A traditional Chinese medicine composition for treating erythema nodosum, a preparation method and use thereof

Abstract

The application discloses a traditional Chinese medicine composition for treating nodular erythema, which is prepared from the following raw materials in a proportion by weight: 3-15 parts of Bupleurum, 3-20 parts of Artemisia annua, 3-15 parts of Angelica sinensis, 3-15 parts of Radix Angelicae Pubescentis, 3-20 parts of Cynanchum, 3-15 parts of Notopterygium, 3-20 parts of Fructus Kochiae, 3-15 parts of Cnidium, 3-20 parts of Alnus, 3-10 parts of Glycyrrhiza, 3-20 parts of Salvia miltiorrhiza, 3-15 parts of Saposhnikovia divaricata, 3-15 parts of Paeonia suffruticosa, 3-10 parts of honeycomb, 3-12 parts of Tripterygium wilfordii, 5-30 parts of Crataegus pinnatifida, and 5-30 parts of Sorsastrum hemningsii. The composition can fade the skin rash and nodular erythema, has a low recurrence rate, and is superior to methylprednisolone which is commonly used in the clinic. The application can effectively treat the nodular erythema related to connective tissue disease, and has the clinical popularization and application value.

Description

Technical Field

[0001] This invention specifically relates to a traditional Chinese medicine composition for treating erythema nodosum, its preparation method, and its uses. Background Technology

[0002] Erythema nodosum is a recurrent inflammatory skin disease with complex etiologies related to multiple factors, such as various pathogenic infections, medications, connective tissue diseases, and Behcet's disease. It commonly appears on the extensor surfaces of the lower legs, clinically presenting as painful, red or purplish-red inflammatory nodules. It is prevalent in young and middle-aged adults, especially young women, and exhibits a seasonal pattern, often occurring more frequently in spring and autumn. Currently, erythema nodosum caused by connective tissue diseases is considered a delayed-type hypersensitivity reaction to certain exogenous antigens. Connective tissue diseases have a long course, complex symptoms, and high incidence, leading to a high recurrence rate of erythema nodosum caused by them.

[0003] Currently, the treatment of erythema nodosum primarily relies on Western medicine, including antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), or corticosteroids. While there is considerable research on traditional Chinese medicine (TCM) treatment, the results are not ideal; most TCM formulas require combination with Western medicine to achieve good efficacy. For example, Li Qingsong et al. achieved a 90% efficacy rate in treating erythema nodosum using a modified Simiao Yong'an Decoction combined with topical Longzhu ointment. Therefore, it is necessary to provide a safe, low-side-effect, and highly effective TCM composition for treating erythema nodosum, especially connective tissue disease-related erythema nodosum, for clinical application. Summary of the Invention

[0004] To address the above problems, this invention provides a traditional Chinese medicine composition for treating erythema nodosum, which is prepared from the following raw materials in the indicated weight ratios:

[0005] Bupleurum chinense 3-15 parts, Artemisia annua 3-20 parts, Angelica sinensis 3-15 parts, Angelica pubescens 3-15 parts, Lycium chinense root bark 3-20 parts, Notopterygium incisum 3-15 parts, Kochia scoparia fruit 3-20 parts, Cnidium monnieri fruit 3-15 parts, Dictamnus dasycarpus root bark 3-20 parts, Glycyrrhiza uralensis 3-10 parts, Salvia miltiorrhiza 3-20 parts, Saposhnikovia divaricata 3-15 parts, Paeonia suffruticosa root bark 3-15 parts, Vespa nidus 3-10 parts, Tripterygium wilfordii 3-12 parts, Crataegus pinnatifida fruit 5-30 parts, Hedyotis diffusa 5-30 parts.

[0006] Furthermore, it is prepared from the following raw materials in the indicated weight ratios:

[0007] Bupleurum chinense 6 parts, Artemisia annua 9 parts, Angelica sinensis 9 parts, Angelica pubescens 10 parts, Lycium chinense root bark 10 parts, Notopterygium incisum 9 parts, Kochia scoparia 15 parts, Cnidium monnieri 10 parts, Dictamnus dasycarpus root bark 12 parts, Glycyrrhiza uralensis 6 parts, Salvia miltiorrhiza 9 parts, Saposhnikovia divaricata 9 parts, Paeonia suffruticosa root bark 12 parts, Vespa nidus 3 parts, Tripterygium wilfordii 6 parts, Crataegus pinnatifida 9 parts, Hedyotis diffusa 15 parts.

[0008] Furthermore, the hawthorn mentioned is charred hawthorn.

