A traditional Chinese medicine composition for relieving rheumatoid arthritis and a preparation method thereof

Abstract

The present application relates to the technical field of traditional Chinese medicine composition, and discloses a traditional Chinese medicine composition for relieving rheumatoid arthritis and a preparation method thereof, which comprises Qingfengteng, Huangqi, Chuanshanyang, propolis, turmeric, Fuling, soybean isoflavone peptide, chitosan, Gancao, Chufu, Guizhi and Dangui, and the preparation method comprises raw material pretreatment, extraction, active ingredient mixing and preparation forming. The traditional Chinese medicine composition prepared by the present application has a maximum inhibition rate of 88.6% and 86.4% on TNF-alpha and IL-6, a bioavailability of 87.5%, and can improve immune function and quickly relieve joint swelling and pain. Moreover, the preparation process of the composition is stable and suitable for industrial production, and the composition has significant clinical application value in the treatment of rheumatoid arthritis.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine composition technology, and more specifically, to a traditional Chinese medicine composition for relieving rheumatoid arthritis and its preparation method. Background Technology

[0002] Rheumatoid arthritis (RA) is an autoimmune disease centered on synovitis of the joints. Clinical manifestations include joint swelling, pain, stiffness, and functional impairment, which can lead to joint deformities and disability in later stages. Current clinical treatments mainly include nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and immunosuppressants. While these can provide short-term symptom relief, long-term use can easily cause side effects such as gastrointestinal damage, abnormal liver and kidney function, and weakened immunity.

[0003] Traditional Chinese medicine has the advantage of addressing both the symptoms and the root cause in the treatment of rheumatoid arthritis (RA). However, existing Chinese medicine compositions have the following drawbacks: ① They are composed of single ingredients and rely heavily on traditional anti-inflammatory Chinese medicine combinations, lacking synergistic innovation with modern bioactive components; ② They have low bioavailability, as the active ingredients of Chinese medicine are easily degraded by the gastrointestinal tract, resulting in poor absorption efficiency; ③ They have a single anti-inflammatory mechanism and limited inhibitory effect on key inflammatory factors such as TNF-α and IL-6; ④ They improve joint function slowly and are difficult to quickly relieve patients' pain and swelling symptoms.

[0004] Therefore, developing traditional Chinese medicine compositions that are novel in ingredients, have significant anti-inflammatory effects, high bioavailability, and good safety profiles for relieving rheumatoid arthritis is of great practical significance. Summary of the Invention

[0005] In view of this, the present invention proposes a traditional Chinese medicine composition for relieving rheumatoid arthritis and its preparation method, aiming to solve the problems of limited anti-inflammatory effect, low bioavailability, large side effects and slow improvement of joint function in the current technology.

[0006] This invention proposes a traditional Chinese medicine composition for relieving rheumatoid arthritis, the composition comprising the following components in parts by weight: 6-12 parts of Qingfengteng, 9-15 parts of Huangqin, 8-15 parts of Chuanshanlong, 0.2-1.5 parts of propolis, 3-10 parts of turmeric, 10-18 parts of Poria cocos, 5-10 parts of soybean isoflavone peptides, 3-8 parts of chitosan, 2-10 parts of licorice, 9-12 parts of chicory, 3-6 parts of cinnamon twig, and 6-10 parts of angelica sinensis.

[0007] Furthermore, the molecular weight distribution of the soybean isoflavone peptides is 500~3000 Da.

[0008] A method for preparing a traditional Chinese medicine composition for relieving rheumatoid arthritis includes the following steps: (1) Raw material pretreatment: crush and sieve the following herbs: scutellaria baicalensis, scutellaria baicalensis, turmeric, poria cocos, chicory, cinnamon twig, angelica sinensis, and licorice to obtain mixed Chinese herbal powder; (2) Extraction: Add an aqueous ethanol solution to the mixed Chinese herbal powder, then reflux extract, combine the extracts, and concentrate under reduced pressure to obtain an extract; (3) Mixing of active ingredients: Powder propolis, soybean isoflavone peptides and chitosan, mix with the extract, stir evenly to obtain mixture A; (4) Formulation: Add optional excipients to mixture A, stir evenly, refrigerate at low temperature and then spray dry to obtain the finished traditional Chinese medicine composition.

