Application of traditional Chinese medicine composition in preparation of medicine for treating anaphylactoid purpura
By using traditional Chinese medicine compositions composed of Chinese medicine compositions composed of dried ginger, astragalus, etc., to make granules or capsules, the treatment problem of allergic purpura is solved, and the skin reaction and serum factor levels are significantly improved, and effective treatment of allergic purpura is achieved.
Patent Information
- Application Number
- CN202410211108.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-02-27
- Publication Date
- 2025-08-29
AI Technical Summary
The prior art has not yet effectively solved the treatment methods for allergic purpura, especially the protection of vascular endothelial cells and the regulation of inflammatory responses, which leads to complex and difficult to control.
A Chinese medicine composition is used, consisting of dried ginger, astragalus, salted Morindae, white fresh skin, calcined oyster, Schisandra and windbreak, and is made into an intermediate by decoction, filtering, concentration and spray-drying, and then adding auxiliary materials to make granules or capsules for the treatment of allergic purpura.
It significantly inhibited the skin allergic reactions of allergic purpura rats and mice, reduced the serum IL-6 and SAA content, increased the anti-inflammatory factor IL-10, and showed good therapeutic effects.
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Abstract
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 Henoch-Schonlein purpura. Background Art
[0002] Henoch-Schnlein purpura (HSP) is an inflammation of the capillaries caused by an allergic reaction to certain allergens. This increases the permeability and fragility of the capillary walls, leading to bleeding and edema in the subcutaneous tissue, mucous membranes, internal organs, and joints. The disease is most common in children and adolescents. Clinically, it is divided into five types: simple cutaneous, articular, abdominal, nephritic, and mixed. The etiology of HSP is complex, with risk factors including infection, genetics, vaccination, food, and medications. However, its exact etiology and pathogenesis are still under investigation. Studies have shown that during the acute phase of HSP, the serum of children can stimulate endothelial cells to secrete and synthesize various inflammatory factors, leading to vascular damage. These factors play a key role in the pathogenesis of HSP in children. Other researchers believe that immune disorders, influenced by genetic and environmental factors, also contribute to the pathogenesis of HSP. Immunoglobulin A (IgA), in particular, IgA immune complex deposition and abnormal glycosylation, all suggest a crucial role in the development and progression of HSP. Endothelial cells, also known as vascular endothelial cells, are a highly differentiated single cell layer that forms the inner lining of blood vessels and possess phagocytic and immune functions. Endothelial cell damage under the influence of various pathogenic factors is a key component of the pathogenesis of various vasculitides, including HSP. Studies have shown that endothelial cell damage is closely associated with the pathogenesis of HSP. Related experiments have also demonstrated that cytokines secreted by damaged endothelial cells can promote the development and progression of Henoch-Schönlein purpura by activating the complement system, regulating immune function, and participating in inflammatory responses. Therefore, selective protection of endothelial cells, modulation of endothelial cell inflammatory responses, and targeted therapy for endothelial cells offer novel interventional approaches and avenues for the prevention and treatment of HSP. In view of the above problems, the field of traditional Chinese medicine should actively participate in the prevention and treatment of allergic purpura and develop appropriate prescriptions. Summary of the Invention
[0003] The technical problem to be solved by the present invention is to provide a medicine for treating Henoch-Schonlein purpura, which has a significant effect in treating Henoch-Schonlein purpura.
[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 remedy for Henoch-Schonlein purpura, wherein the use can be any form beneficial for improving the patient's corresponding symptoms, 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 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 an application of a traditional Chinese medicine composition in the preparation of an anti-inflammatory drug, wherein the inflammation may be inflammation caused by Henoch-Schonlein purpura.
[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 the allergic reaction of the back skin of rats with Henoch-Schonlein purpura, reduce skin redness, swelling or bleeding, and lower the serum IL-6 content; significantly inhibit the serum inflammatory factor SAA content of mice with Henoch-Schonlein purpura, and increase the anti-inflammatory factor IL-10 content, indicating that the composition of the present invention has a good therapeutic effect on Henoch-Schonlein purpura. 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 Henoch-Schonlein purpura. 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 Chinese medicine composition on rats with Henoch-Schonlein purpura
[0024] 1. Experimental Materials
[0025] 1.1 Animals
[0026] 80 SPF-grade Sprague-Dawley rats, weighing 120-140 g, half male and half female, were purchased from Zhejiang Weitonglihua Laboratory Animal Technology Co., Ltd., production license number: SCXK(Zhe)2019-0001. They were housed in a barrier system at a room temperature of 20-23°C and a relative humidity of 40-70%. Males and females were housed in separate cages, with 5 rats per cage per sex.
[0027] 1.2 Medication
[0028] The Chinese medicine composition, the intermediate prepared according to the method of Example 1, was purchased from Jiangsu Kangyuan Pharmaceutical Co., Ltd.; dexamethasone acetate tablets were purchased from Xinxiang Changle Pharmaceutical Co., Ltd., batch number: 1911056; egg albumin was purchased from Bainova Biotechnology Co., Ltd., item number: RH42844; Freund's complete adjuvant and Freund's incomplete adjuvant were purchased from Sigma, batch number: 1002749695; and a rat IL-6 assay kit was purchased from Raybiotech, batch number: 0308190724.
