Pharmaceutical composition and application thereof in preparation of medicine for treating or improving diseases

Abstract

The invention relates to a pharmaceutical composition, the pharmaceutical composition contains an effective amount of active ingredients and pharmaceutically acceptable auxiliary materials, and the active ingredients comprise mangiferin, glycyrrhizic acid and cinnamic acid. The invention also relates to an application of the pharmaceutical composition in preparation of a medicine for treating or improving diseases, wherein the diseases are rheumatoid arthritis; the pharmaceutical composition contains an effective amount of active ingredients, and the active ingredients comprise mangiferin, glycyrrhizic acid and cinnamic acid. The pharmaceutical composition disclosed by the invention can be used for remarkably improving the severity of rheumatoid arthritis of a rat suffering from adjuvant-induced rheumatoid arthritis. And almost no adverse reaction or side effect exists.

Description

Technical Field

[0001] This invention relates to a pharmaceutical composition, and more specifically, to a pharmaceutical composition and its use in the preparation of a medicament for treating or improving a disease. Background Technology

[0002] Rheumatoid arthritis (RA) is a chronic, systemic disease of unknown etiology, primarily characterized by inflammatory synovitis. It is characterized by polyarticular, symmetrical, and invasive joint inflammation of the small joints of the hands and feet, often accompanied by extra-articular organ involvement and positive serum rheumatoid factor, which can lead to joint deformities and loss of function.

[0003] Conventional treatments for rheumatoid arthritis (RA) typically involve nonsteroidal anti-inflammatory drugs (NSAIDs), antirheumatic drugs (ART), or corticosteroids. While these medications can alleviate symptoms, they often cause numerous adverse reactions, resulting in significant side effects and high costs. Research has found that various traditional Chinese medicine (TCM) formulas have achieved significant effects in treating rheumatoid arthritis and its key pathological processes. Utilizing TCM formulas or their effective components to prepare combination drugs for disease treatment has become a major research direction.

[0004] Baihu Jia Guizhi Tang (White Tiger Decoction with Cinnamon Twig) includes: Anemarrhena asphodeloides, Gypsum fibrosum, Glycyrrhiza uralensis, Japonica rice, and Cinnamon twig. Clinically, it was used to treat 12 patients with active rheumatoid arthritis, presenting with joint pain, local burning and swelling, unbearable pain, and immobility of the joints. The pain was relieved by cold and aggravated by heat, often migratory, and accompanied by systemic symptoms such as fever, thirst, and restlessness. Biochemical tests showed elevated white blood cell count and accelerated erythrocyte sedimentation rate. Based on the syndrome differentiation, all were diagnosed as heat-related arthralgia, and Baihu Jia Guizhi Tang was the primary treatment, with adjustments made according to the patient's constitution and condition. For example, if heat was predominant, Phellodendron bark, Scutellaria baicalensis, and Gardenia jasminoides were added; if dampness was predominant, Coix seed, Poria cocos, Liu Yi San (a traditional Chinese medicine formula), and Bombyx mori excrement were added; if Yin was deficient, Rehmannia glutinosa, Dendrobium nobile, and Ophiopogon japonicus were added; if Qi was deficient, Astragalus membranaceus and Codonopsis pilosula were added; for dispelling wind and relieving pain, Saposhnikovia divaricata, Morus alba twig, Clematis chinensis, and Myrrh were used; and for promoting blood circulation and unblocking collaterals, Angelica sinensis tail, Paeonia lactiflora, Paeonia suffruticosa, Chaenomeles speciosa, and Trachelospermum jasminoides were used. Generally, after taking two doses of the medication, body temperature begins to decrease, and joint pain lessens. After 6-10 doses, body temperature returns to normal, joint redness, swelling, and pain significantly decrease, and other symptoms gradually disappear. The average treatment time is 11 days. However, because Baihu Jia Guizhi Tang is a compound traditional Chinese medicine formula with complex components, its mechanism of action and pharmacodynamic material basis remain unclear, making it difficult to gain international recognition. There is an urgent need to develop therapeutic drugs with clearly defined components and good efficacy. Summary of the Invention

[0005] The purpose of this disclosure is to further improve the clinical efficacy of drugs for the treatment or improvement of rheumatoid arthritis.

