CN117959369A - An oral Chinese medicine composition for treating acute gouty arthritis and its application - Google Patents

Abstract

The invention relates to an oral traditional Chinese medicine composition for treating acute gouty arthritis, which is prepared from the following raw materials in parts by weight: 7-11 parts of notopterygium root, 7-11 parts of radix angelicae pubescentis, 10-14 parts of angelica sinensis, 8-12 parts of ligusticum wallichii, 10-14 parts of rhizoma atractylodis, 10-14 parts of cortex phellodendri, 10-14 parts of radix achyranthis bidentatae, 13-17 parts of herba artemisiae capillaries, 13-17 parts of polygonum cuspidatum, 7-11 parts of radix stephaniae tetrandrae, 13-17 parts of poria cocos and 13-17 parts of paniculate swallowwort root. The invention also provides application of the traditional Chinese medicine composition. The oral Chinese medicinal composition of the invention takes giant knotweed, notopterygium root, pubescent angelica root and paniculate swallowwort root as monarch drugs, and has the functions of dispelling wind, clearing heat, promoting diuresis and relieving pain; herba Artemisiae Scopariae, cortex Phellodendri, radix Angelicae sinensis, rhizoma Ligustici Chuanxiong, and used as ministerial drugs for clearing heat, removing dampness, promoting blood circulation and activating qi-flowing; poria cocos and rhizoma atractylodis are adjuvant drugs for preventing bitter and cold from hurting stomach, eliminating dampness and strengthening spleen; radix stephaniae tetrandrae and achyranthes root induce diuresis and excrete dampness, and act as guiding drugs to guide the drugs. The medicines are combined to play the roles of clearing heat, promoting diuresis, dispelling wind and dredging collaterals, can well treat acute gouty arthritis, and has the advantages of clear and obvious curative effect, safety, economy and convenient operation.

Description

An oral Chinese medicine composition for treating acute gouty arthritis and its application

Technical Field

The invention relates to the technical field of traditional Chinese medicines, in particular to an oral traditional Chinese medicine composition for treating acute gouty arthritis and application thereof.

Background technique

Gouty arthritis is a sterile inflammatory disease characterized by self-limitation and severe pain. During the acute attack of gouty arthritis, sodium urate crystals fall off from the attached synovium into the synovial fluid and are deposited around the articular cartilage, causing the activation of mast cells and mononuclear macrophage systems. Through a series of complex intracellular cascade reactions, inflammatory mediators such as IL-1, IL-8 and TNF-α are secreted, thereby promoting the occurrence and development of inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine or glucocorticoids are recommended. NSAIDs include traditional NSAIDs and selective cyclooxygenase-2 (COX-2) inhibitors. The efficacy of COX-2 inhibitors is comparable to that of traditional NSAIDs, and they have fewer adverse reactions, especially gastrointestinal adverse reactions. However, both have clear contraindications: peptic ulcers and renal insufficiency (grade 2B). Colchicine can be used to treat gout attacks and to prevent acute attacks in the early stages of uric acid-lowering treatment. It is a specific drug for the treatment of acute gouty arthritis. However, in the early stage of medication, colchicine may cause gastrointestinal symptoms, such as abdominal pain, diarrhea, vomiting and lack of appetite, with an incidence rate of up to 80%. In severe cases, it may lead to dehydration, electrolyte imbalance and other problems. A small number of patients may also experience bone marrow suppression, liver and kidney damage, etc. Glucocorticoids can reduce inflammatory responses and quickly relieve pain in patients with acute gout, but the use of hormone drugs may induce or aggravate ulcers, induce mental symptoms, osteoporosis and muscle atrophy, and long-term use may also be complicated by infection.

Traditional Chinese medicine has shown certain advantages in relieving the symptoms of joint redness, swelling, heat and pain in acute gouty arthritis, and reducing blood uric acid and inflammatory indicators. However, patients' self-decocting of Chinese herbal medicines has certain complexities and limitations, and Chinese herbal decoctions are not easy to store for a long time. Therefore, the use of Chinese herbal decoctions is limited to a certain extent. As people's requirements for quality of life and physical health continue to increase, people are increasingly in need of more convenient and comprehensive treatment methods. Therefore, when formulating clinical treatment plans for acute gouty arthritis, the principles of safer, more effective, economical and convenient should be followed.

