental health. Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Its basic clinical features are dry skin, obvious itching, and chronic eczematous skin lesions, which have a serious impact on the patient's quality of life. The clinical manifestations of AD at different age stages have different characteristics and can be divided into the following four stages: infancy, childhood, adolescence and adulthood, and old age. Infancy (birth to 2 years old): usually manifested as erythema and scaling on both sides of the cheeks. The rash can extend to the scalp, neck, forehead and other parts. There may be severe exudation and secondary changes due to scratching and friction. Childhood (2 to 12 years old): It may be a delay from the previous stage or may directly start from this stage. It often occurs in the antecubital and popliteal fossae, wrist flexor side, eyelids, neck, etc. It is usually a lichenified hard plaque with visible scratches and scabs. Adolescence and adulthood (12 to 60 years old): In adolescent patients, the rash typically appears in the antecubital and popliteal fossae, the front and sides of the neck, and around the eyes. The distribution of adult patients often has no obvious characteristics. Overall, the skin is obviously dry, and lichenification and prurigo-like papules are common. Elderly stage (over 60 years old): There are more elderly male patients, and the rash is often more severe than in the previous stages, and may even spread all over the body, with erythroderma (Lü Ting, Wang Hongwei. Understanding and management of atopic dermatitis in the elderly [J]. Chinese Journal of Dermatology and Venereology, 2019, 33(08):949-54). It is estimated that the global prevalence of AD in children is 15%-30% and in adults is 1%-3% ( S. Atopic Dermatitis [J]. New England Journal of Medicine, 2021, 384 (12): 1136-1143.), and has shown a continuous upward trend in recent years. Generally speaking, atopic dermatitis is considered to be the result of the combined effects of genetic specificity, immune abnormalities and environmental factors (Brown S, Elias M, Bradley M. Genetics in Atopic Dermatitis: Historical Perspective and Future Prospects [J]. Acta Derm Venereol, 2020, 100 (12): adv00163.). A damaged skin barrier can lead to greater transepidermal water loss and transepidermal penetration of microorganisms and allergens, which may ultimately trigger an inflammatory cascade (Baurecht H, Rühlemann MC, Rodríguez E, et al. Epidermal lipid composition, barrier integrity, and eczematous inflammation are associated with skin microbiome configuration [J]. Journal of Allergy and Clinical Immunology, 2018, 141(5): 1668-1676. e16.).

[0003] The severity of AD lesions can be quantified using multiple scoring tools, the main ones being the Eczema Area and Severity Index (EASI) and the Scoring Atopic Dermatitis (SCORAD) scale, both of which are widely used in clinical diagnosis and clinical trials (Chopra R, Vakharia PP, Sacotte R, et al. Severity strata for Eczema Area and Severity Index (EASI), modified EASI, Scoring Atopic Dermatitis (SCORAD), objective SCORAD, Atopic Dermatitis Severity Index and body surface area in adolescents and adults with atopic dermatitis [J]. British Journal of Dermatology, 2017, 177(5): 1316-1321.). The EASI score assesses the severity of redness, thickness, scratches, and lichenification in four areas of the body (head, trunk, arms, and legs), as well as the percentage of skin involvement. Compared with the EASI score, the SCORAD score combines the doctor's objective evaluation of the scope and severity of eczema lesions, and is calculated based on the severity of the affected skin area, redness, swelling, exudation, crusting, lichenoid lesions, and dryness, and evaluates the severity of the head and neck, arms and legs, front trunk, back, and genitals (Charman CR, Venn AJ, Williams H, et al. Measuring Atopic Eczema Severity Visually: Which Variables Are Most Important to Patients? [J]. Archives of Dermatology, 2005, 141 (9).). The score also includes two subjective assessments made by the patient himself, one for lack of sleep and the other for itching.

[0004] Atopic dermatitis is a chronic relapsing disease that requires long-term treatment. my country's guidelines recommend a step-by-step treatment model based on the severity of the disease (Chinese Society of Dermatology and Venereology, Immunology Group, Atopic Dermatitis Collaborative Research Center. Chinese Guidelines for the Diagnosis and Treatment of Atopic Dermatitis (2020 Edition) [J]. Chinese Journal of Dermatology, 2020, (02): 81-8.). Mild atopic dermatitis is mainly treated with topical topical treatments such as glucocorticoids (TCS), topical calcineurin inhibitors (TCI), and topical phosphodiesterase-4 (PDE-4) inhibitors. For moderate to severe atopic dermatitis that seriously affects the health of patients, topical topical medications alone are often unable to effectively control the disease and require systemic treatment. Traditional systemic treatments include cyclosporine, methotrexate, and azathioprine. In recent years, the clinical application of biological agents and Janus inhibitors has provided a more effective and relatively safe option for systemic treatment of patients with moderate to severe AD. However, although there are many treatments for AD, many traditional methods cannot achieve satisfactory results or cannot be used for a long time due to safety reasons. Topical glucocorticoids and calcineurin inhibitors have limited efficacy in patients with moderate to severe AD. Common adverse reactions of cyclosporine include renal dysfunction, headache, hypertension and hyperlipidemia; methotrexate has adverse reactions such as ulcerative stomatitis, leukopenia hepatotoxicity, and bone marrow suppression; azathioprine may cause hemoglobin, leukopenia and liver function damage. Dupilumab has no sufficient effect on some patients, while other patients lose response over time (possibly due to the formation of drug neutralizing antibodies) (HENDRICKS AJ, LIO PA, SHI V Y. Management Recommendations for Dupilumab Partial and Non-durable Responders in Atopic Dermatitis [J]. American Journal of Clinical Dermatology, 2019, 20 (4): 565-9.). In addition, its administration method is subcutaneous injection, and some patients refuse to use it because they are unwilling to be injected. Therefore, an oral treatment with good benefits and low risks is needed for AD patients.