[0006] To achieve the above objectives, this disclosure provides a pharmaceutical composition containing a therapeutically effective amount of an active ingredient and pharmaceutically acceptable excipients, said active ingredient including mangiferin, glycyrrhizic acid and cinnamic acid.

[0007] Optionally, in the pharmaceutical composition, based on the total weight of the pharmaceutical composition, the content of mangiferin is 5.00-7.50% by weight; the content of glycyrrhizic acid is 11.00-13.00% by weight; and the content of cinnamic acid is 0.50-2.00% by weight.

[0008] Optionally, in the pharmaceutical composition, based on the total weight of the pharmaceutical composition, the content of mangiferin is 5.50-7.00% by weight; the content of glycyrrhizic acid is 11.50-12.50% by weight; and the content of cinnamic acid is 1.00-1.50% by weight.

[0009] Optionally, in the pharmaceutical composition, the weight ratio of mangiferin, glycyrrhizic acid and cinnamic acid is 1:(1.46-2.60):(0.06-0.40).

[0010] Optionally, in the pharmaceutical composition, the weight ratio of mangiferin, glycyrrhizic acid and cinnamic acid is 1:(1.64-2.27):(0.14-0.27).

[0011] Optionally, the pharmaceutically acceptable excipients include at least one of soluble starch, lactose, and micronized silica gel.

[0012] Optionally, in the pharmaceutical composition, based on the total weight of the pharmaceutical composition, the content of the soluble starch is 26.40-36.00% by weight, preferably 28.80-33.60% by weight; the content of the lactose is 26.4-36.00% by weight, preferably 28.80-33.60% by weight; and the content of the micronized silica gel is 13.20-18.00% by weight, preferably 14.40-16.80% by weight.

[0013] Optionally, the pharmaceutical composition contains: 5.00-7.50% by weight mangiferin, 11.00-13.00% by weight glycyrrhizic acid, 0.50-2.00% by weight cinnamic acid, 26.40-33.60% by weight soluble starch, 26.40-33.60% by weight lactose, 13.20-18.00% by weight micronized silica gel, and 8.00-10.00% by weight ethanol.

[0014] Optionally, the dosage form of the pharmaceutical composition is granules; the combined drug is a pharmaceutical composition for treating or improving rheumatoid arthritis and its complications.

[0015] This disclosure also provides the use of the pharmaceutical composition in the preparation of a medicament for treating or improving a disease, said disease being rheumatoid arthritis; said pharmaceutical composition contains a therapeutically effective amount of an active ingredient, said active ingredient including mangiferin, glycyrrhizic acid and cinnamic acid.

[0016] Through the above-described technical solution, the inventors of this disclosure have surprisingly discovered that a pharmaceutical composition containing mangiferin, glycyrrhizic acid, and cinnamic acid can significantly improve the severity of rheumatoid arthritis in rats with adjuvant-induced arthritis (AIA), with virtually no adverse reactions or side effects.

[0017] Other features and advantages of the present invention will be described in detail in the following detailed description section. Attached Figure Description

[0018] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used together with the following detailed description to explain the invention, but do not constitute a limitation thereof. In the drawings:

[0019] Figure 1 The graphs show the degree of redness and swelling of the right hind limb joint in rats in the blank group, AIA model group, Baihu Jia Guizhi Tang group, and Zhigui Qingre Juanbi Granules group, as well as bar charts showing the incidence rate, joint clinical score, joint swelling degree, and time of first onset in rats.

[0020] Figure 2 This is a graph showing the analysis of pain threshold-related indicators in the right hind limb of rats in the blank group, AIA model group, Baihu Jia Guizhi Tang group, and Zhigui Qingre Juanbi Granules group.

[0021] Figure 3 This is an analysis of knee joint lesion-related indicators in the right hind limb of rats in the blank group, AIA model group, Baihu Jia Guizhi Tang group, and Zhigui Qingre Juanbi Granules group.

[0022] Figure 4 The diagram shows the analysis of the visceral brain index of rats in the blank group, AIA model group, Baihu Jia Guizhi Tang group, and Zhigui Qingre Juanbi Granules group.

[0023] Figure 5 The image shows the joint surface temperature analysis of the right hind limb of rats in the blank group, AIA model group, Baihu Jia Guizhi Tang group, and Zhigui Qingre Juanbi Granules group. Detailed Implementation

[0024] The following provides a detailed description of specific embodiments of the present invention. It should be understood that the specific embodiments described herein are for illustrative and explanatory purposes only and are not intended to limit the scope of the invention.