Summary of the invention

In order to overcome the shortcomings of the above-mentioned prior art, the present invention provides an oral Chinese medicine composition for treating acute gouty arthritis, namely, Huyin Analgesic Recipe. The various medicinal ingredients work synergistically to clear away heat and dampness, dispel wind and dredge meridians. It has significant therapeutic effect in the oral treatment of acute gouty arthritis, and has the advantages of safety, economy and easy operation.

In a first aspect, the present invention provides an oral Chinese medicine composition for treating acute gouty arthritis, wherein the Chinese medicine composition is prepared from the following raw materials in parts by weight: 7-11 parts of Notopterygium wilfordii, 7-11 parts of Duhuo, 10-14 parts of Angelica sinensis, 8-12 parts of Chuanxiong, 10-14 parts of Atractylodes macrocephala, 10-14 parts of Phellodendron chinense, 10-14 parts of Achyranthes bidentata, 13-17 parts of Artemisia capillaris, 13-17 parts of Polygonum cuspidatum, 7-11 parts of Stephania tetrandra, 13-17 parts of Poria cocos, and 13-17 parts of Cynanchum wilfordii.

As a preferred example, the Chinese medicine composition is made of the following raw materials in parts by weight: 8-10 parts of Notopterygium wilfordii, 8-10 parts of Pubescent Angelica dahurica, 11-13 parts of Angelica sinensis, 9-11 parts of Ligusticum chuanxiong, 11-13 parts of Atractylodes macrocephala, 11-13 parts of Phellodendron chinense, 11-13 parts of Achyranthes bidentata, 14-16 parts of Artemisia capillaris, 14-16 parts of Polygonum cuspidatum, 8-10 parts of Stephania tetrandra, 14-16 parts of Poria cocos, and 14-16 parts of Cynanchum wilfordii.

As another preferred example, 9 parts of Notopterygium wilfordii, 9 parts of Duhuo, 12 parts of Angelica sinensis, 10 parts of Chuanxiong, 12 parts of Atractylodes lancea, 12 parts of Phellodendron chinense, 12 parts of Achyranthes bidentata, 15 parts of Artemisia capillaris, 15 parts of Polygonum cuspidatum, 9 parts of Stephania tetrandra, 15 parts of Poria cocos, and 15 parts of Cynanchum cyrtonema.

In a second aspect, the present invention provides use of a Chinese medicine composition in preparing a drug for treating acute gouty arthritis.

The advantages of the present invention are: Polygonum cuspidatum, Notopterygium incisum, Angelica pubescens, and Cynanchum chinense are the main drugs in the oral Chinese medicine composition of the present invention, and the functions are to dispel wind and heat, remove dampness and relieve pain; Artemisia capillaris, Phellodendron chinense, Angelica sinensis, and Ligusticum chuanxiong are to clear heat and remove dampness, and to promote blood circulation and qi, and are the ministerial drugs; Poria cocos and Atractylodes macrocephala are the main drugs that hurt the stomach, dry dampness and strengthen the spleen, and are the adjuvant drugs; Stephania tetrandra and Achyranthes bidentata are to promote diuresis and eliminate dampness, and are the guiding drugs. All the drugs are used together to play the role of "clearing heat and removing dampness, dispelling wind and unblocking collaterals", and can treat acute gouty arthritis well, with the advantages of clear and significant curative effect, safety, economy and convenient operation. The oral Chinese medicine composition of the present invention preferably plays a therapeutic effect by reducing joint inflammatory reactions, down-regulating the expression of inflammatory factors, etc., and specifically plays a therapeutic effect through the IL-1β signaling pathway, the IL-17 signaling pathway, and down-regulating the expression of SFRP5 and Wnt5a.

Description of the drawings:

Figure 1 Subject flow chart

Figure 2 Changes in the main outcome indicators of the two groups of patients (n=90), i.e., comparison of VAS scores of joint pain in the two groups of patients at different time points. Note: Compared with the baseline period (day 0), ***P<0.001.

