Application of traditional Chinese medicine composition in preparation of medicine for atopic dermatitis

Abstract

The invention relates to an application of a traditional Chinese medicine composition in preparing a medicine for atopic dermatitis, which is characterized in that the traditional Chinese medicine composition is prepared from astragalus membranaceus, dried ginger, salted morinda officinalis, cortex dictamni, calcined oyster shell, schisandra chinensis and divaricate saposhnikovia root. The composition provided by the invention can obviously inhibit increase of spleen index and thymus index of infected mice, reduce back skin lesion score of the infected mice, reduce content of IL-6, IL-33 and TNF-alpha in serum of the infected mice, and has a good treatment effect on the specific dermatitis.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicines, relates to a new use of a traditional Chinese medicine composition, and particularly relates to the use of the traditional Chinese medicine composition in preparing a medicine for atopic dermatitis. Background Art

[0002] Atopic dermatitis (AD), also known as atopic eczema and formerly known as "atopic dermatitis" or "genetic allergic dermatitis," is a common dermatological disease and has become a major global public health concern. The etiology of AD remains unclear, but it may be related to genetic, immune, environmental factors, and abnormal skin barrier function. Common clinical manifestations include dry skin, eczematous rashes, and intense itching. Severe cases can negatively impact daily life. Treatment typically involves medications and physical therapy. Atopic dermatitis can be divided into simple and mixed types based on the presence or absence of other allergic conditions. The simple type manifests solely as dermatitis. It can be further divided into endogenous and exogenous types. Exogenous patients have elevated serum total IgE, specific IgE levels, and peripheral blood eosinophils, while endogenous patients have minimal or no such changes. Endogenous atopic dermatitis is easily missed. In addition to the manifestations of dermatitis, mixed atopic dermatitis is also associated with allergic asthma, allergic rhinitis, and allergic conjunctivitis. In view of the above problems, the field of traditional Chinese medicine should actively participate in the prevention and treatment of atopic dermatitis and develop appropriate prescriptions. Summary of the Invention

[0003] The technical problem to be solved by the present invention is to provide an oral medicine for treating atopic dermatitis, which has a significant effect in treating atopic dermatitis.

[0004] The technical solutions of the present invention for solving the above problems are as follows:

[0005] A Chinese medicine composition for use in preparing a medicament for atopic dermatitis, wherein the use can be any form beneficial to improving the corresponding symptoms of the patient, including treatment or prevention. The Chinese medicine composition is made from the following components: 5-15 parts of dried ginger, 15-25 parts of astragalus root, 5-15 parts of salt-cured Morinda officinalis root, 5-15 parts of Dictamni root bark, 25-35 parts of calcined oyster shell, 5-10 parts of Schisandra chinensis fruit, and 5-15 parts of Saposhnikovia divaricata. The composition of the present invention can be directly ground into a powder or can be an extract prepared by conventional means in the art. The Chinese medicine used in the composition of the present invention can also be used in the form of a direct powder, an extract, or other processed form.

[0006] The present invention also provides a use of a traditional Chinese medicine composition in the preparation of an anti-inflammatory drug. The anti-inflammatory drug can be an inflammation caused by atopic dermatitis.

[0007] Furthermore, the aforementioned Chinese medicine composition is made from the following components: 9-11 parts of dried ginger, 19-23 parts of astragalus, 9-11 parts of salt Morinda officinalis, 9-11 parts of Dictamni cortex, 28-34 parts of calcined oyster shell, 6-7 parts of Schisandra chinensis, and 9-11 parts of Saposhnikovia divaricata.

[0008] Furthermore, the Chinese medicine composition is prepared from the following components: 10 parts of dried ginger, 20 parts of astragalus root, 10 parts of salt Morinda officinalis root, 10 parts of white peony root, 30 parts of calcined oyster shell, 6 parts of Schisandra chinensis, and 10 parts of siler. Furthermore, the preparation method of the aforementioned Chinese medicine composition includes:

[0009] Take dried ginger, salt Morinda officinalis, Astragalus membranaceus, Dictamni cortex, calcined oyster shell, Schisandra chinensis and Saposhnikovia divaricata, add 10 times the amount of water, decoct twice, each time for 1 hour, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.07-1.15 (60℃), spray dry, and obtain dry paste powder.

[0010] Specifically, the drug includes pharmaceutically acceptable excipients or additives.