[0025] This disclosure provides a pharmaceutical composition containing a therapeutically effective amount of an active ingredient and pharmaceutically acceptable excipients, said active ingredient including mangiferin, glycyrrhizic acid and cinnamic acid.

[0026] The inventors of this disclosure have surprisingly discovered that a pharmaceutical composition containing mangiferin, glycyrrhizic acid, and cinnamic acid can significantly improve the severity of adjuvant-induced arthritis (AIA) in rats. This pharmaceutical composition exerts its effects by inhibiting imbalances in the body's immune-inflammatory pathways (e.g., the TLR4-PI3K-AKTI-NFκB-NLRP3-IL-1β signaling pathway), regulating angiogenesis disorders (e.g., the VEGFA-VEGFR2-SRC-PI3K-AKT signaling pathway), and modulating energy metabolism disorders (e.g., the PKA-ADCY5-PPARγ-PGC 1α-UCP1-PRDM16 signaling pathway).

[0027] In this disclosure, the content of the active ingredients mangiferin, glycyrrhizic acid, and cinnamic acid in the pharmaceutical composition can vary within a wide range. In one embodiment, based on the total weight of the pharmaceutical composition, the content of mangiferin is 5.00-7.50% by weight; the content of glycyrrhizic acid is 11.00-13.00% by weight; and the content of cinnamic acid is 0.50-2.00% by weight. In a preferred embodiment, based on the total weight of the pharmaceutical composition, the content of mangiferin is 5.50-7.00% by weight; the content of glycyrrhizic acid is 11.50-12.50% by weight; and the content of cinnamic acid is 1.00-1.50% by weight. When the content of the active ingredients mangiferin, glycyrrhizic acid, and cinnamic acid in the pharmaceutical composition of this disclosure is within the above range, it is more conducive to the synergistic effect of mangiferin, glycyrrhizic acid, and cinnamic acid in the composition, thereby better achieving the therapeutic or symptom-improving effect of rheumatoid arthritis.

[0028] In this disclosure, the weight ratio of the active ingredients mangiferin, glycyrrhizic acid, and cinnamic acid can vary within a wide range. In one embodiment, the weight ratio of mangiferin, glycyrrhizic acid, and cinnamic acid in the pharmaceutical composition is 1:(1.46-2.60):(0.06-0.40). In a preferred embodiment, the weight ratio of mangiferin, glycyrrhizic acid, and cinnamic acid in the pharmaceutical composition is 1:(1.64-2.27):(0.14-0.27).

[0029] In this disclosure, pharmaceutically acceptable excipients can be substances known to those skilled in the art. In one embodiment, the pharmaceutically acceptable excipient includes at least one of soluble starch, lactose, and micronized silica gel. In the above embodiments, soluble starch can improve the flowability of the drug, lactose can act as a flavoring agent and binder, and micronized silica gel has a flow-aiding effect.

[0030] In one embodiment, based on the total weight of the pharmaceutical composition, the content of the soluble starch is 26.40-36.00% by weight, preferably 28.80-33.60% by weight; the content of the lactose is 26.40-36.00% by weight, preferably 28.80-33.60% by weight; and the content of the micronized silica gel is 13.20-18.00% by weight, preferably 14.40-16.80% by weight.

[0031] In one embodiment of this disclosure, the pharmaceutical composition contains: 5.00-7.50% by weight mangiferin, 11.00-13.00% by weight glycyrrhizic acid, 0.50-2.00% by weight cinnamic acid, 26.40-33.60% by weight soluble starch, 26.40-33.60% by weight lactose, 13.20-18.00% by weight micronized silica gel, and 8.00-10.00% by weight ethanol.

