Application of traditional Chinese medicine composition in preparation of medicine for treating acne

Abstract

The invention relates to an application of a traditional Chinese medicine composition in preparation of a medicine for treating acne, 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 obviously relieving the inflammatory response of acne model mice and rats and reducing the contents of TNF-alpha, IL-6 and S100 calcium binding protein A9 (S100A9) in model animal bodies, and has a relatively good treatment effect on acne.

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 acne. Background Art

[0002] Acne is a common chronic inflammatory disease of the sebaceous glands and pilofollicles, with an incidence rate of 70%-87%. It can affect people of all ages, but is most common in young men and women aged 15-30. It has a significant psychological and social impact on adolescents, but often subsides or resolves naturally after puberty. Clinical manifestations are characterized by polymorphic skin lesions, including comedones, papules, pustules, and nodules, often occurring on the face. Acne initially manifests as pimples, such as whiteheads and blackheads. Whiteheads can be plucking out a yellowish-white, dreg-like substance, while blackheads can be squeezed out to reveal a black top and a yellowish-white, translucent bottom. When blocked pores become inflamed or infected by bacteria, inflammatory papules develop—small, firm, raised bumps on the skin. The skin surrounding the rash may be red and tender. When the inflammation is severe and invades deeper layers of the skin, the papules may have a small pustule at the top, with a white center at the tip containing pus. As the disease progresses, dark red nodules or cysts of varying sizes may form, which may even suppurate and form abscesses. Upon rupture, sinus tracts and bruises often form. Acne is a multifactorial disease caused by blocked hair follicles, but its specific pathogenesis remains incompletely understood. The occurrence of acne may be related to androgen levels, the proliferation of Propionibacterium acnes, and genetics. Furthermore, in some patients, the onset of acne is also influenced by factors such as mood and diet. In light of these issues, Traditional Chinese Medicine (TCM) should proactively intervene in the prevention and treatment of acne 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 acne, which has a significant effect in treating acne.

[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 acne, wherein the use can be any form beneficial for 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 an application of a traditional Chinese medicine composition in the preparation of a composition for treating inflammation caused by acne.

[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 reduce the inflammatory response of acne model mice and rats and improve the degree of skin lesions; it can significantly reduce the levels of typical inflammatory factors TNF-α, IL-6 and S100A9 in the blood of mice caused by acne, and significantly reduce the levels of inflammatory factors TNF-α and IL-6 in the blood and the degree of skin lesions in acne model rats, indicating that the traditional Chinese medicine composition can significantly improve the inflammatory response and the degree of skin lesions in acne and has a good therapeutic effect on acne. DETAILED DESCRIPTION

[0018] As mentioned above, the present invention aims to provide a use of a traditional Chinese medicine composition in the preparation of a drug for treating acne. A detailed description will be provided 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 Effects of a Traditional Chinese Medicine Composition on an Antimicrobial Peptide-Induced Rosacea Model in Mice 1. Experimental Materials

[0024] 1.1 Animals

[0025] BALB / c mice, SPF grade, 60 females, weighing 20-22 g.

[0026] Rearing environment: Room temperature 20-26℃, relative humidity controlled at 40-70%. Rear in separate cages, 5 per group.

[0027] 1.2 Medication

[0028] The Chinese medicine composition, the intermediate prepared according to the method of Example 1, was provided by Jiangsu Kangyuan Pharmaceutical Co., Ltd.; doxycycline hydrochloride (Yisheng Biotechnology Co., Ltd., catalog number 60267ES03); ether (Nanjing Chemical Reagent Co., Ltd., catalog number C0650110274); antimicrobial peptide LL-37 (Shanghai Sangon, sequence: LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES); 0.9% sodium chloride solution (Shijiazhuang Siyao Co., Ltd., catalog number 69900793); IL-6 Mouse ELISA kit (Invitrogen, catalog number BMS603-2); S100A9 Mouse ELISA kit (Invitrogen, catalog number EM67RB); TNF-α Mouse ELISA kit (Invitrogen, catalog number BMS607-3).

[0029] 1.3 Instruments

[0030] Electronic balance, METTLER TOLEOD, model: MS1003S101; animal weighing scale, Kagawa, model: ACX-SC-DA; low-temperature centrifuge (Eppendorf, Germany, model 5804R); microplate reader (Megu Molecular, USA, model Flexstation 3).

