Application of traditional Chinese medicine composition in preparation of medicine for treating allergic contact dermatitis

Abstract

The invention relates to an application of a traditional Chinese medicine composition in preparing a medicine for treating allergic contact 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 disclosed by the invention can be used for remarkably inhibiting ear swelling of allergic contact model mice, remarkably reducing the content of IL-5 and IL-9 in ear tissues of the model mice and remarkably reducing the spleen index of the model mice, and has a relatively good treatment effect on the allergic contact 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 allergic contact dermatitis. Background Art

[0002] Allergic contact dermatitis, also known as allergic contact dermatitis, is a common dermatological condition, affecting approximately 15%-20% of the population. When the skin comes into contact with an allergen (such as chemical raw materials, metals, and their products), the body's immune system overreacts, causing an inflammatory reaction at the site of contact and even beyond. Mild symptoms may include erythema, edema, and papules, while severe cases may develop erosions, exudates, and even necrosis, often accompanied by itching. Allergic contact dermatitis is a type IV delayed hypersensitivity reaction, primarily caused by an overreaction of the immune system to the allergen. Generally, after the first exposure to an allergen, immune cells in the skin capture the allergen and present it to T lymphocytes. These T lymphocytes are then activated and develop immune memory, and during this period, the patient generally does not experience allergic symptoms. Upon further exposure to the same allergen, this immune memory is reactivated, leading to the production of inflammatory factors by immune cells, triggering an inflammatory response in the skin. Symptoms typically develop within 24-48 hours of further exposure. Allergic contact dermatitis is caused by three main types of allergens: chemical, plant, and animal. While not life-threatening, severe cases can cause distress and affect patients' quality of life. In light of these issues, Traditional Chinese Medicine (TCM) should proactively participate in the prevention and treatment of allergic contact 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 allergic contact dermatitis, and the oral medicine has a significant effect in treating allergic contact dermatitis.

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

[0005] A Chinese medicine composition is used in the preparation of a medicament for allergic contact 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 directly ground into a powder, an extract, or other processed forms.

[0006] The present invention also provides an application of a traditional Chinese medicine composition in the preparation of an anti-inflammatory drug, wherein the inflammation may be inflammation caused by allergic contact dermatitis.

[0007] Furthermore, the Chinese medicine composition is made of 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 ear swelling in allergic contact model mice, significantly reduce the IL-5 and IL-9 contents in ear tissues of model mice, and significantly reduce the spleen index of model mice, and has a good therapeutic effect on allergic contact 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 allergic contact 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 the Chinese Medicine Composition on Fluorescein Isothiocyanate-Induced Allergic Contact Dermatitis Model in Mice

[0024] 1. Experimental Materials

[0025] 1.1 Animals

[0026] Animals: 60 SPF male BALB / c mice, weighing 18-22 g.

[0027] Breeding environment: room temperature 20-26℃, relative humidity controlled at 40-70%, 5 birds per cage.

[0028] 1.2 Medication

[0029] Chinese medicine composition, intermediate prepared according to the method of Example 1, Jiangsu Kangyuan Pharmaceutical Co., Ltd.; dexamethasone acetate tablets (Chenxin Pharmaceutical Co., Ltd., batch number 2204070213).

[0030] 1.3 Reagents

[0031] Fluorescein isothiocyanate (FITC) (Sigma, batch number: 100125); acetone (Shanghai Lingfeng Chemical Reagent Co., Ltd., batch number: 20120803); dibutyl phthalate (Shanghai Lingfeng Chemical Reagent Co., Ltd.; batch number: 20130829); mouse IL-5 ELISA kit (eBioscience, USA, batch number: 4277363); mouse IL-9 ELISA kit (eBioscience, USA, batch number: E16520-112).

[0032] 1.4 Instruments

[0033] Electronic balance (Mettler-Toledo, Switzerland, model: ME104E); thickness gauge (Mitutoyo, Japan, model: 7301); multi-sample tissue grinder (Jingxin, Shanghai, model: Tiss-24); multi-mode micropore detection system (MD, USA, model: Flex Station 3).

[0034] 2. Dosage design

[0035] Based on the clinical adult (60 kg) dose of 96 g of crude drug per day, the equivalent dose for mice, calculated using the body surface area method, is approximately 18.0 g / kg. Using a 1 / 4:1 / 2:1 dosing regimen, the low dose of the Chinese medicine composition is 4.5 mg / kg, and the medium dose is 9.0 g / kg.

[0036] The clinical dosage of hydrocortisone acetate tablets for adults (60 kg) is 20-30 mg / day. Based on 30 mg / day, the equivalent dosage for mice converted according to the body surface area method is approximately 6.0 mg / kg.