[0009] Furthermore, the pulverization mentioned in step (1) is pulverization to 20~40 mesh.

[0010] Furthermore, in step (2), the volume fraction of the ethanol-water solution is 50-70%, the solid-liquid ratio is 8-12, and the reflux extraction parameters are: temperature 50-70℃, extraction times 2-4 times, and extraction time 1.5-2.5h.

[0011] Furthermore, the reduced pressure concentration parameters in step (2) are: temperature 55~65℃, pressure -0.07~-0.09MPa, and time 1.5~3h.

[0012] Furthermore, the pulverization in step (3) is pulverized to 100~120 mesh; the mixing temperature is 30~40℃.

[0013] Furthermore, the stirring parameters in step (3) are: rotation speed 300~500 r / min and time 30~60 min.

[0014] Furthermore, the excipients mentioned in step (4) are selected from one or more of β-cyclodextrin, polyethylene glycol 6000, microcrystalline cellulose, and magnesium stearate, and the total mass of the excipients is 5% to 15% of the mass of mixture A.

[0015] Furthermore, the refrigeration parameters in step (4) are: temperature 0~5℃, time 12~24h; the spray drying parameters are: air inlet temperature 160~180℃, air outlet temperature 70~80℃, feeding speed 10~20mL / min, atomization pressure 0.2~0.4MPa.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows: The traditional Chinese medicine composition prepared in this invention has a higher inhibition rate against TNF-α and IL-6 than existing traditional Chinese medicine compositions. It can quickly relieve joint swelling and pain, and the traditional Chinese medicine composition has a fast onset of action and a high degree of improvement in joint mobility.

[0017] All raw materials used in this invention are natural ingredients. Licorice harmonizes the various medicines, and there are no obvious gastrointestinal reactions, allergic reactions or other side effects. Long-term use has no abnormal effect on liver and kidney function. Moreover, chitosan and soybean isoflavone peptides work synergistically, resulting in high bioavailability.

[0018] The present invention uses conventional reflux extraction and mixing molding processes, which do not require special equipment, have low production costs, and are suitable for industrial production. Detailed Implementation

[0019] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention. It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the present invention.

[0020] Furthermore, regarding the numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included within this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0021] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0022] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0023] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0024] This invention provides a traditional Chinese medicine composition for relieving rheumatoid arthritis, the composition comprising the following components in parts by weight: 6-12 parts of Qingfengteng, 9-15 parts of Huangqin, 8-15 parts of Chuanshanlong, 0.2-1.5 parts of propolis, 3-10 parts of turmeric, 10-18 parts of Poria cocos, 5-10 parts of soybean isoflavone peptides, 3-8 parts of chitosan, 2-10 parts of licorice, 9-12 parts of chicory, 3-6 parts of cinnamon twig, and 6-10 parts of angelica sinensis.

[0025] In this invention, the traditional Chinese medicine composition is further preferably composed of the following components in parts by weight: 6-10 parts of Qingfengteng, 9-12 parts of Huangqin, 8-12 parts of Chuanshanlong, 0.2-1.2 parts of propolis, 3-9 parts of turmeric, 10-15 parts of Fuling, 5-8 parts of soybean isoflavone peptides, 3-7 parts of chitosan, 2-8 parts of licorice, 9-11 parts of chicory, 3-5 parts of cinnamon twig, and 6-9 parts of angelica.

[0026] In this invention, the molecular weight distribution of the soybean isoflavone peptides is 500~3000 Da.

[0027] The present invention adds Sinomenium acutum to the traditional Chinese medicine composition. The key active ingredient of Sinomenium acutum is sinomenine, which inhibits the release of inflammatory mediators through multiple targets and blocks the transmission of pain signals.

[0028] The present invention adds Scutellaria baicalensis to the traditional Chinese medicine composition, and the key active ingredient of Scutellaria baicalensis is baicalin, which protects articular cartilage through anti-oxidation and downregulation of inflammatory factor expression.

[0029] The present invention adds Dioscorea nipponica to the traditional Chinese medicine composition. The key active ingredient of Dioscorea nipponica is diosgenin, which reduces joint swelling by inhibiting the NF-κB signaling pathway.

[0030] The present invention adds propolis to the traditional Chinese medicine composition, wherein the active ingredients of propolis are flavonoids and phenolic acids, which regulate immunity, relieve pain and protect the stomach, and clear inflammation.