[0032] In this disclosure, the preparation method of the pharmaceutical composition can be the method conventionally used by those skilled in the art. For example, granules can be prepared using a wet formulation process. Mangiferin, glycyrrhizic acid, cinnamic acid, soluble starch, lactose, and micronized silica gel are passed through an 80-mesh sieve for later use. The corresponding components are accurately weighed according to the formula. The excipients are added in an equal and incremental manner to ensure uniform mixing with the active ingredients. The wetting agent (ethanol) is added in an atomized form and stirred thoroughly until a soft material is formed. The soft material is passed through a 16-mesh sieve to obtain wet granules, which are then transferred to an electric heating drying oven for drying. After cooling to room temperature, the granules are sieved through a 24-mesh sieve to obtain Zhigui Qingre Juanbi granules. The Zhigui Qingre Juanbi granules prepared in this disclosure should meet the granule preparation process evaluation indicators of forming rate, angle of repose, and solubility.

[0033] In this disclosure, the dosage form of the pharmaceutical composition is not specifically limited. For example, the dosage form of the pharmaceutical composition is granules; the combined drug is a pharmaceutical composition for treating or improving rheumatoid arthritis and its complications.

[0034] This disclosure also provides the use of the pharmaceutical composition in the preparation of a medicament for treating or improving a disease, said disease being rheumatoid arthritis; said pharmaceutical composition contains a therapeutically effective amount of an active ingredient, said active ingredient including mangiferin, glycyrrhizic acid and cinnamic acid.

[0035] The present disclosure will be further illustrated by the following examples, but the present disclosure is not limited thereto.

[0036] Unless otherwise specified, the raw materials, reagents, instruments and equipment involved in the embodiments of this disclosure can all be obtained by purchase.

[0037] The rats used in the embodiments of this disclosure are from the following sources:

[0038] Fifty-four male SPF-grade Lewis rats, 6-8 weeks old and weighing 200±20g, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Production License No.: SCXK2016-0006, Beijing, China).

[0039] The experimental rats were housed at the Laboratory Animal Center of the China Academy of Chinese Medical Sciences, and all studies were conducted in accordance with the ethical standards of the Laboratory Animal Center. Prior to the formal experiments, all rats were housed under specific pathogen-free conditions for one week.

[0040] The drugs and reagents used in the embodiments of this disclosure are from the following sources:

[0041] Mangiferin (Catalog No. ST00350120) was purchased from Shanghai Shidander Standard Technical Service Co., Ltd.; glycyrrhizic acid (Catalog No. ST00660120) was purchased from Shanghai Shidander Standard Technical Service Co., Ltd.; cinnamic acid (Catalog No. ST04320120) was purchased from Shanghai Shidander Standard Technical Service Co., Ltd.; dimethyl sulfoxide (Catalog No.: D8418-50ML) was purchased from Sigma-Aldrich, Inc.; PBS buffer (Catalog No.: AR0030) was purchased from Boster Biological Engineering Co., Ltd.

[0042] Statistical analysis:

[0043] Unless otherwise specified, statistical data were analyzed using GraphPad Prism 8.0.1 software, and all experimental data are expressed as mean ± standard deviation. The results indicate that the t-test was used to analyze and compare the two groups. Non-parametric tests were performed on non-normally distributed data. When P < 0.05, the difference between the groups was statistically significant.

[0044] Among them, compared with the blank group, "*" represents P<0.05, "**" represents P<0.01, and "***" represents P<0.001; compared with the AIA model group, "#" represents P<0.05, "##" represents P<0.01, and "###" represents P<0.001; "ns" represents P>0.05, that is, the difference is not significant.

[0045] Example 1

[0046] The active ingredients, 7% by weight of mangiferin, 12.00% by weight of glycyrrhizic acid and 1.00% by weight of cinnamic acid powder, were mixed and dissolved in dimethyl sulfoxide (DMSO). The solution was then diluted 10 times with phosphate-balanced saline (PBS) and stored at -20°C for later use.

[0047] Example 2

[0048] This embodiment illustrates the construction of an adjuvant-induced arthritis (AIA) rat model.

[0049] (1) Preparation of modeling agent: 100 mg of inactivated Mycobacterium tuberculosis H37Ra was dissolved in 10 mL of liquid paraffin to prepare a suspension (concentration: 10 mg / mL). To avoid precipitation and inaccurate concentration, the suspension was blown every 10 minutes and stored away from light. Based on previous studies, the best results were obtained when the agent was prepared 2 hours before modeling.