[0009] Furthermore, it is a formulation prepared by adding pharmaceutically acceptable excipients to a fine powder of raw materials or water or organic solvent extracts of raw materials as active ingredients.

[0010] Furthermore, the formulation is an oral formulation.

[0011] Furthermore, the oral preparation is a granule, tablet, powder, pill, or solution.

[0012] The present invention also provides a method for preparing the aforementioned traditional Chinese medicine composition, which includes the following steps:

[0013] (1) Weigh the raw materials according to the stated proportions;

[0014] (2) The raw material is ground into powder, or the water or organic solvent extract of the raw material is added to the excipients or auxiliary ingredients commonly used in pharmaceuticals.

[0015] Finally, this invention provides the use of the aforementioned traditional Chinese medicine composition in the preparation of a medicament for treating erythema nodosum.

[0016] Furthermore, the drug is a treatment for erythema nodosum associated with connective tissue diseases.

[0017] In this invention, the composition uses peony bark and salvia miltiorrhiza to clear heat, cool blood, and promote blood circulation and remove blood stasis. Bupleurum chinense is used to harmonize the exterior and interior. Tripterygium wilfordii is used as the principal drug to promote blood circulation, unblock collaterals, dispel wind and dampness. Angelica sinensis is used to nourish blood and regulate the nutritive qi. Lycium chinense root bark is used to treat wind-evil that is not fixed on the surface. Dictamnus dasycarpus root bark is used to dispel wind and dampness. Saposhnikovia divaricata is used to dispel evil by dispersing and relieving itching. Cnidium monnieri, Kochia scoparia, Vespa nidus, and Artemisia annua are used as assistant drugs to dispel wind and relieve itching. Hedyotis diffusa is used to clear heat, detoxify, and promote diuresis. Angelica pubescens and Notopterygium incisum are used as adjuvant drugs to dispel wind, eliminate dampness, and relieve pain. Crataegus pinnatifida is used to promote digestion, strengthen the stomach, regulate qi and remove blood stasis. Glycyrrhiza uralensis is used to relieve spasms and pain and harmonize the other drugs as the guiding drug. The whole formula works together to cool blood and remove blood stasis, dispel wind and relieve itching, and disperse nodules and relieve pain.

[0018] Clinical trials have demonstrated that the composition of this invention can reduce rashes and erythema nodosum with a low recurrence rate, and its efficacy is superior to that of methylprednisolone, which is currently widely used in clinical practice. This invention can effectively treat erythema nodosum, especially erythema nodosum associated with connective tissue diseases, and has clinical application value.

[0019] Obviously, based on the above description of the present invention, and according to common technical knowledge and conventional methods in the field, various other modifications, substitutions, or alterations can be made without departing from the basic technical concept of the present invention.

[0020] The above content of the present application is further explained in detail by way of specific embodiments in the form of examples. However, it should not be understood that the above-mentioned subject matter of the present application is limited to the following examples. Any technology realized based on the above content of the present application falls within the scope of the present application. DETAILED DESCRIPTION

[0021] The raw materials and equipment used in the detailed description of the present application are known products, which are obtained by purchasing commercially available products. The preparation process of modern Chinese medicine preparations made of the traditional Chinese medicine composition of the present application is mature, and can be prepared by referring to conventional methods of existing technologies.

[0022] Example 1, preparation of the medicine of the present application

[0023] Formula: Bupleurum 3g, Artemisia 3g, Angelica 3g, Rhizoma 3g, Psoralea 3g, Notopterygium 3g, Semen Euphorbiae 3g, Cnidium 3g, White willow bark 3g, Licorice 3g, Salvia 3g, Saposhnikovia 3g, Tree peony bark 3g, Honeycomb 3g, Radix et Rhizoma 3g, Fritillaria 5g, White flower snake tongue grass 5g

[0024] Preparation method: the above-mentioned raw materials are weighed according to the proportion, decocted with 10 times the amount of water for 2 times, each time for 20-30 minutes, filtered, the filtrates are combined, the filtrate is concentrated into thick paste under reduced pressure, and the tablet is prepared by adding the auxiliary materials commonly used in medicines.

[0025] Example 2, preparation of the medicine of the present application

[0026] Formula: Bupleurum 15g, Artemisia 20g, Angelica 15g, Rhizoma 15g, Psoralea 20g, Notopterygium 15g, Semen Euphorbiae 20g, Cnidium 15g, White willow bark 20g, Licorice 10g, Salvia 20g, Saposhnikovia 15g, Tree peony bark 15g, Honeycomb 10g, Radix et Rhizoma 12g, Fritillaria 30g, White flower snake tongue grass 30g

[0027] Preparation method: the above-mentioned raw materials are weighed according to the proportion, decocted with 10 times the amount of water for 2 times, each time for 20-30 minutes, filtered, the filtrates are combined, the filtrate is concentrated into thick paste under reduced pressure, and the granules are prepared by adding the auxiliary materials commonly used in medicines.