[0005] In recent years, with the development and improvement of traditional Chinese medicine, Chinese medicine has the characteristics of low cost and low adverse reactions, and is favored by clinical doctors and patients. Traditional Chinese medicine has a long history of treating atopic dermatitis, but there is no such name as "atopic dermatitis" in the relevant literature of traditional Chinese medicine. Instead, it is classified and recorded as "milk ringworm", "milk ringworm", "four-bend wind" and other names based on similar clinical characteristics (Liu Liang, Pi Xianming, Li Wenxia. Pathogenesis of atopic dermatitis and regulation of traditional Chinese medicine [J]. Shizhen Chinese Medicine, 2022, 33(6): 1418-1420.). Traditional Chinese medicine believes that the pathogenesis of AD is mainly due to congenital intolerance, dampness and heat in the five internal organs, spleen deficiency and hyperactivity of heart fire, and rheumatism and heat evil invading the skin. The internal and external conflicts lead to the onset of the disease (Chen Yanhua. Clinical research progress of traditional Chinese medicine treatment of atopic dermatitis [J]. Modern Distance Education of Traditional Chinese Medicine, 2023, 21(2): 200-202.). In recent years, the incidence of atopic dermatitis has continued to increase. The State Administration of Traditional Chinese Medicine pointed out that the treatment of this disease is similar to that of acute, subacute, and chronic eczema, and it should be treated according to the different stages (State Administration of Traditional Chinese Medicine. Diagnosis and Efficacy Standards of TCM Diseases and Syndromes [S]. Nanjing: Nanjing University Press, 1994: 73-75.). However, in actual clinical practice, the phenomenon of multiple syndromes of atopic dermatitis interweaving is relatively common, and it is difficult to achieve ideal results with a single treatment. Therefore, modern Chinese medicine summarizes their respective clinical experiences based on ancient literature, combines syndrome differentiation and individual treatment, and treats this disease from different aspects. The idea of ​​TCM treatment of AD usually starts with internal and external treatment, and usually uses the angles of clearing heat and removing dampness, strengthening the spleen and nourishing yin, nourishing blood and moistening dryness to carry out treatment. For AD skin lesions, TCM uses fumigation, medicated bath, wet compress, smearing and other methods. According to the different parts of the skin lesions, different Chinese medicines and dosage forms are selected, and acupuncture, cupping, massage and other means can also be used to relieve the patient's itching and pain. Summary of the invention

[0006] The present invention is a further optimization based on Zishui Qingxin Yin, with "nourishing the kidney and clearing the heart, eliminating accumulation and relieving stagnation" as the core treatment principle, to provide a Chinese medicine for treating skin diseases with less taste, good taste, fast onset, high safety and better efficacy, and to provide a treatment plan for patients with atopic dermatitis and heart and spleen heat accumulation syndrome. Based on this, the present invention is completed.

[0007] In a first aspect, the present invention provides a traditional Chinese medicine composition, wherein the traditional Chinese medicine composition is made of the following traditional Chinese medicines in parts by weight:

[0008] The main drug is selected from one or more of 5-50 parts of Radix Rehmanniae and / or 2-20 parts of Fructus Gardeniae;

[0009] The ministerial drug is selected from one or more of 5-30 parts of hawthorn and / or 5-20 parts of Shenqu;

[0010] The adjuvant is selected from one or more of 2-20 parts of Scutellaria baicalensis, 2-20 parts of Lophatherum gracile, 5-20 parts of Uncaria rhynchophylla and / or 10-90 parts of Portulaca oleracea;

[0011] The drug is selected from one or more of 2-30 parts of Fructus Aurantii Immaturus, 5-60 parts of Flos Lonicerae and / or 5-20 parts of Cortex Dictamni and / or 2-10 parts of Areca Nut.

[0012] Preferably, the Chinese medicine composition is made of the following Chinese medicines in parts by weight:

[0013] The main drug is selected from one or more of 10-40 parts of Radix Rehmanniae and / or 5-18 parts of Fructus Gardeniae;

[0014] The ministerial drug is selected from one or more of 5-20 parts of hawthorn and / or 8-18 parts of Shenqu;

[0015] The adjuvant is selected from one or more of 3-15 parts of Scutellaria baicalensis, 3-18 parts of Lophatherum gracile, 7-18 parts of Uncaria rhynchophylla and / or 20-80 parts of Portulaca oleracea;

[0016] The drug is selected from one or more of 3-25 parts of Fructus Aurantii Immaturus, 10-40 parts of Flos Lonicerae and / or 8-18 parts of Cortex Dictamni and / or 2-8 parts of Areca Nut.

[0017] More preferably, the Chinese medicine composition is made of the following Chinese medicines in parts by weight:

[0018] The main drug is selected from one or more of 15-30 parts of Radix Rehmanniae and / or 8-15 parts of Fructus Gardeniae;

[0019] The ministerial drug is selected from one or more of 10-20 parts of hawthorn and / or 10-15 parts of Shenqu;

[0020] The adjuvant is selected from one or more of 4-10 parts of Scutellaria baicalensis, 4-15 parts of Lophatherum gracile, 9-15 parts of Uncaria rhynchophylla and / or 30-70 parts of Portulaca oleracea;

[0021] The drug is selected from one or more of 4-20 parts of Fructus Aurantii Immaturus, 10-20 parts of Flos Lonicerae and / or 10-15 parts of Cortex Dictamni and / or 2-6 parts of Areca Nut.