[0011] Specifically, the pharmaceutically acceptable excipients or additives include fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, and bases.

[0012] Specifically, the pharmaceutical dosage forms of the drug provided by the present invention include oral dosage forms, injection dosage forms or external dosage forms.

[0013] The dosage forms of the drugs of the present invention are prepared by weighing the raw materials in proportion, adding pharmaceutically acceptable excipients or additives, such as fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, bases, etc., and preparing according to conventional production methods in the pharmaceutical field to prepare conventional pharmaceutically acceptable dosage forms, including but not limited to decoctions, granules, capsules, tablets, oral liquids, pills, soft capsules, dripping pills, tinctures, syrups, suppositories, gels, sprays, and injections.

[0014] The medicine of the present invention can be prepared by the following method:

[0015] Take 10kg of dried ginger, 10kg of salt Morinda officinalis, 20kg of Astragalus membranaceus, 10kg of Dictamnus cortex, 30kg of calcined oyster shell, 6kg of Schisandra chinensis and 10kg of Saposhnikovia divaricata, add 10 times the amount of water, decoct twice, each time for 1 hour, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.07-1.15 (60°C), spray dry to obtain a Chinese medicine composition intermediate, add dextrin, mix well, granulate with 90% ethanol, dry, and granulate to obtain the product.

[0016] The medicine of the present invention is a conventional granule, tablet or capsule.

[0017] The composition of the present invention can significantly inhibit the increase of spleen index and thymus index of mice with atopic dermatitis, reduce the back skin lesion score of infected mice, and alleviate the damage to the back skin of mice with atopic dermatitis; it can significantly reduce the IL-6, IL-33 and TNF-α levels in the serum of infected mice, indicating that the traditional Chinese medicine composition has a good therapeutic effect on atopic dermatitis. DETAILED DESCRIPTION

[0018] As mentioned above, the present invention aims to provide a use of a Chinese medicine composition in the preparation of a medicament for atopic dermatitis. Detailed description will be given below in conjunction with specific experimental content.

[0019] Unless otherwise specified, the following experiments were conducted under conventional conditions or those recommended by the manufacturer. All APIs, excipients, reagents, and instruments used, unless the manufacturer is specified, are commercially available. Unless otherwise specified, all percentages, ratios, proportions, and parts are by weight.

[0020] Unless otherwise defined, all professional and scientific terms used herein have the same meaning as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein can be applied to the present invention.

[0021] Example 1 Preparation of granules of the composition of the present invention

[0022] Take 10kg of dried ginger, 10kg of salt Morinda officinalis, 20kg of Astragalus membranaceus, 10kg of Dictamnus cortex, 30kg of calcined oyster shell, 6kg of Schisandra chinensis and 10kg of Saposhnikovia divaricata, add 10 times the amount of water, decoct twice, each time for 1 hour, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.07-1.15 (60°C), spray dry to obtain a Chinese medicine composition intermediate, add dextrin, mix well, granulate with 90% ethanol, dry, and granulate to obtain the product.

[0023] Example 2 Therapeutic Effect of a Traditional Chinese Medicine Composition on Calcipotriol-Induced Atopic Dermatitis Model in Mice 1. Experimental Materials

[0024] 1.1 Animals

[0025] 60 BALB / c mice, SPF grade, weighing 17-20 g, half male and half female.

[0026] Rearing environment: Room temperature 20-26°C, relative humidity controlled at 40-70%. Males and females were housed in separate cages, with 5 per cage per group.

[0027] 1.2 Drugs and reagents

[0028] Traditional Chinese medicine composition, intermediate prepared according to the method of Example 1, Jiangsu Kangyuan Pharmaceutical Co., Ltd.; mometasone furoate gel, China Resources Sanjiu Pharmaceutical Co., Ltd., specification: 0.1% × 10g / tube, batch number: 2208008J; MC903 (calcipotriol), Shanghai MacLean Biochemical Technology Co., Ltd., item number: C798292. Anhydrous ethanol, Sangon Biotech (Shanghai) Co., Ltd., specification: 500mL / bottle, item number: A500737-0500.

[0029] 1.3 Instruments

[0030] Electronic balance, METTLER TOLEOD, model: MS1003S101; animal weighing scale, Kagawa, model: ACX-SC-DA.