[0031] The present invention adds turmeric to the traditional Chinese medicine composition, wherein the active ingredient of turmeric is curcumin, which reduces joint edema by inhibiting the synthesis of inflammatory mediators.

[0032] The present invention adds Poria cocos to the traditional Chinese medicine composition, wherein the active ingredient of Poria cocos is Poria cocos polysaccharide, which can promote diuresis and eliminate dampness, reduce joint effusion, and regulate immunity.

[0033] The present invention adds soy isoflavone peptides to the traditional Chinese medicine composition. The active ingredient of the soy isoflavone peptides is a small molecule peptide, which improves bioavailability by directly inhibiting inflammatory factors.

[0034] The present invention adds chitosan to the traditional Chinese medicine composition. Chitosan has good biocompatibility and enhances the stability of the components by protecting the drug, promoting intestinal absorption, and improving the stability of the components.

[0035] The present invention adds licorice to the traditional Chinese medicine composition, the active ingredient of which is glycyrrhizic acid. By harmonizing the various drugs and reducing irritation, it synergistically relieves pain and inflammation.

[0036] The present invention adds chicory to the traditional Chinese medicine composition, the active ingredient of which is chicoric acid, which can delay the progression of the disease by anti-oxidation and protecting articular cartilage.

[0037] The present invention adds cinnamon twig to the traditional Chinese medicine composition, wherein the active ingredient of cinnamon twig is cinnamaldehyde, which relieves joint stiffness by dilating blood vessels and improving circulation.

[0038] The present invention adds Angelica sinensis to the traditional Chinese medicine composition, wherein the active ingredient of Angelica sinensis is ferulic acid, which improves joint function by promoting hematopoiesis, repairing damaged tissues.

[0039] In this invention, the components work synergistically to achieve multiple effects including anti-inflammatory, analgesic, anti-swelling, repair, and absorption promotion. Specifically, the sinomenine in *Sinomenium acutum* can block voltage-dependent calcium channels and inhibit the release of inflammatory mediators; baicalin in *Scutellaria baicalensis* can scavenge oxygen free radicals and downregulate the expression of TNF-α and IL-1β; and diosgenin in *Dioscorea nipponica* can inhibit the NF-κB signaling pathway. The synergistic effect of these three components enhances the anti-inflammatory rate compared to a single component, achieving multi-target inhibition of the inflammatory response.

[0040] The propolis contains flavonoids and phenolic acids, which can regulate T / B lymphocyte activity and enhance immune tolerance; the glycyrrhizic acid in the licorice can inhibit cyclooxygenase-2 (COX-2) activity, exert an analgesic effect, and at the same time harmonize the various drugs, reduce the potential irritation of propolis, and improve the safety of the composition.

[0041] The curcumin can inhibit the synthesis of inflammatory mediators and reduce joint edema; the cinnamaldehyde in the cinnamon twig can dilate blood vessels and improve local blood circulation in the joint; the ferulic acid in the angelica can promote erythrocyte production and accelerate the repair of damaged joint tissues. The three work synergistically to improve joint stiffness and dysfunction.

[0042] The polysaccharide in Poria cocos has a diuretic effect and can reduce joint effusion; the chicoric acid in chicory can inhibit lipid peroxidation, protect articular cartilage from oxidative damage, and delay the progression of rheumatoid arthritis (RA).

[0043] The soybean isoflavone peptides are small molecule peptides that are easily absorbed by the intestines and can directly act on the site of inflammation to inhibit IL-6 expression. The chitosan, as a biocompatible carrier, can encapsulate the active ingredients of traditional Chinese medicine, protect them from degradation by gastric acid and gastric enzymes, and promote intestinal mucosal absorption, thereby improving the bioavailability of the composition.

[0044] A method for preparing a traditional Chinese medicine composition for relieving rheumatoid arthritis includes the following steps: (1) Raw material pretreatment: crush and sieve the following herbs: scutellaria baicalensis, scutellaria baicalensis, turmeric, poria cocos, chicory, cinnamon twig, angelica sinensis, and licorice to obtain mixed Chinese herbal powder; (2) Extraction: Add an aqueous ethanol solution to the mixed Chinese herbal powder, then reflux extract, combine the extracts, and concentrate under reduced pressure to obtain an extract; (3) Mixing of active ingredients: Powder propolis, soybean isoflavone peptides and chitosan, mix with the extract, stir evenly to obtain mixture A; (4) Formulation: Add optional excipients to mixture A, stir evenly, refrigerate at low temperature and then spray dry to obtain the finished traditional Chinese medicine composition.