[0029] 1.3 Instruments
[0030] Electronic balance (Sartorius Scientific Instruments, model BS224S); electronic balance (G&G, model TC3K). Microplate reader (Mercury Molecular, USA, model Flexstation 3).
[0031] 2. Dosage design
[0032] The clinical dosage of the Chinese medicine composition for humans is 96g of crude drug per day, and the clinical daily dose is 96g of crude drug / 60kg = 1.6g of crude drug / kg. Based on the body surface area conversion method, the equivalent dose in rats is 1.6g of crude drug / kg * 5.6 = 8.96g of crude drug / kg. The rats were given doses of 9.0g of crude drug / kg, 4.5g of crude drug / kg, and 2.25g of crude drug / kg, respectively. These are equivalent to 1, 1 / 2, and 1 / 4 of the clinical daily dose for humans, respectively.
[0033] Dexamethasone acetate tablets, 0.75 mg / tablet. The clinical daily dose is 3 mg. Based on the body surface area conversion method, the equivalent dose for rats is 3 mg / 60 kg * 5.6 = 0.28 mg / kg.
[0034] 3. Experimental Methods
[0035] Ovalbumin was dissolved in physiological saline to prepare a 0.5 g / L solution, which was suspended with an equal amount of Freund's complete adjuvant to prepare ovalbumin-Freund's complete adjuvant, and suspended with an equal amount of Freund's incomplete adjuvant to prepare ovalbumin-Freund's incomplete adjuvant.
[0036] After three days of adaptive feeding, SD rats were randomly divided into six groups according to body weight: a blank control group, a model control group, a dexamethasone group, and low-, medium-, and high-dose groups of the traditional Chinese medicine composition, with 10 rats in each group. Except for the blank control group, all rats received intramuscular injections of ovalbumin-Freund's complete adjuvant (0.5 mL per rat) once weekly for the first three weeks and ovalbumin-Freund's incomplete adjuvant (0.5 mL per rat) once weekly for the next three weeks. The blank control group received an equal volume of normal saline. On the day of the final sensitization, each group began receiving the corresponding drug by gavage. The blank control group received an equal volume of purified water by gavage for 14 consecutive days, with daily dosing. On the 13th day of administration, the rats' backs were depilated and skin prepared. On the 14th day, one hour after administration, the rats were challenged with an antigen, with 0.2 mL of 1% ovalbumin solution injected intradermally at three sites on the back. The blank control group received an equal volume of normal saline. The appearance of allergic purpura on the back skin was observed within 24 hours after antigen challenge.
[0037] Detection indicators:
[0038] 1) Reaction severity grading: 3 points: Obvious congestion and hemorrhage with a confluent appearance within 2 or 5 hours; obvious hemorrhagic discoloration within 24 hours. 2 points: Moderate congestion and hemorrhage with a patchy appearance within 2 or 5 hours; moderate hemorrhagic discoloration within 24 hours. 1 point: Mild congestion and hemorrhage within 2 or 5 hours; mild hemorrhagic discoloration within 24 hours. 0 point: No reaction within 2 or 24 hours. Calculate the mean score for each group.
[0039] 2) Serum index detection: ELISA kit was used to detect the interleukin-6 (IL-6) content in rat serum.
[0040] 4. Experimental Results
[0041] Four hours after antigen challenge, the model control group developed redness, swelling, and hemorrhagic spots on the back skin. Moderate redness and hemorrhage, forming patchy patches, occurred in the model control group at two or five hours, and moderate hemorrhagic discoloration developed at 24 hours. Compared with the model control group, the dexamethasone group and the low-, medium-, and high-dose groups of the traditional Chinese medicine composition showed reduced dorsal skin reactions (p < 0.05, p < 0.01, respectively). The results are shown in Table 1.
[0042] Compared with the blank control group, the level of inflammatory factor IL-6 in the serum of the model control group was significantly increased (p<0.01); compared with the model control group, the level of IL-6 in the serum of the dexamethasone group and the medium and high-dose Chinese medicine combination groups was significantly decreased (p<0.05, p<0.01). The results are shown in Table 1.
[0043] Table 1 Effects of Chinese herbal medicine combination on the degree of skin reaction on the back of rats and the serum IL-6 content
[0044]
[0045] Note: Compared with the blank control group, ## p<0.01; compared with the model control group, *p<0.05, **p<0.01.
[0046] 5. Experimental Conclusion
[0047] The Chinese medicine composition can significantly improve the redness, swelling and bleeding of the back skin of rats with Henoch-Schonlein purpura model and reduce the serum inflammatory factor IL-6 content, suggesting that the Chinese medicine composition has a therapeutic effect on rats with Henoch-Schonlein purpura.