[0022] In some specific embodiments of the present invention, the Chinese medicine composition is made of the following Chinese medicines: 5-50 parts of raw rehmannia and 2-20 parts of gardenia, 5-30 parts of hawthorn, 5-20 parts of Shenqu, 2-20 parts of scutellaria, 2-20 parts of lophatherum gracile, 2-30 parts of fructus aurantii, 5-20 parts of Uncaria rhynchophylla and 10-90 parts of purslane.

[0023] In some specific embodiments of the present invention, the Chinese medicine composition is made of the following Chinese medicines: 5-50 parts of raw rehmannia and 2-20 parts of gardenia, 5-30 parts of hawthorn, 5-20 parts of Shenqu, 2-20 parts of scutellaria, 2-20 parts of loquat leaves, 2-30 parts of fructus aurantii, 5-20 parts of Uncaria rhynchophylla, 10-90 parts of purslane and 5-60 parts of honeysuckle.

[0024] In some specific embodiments of the present invention, the Chinese medicine composition is made of the following Chinese medicines: 5-50 parts of raw rehmannia and 2-20 parts of gardenia, 5-30 parts of hawthorn, 5-20 parts of Shenqu, 2-20 parts of scutellaria, 2-20 parts of loquat leaves, 2-30 parts of fructus aurantii, 5-20 parts of Uncaria rhynchophylla, 10-90 parts of purslane, 5-60 parts of honeysuckle, 5-20 parts of difficile cortex and 2-10 parts of areca.

[0025] In a second aspect, the present invention provides a Chinese medicine preparation made from the Chinese medicine composition described in the first aspect, wherein the Chinese medicine preparation is one or more of a paste prescription, a pill, a pill, a decoction, a granule, a capsule, a powder and / or a tablet.

[0026] Furthermore, the traditional Chinese medicine preparation contains pharmaceutically acceptable excipients required for the corresponding preparation.

[0027] Furthermore, the excipient is a pharmaceutical excipient that enhances the efficacy, reduces toxicity and / or alleviates side effects of the main drug.

[0028] In a third aspect, the present invention provides use of the traditional Chinese medicine composition described in the first aspect in preparing a medicine for treating skin diseases.

[0029] Furthermore, the skin diseases include atopic dermatitis, eczema, dermatitis, allergic dermatitis, and psoriasis.

[0030] Preferably, the skin disease is atopic dermatitis.

[0031] More preferably, the skin disease is atopic dermatitis with heart and spleen heat accumulation syndrome.

[0032] The medicinal properties and effects of each Chinese medicinal material in the present invention are as follows:

[0033] Radix Rehmanniae: sweet in taste, cold in nature. It enters the heart, liver and kidney meridians. It has the effects of clearing away heat and cooling blood, nourishing yin and promoting body fluid. It is used for heat entering the blood, fever due to warm toxins, vomiting blood and epistaxis, yin damage caused by febrile diseases, red tongue and thirst, constipation caused by body fluid damage, fever due to yin deficiency, bone steaming and fatigue fever, and internal heat and thirst.

[0034] Gardenia: bitter in taste, cold in nature. Enters the heart, lung and triple burner meridians. It has the effects of purging fire and relieving restlessness, clearing heat and removing dampness, cooling blood and detoxifying; external use for relieving swelling and relieving pain. It is used for restlessness due to febrile diseases, jaundice due to damp heat, astringent pain due to stranguria, vomiting and bleeding due to blood heat, red and swollen eyes, and fire poison sores; external treatment of sprains and contusions.

[0035] Hawthorn: sour, sweet, slightly warm. Enters the spleen, stomach, and liver meridians. Has the effects of digesting food and strengthening the stomach, promoting qi and dispersing blood stasis, clearing turbidity and reducing fat. Used for meat stagnation, stomach distension, diarrhea and abdominal pain, blood stasis and amenorrhea, postpartum blood stasis, heart and abdomen stabbing pain, chest pain, hernia pain, and hyperlipidemia.

[0036] Shenqu: sweet and spicy, warm in nature. Enters the spleen and stomach meridians. Has the effects of strengthening the spleen and stomach, digesting food and regulating the middle. Treats food stagnation, chest distension and abdominal distension, vomiting and diarrhea, abdominal pain due to blood stasis after childbirth, and large and hard abdominal mass in children.

[0037] Scutellaria baicalensis: bitter in taste, cold in nature. Enters the lung, gallbladder, spleen, large intestine, and small intestine meridians. It has the effects of clearing away heat and dampness, purging fire and detoxifying, stopping bleeding, and calming the fetus. It is used for damp-heat, summer dampness, chest tightness and nausea, damp-heat fullness, diarrhea, jaundice, lung heat cough, high fever and thirst, blood heat vomiting and bleeding, carbuncle, sore, and fetal movement disorder.

[0038] Bamboo Leaves: Sweet, light, cold in nature. Enters the heart, stomach, and small intestine meridians. Has the effects of clearing away heat and purging fire, relieving restlessness and thirst, and promoting diuresis and relieving stranguria. Used for fever, thirst, short, red, painful urination, and sores in the mouth and tongue.

[0039] Citrus aurantium: bitter, pungent, sour, slightly cold. Enters the spleen and stomach meridians. Has the effects of regulating qi, relieving fullness, relieving stagnation and relieving swelling. Used for qi stagnation in the chest and flanks, fullness and pain, indigestion, phlegm and fluid retention, and sagging organs.