[0045] In this invention, the pulverization in step (1) is preferably pulverized to 20-40 mesh, and more preferably to 25-40 mesh.

[0046] In this invention, the volume fraction of the ethanol-water solution in step (2) is preferably 50-70%, more preferably 55-70%; the solid-liquid ratio of the mixed Chinese herbal powder to the ethanol-water solution is preferably 8-12, more preferably 9-12; the reflux extraction parameters are preferably: temperature 50-70℃, extraction times 2-4 times, extraction time 1.5-2.5h, more preferably temperature 55-70℃, extraction times 2-3 times, extraction time 1.8-2.5h.

[0047] In this invention, the vacuum concentration parameters in step (2) are preferably: temperature 55~65℃, pressure -0.07~-0.09MPa, and time 1.5~3h, and more preferably temperature 58~65℃, pressure -0.08~-0.09MPa, and time 1.8~3h.

[0048] In this invention, the pulverization in step (3) is preferably pulverized to 100~120 mesh, and more preferably to 110~120 mesh; the mixing temperature is preferably 30~40℃, and more preferably 32~40℃.

[0049] In this invention, the stirring parameters in step (3) are preferably: rotation speed 300~500 r / min and time 30~60 min, and more preferably 350~500 r / min and time 30~50 min.

[0050] In this invention, the excipients in step (4) are selected from one or more of β-cyclodextrin, polyethylene glycol 6000, microcrystalline cellulose, and magnesium stearate. The total mass of the excipients is preferably 5% to 15% of the mass of mixture A, and more preferably 7% to 15% of the mass of mixture A.

[0051] In this invention, the refrigeration parameters in step (4) are preferably: temperature 0~5℃, time 12~24h, and more preferably temperature 0~4℃, time 12~20h; the spray drying parameters are preferably: inlet air temperature 160~180℃, outlet air temperature 70~80℃, feed rate 10~20mL / min, atomization pressure 0.2~0.4MPa, and more preferably inlet air temperature 165~180℃, outlet air temperature 72~80℃, feed rate 12~20mL / min, atomization pressure 0.25~0.4MPa.

[0052] In this invention, unless otherwise specified, all raw materials required for preparation are commercially available products well known to those skilled in the art.

[0053] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0054] Example 1 Ingredients: 6 parts of Chinese pine, 9 parts of scutellaria baicalensis, 8 parts of smilax china, 0.2 parts of propolis, 3 parts of turmeric, 10 parts of poria cocos, 5 parts of soybean isoflavone peptides, 3 parts of chitosan, 2 parts of licorice, 9 parts of chicory, 3 parts of cinnamon twig, 6 parts of angelica sinensis, and 3 parts of β-cyclodextrin.

[0055] Preparation method: (1) Raw material pretreatment: The following herbs were pulverized to 25 mesh and sieved to obtain mixed Chinese medicine powder: *Sinomenium acutum*, *Scutellaria baicalensis*, *Dioscorea nipponica*, *Curcuma longa*, *Poria cocos*, *Citrullus cum Bile*, *Cinnamomum cassia*, *Angelica sinensis*, and *Glycyrrhiza uralensis*. (2) Extraction: Add 70% ethanol aqueous solution to the mixed Chinese herbal powder, wherein the mass of the ethanol aqueous solution is 9 times that of the mixed Chinese herbal powder. Then, reflux extraction is performed twice at 55℃ for 1.8h each time. The extracts are combined and concentrated under reduced pressure at 58℃ and -0.08MPa for 1.8h to obtain the extract. (3) Mixing of active ingredients: Powder propolis, soybean isoflavone peptides and chitosan to 110 mesh, mix with the extract at 32°C, and then stir at 350 r / min for 50 min to mix evenly to obtain mixture A; (4) Formulation: Add β-cyclodextrin to mixture A, stir evenly, refrigerate at 0°C for 12 hours, and then spray dry at an inlet air temperature of 165°C, an outlet air temperature of 72°C, a feed rate of 20 mL / min, and an atomization pressure of 0.25 MPa to obtain the finished product of the traditional Chinese medicine composition.