Figure 3 Changes in secondary outcome indicators between the two groups of patients (n=90), where A: comparison of joint tenderness scores between the two groups of patients at different time points; B: comparison of joint swelling scores between the two groups of patients at different time points, Note: Compared with the baseline period (day 0), ***P<0.001.

Figure 4 Changes in vital signs of the two groups before and after treatment (n=90), wherein A: comparison of vital signs of the two groups of patients at baseline (day 0); B: comparison of vital signs of the two groups of patients after 5 days of treatment; C: comparison of vital signs of the two groups of patients during the follow-up period (day 12).

Figure 5 Comparison of blood routine tests (white blood cell count, neutrophil count, liver function, and kidney function) between the two groups before and after treatment (n=90). Note: *P<0.05 compared with the baseline period.

Figure 6 Comparison of the incidence of non-serious adverse events (NSAEs) between the two groups after treatment (n=90), Note: Compared with the control group, #P<0.05.

Fig. 7 Comparison of serum inflammatory factors between the two groups before and after treatment (n=90), Note: *P<0.05 compared with the baseline period.

Detailed ways

Below in conjunction with specific embodiment, further elaborate the present invention.Should be understood that these embodiments are only used to illustrate the present invention and are not used to limit the scope of the present invention.In addition, should be understood that after reading the content of the present invention record, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms fall equally within the scope limited by the appended claims of the application.

Example 1 Oral Chinese medicine composition for treating acute gouty arthritis of the present invention (I)

9 parts of Notopterygium root, 9 parts of Duhuo, 12 parts of Angelica sinensis, 10 parts of Ligusticum chuanxiong, 12 parts of Atractylodes, 12 parts of Phellodendron, 12 parts of Achyranthes bidentata, 15 parts of Artemisia capillaris, 15 parts of Polygonum cuspidatum, 9 parts of Stephania tetrandra, 15 parts of Poria, and 15 parts of Cynanchum cyrtonema.

Example 2 Oral Chinese medicine composition for treating acute gouty arthritis of the present invention (II)

9 parts of Notopterygium root, 7 parts of Duhuo, 10 parts of Angelica sinensis, 8 parts of Chuanxiong, 10 parts of Atractylodes, 10 parts of Phellodendron, 12 parts of Achyranthes bidentata, 13 parts of Artemisia capillaris, 13 parts of Polygonum cuspidatum, 7 parts of Stephania tetrandra, 13 parts of Poria, and 15 parts of Cynanchum wilfordii.

Example 3 Oral Chinese medicine composition for treating acute gouty arthritis of the present invention (III)

11 parts of Notopterygium root, 9 parts of Angelica sinensis, 14 parts of Rhizoma Chuanxiong, 14 parts of Atractylodes, 12 parts of Cortex Phellodendri, 14 parts of Achyranthes bidentata, 15 parts of Artemisia capillaris, 17 parts of Polygonum cuspidatum, 9 parts of Stephania tetrandra, 15 parts of Poria, and 17 parts of Cynanchum cyrtonema.

Example 4 Oral Chinese medicine composition for treating acute gouty arthritis of the present invention (IV)

8 parts of Notopterygium root, 8 parts of Angelica root, 11 parts of Ligusticum chuanxiong, 11 parts of Atractylodes, 11 parts of Phellodendron, 11 parts of Achyranthes bidentata, 14 parts of Artemisia capillaris, 14 parts of Polygonum cuspidatum, 8 parts of Stephania tetrandra, 14 parts of Poria, and 14 parts of Cynanchum cyrtonema.

Example 5 Oral Chinese medicine composition for treating acute gouty arthritis of the present invention (V)

10 parts of Notopterygium root, 10 parts of Angelica sinensis, 10 parts of Rhizoma Chuanxiong, 13 parts of Atractylodes, 13 parts of Cortex Phellodendri, 13 parts of Achyranthes bidentata, 16 parts of Artemisia capillaris, 16 parts of Polygonum cuspidatum, 10 parts of Stephania tetrandra, 14 parts of Poria, and 16 parts of Cynanchum cyrtonema.