[0040] Uncaria rhynchophylla: sweet in taste, cool in nature. Enters the liver and pericardium meridians. It has the effects of calming wind and calming convulsions, clearing away heat and calming the liver. It is used for internal liver wind movement, epilepsy and convulsions, high fever convulsions, colds and convulsions, children crying, eclampsia during pregnancy, headache and dizziness.

[0041] Purslane: sour, cold in nature. Enters the liver and large intestine meridians. Has the effects of clearing away heat and detoxifying, cooling blood and stopping bleeding, and stopping dysentery. Used for heat toxic bloody dysentery, carbuncle, furuncle, eczema, erysipelas, snake and insect bites, blood in stool, hemorrhoids, and metrorrhagia.

[0042] Honeysuckle: sweet in taste, cold in nature. Enters the lung, heart and stomach meridians. Has the effects of clearing away heat and detoxifying, and dispersing wind-heat. Used for carbuncle, furuncle, throat paralysis, erysipelas, dysentery due to heat toxins, wind-heat cold, and fever due to febrile diseases.

[0043] Dictamni: bitter, cold in nature. Enters the spleen, stomach, and bladder meridians. Has the effects of clearing away heat and dampness, dispelling wind and detoxifying. Used for damp-heat sores, yellow water dripping, eczema, rubella, scabies, sores, rheumatism, heat arthralgia, jaundice, and red urine.

[0044] Betel nut: bitter, pungent and warm. Enters the stomach and large intestine meridians. Has the effects of killing insects, eliminating accumulation, lowering qi, promoting water circulation, and stopping malaria. Used for tapeworms, roundworms, ginger worm diseases, abdominal pain caused by worm accumulation, diarrhea caused by accumulation, tenesmus, edema, beriberi, and malaria.

[0045] The treatment principle of the present invention is:

[0046] This prescription is a further optimization based on Zishui Qingxin Drink. It has the characteristics of less medicine, good taste, fast onset, good efficacy and high safety.

[0047] The Chinese medicine prescription of the present invention takes nourishing the kidney and clearing the heart, eliminating accumulation and relieving stagnation as the basic treatment method, takes raw rehmannia and gardenia as the main medicines, nourishing kidney water and clearing heart fire; takes scutellaria baicalensis and Shenqu as the assistant medicines, clearing away heat and purging fire, invigorating the spleen and harmonizing the stomach, and promoting digestion and regulating the middle; takes lophatherum gracile, purslane, hawthorn and Uncaria rhynchophylla as the adjuvant medicines, guiding the heart fire downward, clearing away heat and detoxifying, stopping wind and relieving itching; takes fructus aurantii as the guiding medicine, promoting qi and relieving stagnation.

[0048] For those with bright red skin lesions and severe itching, honeysuckle, Dictamni bark and betel nut can be used to enhance the detoxification, antipruritic and digestive effects.

[0049] Beneficial Effects

[0050] The Chinese medicine formula of the present invention can quickly reduce skin lesions and relieve itching in the treatment of mild and moderate AD patients, and has obvious superior efficacy in controlling recurrence. At the same time, the Zishen Qingxin Daozhi Decoction has good safety.

[0051] At present, there is a lack of oral drugs for treating atopic dermatitis or eczema in children or adolescents on the market. The Chinese medicine formula of the present invention has a significant therapeutic effect in treating atopic dermatitis. In patients with mild and moderate AD, the efficacy is better than that of Zishui Qingxin Yin. It tastes better to children and is more easily accepted by children. It has good application prospects in the market. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] Figure 1 These are the initial physical examination and tongue and pulse results for a typical case.

[0053] Figure 2 These are the results of the second follow-up physical examination and tongue and pulse for a typical case. DETAILED DESCRIPTION

[0054] The specific embodiments of the present invention are further described below. It should be noted that the description of these embodiments is used to help understand the present invention, but does not constitute a limitation of the present invention. In addition, the technical features involved in the embodiments described below can be combined with each other as long as they do not conflict with each other.

[0055] The experimental methods in the following examples are conventional methods unless otherwise specified, and the experimental materials used in the following examples are commercially available unless otherwise specified.

[0056] Explanation of terms

[0057] The "Zhishui Qingxin Yin" of the present invention is a Chinese medicine composition in Chinese patent CN 115054662 B, which is made of the following Chinese medicines in parts by weight: the main medicine is composed of the following medicines: 10-30 parts of raw earth and 5-25 parts of gardenia; the auxiliary medicine is composed of the following medicines A or B: A is 5-20 parts of Scrophularia and 5-15 parts of Lophatherum gracile; B is 5-20 parts of Scrophularia and 5-15 parts of Lophatherum gracile, and one or two selected from 5-15 parts of chicken gizzard lining and 5-10 parts of betel nut; the adjuvant is composed of the following medicines C or D: C comprises: 5-20 parts of Uncaria rhynchophylla, 10-30 parts of Imperata rhizome, and 5-15 parts of Hawthorn; D comprises: 5-20 parts of Uncaria rhynchophylla, 10-30 parts of Imperata rhizome, 5-15 parts of Hawthorn, and one or more selected from 5-15 parts of Honeysuckle, 5-15 parts of Malt, 5-15 parts of Lycium bark, 1-5 parts of Juncus effusus, 5-30 parts of Portulaca oleracea, 5-15 parts of Forsythia suspensa, 5-30 parts of Oyster, 5-15 parts of Tangerine peel or 5-15 parts of Poria.

[0058] Example 1 Chinese medicine composition

[0059] Oral nourishing kidney, clearing heart and guiding stagnation drink 1:30 parts of raw rehmannia and 15 parts of gardenia, 15 parts of hawthorn, 15 parts of Shenqu, 10 parts of scutellaria, 15 parts of lophatherum gracile, 10 parts of aurantium, 15 parts of Uncaria rhynchophylla and 60 parts of purslane.