[0050] (2) Simple RA model induction: 0.1 mL of 10 mg / mL Mtuberculosis H37 Ra inactivated Mycobacterium tuberculosis liquid paraffin suspension was injected intradermally into the tail root of each group of model rats to induce AIA rat model. The severity of the disease in the rats after modeling was observed and recorded (overall animal condition, disease incidence, swelling of the right hind limb, clinical score of arthritis, radiographic changes of the affected joint, body weight, inflammatory factor level, IgG and IgM content, thymus index, spleen index).

[0051] Onset time and incidence rate: The first onset time in rheumatoid arthritis rats was 12-14 days after modeling, and the incidence rate was 100%.

[0052] Disease symptoms: Rheumatoid arthritis rats exhibited lethargy, loss of appetite, joint redness and swelling, elevated clinical arthritis scores, deformities, and significant pathological changes.

[0053] Indicators related to the regulation of the "inflammation-immune" system: The levels of inflammatory factors such as high-sensitivity C-reactive protein, TNF-α, IL-6, IL-17 and IL-23, IgG and IgM content, and thymus or spleen index in rheumatoid arthritis rats were all higher than those in the normal group rats.

[0054] Example 3

[0055] Normal mice were used as the control group, and adjuvant-induced rheumatoid arthritis rats were used as the AIA model group. No drugs were administered to either the control group or the AIA model group.

[0056] Baihu Jia Guizhi Tang group: AIA model rats were administered Baihu Jia Guizhi Tang 21.4g / kg / day by gavage once a day, starting from the day of initial immunization and continuing for 30 days. Baihu Jia Guizhi Tang consisted of gypsum (60g), anemarrhena (15g), licorice (5g), cinnamon twig (10g), and japonica rice (30g).

[0057] The pharmaceutical composition group disclosed herein: Administering (by gavage) 2 mg / kg / day of the diluted solution in Example 1 to AIA model rats once daily, starting from the day of initial immunization, for 30 consecutive days, is designated as the Zhigui Qingre Juanbi Granules group.

[0058] Example 4

[0059] The degree of redness and swelling of the right hind limb joint of rats in the blank group, AIA model group, Baihu Jia Guizhi Tang group, and Zhigui Qingre Juanbi Granules group were observed. The incidence rate, joint clinical score, degree of joint swelling, time of first onset, and rat weight were also recorded. Results are as follows: Figure 1 As shown.

[0060] Incidence rate in rats = (Number of rats with rheumatoid arthritis / Total number of rats) × 100%;

[0061] Joint clinical scoring: A 40-point system for assessing arthritis clinical scoring was used (ankle joint: severe swelling 1 point, moderately severe 0.5 points, no swelling 0 points; fingers: swelling 0.1 points, no swelling 0 points. The swelling of the limbs was statistically analyzed and converted to a 40-point system).

[0062] Joint swelling: Starting 8 days after immunization, the diameter of the rat's right hind limb was measured every 2 days using calipers until the day before sampling.

[0063] Depend on Figure 1 It can be seen that the Zhi Gui Qing Re Juan Bi Granules group disclosed in this paper can significantly improve the redness and swelling of the joints in rats in the AIA model group. The incidence rate, joint clinical score, joint swelling degree, time to first onset, and rat body weight of rats in the Zhi Gui Qing Re Juan Bi Granules group and the Bai Hu Jia Gui Zhi Tang group were not significantly different. Compared with the AIA model group, the Zhi Gui Qing Re Juan Bi Granules group showed a significant reduction in joint clinical score and joint swelling degree, and a significantly delayed time to first onset, indicating that the Zhi Gui Qing Re Juan Bi Granules group can significantly improve the basic severity of AIA model rats, with no significant difference compared to the Bai Hu Jia Gui Zhi Tang group.

[0064] Example 5

[0065] Pain threshold-related indices in the right hind limb of rats in the blank control group, AIA model group, Baihu Jia Guizhi Tang group, and Zhigui Qingre Juanbi Granules group were detected. Pain threshold-related indices included mechanical pain, thermal radiation pain, and cold pain. Results are as follows: Figure 2 As shown.

[0066] The mechanical pain test method is as follows: rats are placed in a closed grid frame with their feet exposed. The surface of the rat's hind feet is stimulated by test needles of different weights from the Von Freyhair (Shanghai Yuyan Scientific Instruments Co., Ltd.) mechanical pain test instrument. The frequency of their withdrawal response is measured based on the up-and-down method.