Example 6 Oral Chinese medicine composition for treating acute gouty arthritis of the present invention (VI)

7 parts of Notopterygium root, 10 parts of Angelica sinensis, 12 parts of Rhizoma Chuanxiong, 10 parts of Atractylodes, 10 parts of Cortex Phellodendri, 10 parts of Achyranthes bidentata, 16 parts of Artemisia capillaris, 13 parts of Polygonum cuspidatum, 7 parts of Stephania tetrandra, 13 parts of Poria, and 13 parts of Cynanchum cyrtonema.

Example 7 Oral Chinese medicine composition for treating acute gouty arthritis of the present invention (VII)

11 parts of Notopterygium root, 9 parts of Angelica sinensis, 14 parts of Rhizoma Chuanxiong, 12 parts of Rhizoma Atractylodis Macrocephalae, 14 parts of Cortex Phellodendri, 14 parts of Rhizoma Achyranthis Bidentatae, 15 parts of Herba Artemisiae Scopariae, 16 parts of Rhizoma Polygoni Cuspidati, 11 parts of Radix Stephaniae Tetrandrae, 17 parts of Poria, and 17 parts of Radix Cynanchum.

Example 8 Oral Chinese medicine composition for treating acute gouty arthritis of the present invention (VIII)

8 parts of Notopterygium root, 7 parts of Duhuo, 11 parts of Angelica sinensis, 9 parts of Chuanxiong, 11 parts of Atractylodes, 11 parts of Phellodendron, 11 parts of Achyranthes bidentata, 13 parts of Artemisia capillaris, 14 parts of Polygonum cuspidatum, 8 parts of Stephania tetrandra, 14 parts of Poria, and 14 parts of Cynanchum cyrtonema.

Example 9 Oral Chinese medicine composition for treating acute gouty arthritis of the present invention (IX)

10 parts of Notopterygium root, 11 parts of Angelica sinensis, 11 parts of Rhizoma Chuanxiong, 13 parts of Atractylodes, 13 parts of Cortex Phellodendri, 13 parts of Achyranthes bidentata, 17 parts of Artemisia capillaris, 16 parts of Polygonum cuspidatum, 10 parts of Stephania tetrandra, 16 parts of Poria, and 16 parts of Cynanchum cyrtonema.

Example 10 Clinical efficacy experiment

1. Materials and Methods

1.1 Design Method

This study adopted a randomized, double-blind, controlled research method. The study followed the CONSORT statement (2010 version) and the Standard Reporting Guidelines for Randomized Controlled Trials of Traditional Chinese Medicine Compounds (2017 version) ^[1] . The treatment group and the control group were allocated in a 1:1 ratio.

1.2 Subjects

1.2.1 Place and time

The patients in this study were all patients who received treatment in the gout department of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated to Shanghai University of Traditional Chinese Medicine from April 28, 2021 to July 27, 2022. Relevant diagnosis, treatment, intervention, and data collection activities were completed in the outpatient department of Yueyang Hospital. All subjects met the following criteria and signed the informed consent form.

1.2.2 Western medicine diagnostic criteria

According to the diagnostic criteria established by the American College of Rheumatology in 1977:

(1) Specific urate crystals are found in the joint fluid;

(2) Gout nodules were confirmed to contain sodium urate crystals by chemical methods or polarized light microscopy;

(3) Those with 6 of the following 12 clinical manifestations, laboratory tests, and X-ray signs:

① More than one acute arthritis attack;

②Inflammation symptoms reach their peak within 1 day;

③Monoarthritis attack;

④The skin of the affected joint is dark red;

⑤Pain or swelling in the first metatarsophalangeal joint;

⑥Unilateral attack involving the first metatarsophalangeal joint;

⑦ Unilateral attack involving the tarsal joint;

⑧There are suspected tophi;

⑨Hyperuricemia;

⑩X-ray shows asymmetric swelling of the joints;

X-rays showed subcortical cysts without bone erosion;

Microbiological cultures of joint fluid were negative during inflammatory episodes of the joints.

The diagnosis can be established if one or more of the above three items are met.