[0048] Example 3 Therapeutic effect of the Chinese medicine composition on Henoch-Schonlein purpura model mice
[0049] 1. Experimental Materials
[0050] 1.1 Animals
[0051] 60 SPF Balb / c mice, weighing 20-22 g, half male and half female. Purchased from Zhejiang Weitonglihua Laboratory Animal Technology Co., Ltd. Production License No.: SCXK(Zhe)2019-0001. Housed in a barrier system, the environment was: room temperature 20-23°C, relative humidity controlled at 40-70%. Males and females were housed in separate cages, with 5 mice per cage per sex.
[0052] 1.2 Medication
[0053] The Chinese medicine composition, the intermediate obtained by preparing according to the method of Example 1, was provided by Jiangsu Kangyuan Pharmaceutical Co., Ltd.; cimetidine was purchased from Harbin Pharmaceutical Group Sanjing Pharmaceutical Co., Ltd. (National Medicine Standard No. H230229); India ink was purchased from Beijing Chemical Plant Co., Ltd.; gliadin was purchased from Nippon Chemical Industry Co., Ltd.; mouse amyloid protein A (SAA) and interleukin 10 (IL-10) Elisa detection kits were purchased from Shanghai Biyuntian Biotechnology Co., Ltd.
[0054] 1.3 Instruments
[0055] Electronic balance (Sartorius Scientific Instruments, model BS224S); animal weighing scale (Kagawa, model: ACX-SC-DA); microplate reader (American Meigu Molecular, model Flexstation3).
[0056] 2. Dosage design
[0057] The clinical dosage of the Chinese medicine composition for humans is 96g of crude drug per day, and the clinical daily dose is 96g of crude drug / 60kg = 1.6g of crude drug / kg. Based on the body surface area conversion method, the equivalent dose in mice is 1.6g of crude drug / kg * 11 = 17.6g of crude drug / kg. The mice were given doses of 18.0g of crude drug / kg, 9.0g of crude drug / kg, and 4.5g of crude drug / kg, respectively. These are equivalent to 1, 1 / 2, and 1 / 4 of the clinical daily dose for humans, respectively.
[0058] Cimetidine: For adults, the clinical daily dose is 1.6g / 60kg = 0.027g / kg. Based on the body surface area conversion method, the equivalent dose for mice is 0.027g / kg * 11 = 0.297g / kg.
[0059] 3. Experimental Methods
[0060] After 5 days of adaptive feeding, Balb / c mice were randomly divided into blank control group, model control group, cimetidine-positive group, and low-, medium-, and high-dose groups of the Chinese medicine composition according to body weight, with 10 mice in each group, half male and half female. Except for the blank control group, the remaining mice were injected with 40 mg / kg India ink via the tail vein once a week for 3 consecutive weeks; gliadin was dissolved in 6 mmol / L HCl acidified water to prepare a 0.1% solution. Each group (except the blank group) was gavaged with 0.5 mL of gliadin solution per mouse every other day for 14 consecutive weeks. On the last 3 days of gavage, 0.2 mL / 20 g of gliadin solution was injected into the tail vein every day. The control group was gavaged or injected with the same dose of HCl acidified water at the same time. After the model was established, the mice in each group were gavaged with the corresponding drug once a day for 3 consecutive weeks.
[0061] Detection indicators: serum inflammatory indicators SAA and IL-10 levels.
[0062] 4. Experimental Results
[0063] SAA is an apolipoprotein. The body releases large amounts of SAA under the influence of inflammatory reactions and pathogen infection, leading to a significant increase in its concentration in the blood. Compared with the blank control group, the serum inflammatory marker SAA level in the model control group was significantly increased, and the anti-inflammatory factor IL-10 level was significantly decreased (p < 0.01). Compared with the model control group, the serum inflammatory marker SAA level in the cimetidine group and the low-, medium-, and high-dose groups of the traditional Chinese medicine composition was significantly decreased (p < 0.05, p < 0.01); the serum anti-inflammatory factor IL-10 level was significantly increased in the cimetidine and medium- and high-dose groups of the traditional Chinese medicine composition (p < 0.05, p < 0.01). The results are shown in Table 1.
[0064] Table 1 Effect of Chinese herbal medicine combination on serum SAA and IL-10 levels in mice with Henoch-Schonlein purpura
[0065]
[0066] Note: Compared with the blank control group, ## p<0.01; compared with the model control group, *p<0.05, **p<0.01.
[0067] 5. Experimental Conclusion
[0068] The Chinese medicine composition can significantly reduce the content of the inflammatory factor SAA in the serum of mice with Henoch-Schonlein purpura and upregulate the content of the anti-inflammatory factor IL-10, indicating that the Chinese medicine composition has anti-inflammatory and other therapeutic effects on mice with Henoch-Schonlein purpura.
[0069] 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 medicine for Henoch-Schonlein purpura, 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 the Chinese medicine composition according to any one of claims 1 to 4 in the preparation of a medicament for treating or preventing inflammation, 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.