[0067] The testing method for thermal radiation pain was as follows: Rats were placed in a sealed transparent frame, and the stimulation intensity of the thermal radiation pain tester (IITC Life Science, USA, Model 390) was adjusted so that the withdrawal response time of the normal control group rats was approximately 15 seconds. This intensity was used as the baseline to stimulate the soles of rats in the AIA model group, the Baihu Jia Guizhi Tang group, and the Zhigui Qingre Juanbi Granules group, and the response time was recorded. The shorter the response time, the higher the thermal radiation pain, and the longer the response time, the lower the thermal radiation pain.

[0068] The method for testing cold pain is as follows: Rats are placed in a closed mesh frame with their paws exposed. 50 μL of acetone is sprayed onto the surface of the rat's hind paw using a 1 mL syringe. The rat's response is monitored and scored within one minute using a 3-point scale. 0 points: no response in the hind paw; 1 point: one withdrawal response in the hind paw; 2 points: multiple withdrawal responses in the hind paw, accompanied by one licking; 3 points: multiple withdrawal responses in the hind paw, accompanied by multiple licking.

[0069] Statistical analysis was performed using Graphpad Prism (Version 7.0) software. Data are expressed as mean ± standard deviation. Analysis of variance was used for comparisons between groups. P < 0.05 was considered statistically significant. Charts were created using Microsoft Office 2013, GraphPrism, and Adobe Photoshop CS6 software.

[0070] Depend on Figure 2 It can be seen that compared with the AIA group rats, the Zhi Gui Qing Re Juan Bi Granules group rats showed significantly reduced mechanical pain, cold pain, and heat radiation pain. Mechanical pain, heat radiation pain, and cold pain can all reflect the degree of inflammation and are used to detect the strength of the anti-inflammatory effect of drugs. Increased mechanical pain, heat radiation pain, and cold pain indicate persistent and severe inflammation, while decreased pain indicates that the inflammation has been relieved. Treatment with Zhi Gui Qing Re Juan Bi Granules can effectively improve the thresholds of mechanical pain, heat radiation pain, and acetone cold stimulation pain in rheumatoid arthritis rats, and the efficacy is not significantly different from that of the Bai Hu Jia Gui Zhi Tang group. This indicates that the Zhi Gui Qing Re Juan Bi Granules group can exert a strong anti-inflammatory and immune-boosting effect.

[0071] Example 6

[0072] The knee joint lesion-related indicators of the right hind limb of rats in the blank group, AIA model group, Baihu Jia Guizhi Tang group, and Zhigui Qingre Juanbi Granules group were measured. Knee joint lesion-related indicators included: tissue mineral density (TMD), bone mineral density (BMD), bone volume / total volume (BV / TV), bone surface area / bone volume (BS / BV), trabecular thickness (Tb.Th.), and trabecular separation (Tb.Sp.). The knee joint lesion-related indicators were measured using a three-dimensional computed tomography (CT) system (IKA). Pathological results and knee joint lesion-related indicators of rats in the blank group, AIA model group, Baihu Jia Guizhi Tang group, and Zhigui Qingre Juanbi Granules group are as follows: Figure 3 As shown.

[0073] Depend on Figure 3 It can be seen that the Zhi Gui Qing Re Juan Bi Granules group significantly increased tissue bone mineral density (TMD), bone volume / total volume (BV / TV), and significantly decreased bone surface area / bone volume (BS / BV) and trabecular separation (Tb.Sp.) in the knee joint of AIA model rats, with slightly better results than the Bai Hu Jia Gui Zhi Tang group. This indicates that the Zhi Gui Qing Re Juan Bi Granules group can significantly improve knee joint lesions in AIA model rats.

[0074] Example 7

[0075] The visceral brain index of rats in the blank control group, AIA model group, Baihu Jia Guizhi Tang group, and Zhigui Qingre Juanbi Granules group was measured. The visceral brain index included: liver index, kidney index, spleen index, and thymus index. The results are as follows: Figure 4 As shown.

[0076] The specific method involves collecting and weighing the rat liver, kidneys, thymus, and spleen on the day of collection, and calculating the visceral-brain index. Visceral-brain index (mg / g) = organ mass / brain mass.