[0028] Example 3, preparation of the medicine of the present application

[0029] Formula: Bupleurum 6g, Artemisia 9g, Angelica 9g, Rhizoma 10g, Psoralea 10g, Notopterygium 9g, Semen Euphorbiae 15g, Cnidium 10g, White willow bark 12g, Licorice 6g, Salvia 9g, Saposhnikovia 9g, Tree peony bark 12g, Honeycomb 3g, Radix et Rhizoma 6g, Fritillaria 9g, White flower snake tongue grass 15g.

[0030] Preparation method: the prescription granules of each raw material medicine (produced by Guangdong Yifang Pharmaceutical Co., Ltd.) are mixed, and the granules are obtained.

[0031] The beneficial effects of the present application are illustrated below by test examples.

[0032] Test Example 1, Clinical therapeutic effect of the pharmaceutical composition of the present application

[0033] 1. Clinical data

[0034] The clinical research cases originated from the outpatients and inpatients of the Department of Rheumatology and Immunology of the First Affiliated Hospital of Chengdu Medical College, and were patients with nodular erythema related to connective tissue disease. According to the random number table method, they were divided into an experimental group and a control group. Among them, the experimental group included 32 patients, of which 6 were male and 26 were female, with an average age of 32.22±2.12 years and an average disease duration of 2.73±0.91 years. The control group included 27 patients, of which 8 were male and 19 were female, with an average age of 34.11±2.91 years and an average disease duration of 2.77±0.69 years.

[0035] 1.1 Diagnostic criteria

[0036] (1) Western medicine inclusion criteria:

[0037] Connective tissue disease adopts the American Sharp diagnostic criteria:

[0038] 1) Main criteria

[0039] ① Severe myositis; ② Lung involvement (carbon dioxide diffusion function less than 70%, pulmonary hypertension, lung biopsy showing proliferative vascular damage); ③ Raynaud's phenomenon / decreased esophageal peristalsis; ④ Joint swelling, tenderness or finger stiffness; ⑤ Positive antinuclear antibody, titer >1:320, and / or positive ENA antibody.

[0040] 2) Secondary criteria

[0041] ① Alopecia; ② Leukopenia; ③ Anemia; ④ Pleurisy; ⑤ Pericarditis; ⑥ Arthritis; ⑦ Trigeminal nerve disorder; ⑧ Cheek erythema; ⑨ Thrombocytopenia; ⑩ Mild myositis.

[0042] 3) Definite diagnosis

[0043] ① 4 main criteria; ② Serological antinuclear antibody positive, titer >1:320, excluding infectious or neoplastic diseases.

[0044] Nodular erythema was diagnosed according to Zhu Xuejun's "Modern Dermatology Diagnosis Manual" through clinical manifestations and biopsy (according to typical skin lesions, good for the shins, with tenderness, not broken, combined with skin histopathology showing interstitial panniculitis of subcutaneous fat lobules).

[0045] (2) TCM inclusion criteria:

[0046] TCM syndrome differentiation basis of erythema nodosum is "TCM clinical diagnosis and treatment terminology·syndrome type part"

[0047] 1.2 Exclusion criteria

[0048] ① Patients with severe diseases of heart, liver, lung, kidney, endocrine system, etc.; ② Patients with severe upper respiratory tract infections and other infections; ③ Pregnant or lactating women; ④ Patients with severe illness that may affect the effectiveness and safety of this study. ⑤ Patients allergic to the drug components in this study.

[0049] 2. Treatment method

[0050] Test group: Patients take the pharmaceutical composition prepared in Example 3 of the application, each time taking a dose of 10-15g; the taking method is to take it with warm water, three times a day, and 7 days as a course of treatment, taking 4 courses.

[0051] Control group: 8-16mg of methylprednisolone is taken orally.

[0052] 3. Efficacy evaluation criteria

[0053] According to "Guiding principles for clinical research on new drugs of traditional Chinese medicine", the clinical efficacy is divided into improvement, significant effect and no effect.

[0054] Improvement: Clinical symptoms (fever, myalgia, arthralgia, skin lesion redness, swelling, heat and pain) and signs (papules, purpura, erythema, nodules, local edema) are significantly improved, and the symptom score reduction rate is ≥70%;

[0055] Significant effect: Clinical symptoms and signs are improved, and the symptom score reduction rate is ≥30%;

[0056] No effect: There is no significant improvement or significant aggravation in clinical symptoms and signs, and the symptom score reduction rate is <30%.