[0056] Example 2 Ingredients: 8 parts of Chinese pine, 10 parts of scutellaria baicalensis, 10 parts of smilax china, 0.8 parts of propolis, 5 parts of turmeric, 12 parts of poria cocos, 6 parts of soybean isoflavone peptides, 5 parts of chitosan, 5 parts of licorice, 10 parts of chicory, 4 parts of cinnamon twig, 8 parts of angelica sinensis, and 2 parts of β-cyclodextrin.

[0057] Preparation method: (1) Raw material pretreatment: The following herbs were pulverized to 30 mesh and sieved to obtain mixed Chinese medicine powder: *Sinomenium acutum*, *Scutellaria baicalensis*, *Dioscorea nipponica*, *Curcuma longa*, *Poria cocos*, *Citrullus cuminata*, *Cinnamomum cassia*, *Angelica sinensis*, and *Glycyrrhiza uralensis*. (2) Extraction: Add 60% ethanol aqueous solution to the mixed Chinese herbal powder, wherein the mass of the ethanol aqueous solution is 10 times that of the mixed Chinese herbal powder. Then, reflux extraction is performed twice at 60℃ for 2 hours each time. The extracts are combined and concentrated under reduced pressure at 60℃ and -0.08MPa for 2.5 hours to obtain the extract. (3) Mixing of active ingredients: Powder propolis, soybean isoflavone peptides and chitosan to 120 mesh, mix with the extract at 35°C, and then stir at 400 r / min for 40 min to mix evenly to obtain mixture A; (4) Formulation: Add β-cyclodextrin to mixture A, stir evenly, refrigerate at 2°C for 18 hours, and then spray dry at an inlet air temperature of 170°C, an outlet air temperature of 75°C, a feed rate of 15 mL / min, and an atomization pressure of 0.3 MPa to obtain the finished product of the traditional Chinese medicine composition.

[0058] Example 3 Ingredients: 10 parts of Chinese pine, 12 parts of scutellaria baicalensis, 12 parts of smilax china, 1.2 parts of propolis, 9 parts of turmeric, 15 parts of poria cocos, 8 parts of soybean isoflavone peptides, 7 parts of chitosan, 8 parts of licorice, 11 parts of chicory, 5 parts of cinnamon twig, 9 parts of angelica sinensis, 4 parts of microcrystalline cellulose and 3 parts of magnesium stearate.

[0059] Preparation method: (1) Raw material pretreatment: crush the Chinese herbal medicine powder into 40 mesh and sieve the powder, including the following herbs: Qingfengteng, Huangqin, Chuanshanlong, Jianghuang, Fuling, Juju, Guizhi, Danggui, and Gancao. (2) Extraction: Add 55% ethanol aqueous solution to the mixed Chinese herbal powder, wherein the mass of the ethanol aqueous solution is 12 times that of the mixed Chinese herbal powder. Then, reflux extraction is performed 3 times at 70℃, each time for 2.5h. The extracts are combined and concentrated under reduced pressure at 65℃ and -0.09MPa for 3h to obtain the extract. (3) Mixing of active ingredients: Powder propolis, soybean isoflavone peptides and chitosan to 120 mesh, mix with the extract at 40°C, and then stir at 500 r / min for 30 min to mix evenly to obtain mixture A; (4) Formulation: Microcrystalline cellulose and magnesium stearate are added to mixture A, stirred evenly, and then stored at 4°C for 20 hours. After that, spray drying is carried out at an inlet air temperature of 180°C, an outlet air temperature of 80°C, a feed rate of 12 mL / min, and an atomization pressure of 0.4 MPa to obtain the finished product of the traditional Chinese medicine composition.

[0060] Comparative Example 1 Raw materials: 15 parts of soybean isoflavone peptides were used, and other raw materials were the same as in Example 1.

[0061] Preparation method: Same as in Example 1.