[0077] Depend on Figure 4It can be seen that the Zhi Gui Qing Re Juan Bi Granules group and the Bai Hu Jia Gui Zhi Tang group did not produce liver and kidney toxicity in AIA rats; the Zhi Gui Qing Re Juan Bi Granules group could significantly inhibit the increase of thymus index and spleen index in AIA model rats, and the effect was slightly better than that of the Bai Hu Jia Gui Zhi Tang group.

[0078] Example 8

[0079] The joint surface temperature of the right hind limb of rats in the blank group, AIA model group, Baihu Jia Guizhi Tang group, and Zhigui Qingre Juanbi Granules group was measured. Results are as follows: Figure 5 As shown.

[0080] The specific method is as follows: starting from the first day of the disease, the joint surface temperature of the rat's right hind limb was measured daily using an infrared thermal imager (TESTO-875, Testo Instruments International Trading Co., Ltd., Germany).

[0081] Depend on Figure 5 It can be seen that the Zhi Gui Qing Re Juan Bi Granules group can significantly reduce the joint surface temperature of AIA rats, and the effect is slightly better than that of the Bai Hu Jia Gui Zhi Tang group.

[0082] In summary, the pharmaceutical composition disclosed herein can significantly improve the severity of rheumatoid arthritis in rats with adjuvant-induced arthritis (AIA), with virtually no adverse reactions or side effects.

[0083] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0084] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

[0085] Furthermore, various different embodiments of the present invention can be combined in any way, as long as they do not violate the spirit of the present invention, they should also be regarded as the content disclosed by the present invention.

Claims

1. A pharmaceutical composition, characterized in that, The pharmaceutical composition contains a therapeutically effective amount of an active ingredient and pharmaceutically acceptable excipients, said active ingredient including mangiferin, glycyrrhizic acid and cinnamic acid.

2. The pharmaceutical composition according to claim 1, wherein, In the pharmaceutical composition, based on the total weight of the pharmaceutical composition, the content of mangiferin is 5.00-7.50% by weight; the content of glycyrrhizic acid is 11.00-13.00% by weight; and the content of cinnamic acid is 0.50-2.00% by weight.

3. The pharmaceutical composition according to claim 2, wherein, In the pharmaceutical composition, based on the total weight of the pharmaceutical composition, the content of mangiferin is 5.50-7.00% by weight; the content of glycyrrhizic acid is 11.50-12.50% by weight; and the content of cinnamic acid is 1.00-1.50% by weight.

4. The pharmaceutical composition according to any one of claims 1-3, wherein, In the pharmaceutical composition, the weight ratio of mangiferin, glycyrrhizic acid and cinnamic acid is 1:(1.46-2.60):(0.06-0.40).

5. The pharmaceutical composition according to claim 4, wherein, In the pharmaceutical composition, the weight ratio of mangiferin, glycyrrhizic acid and cinnamic acid is 1:(1.64-2.27):(0.14-0.27).

6. The pharmaceutical composition according to claim 1, wherein, The pharmaceutically acceptable excipients include at least one of soluble starch, lactose, and micronized silica gel.

7. The pharmaceutical composition according to claim 6, wherein, In the pharmaceutical composition, based on the total weight of the pharmaceutical composition, the content of soluble starch is 26.40-36.00% by weight, preferably 28.80-33.60% by weight; The lactose content is 26.4-36.00% by weight, preferably 28.80-33.60% by weight; The content of the micronized silica gel is 13.20-18.00% by weight, preferably 14.40-16.80% by weight.

8. The pharmaceutical composition according to claim 1, wherein, The pharmaceutical composition contains: 5.00-7.50% by weight mangiferin, 11.00-13.00% by weight glycyrrhizic acid, 0.50-2.00% by weight cinnamic acid, 26.40-33.60% by weight soluble starch, 26.40-33.60% by weight lactose, 13.20-18.00% by weight micronized silica gel, and 8.00-10.00% by weight ethanol.

9. The pharmaceutical composition according to claim 1, wherein, The dosage form of the pharmaceutical composition is granules; the combined drug is a pharmaceutical composition used to treat or improve rheumatoid arthritis and its complications.

10. Use of the pharmaceutical composition in the preparation of a medicament for treating or improving a disease, wherein, The disease in question is rheumatoid arthritis; The pharmaceutical composition contains a therapeutically effective amount of active ingredients, including mangiferin, glycyrrhizic acid, and cinnamic acid.

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