[0060] Oral nourishing kidney, clearing heart and guiding stagnation drink 2: 20 parts of raw rehmannia and 10 parts of gardenia, 15 parts of hawthorn, 15 parts of Shenqu, 6 parts of scutellaria, 6 parts of loquat leaves, 6 parts of bitter orange, 15 parts of Uncaria rhynchophylla, 30 parts of purslane, and 10 parts of honeysuckle.

[0061] Oral nourishing the kidney, clearing the heart and guiding away stagnation drink 3: 15 parts of raw rehmannia and 10 parts of gardenia, 10 parts of hawthorn, 10 parts of Shenqu, 5 parts of scutellaria, 5 parts of lophatherum gracile, 5 parts of aurantium, 10 parts of Uncaria rhynchophylla, 30 parts of purslane, 15 parts of honeysuckle, 15 parts of Dictamni cortex and 6 parts of areca.

[0062] Preparation method

[0063] Put the medicinal materials into a boiling pot, add 8 times the amount of water and soak for 30 minutes. Boil for 25 minutes for the first time and add 6 times the amount of water for the second time and boil for 25 minutes. After concentrating the combined medicinal liquid, filter it into 400mL (for children, it can be concentrated to 150-200mL).

[0064] Example 2 Clinical Study

[0065] 1. Methods

[0066] A prospective, randomized, single-blind, controlled study design was used to conduct a standardized clinical study on patients with atopic dermatitis (Siwanfeng) with heart and spleen heat accumulation syndrome to verify the efficacy of the optimized TCM treatment plan for atopic dermatitis.

[0067] 2. Research subjects

[0068] This study selected patients with atopic dermatitis (Siwanfeng) and heart and spleen heat accumulation syndrome from the Beijing Huairou District Hospital of Traditional Chinese Medicine and the Dermatology Clinic of Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University as research subjects.

[0069] 3. Diagnostic criteria

[0070] 3.1 Western medicine diagnostic criteria

[0071] Refer to the clinical diagnostic criteria for mild and moderate atopic dermatitis in the "Guidelines for the Diagnosis and Treatment of Atopic Dermatitis in China 2020 Edition" and "Chinese Journal of Clinical Dermatology".

[0072] The severity of atopic dermatitis was assessed using the Scoring Index of Atopic Dermatitis (SCORAD score): mild: SCORAD score 0-24 points; moderate: SCORAD score 25-50 points; severe: SCORAD score >50 points.

[0073] 3.2 TCM diagnostic criteria

[0074] The following guidelines were drawn up with reference to the Expert Consensus on TCM Diagnosis and Treatment of Atopic Dermatitis (Chinese Journal of Integrated Traditional Chinese and Western Medicine Dermatology and Venereology, 2013) and the TCM Disease Diagnosis and Efficacy Standards (National TCM Industry Standards):

[0075] Heart and spleen heat accumulation syndrome:

[0076] Recurrent erythema, edema, papules, blisters, or nodules on the face, neck, elbows, popliteal fossa, trunk, etc., may be accompanied by erosion and exudation, and severe itching. Feeling upset, dry mouth, restless sleep, dry stool or frequent bowel movements, red tongue or red tip of tongue or with thorns, thick or greasy tongue coating, and slippery pulse.

[0077] 4. Inclusion and exclusion standards

[0078] 4.1 Inclusion criteria

[0079] ① Meet the above-mentioned Western medicine clinical diagnostic criteria for moderate atopic dermatitis (25<SCORAD score≤50);

[0080] ②Meet the syndrome differentiation criteria for heart and spleen heat accumulation syndrome;

[0081] ③Age 2-18, no gender limit;

[0082] ④Good compliance and able to cooperate in collecting clinical data;

[0083] ⑤ No systemic use of glucocorticoids, immunosuppressants, biological agents or ultraviolet light within 4 weeks before the study;

[0084] ⑥ No oral antihistamines within 1 week before the study;

[0085] ⑦ No topical glucocorticoids, calcineurin inhibitors, or phosphodiesterase 4 drugs were used within 1 week before the study;

[0086] ⑧ The subject shall, with the permission of the guardian, sign the informed consent form (signed by the guardian on behalf of the subject) and volunteer to be tested. The informed consent process shall comply with the provisions of GCP.

[0087] Those who met the above conditions at the same time met the inclusion criteria and were included in this study.

[0088] 4.2 Exclusion criteria

[0089] ① Patients with any other skin diseases that may interfere with the evaluation of test results;

[0090] ② Patients with serious primary diseases such as cardiovascular, cerebrovascular, liver, kidney and hematopoietic system diseases, autoimmune diseases, skin tumor diseases, and mental illness;

[0091] ③ Patients with more serious skin infection or systemic infection;

[0092] ④ Patients with a history of allergy to any component of the study drug;

[0093] ⑤ Patients who cannot accept Chinese herbal medicine decoction treatment;

[0094] ⑥ Patients who are participating in clinical trials of other drugs.

[0095] Patients who met any of the above criteria were excluded and not included in this study.

[0096] 4.3 Elimination criteria

[0097] ① Those who did not meet the inclusion criteria and were mistakenly included;

[0098] ② The use of other drugs or treatment plans during the treatment process affects the judgment of the efficacy.

[0099] 4.4 Shedding Standard

[0100] ① Those who entered the trial treatment but ultimately failed to complete the clinical observation;

[0101] ② Those who did not have regular follow-up during treatment and were lost to follow-up due to various reasons;

[0102] ③ Those who are unwilling to continue the clinical trial during the treatment process.