[0037] 3. Experimental Methods

[0038] BALB / c mice were adaptively fed for 3 days with free access to feed and water. They were randomly divided according to body weight into a normal group, a model control group, a hydrocortisone-positive drug group, and low-, medium-, and high-dose groups of the Chinese herbal composition, with 10 mice in each group. Starting on modeling day 1, the Chinese herbal composition and the positive drug hydrocortisone tablets were administered orally once daily at a volume of 0.2 mL / 10 g for 7 consecutive days. The normal and model control groups were also given the same volume of physiological saline.

[0039] BALB / c mice were shaved on the abdomen (approximately 3 cm × 3 cm) on day 0. On days 1 and 2, 80 μL of 1.5% FITC solution was evenly applied to the shaved area of ​​the abdomen of mice in all other groups except the normal group, which was coated with an equal volume of solvent (dibutyl phthalate (V): acetone (V) = 1:1) for sensitization. On day 6, 20 μL of 0.6% FITC solution was applied to the right ear of the mice for challenge. After 24 hours, the thickness of the left and right ears of the mice was measured, and the ear swelling was calculated (ear swelling = right ear thickness - left ear thickness); ear discs were knocked out at the same position on the left and right ears using an 8 mm diameter punch, and the ear weight difference was calculated after accurate weighing (ear weight difference = right ear tissue block weight - left ear tissue block weight); the right ear discs of the mice were accurately weighed and prepared into a 2.5% homogenate with pre-cooled PBS. The supernatant was centrifuged at 4°C and 12,000 r / min for 10 minutes, and the supernatant was stored in a -20°C refrigerator. The cytokine levels of IL-5 and IL-9 in the ear tissue homogenate were detected using a kit.

[0040] 4. Statistical methods

[0041] Graphpad Prism 9 software was used for statistical analysis and plotting. The data were normal distributed after homogeneity of variance test. One-way ANOVA was used to compare multiple groups of data, and P < 0.05 was considered to be significantly different.

[0042] 5. Experimental Results

[0043] The allergic contact dermatitis model was induced in mice using FITC. The ear thickness and weight of each group of mice were detected. The results showed that compared with the normal group, the ear swelling and ear weight difference of the model group were significantly increased (P < 0.0001, P < 0.0001); compared with the model group, after 7 days of continuous administration, the low, medium and high doses of the Chinese medicine composition groups could significantly reduce the ear swelling of the model mice (P < 0.05, P < 0.01, P < 0.001), and the low, medium and high doses of the Chinese medicine composition groups also significantly reduced the ear weight difference of the model mice (P < 0.05, P < 0.01, P < 0.01), see Table 1 for details.

[0044] Table 1 Effect of Chinese herbal composition on reducing ear swelling in FITC-induced allergic contact dermatitis model mice

[0045]

[0046] Note: Compared with the normal control group, #### P<0.0001; compared with the model control group, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

[0047] The results of detecting the cytokine levels of IL-5 and IL-9 in the right ear tissue homogenates of mice in each group showed that compared with the normal group, the IL-5 content in the right ear tissue of mice in the model group was significantly increased (P < 0.0001). Compared with the model group, after continuous administration for 7 days, the low, medium and high dose groups of the Chinese medicine composition could significantly reduce the IL-5 content in the ear tissue of the model mice (P < 0.05, P < 0.001, P < 0.0001). At the same time, the low, medium and high dose groups of the Chinese medicine composition could also significantly reduce the IL-9 content in the ear tissue of mice (P < 0.05, P < 0.0001, P < 0.001). See Table 2 for details.

[0048] Table 2 The Chinese herbal composition reduces the levels of IL-5 and IL-9 in the right ear of mice with FITC-induced allergic contact dermatitis

[0049]

[0050] Note: Compared with the normal control group, #### P<0.0001; compared with the model control group, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

[0051] 6. Experimental Conclusion

[0052] The Chinese medicine composition at doses of 4.5, 9.0 and 18.0 g crude drug / kg can significantly inhibit ear swelling in FITC-induced allergic contact dermatitis model mice, and significantly reduce the IL-5 and IL-9 levels in the model mice, suggesting that the Chinese medicine composition has a certain therapeutic effect on allergic contact dermatitis and related inflammations.

[0053] Example 3 Therapeutic Effect of the Chinese Medicine Composition on 2,4-Dinitrofluorobenzene-Induced Allergic Contact Dermatitis Model in Mice

[0054] 1. Experimental Materials

[0055] 1.1 Animals

[0056] Animals: 60 SPF male BALB / c mice, weighing 18-22 g.

[0057] Breeding environment: room temperature 20-26℃, relative humidity controlled at 40-70%, 5 birds per cage.

[0058] 1.2 Medication

[0059] Chinese medicine composition, intermediate prepared according to the method of Example 1, Jiangsu Kangyuan Pharmaceutical Co., Ltd.; dexamethasone acetate tablets (Chenxin Pharmaceutical Co., Ltd., batch number 2204070213).