1.2.3 TCM disease diagnosis criteria

Refer to the diagnosis and classification of gout in the "Standards for Diagnosis and Efficacy of TCM Diseases and Syndromes" and "Guidelines for Clinical Research of New Chinese Medicines (Volume 3)":

(1) Sudden redness, swelling and pain in a single toe or finger joint, which gradually becomes more severe as if bitten by a tiger, and is mild during the day but worse at night. It recurs repeatedly and may be accompanied by fever, headache and other symptoms.

(2) It is more common in middle-aged and elderly men, who may have a family history of gout. It is often caused by fatigue, overeating, eating high-purine foods, drinking, and exogenous colds.

(3) Initially, the disease may affect only one joint, most commonly the first toe joint. Subsequently, the ankle, heel, fingers, and other small joints may become red, swollen, hot, and painful, and even exudate may form in the joint cavity. After repeated attacks, "lumps" (tophus) may appear around the joints, as well as between the auricle, helix, toes, and phalanges.

(4) Laboratory tests show elevated blood uric acid and urine uric acid. The total white blood cell count may increase during an attack.

(5) If necessary, renal B-ultrasound scan, urine routine, renal function tests, etc. should be performed to understand the status of post-gout renal lesions. X-ray examinations show irregular circular perforated defects in the bone adjacent to the joint at the edge of the cartilage, which is helpful for diagnosis.

Damp-heat accumulation syndrome:

Main symptoms: Sudden redness, swelling, heat and pain in the small joints of the lower limbs, resistance to pressure, local burning sensation when touched, relief when cooled, and limited joint movement;

Secondary symptoms: fever, thirst, heaviness of limbs, loose and uncomfortable stools, and yellow urine;

Tongue and pulse: red tongue, yellow and greasy coating, slippery and rapid pulse.

If one of the above main symptoms and two of the secondary symptoms are present at the same time, combined with tongue and pulse, this syndrome can be diagnosed.

1.2.4 Inclusion criteria

(1) Those who meet the diagnostic criteria of Western medicine and TCM diseases and syndromes;

(2) Aged ≥18 and ≤70 years old, regardless of gender;

(3) The acute attack occurred within 48 hours, and the baseline assessment showed a total score of pain, tenderness, and swelling ≥ 5; (4) No nonsteroidal anti-inflammatory drugs or drugs that affect uric acid metabolism were taken within one week before this observation;

(5) Understand and agree to participate in this study and sign the informed consent form.

Only those who meet all the above conditions can be included.

1.2.5 Exclusion criteria

(1) Acute polyarticular gout, involving more than 4 joints;

(2) combined with other arthritis diseases such as osteoarthritis and rheumatoid arthritis;

(3) Patients with serious primary diseases such as cardiovascular, cerebrovascular, liver, kidney and hematopoietic system diseases, and mental illness;

(4) Patients with active gastrointestinal diseases and patients with peptic ulcers within 30 days before this study;

(5) Patients whose condition is critical and it is difficult to make an accurate evaluation of the effectiveness and safety of this clinical observation;

(6) Patients with advanced arthritis, severe deformity, stiffness, and loss of ability to work;

(7) Those who are known to be allergic to the drugs used in this study.

If any of the above conditions are met, the applicant will be excluded.

1.2.6 Elimination criteria

(1) Those who have severe adverse reactions to the drugs used in this study;

(2) Failure to take medication as prescribed, discontinuation of medication, or incomplete data that may affect the judgment of efficacy or safety;

(3) A serious illness occurs during treatment and the patient cannot continue the treatment.

If any of the above conditions are met, the applicant will be eliminated.

1.2.7 Shedding Standard

Investigator's decision to withdraw:

(1) Allergic reactions or serious adverse events occur, and the trial should be stopped according to the doctor's judgment;

(2) During the study, the laboratory test results of two consecutive tests were compared and affected the judgment of efficacy and safety;

(3) Patients with poor compliance (compliance with trial medication <80%) or who automatically changed medications midway or added Chinese and Western medicines that were prohibited by the prescription;

Patient voluntarily withdraws:

(1) For whatever reason, the patient is unwilling or unable to continue the clinical study and requests the attending physician to withdraw from the trial, thereby terminating the study;

(2) Patients who did not explicitly request to withdraw from the study but no longer received medication or testing and were lost to follow-up.