[0031] 2. Dosage design

[0032] The daily dosage of the Chinese herbal medicine composition is 96g of crude drug per day. Based on the body surface area conversion method, the equivalent dose for mice is 96g / 60kg*11 = 17.6g of crude drug / kg. Using a 1 / 4:1 / 2:1 dosing ratio, the low dose is 4.5g of crude drug / kg, the medium dose is 9.0g of crude drug / kg, and the high dose is 18.0g of crude drug / kg. Administration is by oral gavage at 0.2mL / 10g twice daily.

[0033] 3. Experimental Methods

[0034] Sixty BALB / c mice, weighing 17-20 g (half male and half female), were acclimated for 3 days with free access to feed and water. The day before the experiment, hair was removed from the back of the mice, measuring approximately 2 cm × 2 cm. Ten mice (half male and half female) were randomly selected based on body weight as a normal control group, while the remaining mice were used for modeling. On day 1 of the experiment, 50 μL of a 0.05 nmol / μL MC903 / ethanol solution was applied to the backs of the model mice. The normal control group was treated with anhydrous ethanol once daily for 7 consecutive days. On day 7, the back lesions of the mice were scored. Based on the scores, the model mice were divided into five groups: a model group, low-, medium-, and high-dose Chinese herbal medicine groups (4.5 g crude drug / kg, 9.0 g crude drug / kg, and 18.0 g crude drug / kg), and a positive control group (0.1% mometasone furoate gel, 50 μL). Each group consisted of 10 mice (half male and half female). On day 8, each treatment group began receiving the corresponding drug by gavage. The normal control and model groups received distilled water twice daily for 7 consecutive days. Simultaneously with the drug administration, 50 μL of a 0.05 nmol / μL MC903 / ethanol solution was administered to maintain the model. The normal control group continued to be coated with anhydrous ethanol. On day 15, the mice were weighed and sacrificed. The thymus and spleen were removed and weighed, and the organ coefficients were calculated. The back skin lesions of the mice were scored according to the following criteria: 0: no edema, keratinization, or inflammation; 1: mild edema, keratinization, and inflammation; 2: mild to moderate edema, keratinization, and inflammation; and 3: moderate to severe edema, keratinization, and inflammation.

[0035] Thymus index (%) = thymus wet weight (g) / body weight (g) × 100

[0036] Spleen index (%) = spleen wet weight (g) / body weight (g) × 100

[0037] 4. Statistical methods

[0038] The results were statistically analyzed using t-test.

[0039] 5. Experimental Results

[0040] 5.1 Effects on the immune organ indices of mice

[0041] Compared with the normal control group, the spleen index and thymus index of the model group were significantly increased, with significant differences compared with the normal control group (P < 0.01, P < 0.01), indicating that the atopic dermatitis model was successfully induced. The high and medium dose groups of the Chinese herbal composition significantly reduced the spleen index of mice, with significant differences compared with the model control group (P < 0.01, P < 0.01); the high and medium dose groups of the Chinese herbal composition significantly reduced the thymus index of mice, with significant differences compared with the model control group (P < 0.01, P < 0.05). The results are shown in Table 1.

[0042] Table 1 Comparison of organ indexes of mouse immune organs

[0043]

[0044]

[0045] Note: Compared with the normal control group, ## P<0.01; compared with the model control group, **P<0.01, *P<0.05.

[0046] 5.2 Effects on the back score of mice

[0047] Compared with the normal control group, the back lesion score in the model group was significantly increased, with a significant difference compared to the normal control group (P < 0.01), indicating that the atopic dermatitis model was successfully induced. The back lesion scores in the high, medium, and low dose groups of the Chinese medicine composition were all significantly reduced, with significant differences compared to the model control group (P < 0.01, P < 0.01, and P < 0.05). The results are shown in Table 2.

[0048] Table 2 Comparison of skin lesion scores on the back of mice

[0049]

[0050] Note: Compared with the normal control group, ## P<0.01; compared with the model control group, **P<0.01, *P<0.05.

[0051] 6. Experimental Conclusion

[0052] The high and medium dose groups of the Chinese medicine composition can significantly inhibit the increase of spleen index and thymus index of mice with atopic dermatitis. The high, medium and low dose groups of the Chinese medicine composition can significantly reduce the back skin lesion scores of mice with atopic dermatitis, indicating that the Chinese medicine composition has a certain therapeutic effect on mice with atopic dermatitis.