[0060] 1.3 Reagents

[0061] 2,4-Dinitrofluorobenzene (DNFB) (Sigma, batch number: BCBR8143V); acetone (Shanghai Lingfeng Chemical Reagent Co., Ltd., batch number: 20120803); olive oil (Beijing Longting Riyue Trading Co., Ltd.).

[0062] 1.4 Instruments

[0063] Electronic balance (Mettler-Toledo, Switzerland, model: ME104E); thickness measuring instrument (Mitutoyo, Japan, model: 7301).

[0064] 2. Dosage design

[0065] Based on the clinical adult (60 kg) dose of 96 g of crude drug per day, the equivalent dose for mice, calculated using the body surface area method, is 18.0 g / kg. Using a 1 / 4:1 / 2:1 dosing regimen, the low dose of the Chinese medicine composition is 4.5 mg / kg, and the medium dose is 9.0 g / kg.

[0066] The clinical dosage of hydrocortisone acetate tablets for adults (60 kg) is 20-30 mg / day. Based on 30 mg / day, the equivalent dosage for mice converted according to the body surface area method is approximately 6.0 mg / kg.

[0067] 3. Experimental Methods

[0068] BALB / c mice were adaptively fed for 3 days with free access to feed and water. They were randomly divided according to body weight into a normal group, a model control group, a hydrocortisone-positive drug group, and low-, medium-, and high-dose groups of the Chinese herbal composition, with 10 mice in each group. Starting on modeling day 1, the Chinese herbal composition and the positive drug hydrocortisone tablets were administered orally once daily at a volume of 0.2 mL / 10 g for 7 consecutive days. The normal and model control groups were also given the same volume of physiological saline.

[0069] BALB / c mice were shaved on the abdomen (approximately 3 cm × 3 cm) on day 0. On days 1 and 2, 25 μL of 0.5% DNCB solution was evenly applied to the shaved area of ​​the abdomen in all other groups, except for the control group, where an equal volume of solvent (olive oil (V):acetone (V) = 1:4) was applied. On day 6, 20 μL of 0.25% DNCB was applied to the right ear for challenge, while an equal volume of solvent was applied to the left ear. 24 hours after challenge, the thickness of the left and right ears was measured, and ear swelling was calculated (ear swelling = right ear thickness - left ear thickness). Ear discs were punched out at the same location on both ears using an 8 mm diameter punch and accurately weighed, and the difference in ear weight was calculated (ear weight difference = right ear tissue piece weight - left ear tissue piece weight). Body weight and spleen weight were also measured in each group, and spleen index (mg / g) was calculated as spleen weight / body weight.

[0070] 4. Statistical methods

[0071] Graphpad Prism 9 software was used for statistical analysis and plotting. The data were normal distributed after homogeneity of variance test. One-way ANOVA was used to compare multiple groups of data, and P < 0.05 was considered to be significantly different.

[0072] 5. Experimental Results

[0073] The allergic contact dermatitis model was induced in mice using DNFB, and the ear swelling of each group of mice was detected. The results showed that compared with the normal group, the ear swelling and ear weight difference of the model control group were significantly increased (P < 0.0001, P < 0.0001); compared with the model group, after 7 consecutive days of administration, the medium and high dose groups of the Chinese medicine composition could significantly reduce the ear swelling of the model mice (P < 0.05, P < 0.01), and the medium and high dose groups of the Chinese medicine composition also significantly reduced the ear weight difference of the model mice (P < 0.05, P < 0.01), as shown in Table 3 for details.

[0074] Table 3 Effect of Chinese herbal composition on reducing ear swelling in DNFB-induced allergic contact dermatitis model mice

[0075]

[0076] Note: Compared with the normal control group, #### P<0.0001; compared with the model control group, *P<0.05, **P<0.01, ***P<0.001.

[0077] The results of detecting the spleen index of mice in each group showed that compared with the normal group, the spleen index of mice in the model group was significantly increased (P < 0.0001). Compared with the model group, after continuous administration for 7 days, the low, medium and high dose groups of the Chinese medicine composition could significantly reduce the spleen index of model mice (P < 0.05, P < 0.01, P < 0.01), as shown in Table 4 for details.

[0078] Table 4 The Chinese herbal composition reduces the spleen index of mice with DNFB-induced allergic contact dermatitis model

[0079]

[0080]

[0081] Note: Compared with the normal control group, #### P<0.0001; compared with the model control group, *P<0.05, **P<0.01, ***P<0.001.

[0082] 6. Experimental Conclusion

[0083] The Chinese herbal composition at doses of 4.5, 9.0 and 18.0 g crude drug / kg can significantly inhibit ear swelling in DNFB-induced allergic contact dermatitis model mice, and significantly reduce the spleen index of the model mice, suggesting that the Chinese herbal composition has a certain therapeutic effect on allergic contact dermatitis.

[0084] 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 the preparation of a medicament for allergic contact 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 drug 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 medicine 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 a medicament for treating or preventing inflammation caused by allergic contact 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.

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