[0103] 4.5 General suspension criteria

[0104] ① Those who have serious adverse reactions or allergic reactions during clinical trials;

[0105] ② During the research process, if it is found that the drugs used are not only ineffective in improving symptoms, but further aggravate the condition; or there are major errors in the experimental design; or there are large deviations in the implementation process, making it impossible to evaluate the efficacy of the drugs;

[0106] ③ The researcher considers it necessary to terminate the trial from a medical perspective.

[0107] 5. Grouping and treatment

[0108] 5.1 Grouping

[0109] The subjects were divided into treatment group and control group.

[0110] 5.2 Randomization Scheme

[0111] The computer randomly generates random numbers, and the researchers collect the drugs according to the random numbers in the order in which the subjects are enrolled. After the drug dispensing staff checks the prescription and registers it, they distribute the corresponding drugs and emphasize the precautions for medication. The subjects sign and receive the drugs.

[0112] 5.3 Sampling Method

[0113] The enrolled cases were randomly assigned to the experimental group and the control group in a 1:1 ratio.

[0114] 5.4 Sample size

[0115] This study was an exploratory study. Based on clinical experience and taking into account the clinical dropout rate of 20%, the total number of cases in the trial was 66 (33 cases in the treatment group and 33 cases in the control group).

[0116] 5.5 Treatment methods

[0117] Experimental group: Oral administration of Zishen Qingxin Daozhi Yin. The combined liquid after decoction was concentrated and filtered to 400mL (150-200mL for children), divided into 2 doses, half an hour after meals, once in the morning and once in the evening.

[0118] Control group: Elosong cream (Bayer Pharmaceuticals (Shanghai) Co., Ltd., National Medicine Approval No. H19991418) was applied externally, and a thin layer was applied to the affected skin to evenly cover it. Elosong cream was applied externally once a day for the first 2 weeks, and the frequency and quantity of application were gradually reduced after 2 weeks according to the condition of the skin lesions. Avoid facial and body wrinkles when applying the drug externally.

[0119] Treatment course: 4 weeks. The patients were re-examined every week to record the degree of improvement. Health education was conducted for the children in both groups and their families, who were advised to avoid spicy and irritating food and cold food, avoid washing the affected area with hot water, and use regular topical moisturizers.

[0120] 5.6 Blinding

[0121] Picking up medicine: Patients’ family members pick up medicine at the clinical research drug window according to the random number, and a dedicated person will distribute the medicine and register it.

[0122] 6. Efficacy evaluation

[0123] 6.1 Main efficacy indicator - SCORAD score

[0124] The SCORAD score proposed by the European Atopic Dermatitis Research Group is the most widely used disease severity scale in clinical research and practice. It mainly includes the range of skin lesions (A), the severity of skin lesions (B) and the patient's subjective symptoms (C). The details are as follows (see Table 1):

[0125] A. Calculation of skin lesion range: front of the human body: head 4.5%, trunk 18%, upper limbs (unilateral) 4.5%, lower limbs (unilateral) 9%; the calculation method for the back of the human body is the same as the front; in addition, the vulva is 1%, and the total score is 100 points. (See Appendix 1 for details)

[0126] B. Severity of skin lesions: The severity of skin lesions is divided into four levels: none, mild, moderate, and severe, and is scored using four scores from 0 to 3. It is mainly assessed by evaluating the erythema, papules / edema, crusting, lichenification / hypertrophy, epidermal exfoliation at the lesions, and dry skin at non-lesional areas.

[0127] C. Subjective symptoms (itching and sleep disturbance): Based on the actual situation of the patient, the average level of itch in the past 3 days and the average level of sleep disturbance in the past 3 nights were evaluated, and the visual analog scale (see Appendix 1 for details) was used for scoring. The scoring criteria are as follows: 0 points for no obvious itch; <3 points for itch, but tolerable and will not affect sleep; 4-6 points for moderate itch, still tolerable, but will affect sleep; 7-10 points for severe itch, which the patient cannot tolerate and has difficulty falling asleep.

[0128] The calculation formula for SCORAD score: A / 5+7B / 2+C.

[0129] Table 1 SCORAD scoring scale

[0130]

[0131]

[0132] 6.2 Research evaluation indicators

[0133] Concomitant medication: If other medications are used in combination, they must be recorded in a timely manner. If they have an impact on the trial, they will be excluded.

[0134] Compliance: During the clinical trial, the facility has a system for counting remaining prescription drugs. After the trial, the researchers are responsible for counting the remaining prescription drugs for the subjects in their charge to monitor the subjects' medication compliance.

[0135] 6.3 Efficacy evaluation criteria

[0136] This guideline is formulated based on the "Guidelines for Clinical Research of New Chinese Medicines" (China Medical Science and Technology Press: 2002, 5.).

[0137] The calculation formula (nimodipine method) is: efficacy index = [(SCORAD total score before treatment - SCORAD total score after treatment) / SCORAD total score before treatment] × 100%.

[0138] Efficacy evaluation:

[0139] Clinical cure: The rash has basically subsided, the symptoms have disappeared, and the efficacy rate is ≥90%;

[0140] Markedly effective: Most of the rash disappears, symptoms are significantly improved, 60%≤efficacy rate<90%;

[0141] Effective: The rash partially subsided, symptoms improved, 20% ≤ efficacy rate < 60%;

[0142] Ineffective: The rash does not subside significantly, the symptoms do not improve or even worsen, and the efficacy rate is <20%;

[0143] Total effective rate = [(number of cured cases + number of markedly effective cases + number of effective cases) / total number of cases] × 100%.