[0057] Symptom score reduction rate = [(pre-treatment score - post-treatment score) / pre-treatment score] x 100%.

[0058] The reference for the scoring of erythema nodosum signs is (Gao Jinghong, et al. Journal of Anhui University of Chinese Medicine, 2016, 35(05): 29-31.), and the specific scoring method is as follows:

[0059] ① Papules: no papules, 0 points; up to 2 papules per square centimeter, 1 point; 3-5 papules per square centimeter, 2 points; 6 or more papules per square centimeter, 3 points.

[0060] ② Purpura: no purpura, 0 points; visible purpura upon close examination, 1 point; immediate discovery of purpura, 2 points; very obvious purpura, 3 points.

[0061] ③Erythema: no erythema, 0 points; mild pink, 1 point; easily recognizable distinct erythema, 2 points; significant erythema, 3 points.

[0062] ④Nodules: no nodules, 0 points; less than or equal to 5 nodules, 1 point; more than 5 nodules, less than or equal to 10 nodules, 2 points; more than 10 nodules, 3 points.

[0063] ⑤Local edema: no edema, 0 points; local area dermal edema, not easy to be palpated, 1 point; multiple distinct dermal edema, 2 points; extensive area dermal edema, infiltration, 3 points.

[0064] 4. Therapeutic effect

[0065] (1) The clinical efficacy results of the pharmaceutical composition of the present application are shown in Table 1. (Note: improved cases are included in the cured cases)

[0066] Table 1. Clinical efficacy results of the pharmaceutical composition of the present application

[0067] cases markedly effective (cases) improved (cases) ineffective (cases) effective rate experimental group 32 29 26 3 90.63％ control group 27 24 19 3 88.89％

[0068] (2) After 3 months of follow-up, the recurrence rate of the pharmaceutical composition of the present application is shown in Table 2. (Note: The recurrence rate is calculated from the total number of cases, and the specific formula is recurrence cases / total cases*100%)

[0069] Table 2. Recurrence rate of the pharmaceutical composition of the present application

[0070] cases recurrence (cases) recurrence rate experimental group 32 3 9.38％ control group 27 4 14.81％

[0071] From the statistical results of Tables 1 and 2, it can be seen that the pharmaceutical composition of the present application has good improvement effect on the clinical symptoms of connective tissue disease related nodular erythema, and the effect is better than that of western medicine methylprednisolone, which can effectively treat connective tissue disease related nodular erythema and prevent recurrence.

[0072] In summary, the traditional Chinese medicine composition in the present application has the effects of cooling blood, removing blood stasis, dispelling wind and relieving itching, and resolving nodules and relieving pain, can effectively treat connective tissue disease related nodular erythema, has low recurrence rate, and has clinical application value.

Claims

1. A traditional Chinese medicine composition for treating erythema nodosum, characterized in that: It is prepared from the following raw materials in the following weight ratio: ​ Bupleurum 6 parts, Artemisia 9 parts, Angelica 9 parts, Millettia 10 parts, Periploca 10 parts, Notopterygium 9 parts, Semen Eurycoma 15 parts, Cnidium 10 parts, White Alnus Bark 12 parts, Licorice 6 parts, Salvia 9 parts, Saposhnikovia 9 parts, Tree Peony Bark 12 parts, Honeycomb 3 parts, Radix et Rhizoma Tripterygii 6 parts, Hawthorn 9 parts, Oldenlandia 15 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that: The hawthorn is charred hawthorn.

3. The traditional Chinese medicine composition according to claim 1, characterized in that: It is a preparation prepared from the fine powder of the raw material, or the water or organic solvent extract of the raw material as the active ingredient, plus pharmaceutically acceptable excipients.

4. The traditional Chinese medicine composition according to claim 3, characterized in that: The preparation is an oral preparation.

5. The traditional Chinese medicine composition according to claim 4, characterized in that: The oral preparation is granules, tablets, powder, pills or solution.

6. A method for preparing the traditional Chinese medicine composition according to any one of claims 1-5, characterized in that: It comprises the following steps: (1) The raw materials are weighed according to the ratio; (2) The raw materials are ground into powder, or the water or organic solvent extract of the raw material is added to the commonly used excipients or auxiliary ingredients of pharmaceuticals, and the preparation is obtained.

7. Use of the traditional Chinese medicine composition of any one of claims 1-5 in the preparation of a medicament for treating erythema nodosum.

8. Use according to claim 7, characterized in that: The medicament is a medicament for treating erythema nodosum associated with connective tissue disease.