[0031] 2. Dosage and Administration

[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 crude drug / kg. According to a 1 / 4:1 / 2:1 dosing regimen, the low dose is 4.5g crude drug / kg, the medium dose is 9.0g crude drug / kg, and the high dose is 18.0g crude drug / kg. Administration is by gavage at 0.1mL / 10g once daily for four weeks. The positive control group received 30mg / kg of doxycycline hydrochloride.

[0033] 3. Experimental Methods

[0034] BALB / c mice were adaptively fed for 3 days with free access to feed and water and randomly divided into a normal control group, a model control group, a doxycycline hydrochloride control group, and high-, medium-, and low-dose groups of the Chinese medicine composition, with 10 mice in each group.

[0035] After adaptive feeding, mice were randomly divided into groups. All groups, except the normal control group, underwent modeling as follows: a 3 cm × 3 cm area on the back of the mice was shaved and injected with 320 μmol / L of LL-37 (40 μL per injection) four times every 12 hours. The normal control group received four injections of an equal volume of PBS. Twenty-four hours after modeling, drug administration was performed as described in "Dosage and Administration."

[0036] Sample Collection and Testing: After all mice were modeled and treated with the above-mentioned drugs, they were sacrificed and the skin at the injection site on the back was collected and frozen at -80°C for ELISA. ELISA Assays for IL-6, S100A9, and TNF-α Expression: IL-6, S100A9, and TNF-α levels in the skin at the injection site on the back of mice were measured strictly according to the kit instructions.

[0037] 4. Statistical methods

[0038] The results were analyzed statistically using the t-test, and one-way ANOVA was used for comparisons among multiple groups. P < 0.05 was considered statistically significant.

[0039] 5. Experimental Results

[0040] After using antimicrobial peptides to induce rosacea model mice, compared with the normal control group, the levels of IL-6, S100A9, and TNF-α in the model control group were significantly increased (all P < 0.01); compared with the model control group, the high, medium, and low dose groups of the Chinese medicine composition and the doxycycline hydrochloride group could significantly reduce the levels of IL-6 (P < 0.01, P < 0.01, P < 0.01, P < 0.01), S100A9 (P < 0.01, P < 0.01, P < 0.01, P < 0.01), and TNF-α (P < 0.01, P < 0.01, P < 0.01, P < 0.01) in the skin of the modeling site of the mice, see Table 1.

[0041] Table 1: Effects of antimicrobial peptides on IL-6, S100A9, and TNF-α in the skin of mice with rosacea model induced by rosacea

[0042]

[0043] Note: Compared with the normal control group, ## P<0.01; compared with the model control group, *P<0.05, **P<0.01.

[0044] 6. Experimental Conclusion

[0045] The traditional Chinese medicine composition proposed in the present invention can significantly reduce the relevant inflammatory factors in the skin of the modeling site of rosacea model mice, indicating that the traditional Chinese medicine composition has a certain therapeutic effect on mouse acne.

[0046] Example 3 Therapeutic effect of the Chinese medicine composition on auricle complex acne model rats

[0047] 1. Experimental Materials

[0048] 1.1 Animals

[0049] 60 male SD rats, SPF grade, weighing 250-270 g.

[0050] Rearing environment: Room temperature 22-26℃, relative humidity controlled at 40-70%. Rear in separate cages, 5 per group.

[0051] 1.2 Medication

[0052] The Chinese medicine composition, the intermediate prepared according to the method of Example 1, was provided by Jiangsu Kangyuan Pharmaceutical Co., Ltd.; isotretinoin soft capsules (Chongqing Huabang Pharmaceutical Co., Ltd., national medicine standard H20113060); chloral hydrate (Sinopharm Chemical Reagent Co., Ltd., product number C232475000); oleic acid (Sinopharm Chemical Reagent Co., Ltd., product number 30138518); Propionibacterium acnes (Guangzhou Huankai Microbiology Co., Ltd.); Rat IL-6 ELISA Kit (Invitrogen, product number ERA31RB); Rat TNF-α ELISA Kit (Invitrogen, product number ERA56RB).

[0053] 1.3 Instruments

[0054] Electronic balance (Sartorius Scientific Instruments, model BS224S); electronic balance (G&G, model TC3K); low-temperature centrifuge (Eppendorf, Germany, model 5804R); microplate reader (MeiGu Molecular, USA, model Flexstation 3).

[0055] 2. Dosage and Administration

[0056] The daily dosage of the Chinese medicine composition is 96g of crude drug per day. Based on the body surface area conversion method, the equivalent dose for rats is 96g / 60kg*5.6=8.96g crude drug / kg. According to a 1 / 4:1 / 2:1 dosing regimen, the low dose is 2.25g crude drug / kg, the medium dose is 4.5g crude drug / kg, and the high dose is 9.0g crude drug / kg. Administration is by gavage at 0.1mL / 10g once daily for 21 consecutive days. The positive control group received 3.125mg / kg of isotretinoin soft capsules.