[0144] 7. Research Summary

[0145] For all cases that met the trial protocol, had good compliance, did not take prohibited medications during the trial, completed the content specified in the CRF, or took 80% to 120% of the trial medication, the efficacy of the data set that met the protocol was statistically analyzed.

[0146] 8. Statistical analysis and content

[0147] Statistical analysis will be calculated using SPSS22.0 statistical analysis software. All statistical tests were two-sided, and P values ​​less than or equal to 0.05 were considered statistically significant. The chi-square test was used for count data, and the mean ± standard deviation (x ± s) was used for measurement data. The paired sample t test was used for intra-group comparison, and the independent sample t test was used for inter-group comparison; the rank sum test for graded data was used for clinical efficacy comparison; and the Pearson correlation test was used for correlation analysis.

[0148] 9. Research Results

[0149] 9.1 Case data

[0150] The cases were collected from patients who visited the outpatient department of the Department of Dermatology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University from May 2023 to April 2024. After the patient's case report form (CRF) was completed, two different data entry personnel entered and checked the data twice. A total of 66 patients were enrolled, 5 of whom dropped out due to personal reasons and could not come to the hospital. Finally, 61 cases were included in the statistics. Among them, 31 cases were in the treatment group and 30 cases were in the control group.

[0151] 9.2 Baseline information

[0152] Among the 61 patients, there were 33 males and 28 females, with an average age of 7.93±3.87 years and an average disease course of 4.22±3.65 years. Before treatment, the chi-square test was performed on the gender of the treatment group and the control group. The age and disease course of the patients in the two groups were in accordance with the normal distribution, and the variance was equal. The independent sample T test showed that there was no significant difference between the two groups.

[0153] 9.3 Evaluation of efficacy

[0154] 9.3.1 SCORAD Scoring

[0155] The total SCORAD score before and after treatment was compared. The paired t test showed that the total SCORAD score of the treatment group and the control group decreased before and after treatment, and the difference was statistically significant (P < 0.05). The total SCORAD score of the treatment group decreased more significantly, and the difference in SCORAD score between the treatment group and the control group was statistically significant (P < 0.05), indicating that the condition of the patients in the treatment group was more significantly relieved after 4 weeks. See Table 1.

[0156] Table 1. Comparison of SCORAD scores before and after treatment

[0157]

[0158] Note: After treatment, the treatment group was compared with the control group, P < 0.05.

[0159] 9.3.2 Overall efficacy evaluation

[0160] The SCORAD index of the two groups was divided into four levels, namely, cured, markedly effective, effective, and ineffective, and the chi-square test was used for analysis. The total number of effective cases in the experimental group was 27, and the total effective rate was 87.1%. The total number of effective cases in the control group was 22, and the total effective rate was 63.33%. The two groups were compared, P < 0.05, and there was a statistically significant difference in the efficacy between the two groups. See Table 2.

[0161] Table 2. Comparison of SCORAD scores before and after treatment

[0162]

[0163] 9.4 Adverse Reactions

[0164] No adverse reactions were observed in either the treatment or control group.

[0165] 10. Conclusion

[0166] Through this clinical study, it was shown that Zishen Qingxin Daozhi Yin can quickly reduce skin lesions and relieve itching in the treatment of mild and moderate AD patients, and it has obvious advantages in controlling recurrence. At the same time, Zishen Qingxin Daozhi Yin has good safety. At present, there is a lack of oral drugs for the treatment of atopic dermatitis or eczema in children or adolescents on the market. This project study confirmed the significant efficacy of Zishen Qingxin Daozhi Yin in the treatment of atopic dermatitis. In mild and moderate AD patients, the efficacy is better than Zishui Qingxin Yin, and the children have a better taste and are more easily accepted by the children. It has good application prospects in the market.

[0167] Example 3 Typical Cases

[0168] Patient: Male, 7 years old

[0169] Date of visit: December 17, 2024 ( Figure 1 )

[0170] Chief complaint

[0171] Rash and itching all over the body for 2 years

[0172] History of present illness

[0173] Two years ago, he developed a rash without any obvious cause. He applied topical elosone, but the effect was not obvious.

[0174] Current SCORAD score: 47.6.

[0175] Appetite is good, likes to eat meat, cough, yellow sputum, runny yellow nose, bowel movement every 2-3 days. Red tongue, thick and greasy white coating, slippery pulse.

[0176] past history

[0177] Physical fitness

[0178] History of allergies

[0179] Allergic to eggs, milk, kidney beans.

[0180] Physical examination

[0181] The skin is rough and dry, with multiple red papules, accompanied by epidermal exfoliation, erosion and exudation, blood scabs, and scratches.

[0182] Tongue and pulse

[0183] The tongue is dark red, the tongue coating is white and greasy, and the pulse is slippery.

[0184] diagnosis

[0185] TCM diagnosis: Siwanfeng-heart and spleen heat accumulation syndrome

[0186] Western medicine diagnosis: atopic dermatitis

[0187] Governing Law

[0188] Nourishes water, clears the heart and relieves stagnation

[0189] Prescriptions

[0190] 20g of raw rehmannia, 10g of raw gardenia, 6g of lophatherum gracile, 30g of purslane, 15g of hawthorn, 15g of Shenqu, 6g of Citrus aurantium, 6g of Scutellaria baicalensis, 10g of honeysuckle, and 15g of Uncaria rhynchophylla (added last).

[0191] Follow-up visit 1: December 31, 2023

[0192] After 2 weeks of treatment, the itching was significantly relieved, the skin lesions partially subsided, and pigmentation remained. There were pale red patches on the neck, with a small amount of scabs. There were a small number of red papules scattered on the trunk and limbs, with a small number of scratches and blood scabs.