[0053] Example 3 Anti-inflammatory effect of the Chinese medicine composition on atopic dermatitis model in mice induced by 2,4-dinitrofluorobenzene

[0054] 1. Experimental Materials

[0055] 1.1 Animals

[0056] 60 BALB / c mice, SPF grade, weighing 18-20 g, half male and half female.

[0057] Rearing environment: Room temperature 20-26°C, relative humidity controlled at 40-70%. Males and females were housed in separate cages, with 5 per cage per group.

[0058] 1.2 Drugs and reagents

[0059] The Chinese medicine composition, the intermediate prepared according to the method of Example 1, was provided by Jiangsu Kangyuan Pharmaceutical Co., Ltd.; 2,4-dinitrofluorobenzene (DNFB), Merck (China) Co., Ltd., item number: 70-34-8; olive oil, Shanghai Aladdin Biochemical Technology Co., Ltd., item number: 8001-25-0; dexamethasone acetate tablets, Chenxin Pharmaceutical Co., Ltd., batch number: 2204070213; acetone, Sinopharm Chemical Reagent Co., Ltd., item number: 10000418; sodium sulfide, Shanghai Aladdin Biochemical Technology Co., Ltd., item number S138149; interleukin-6 (IL-6, item number: SEKM-0007) kit, interleukin-33 (IL-33, item number: SEKM-0028) kit, and tumor necrosis factor-α (TNF-α, item number: SEKM-0034) kit, were provided by Beijing Solebold Technology Co., Ltd.

[0060] 1.3 Instruments

[0061] Electronic balance, METTLER TOLEOD, model: MS1003S101; animal weighing scale, Kagawa, model: ACX-SC-DA; low-temperature centrifuge, Eppendorf, Germany, model: 5804R; microplate reader, American Bio-Molecular, model: Flexstation 3.

[0062] 2. Dosage design

[0063] The daily dosage of the Chinese herbal medicine composition is 96g of crude drug / day. Based on the body surface area conversion method, the equivalent dose for mice is 96g / 60kg*11=17.6g of crude drug / kg. According to the 1 / 4:1 / 2:1 dosing method, the low dose is 4.5g of crude drug / kg, the medium dose is 9.0g of crude drug / kg, and the high dose is 18.0g of crude drug / kg. Oral administration: 0.2mL / 10g, twice daily

[0064] 3. Experimental Methods

[0065] Sixty BALB / c mice, weighing 18-20 g (half male and half female), were acclimatized for 3 days with free access to feed and water. They were randomly divided into six groups based on body weight: a normal control group, a model group, low-, medium-, and high-dose groups of the Chinese herbal composition (4.5 g crude drug / kg, 9.0 g crude drug / kg, and 18.0 g crude drug / kg), and a positive control group (dexamethasone, 0.0001 g / kg), with 10 mice in each group. One day before the experiment, the hair on the back of the mice was shaved, approximately 2.5 cm × 2.5 cm, until completely exposed. To ensure efficacy, the exposed skin was smeared with 6% sodium sulfide to fully remove the hair. The DNFB reagent was prepared using a 3:1 volume ratio of acetone to olive oil. On days 1 and 4 of the experiment, mice in the normal control group were smeared with 100 μL of a 3:1 acetone / olive oil solution on the depilated area on the back, while mice in the other groups were smeared with 100 μL of a 0.5% DNFB solution on the depilated area for sensitization and boosted sensitization, respectively. On days 7, 10, and 13, mice in the normal control group were smeared with 100 μL of a 3:1 acetone / olive oil solution on the depilated area, while mice in the other groups were smeared with 100 μL of a 0.2% DNFB solution on the depilated area for secondary challenge. On day 5, after sensitization, each treatment group began receiving the corresponding drug by gavage. The normal control and model groups were treated with distilled water twice daily for 10 consecutive days. One hour after the last treatment, the mice were enucleated and blood was collected. Serum was centrifuged and assayed for IL-6, IL-33, and TNF-α levels using enzyme-linked immunosorbent assay (ELISA).

[0066] 4. Statistical methods

[0067] The results were statistically analyzed using t-test.

[0068] 5. Experimental Results

[0069] 5.1 Effects on IL-6, IL-33, and TNF-α in mouse serum

[0070] Compared with the normal control group, the levels of IL-6, IL-33, and TNF-α in the serum of mice in the model group were significantly increased (P < 0.01), indicating that the atopic dermatitis model was successfully induced. Compared with the model group, the high, medium, and low dose groups of the Chinese medicine composition significantly reduced the IL-6 content in the serum of mice (P < 0.01, P < 0.01, P < 0.05); the high, medium, and low dose groups of the Chinese medicine composition significantly reduced the IL-33 content in the serum of mice (P < 0.01, P < 0.01, P < 0.05); and the high, medium, and low dose groups of the Chinese medicine composition significantly reduced the TNF-α content in the serum of mice (P < 0.01, P < 0.01, P < 0.05). The results are shown in Table 3.