[0062] Comparative Example 2 Ingredients: 6 parts of Qingfengteng (Sinomenium acutum), 9 parts of Huangqin (Scutellaria baicalensis), 8 parts of Chuanshanlong (Dioscorea nipponica), 0.2 parts of propolis, 3 parts of turmeric, 10 parts of Poria cocos, 5 parts of soybean isoflavone peptides, 2 parts of licorice, 9 parts of chicory, 3 parts of cinnamon twig, 6 parts of Angelica sinensis, and 3 parts of β-cyclodextrin.

[0063] Preparation method: Same as in Example 1.

[0064] Comparative Example 3 Ingredients: 6 parts of Chinese pine, 9 parts of scutellaria baicalensis, 8 parts of smilax china, 0.2 parts of propolis, 3 parts of turmeric, 10 parts of poria cocos, 5 parts of soybean isoflavone peptides, 3 parts of chitosan, 2 parts of licorice, 9 parts of chicory, 3 parts of cinnamon twig, 6 parts of angelica sinensis, and 3 parts of β-cyclodextrin.

[0065] Preparation method: (1) Raw material pretreatment: The following herbs were pulverized to 25 mesh and sieved to obtain mixed Chinese medicine powder: *Sinomenium acutum*, *Scutellaria baicalensis*, *Dioscorea nipponica*, *Curcuma longa*, *Poria cocos*, *Citrullus cum Bile*, *Cinnamomum cassia*, *Angelica sinensis*, and *Glycyrrhiza uralensis*. (2) Extraction: Add 70% ethanol aqueous solution to the mixed Chinese herbal powder, wherein the mass of the ethanol aqueous solution is 9 times that of the mixed Chinese herbal powder. Then, reflux extraction is performed twice at 90℃ for 1.8h each time. The extracts are combined and concentrated under reduced pressure at 58℃ and -0.08MPa for 1.8h to obtain the extract. (3) Mixing of active ingredients: Powder propolis, soybean isoflavone peptides and chitosan to 110 mesh, mix with the extract at 32°C, and then stir at 350 r / min for 50 min to mix evenly to obtain mixture A; (4) Formulation: Add β-cyclodextrin to mixture A, stir evenly, refrigerate at 0°C for 12 hours, and then spray dry at an inlet air temperature of 165°C, an outlet air temperature of 72°C, a feed rate of 20 mL / min, and an atomization pressure of 0.25 MPa to obtain the finished product of the traditional Chinese medicine composition.

[0066] Comparative Example 4 Ingredients: 6 parts of Piper kadsura, 9 parts of Scutellaria baicalensis, 8 parts of Dioscorea nipponica, 0.2 parts of propolis, 3 parts of turmeric, 10 parts of Poria cocos, 5 parts of soybean isoflavone peptides, 3 parts of chitosan, 2 parts of licorice, 9 parts of chicory, 3 parts of cinnamon twig, 6 parts of Angelica sinensis, and 3 parts of β-cyclodextrin.

[0067] Preparation method: Same as in Example 1.

[0068] Performance testing (1) The inflammatory factor inhibition rate (%) was detected by ELISA. The inflammatory factor inhibition rate (%) = [1 - (OD value of the drug treatment group - OD value of the blank control group) / (OD value of the model group - OD value of the blank control group)] × 100%. The test was based on GB / T34790-2017 "General Rules for Cytokine Detection".

[0069] (2) The joint swelling inhibition rate (%) was detected by the plantar thickness measurement method. The joint swelling inhibition rate (%) = [(swelling degree of model group - swelling degree of drug treatment group) / (swelling degree of model group - swelling degree of blank control group)] × 100% (swelling degree = plantar thickness after drug treatment - plantar thickness before drug treatment). The test was based on the "Guiding Principles for Pharmacodynamic Evaluation of Traditional Chinese Medicine" (2020 edition of the National Medical Products Administration).

[0070] (3) The analgesic latency (s) was detected by the mouse hot plate method. The latency (s) of the mouse hot plate licking paw 120 min after administration was used as the evaluation index (the longest recorded time was 60 s). The test was based on the "Hot Plate Method Analgesic Test Operation Specification" in "Pharmacological Experimental Methodology" (4th edition, edited by Xu Shuyun).

[0071] (4) Bioavailability (%) was determined by HPLC. Bioavailability (F) = (gavage group blood drug concentration - area under the time curve AUC) 0-24h / Area under the plasma concentration-time curve (AUC) in the intravenous injection group 0-24h The test was conducted at 100% (9012) according to the "Guiding Principles for Bioavailability and Bioequivalence Testing" in Part IV of the 2020 edition of the Chinese Pharmacopoeia.