For cases that drop out midway or are lost to follow-up, researchers should take active measures to complete the last test as much as possible in preparation for analysis of its efficacy and safety. For all dropout cases, the trial conclusion and the reason for the dropout should be filled in the case report form.

1.2.8 Termination criteria

(1) If a case is found to meet the exclusion criteria after entering the trial (if laboratory tests do not support it), the trial can be terminated;

(2) Those who withdrew from the trial due to adverse reactions (not included in the final efficacy but included in the adverse reaction evaluation);

(3) Violation of the trial protocol.

1.2.9 Informed Consent

Before the subjects are included in the study, researchers should explain in detail the purpose of the study, the items that require their cooperation, the trial process, and the risks and benefits that this study may bring to them. After obtaining the understanding and cooperation of the subjects, they will sign the informed consent form and inform the subjects that they have the right to choose to terminate the study at any time during the experiment without affecting their subsequent treatment. The research plan has been approved by the Ethics Committee of this hospital, with the ethics approval number: 2020-123.

1.3 Intervention measures

1.3.1 Trial Grouping

The subjects were randomly divided into the traditional Chinese medicine treatment group and the western medicine treatment group in a 1:1 ratio.

① Traditional Chinese medicine treatment group

Medication: Huyin analgesic prescription + etoricoxib placebo

Dosage and Usage: For Huyin Pain Relief Formula, place each bag of medicine in the same container, pour in about 50 ml of warm water, stir until the granules are basically dissolved, then add appropriate amount of warm water to dilute, and take warm in 2 doses. For etoricoxib placebo, take orally, 1 tablet per day. Take both drugs for 5 consecutive days.

Huyin pain relief prescription: It is composed of 9g of Qianghuo, 9g of Duhuo, 12g of Angelica, 10g of Chuanxiong, 12g of Atractylodes, 12g of Phellodendron, 12g of Achyranthes, 15g of Artemisia Capillaris, 15g of Polygonum Cuspidati, 9g of Stephania Tetrandrae, 15g of Poria, and 15g of Cynanchum indica. It has the effects of clearing away heat, promoting dampness and unblocking meridians. It is mainly used for the treatment of "damp-heat accumulation syndrome" in acute gouty arthritis. It adopts single-ingredient formula granules, produced by China Resources Sanjiu Pharmaceutical Co., Ltd., and adopts a unified packaging and labeling format. The content of the outer packaging label includes the drug number, specification, batch number, expiration date, storage conditions, manufacturer, and the words "free medication for clinical research".

Etoricoxib placebo: produced and provided by Nanjing Hengzheng Pharmaceutical Research Institute Co., Ltd. It uses a unified packaging and labeling format. The content of the outer packaging label includes the drug number, specification, batch number, expiration date, storage conditions, production department and the words "free medication for clinical research".

②Western medicine treatment group

Medication: Etoricoxib + Huyin analgesic prescription placebo

Dosage and Usage: For the Huyin Pain Relief Formula placebo, place each bag of medicine in the daily dose into the same container, pour in about 50 ml of warm water, stir until the granules are basically dissolved, then add appropriate amount of warm water to dilute, and take warm in 2 doses. Etoricoxib, oral, 1 tablet per day. Take both drugs for 5 consecutive days.

Huyin Pain Relief Prescription Placebo: Produced by China Resources Sanjiu Pharmaceutical Co., Ltd., with a unified packaging and labeling format. The outer packaging label includes the drug number, specification, batch number, expiration date, storage conditions, manufacturer, and the words "free medication for clinical research".

Etoricoxib: Produced by Merck, 60 mg, 5 tablets/box, production batch number: S041084. Used a unified packaging and labeling format by Nanjing Hengzheng Pharmaceutical Research Institute Co., Ltd. The outer packaging label includes the drug number, specification, batch number, expiration date, storage conditions, production department and the words "free medication for clinical research".