[0193] SCORAD score: 24.2.

[0194] Appetite is good, bowel movement is one time a day. Red tongue, white fur, slippery pulse.

[0195] Treatment and prescriptions are the same as before.

[0196] Follow-up visit 2: January 7, 2024 ( Figure 2 )

[0197] After 4 weeks of treatment, the pruritus was mild and most of the skin lesions disappeared. Very few red papules, a few scratches and blood scabs were found on the trunk and limbs.

[0198] SCORAD score: 4.5.

[0199] Appetite is good, bowel movement is one time a day. Red tongue, white fur, slippery pulse.

Claims

1. A Chinese medicine composition, which is made from the following Chinese medicines in parts by weight: The main drug is selected from one or more of 5-50 parts of Radix Rehmanniae and / or 2-20 parts of Fructus Gardeniae; The ministerial drug is selected from one or more of 5-30 parts of hawthorn and / or 5-20 parts of Shenqu; The adjuvant is selected from one or more of 2-20 parts of Scutellaria baicalensis, 2-20 parts of Lophatherum gracile, 5-20 parts of Uncaria rhynchophylla and / or 10-90 parts of Portulaca oleracea; The drug is selected from one or more of 2-30 parts of Fructus Aurantii Immaturus, 5-60 parts of Flos Lonicerae and / or 5-20 parts of Cortex Dictamni and / or 2-10 parts of Areca Nut.

2. The Chinese medicine composition according to claim 1, wherein the Chinese medicine composition is made of the following Chinese medicines in parts by weight: The main drug is selected from one or more of 10-40 parts of Radix Rehmanniae and / or 5-18 parts of Fructus Gardeniae; The ministerial drug is selected from one or more of 5-20 parts of hawthorn and / or 8-18 parts of Shenqu; The adjuvant is selected from one or more of 3-15 parts of Scutellaria baicalensis, 3-18 parts of Lophatherum gracile, 7-18 parts of Uncaria rhynchophylla and / or 20-80 parts of Portulaca oleracea; The drug is selected from one or more of 3-25 parts of Fructus Aurantii Immaturus, 10-40 parts of Flos Lonicerae and / or 8-18 parts of Cortex Dictamni and / or 2-8 parts of Areca Nut.

3. The Chinese medicine composition according to any one of claims 1 or 2, wherein the Chinese medicine composition is made of the following Chinese medicines in parts by weight: The main drug is selected from one or more of 15-30 parts of Radix Rehmanniae and / or 8-15 parts of Fructus Gardeniae; The ministerial drug is selected from one or more of 10-20 parts of hawthorn and / or 10-15 parts of Shenqu; The adjuvant is selected from one or more of 4-10 parts of Scutellaria baicalensis, 4-15 parts of Lophatherum gracile, 9-15 parts of Uncaria rhynchophylla and / or 30-70 parts of Portulaca oleracea; The drug is selected from one or more of 4-20 parts of Fructus Aurantii Immaturus, 10-20 parts of Flos Lonicerae and / or 10-15 parts of Cortex Dictamni and / or 2-6 parts of Areca Nut.

4. The Chinese medicine composition as claimed in claim 1, in some specific embodiments of the present invention, the Chinese medicine composition is made of the following Chinese medicines: 5-50 parts of Radix Rehmanniae and 2-20 parts of Gardenia, 5-30 parts of Crataegus, 5-20 parts of Shenqu, 2-20 parts of Scutellaria, 2-20 parts of Lophatherum gracile, 2-30 parts of Fructus Aurantii Immaturus, 5-20 parts of Uncaria rhynchophylla and 10-90 parts of Portulaca oleracea.

5. The Chinese medicine composition as claimed in claim 1, in some specific embodiments of the present invention, the Chinese medicine composition is made of the following Chinese medicines: 5-50 parts of Radix Rehmanniae and 2-20 parts of Gardenia, 5-30 parts of Crataegus, 5-20 parts of Shenqu, 2-20 parts of Scutellaria, 2-20 parts of Lophatherum gracile, 2-30 parts of Fructus Aurantii Immaturus, 5-20 parts of Uncaria rhynchophylla, 10-90 parts of Portulaca oleracea and 5-60 parts of Flos Lonicerae.

6. The Chinese medicine composition as claimed in claim 1, in some specific embodiments of the present invention, the Chinese medicine composition is made of the following Chinese medicines: 5-50 parts of Radix Rehmanniae and 2-20 parts of Gardenia, 5-30 parts of Crataegus, 5-20 parts of Shenqu, 2-20 parts of Scutellaria, 2-20 parts of Lophatherum gracile, 2-30 parts of Fructus Aurantii Immaturus, 5-20 parts of Uncaria rhynchophylla, 10-90 parts of Portulaca oleracea, 5-60 parts of Honeysuckle, 5-20 parts of Dictamni and 2-10 parts of Areca.

7. A Chinese medicine preparation made from the Chinese medicine composition according to claim 1, wherein the Chinese medicine preparation is one or more of a paste prescription, a pill, a pill, a decoction, a granule, a capsule, a powder and / or a tablet.

8. The Chinese medicine preparation according to claim 7, comprising pharmaceutically acceptable excipients required for the corresponding preparation; the excipients are pharmaceutical excipients that enhance the efficacy, reduce toxicity and / or alleviate side effects of the main drug.

9. Use of the Chinese medicine composition as claimed in claim 1 in preparing medicines for treating skin diseases.

10. The use according to claim 9, wherein the skin diseases include atopic dermatitis, eczema, dermatitis, allergic dermatitis, and psoriasis.

Images