[0072] (5) Calculation of thymus index: Thymus index (mg / g) = thymus wet weight (mg) / mouse body weight (g) 30 days after administration. The test is based on GB / T15670.26-2019 "Toxicological Test Methods for Pesticide Registration Part 26: Immune Function Test".

[0073] Mouse specifications: 160 SPF-grade Kunming mice, half male and half female, aged 6-8 weeks and weighing 18-22g, were selected and given free access to standard feed and water. After one week of acclimatization, the experiment began. They were randomly divided into a blank control group, Example 1-3 groups, and Comparative Example 1-4 groups, with 20 mice in each group.

[0074] Drug preparation: The finished traditional Chinese medicine composition (capsules / tablets / granules) described in Examples 1-3 and Comparative Examples 1-3 were pulverized and passed through an 80-mesh sieve, and physiological saline was added and stirred evenly to prepare a suspension with a concentration of 10 mg / mL (ensuring that the dosage is 100 mg / (kg·d), calculated based on the average weight of mice of 20 g, and the single gavage volume is 0.2 mL / mouse); the blank control group used an equal volume of physiological saline as the gavage medium.

[0075] Administration method: Oral administration was performed using a disposable gavage syringe to a depth of 2-3 cm to avoid damaging the mouse esophagus.

[0076] Dosage and frequency of administration: Except for the blank control group, the dosage of all other groups was 100 mg / (kg·d), administered by gavage once a day at a fixed time (9:00-10:00 am) for 30 consecutive days. Dosage should not be interrupted without authorization during the period.

[0077] During the administration period, the mice's food and water intake, mental state, weight changes, and abnormal reactions (such as vomiting, diarrhea, allergies, etc.) should be recorded daily. If serious abnormalities occur, the mice should be removed in time and replaced with mice of the same size.

[0078] Sample collection: 30 days after administration, mice were fasted but allowed free access to water for 12 hours. Blood was collected from the orbital cavity and centrifuged (3000 r / min, 10 min) to separate serum for the detection of inflammatory factors (TNF-α, IL-6). The mice were then sacrificed, the thymus was removed and weighed, and the thymus index was calculated. At the same time, joint-related indicators (such as paw swelling) and analgesia latency data were recorded.

[0079] The performance test results of the drug compositions described in Examples 1-3 and Comparative Examples 1-4 administered to mice are shown in Table 1 below (results are expressed as mean ± standard deviation): Table 1 Performance test results of the pharmaceutical compositions described in Examples 1-3 and Comparative Examples 1-4 In summary, the TNF-α / IL-6 inhibition rates in Examples 1-3 of this invention all exceeded 74%, and the joint swelling inhibition rate exceeded 69%. Furthermore, by rationally increasing the ratio of the core anti-inflammatory components, the synergistic effect of the multi-target anti-inflammatory mechanism can be enhanced. In Comparative Example 1, the TNF-α / IL-6 inhibition rate of excessive soybean isoflavone peptides decreased by 12.4% and 12.8% respectively compared to Example 1, and the bioavailability decreased by 9.8%. In Comparative Example 2, after the absence of chitosan, the bioavailability plummeted from 81.3% in Example 1 to 59.8%, and the TNF-α / IL-6 inhibition rates decreased by 16.8% and 17.3% respectively. In Comparative Example 4, after replacing *Sinomenium acutum* with *Piper kadsura*, the TNF-α inhibition rate decreased by 14.9% and the joint swelling inhibition rate decreased by 16.1% compared to Example 1. In Comparative Example 3, increasing the reflux extraction temperature from 55℃ in Example 1 to 90℃ resulted in a 9.7% decrease in the TNF-α inhibition rate and a 14.6% decrease in bioavailability. The composition prepared by this invention exhibits inhibition rates of up to 88.6% and 86.4% against TNF-α and IL-6, respectively, with a bioavailability of 87.5%. It also improves immune function and rapidly relieves joint swelling and pain. Furthermore, changes in a single variable (excess / deficiency of component, abnormal parameters, or component substitution) all lead to a significant decrease in efficacy. This fully demonstrates the clear technical necessity and inventiveness of the raw material ratio and process parameter limitations of this invention. The composition is stable in preparation and suitable for industrial production, and has significant clinical application value in the treatment of rheumatoid arthritis.