[0071] Table 3 Effects on IL-6, IL-33, and TNF-α in the serum of atopic dermatitis model mice

[0072]

[0073] Note: Compared with the normal control group, ## P<0.01; compared with the model control group, **P<0.01, *P<0.05.

[0074] 6. Experimental Conclusion

[0075] The high, medium and low dose groups of the Chinese medicine composition can significantly reduce the levels of IL-6, IL-33 and TNF-α in the serum of mice with atopic dermatitis, suggesting that the Chinese medicine composition has a certain therapeutic effect on inflammation in mice with atopic dermatitis.

[0076] The above embodiments of the present invention are merely examples for the purpose of clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Those skilled in the art will appreciate that other variations or modifications may be made based on the above description. It is not necessary and impossible to enumerate all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the claims of the present invention.

Claims

1. Use of a Chinese medicine composition in preparing a drug for atopic dermatitis, characterized in that: The traditional Chinese medicine composition is prepared from the following components: 5-15 parts of dried ginger, 15-25 parts of astragalus root, 5-15 parts of salt Morinda officinalis, 5-15 parts of Dictamnus dahurica, 25-35 parts of calcined oyster shell, 5-10 parts of Schisandra chinensis, and 5-15 parts of Saposhnikovia divaricata.

2. The use according to claim 1, characterized in that The traditional Chinese medicine composition is prepared from the following components by weight: 9-11 parts of dried ginger, 19-23 parts of astragalus, 9-11 parts of salt Morinda officinalis, 9-11 parts of Dictamni cortex, 28-34 parts of calcined oyster shell, 6-7 parts of Schisandra chinensis, and 9-11 parts of Saposhnikovia divaricata.

3. The use according to claim 1, characterized in that The traditional Chinese medicine composition is prepared from the following components by weight: 10 parts of dried ginger, 20 parts of astragalus, 10 parts of salt Morinda officinalis, 10 parts of Dictamnus dasycarpus, 30 parts of calcined oyster shell, 6 parts of Schisandra chinensis, and 10 parts of Saposhnikovia divaricata.

4. The use according to any one of claims 1 to 3, characterized in that: The preparation method of the traditional Chinese medicine composition comprises the following steps: taking dried ginger, salt morinda root, astragalus root, white mulberry bark, calcined oyster shell, schisandra chinensis and saposhnikovia root, adding 10 times the amount of water, decocting twice, each time for 1 hour, filtering, combining the filtrate, concentrating to a clear paste with a relative density of 1.07-1.15 (60°C), spray drying, and obtaining a dry paste powder.

5. The use according to claims 1-3, characterized in that The medicine includes pharmaceutically acceptable excipients or additives.

6. The use according to claim 5, characterized in that The pharmaceutically acceptable excipients or additives include fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, and bases.

7. The use according to any one of claims 1 to 3, characterized in that: The dosage form of the medicine is granules, tablets or capsules.

8. The use according to any one of claims 1 to 3, characterized in that: The preparation method of the Chinese medicine composition comprises: Take 10kg of dried ginger, 10kg of salt Morinda officinalis, 20kg of Astragalus membranaceus, 10kg of Dictamnus cortex, 30kg of calcined oyster shell, 6kg of Schisandra chinensis and 10kg of Saposhnikovia divaricata, add 10 times the amount of water, decoct twice, each time for 1 hour, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.07-1.15 (60°C), spray dry to obtain a Chinese medicine composition intermediate, add dextrin, mix well, granulate with 90% ethanol, dry, and granulate to obtain the product.

9. Use of a Chinese medicine composition in the preparation of an anti-inflammatory drug, characterized in that: The traditional Chinese medicine composition is prepared from the following components: 5-15 parts of dried ginger, 15-25 parts of astragalus root, 5-15 parts of salt Morinda officinalis, 5-15 parts of Dictamnus dahurica, 25-35 parts of calcined oyster shell, 5-10 parts of Schisandra chinensis, and 5-15 parts of Saposhnikovia divaricata.

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