[0057] 3. Experimental Methods

[0058] SD rats were adaptively fed for 3 days with free access to feed and water and randomly divided into a normal control group, a model control group, an isotretinoin soft capsule control group, and high-, medium-, and low-dose groups of the Chinese medicine composition, with 10 rats in each group.

[0059] Preparation of P. acnes suspension: Prepare liquid culture medium. Pipette approximately 0.5 mL of sterilized liquid culture medium into a freeze-dried tube containing P. acnes, mix thoroughly, and spread onto two plates, approximately 200 μL per plate, evenly spread. Incubate under anaerobic conditions for 72 hours, then perform streak culture on the plates. Pick a single colony and incubate in liquid culture medium under anaerobic conditions until the logarithmic phase. Use the plate count method to adjust the bacterial concentration to 6 × 10 7 CFU / mL, set aside.

[0060] In the other five groups, except the normal control group, 1 mL of oleic acid was applied to the opening of the right auricle of the rats every day, and 100 μL of Propionibacterium acnes (6×10 7 CFU / mL) for 14 consecutive days. Successful modeling was indicated by significant thickening of the auricle, redness, swelling, hardening, and nodules at the modeling site, and the appearance of sebaceous dandruff on the skin surface. Two rats were randomly selected from the model group for ear pathological sectioning. Successful acne modeling was indicated by the presence of significant epidermal thickening and dermal lymphocyte and neutrophil infiltration. Each drug group was gavaged with the corresponding dose of drug according to the dosing schedule, while the normal control and model groups were gavaged with the corresponding volume of normal saline for 21 consecutive days.

[0061] Sample Collection and Testing: After the final administration, all rats were fasted for 24 hours with or without water. They were then anesthetized intraperitoneally with 10% chloral hydrate. Blood was collected from the abdominal aorta and centrifuged for 10 minutes (3500 rpm / min, 4°C). The supernatant was collected. Serum TNF-α and IL-6 levels were determined by ELISA, strictly following the kit instructions.

[0062] 4. Statistical methods

[0063] The results were analyzed statistically using the t-test, and one-way ANOVA was used for comparisons among multiple groups. P < 0.05 was considered statistically significant.

[0064] 5. Experimental Results

[0065] Acne model rats were established by inducing oleic acid and Propionibacterium acnes. Compared with the normal control group, the serum IL-6 and TNF-α levels of the rats in the model control group were significantly increased (all P < 0.01). Compared with the model control group, the high-, medium-, and low-dose groups of the Chinese medicine composition and the isotretinoin soft capsule group could significantly reduce the IL-6 (P < 0.01, P < 0.01, P < 0.01, P < 0.01) and TNF-α (P < 0.01, P < 0.01, P < 0.01, P < 0.01) contents in the skin of the modeling site of the mice (see Table 2 for details).

[0066] Table 2: Effects on IL-6 and TNF-α in serum of rats with acne model induced by oleic acid and Propionibacterium acnes

[0067]

[0068] Note: Compared with the normal control group, ## P<0.01; compared with the model control group, *P<0.05, **P<0.01.

[0069] 6. Experimental Conclusion

[0070] The Chinese medicine composition at 4.5, 9.0, and 18.0 g / kg of the crude drug can significantly reduce the inflammatory response of acne model mice, and at 2.25, 4.5, and 9.0 g / kg of the crude drug can significantly reduce the inflammatory response of acne model rats and improve the degree of skin lesions; it can significantly reduce the levels of typical inflammatory factors TNF-α and IL-6 and S100A9 in the blood of mice caused by acne, and significantly reduce the levels of inflammatory factors TNF-α and IL-6 in the blood and the degree of skin lesions of acne model rats, indicating that the Chinese medicine composition can significantly improve the inflammatory response and the degree of skin lesions in acne, and has a good therapeutic effect on acne.

[0071] 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 traditional Chinese medicine composition in the preparation of a medicine for acne, 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 traditional Chinese medicine composition in the preparation of a medicament for treating or preventing inflammation caused by acne, comprising: 5-15 parts of dried ginger, 15-25 parts of astragalus, 5-15 parts of salt-cured Morinda officinalis, 5-15 parts of Dictamnus dasycarpus, 25-35 parts of calcined oyster shell, 5-10 parts of Schisandra chinensis, and 5-15 parts of Saposhnikovia divaricata.

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