[0080] The above embodiments are merely preferred embodiments of the present invention and are not intended to limit the present invention. The scope of protection of the present invention is determined by the appended claims.

[0081] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the specific implementation of the present invention. Any modifications or equivalent substitutions that do not depart from the spirit and scope of the present invention should be covered within the scope of protection of the claims of the present invention.

Claims

1. A traditional Chinese medicine composition for relieving rheumatoid arthritis, characterized in that, The traditional Chinese medicine composition comprises the following components in parts by weight: 6-12 parts of Qingfengteng, 9-15 parts of Huangqin, 8-15 parts of Chuanshanlong, 0.2-1.5 parts of propolis, 3-10 parts of turmeric, 10-18 parts of Poria cocos, 5-10 parts of soybean isoflavone peptides, 3-8 parts of chitosan, 2-10 parts of licorice, 9-12 parts of chicory, 3-6 parts of cinnamon twig, and 6-10 parts of angelica sinensis.

2. The traditional Chinese medicine composition for relieving rheumatoid arthritis according to claim 1, characterized in that, The molecular weight distribution of the soybean isoflavone peptides is 500~3000 Da.

3. A method for preparing a traditional Chinese medicine composition for relieving rheumatoid arthritis as described in claim 1 or 2, characterized in that, Includes the following steps: (1) Raw material pretreatment: crush and sieve the following herbs: scutellaria baicalensis, scutellaria baicalensis, turmeric, poria cocos, chicory, cinnamon twig, angelica sinensis, and licorice to obtain mixed Chinese herbal powder; (2) Extraction: Add an aqueous ethanol solution to the mixed Chinese herbal powder, then reflux extract, combine the extracts, and concentrate under reduced pressure to obtain an extract; (3) Mixing of active ingredients: Powder propolis, soybean isoflavone peptides and chitosan, mix with the extract, stir evenly to obtain mixture A; (4) Formulation: Add optional excipients to mixture A, stir evenly, refrigerate at low temperature and then spray dry to obtain the finished traditional Chinese medicine composition.

4. The method for preparing a traditional Chinese medicine composition for relieving rheumatoid arthritis according to claim 3, characterized in that, The pulverization mentioned in step (1) refers to pulverizing to 20~40 mesh.

5. A method for preparing a traditional Chinese medicine composition for relieving rheumatoid arthritis according to claim 3, characterized in that, The volume fraction of the ethanol-water solution in step (2) is 50-70%, and the amount of ethanol-water solution added is 8-12 times the mass of the mixed Chinese herbal powder; the reflux extraction parameters are: temperature 50-70℃, extraction times 2-4 times, and extraction time 1.5-2.5h.

6. A method for preparing a traditional Chinese medicine composition for relieving rheumatoid arthritis according to claim 3, characterized in that, The vacuum concentration parameters in step (2) are: temperature 55~65℃, pressure -0.07~-0.09MPa, and time 1.5~3h.

7. A method for preparing a traditional Chinese medicine composition for relieving rheumatoid arthritis according to claim 3, characterized in that, The pulverization in step (3) is pulverization to 100~120 mesh; the mixing temperature is 30~40℃.

8. A method for preparing a traditional Chinese medicine composition for relieving rheumatoid arthritis according to claim 3, characterized in that, The stirring parameters in step (3) are: rotation speed 300~500 r / min and time 30~60 min.

9. A method for preparing a traditional Chinese medicine composition for relieving rheumatoid arthritis according to claim 3, characterized in that, The excipients mentioned in step (4) are selected from one or more of β-cyclodextrin, polyethylene glycol 6000, microcrystalline cellulose, and magnesium stearate, and the total mass of the excipients is 5% to 15% of the mass of mixture A.

10. A method for preparing a traditional Chinese medicine composition for relieving rheumatoid arthritis according to claim 3, characterized in that, The refrigeration parameters in step (4) are: temperature 0~5℃, time 12~24h; the spray drying parameters are: air inlet temperature 160~180℃, air outlet temperature 70~80℃, feeding speed 10~20mL / min, atomization pressure 0.2~0.4MPa.

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