1.3.2 Basic treatment (health guidance)

Both groups of patients received basic treatment at the same time:

(1) Diet: No drinking, low-purine, low-fat diet, sufficient drinking water (≥2000 ml/day), etc.;

(2) Avoid triggering factors such as cold joints, trauma, and excessive fatigue.

1.3.3 Combined medication

(1) Combination treatments permitted: Combination medications for other diseases (such as hypertension, diabetes, etc.) and other drugs that have not been proven to be effective in the treatment of acute gouty arthritis.

(2) Concomitant treatments prohibited: diuretics, salicylates, glucocorticoids, and other analgesics including aspirin.

1.3.4 Study treatment course

One course of treatment was 5 days, and follow-up was conducted 1 week after treatment.

1.3.5 Blind Design

A double-blind design was used to exclude the influence of subjective bias of researchers and subjects. The random coding table was established by a statistician, who blinded the drug packaging according to the above blind bottom. Each successfully enrolled subject was assigned a medicine box, which contained all the medications during the treatment period. The number was written on the label of the medicine box, and the same number was written on the labels of all the drugs in the box. The experimental index detection was the responsibility of a dedicated person, and the statistical analysis of the results was performed using professional data software. The relevant personnel were unaware of the experimental grouping and treatment.

Unblinding regulations: This study stipulates that the blinding will be unblinded once. After the blind verification data is locked, the staff who keeps the blind bottom will hand over the blind bottom to the statistician for statistical analysis.

Emergency unblinding: When a serious adverse event occurs, the patient needs emergency treatment, etc., and it is necessary to know the drug used by the patient, the trial leader decides to urgently unblind and open the corresponding emergency letter. Once the emergency letter with the corresponding number is opened, the case will be treated as a dropout case.

The subject flow chart is shown in Figure 1 .

The primary outcome of this study was the patient's assessment of pain in the study joint on days 2 to 5. Pain was assessed in the most affected joint using the Visual Analogue Scale/Score (VAS). The total score was 100 points: 0 to 30 for mild pain, no disturbance of sleep; 40 to 60 for moderate pain, mild disturbance of sleep; 70 to 100 for severe pain, inability to sleep or awakening with pain.

Secondary outcomes included assessment of joint tenderness and swelling, and reduction of inflammatory factors. Joint tenderness score: Tenderness of the most severely affected joint was assessed using a 0-3 Likert scale. It was divided into four levels: 0 = no pain; 1 = patient complained of pain; 2 = patient complained of pain and flinched; 3 = patient complained of pain, flinched and withdrew. It was assessed at baseline, days 1-5, and during the follow-up period. Joint swelling score: Swelling of the most severely affected joint was assessed using a 0-3 Likert scale. It was divided into four levels: 0 = none; 1 = palpable; 2 = visible; 3 = swelling beyond the edge of the joint. It was assessed at baseline, days 1-5, and during the follow-up period.

Experimental Results

1) Huyin analgesic prescription can relieve joint pain caused by acute gouty arthritis

The results are shown in Figure 2. The VAS pain scores were analyzed using a mixed effects linear model for repeated measurement data, taking into account the time effect and inter-group differences. During the treatment period, the VAS scores of joint pain in both groups decreased significantly over time, and the intra-group comparison between the scores on the 5th day and the baseline period showed a statistically significant difference (time effect P < 0.05). There was no statistically significant difference in the VAS scores of joint pain between the two groups at each time point (P > 0.05).

2) Huyin analgesic prescription can improve joint tenderness and swelling caused by acute gouty arthritis

The results are shown in Figure 3. Repeated measurement data mixed effects linear model analysis was used to analyze the joint tenderness score and joint swelling score, considering the time effect and inter-group differences. The joint tenderness scores of the two groups of patients decreased significantly with the passage of time points, and the difference between the scores on the 5th day and the baseline period was statistically significant (time effect P < 0.05). There was no statistically significant difference in the joint tenderness scores between the two groups of patients at each time point (P > 0.05). The joint swelling scores of the two groups of patients decreased significantly with the passage of time points, and the difference between the scores on the 5th day and the baseline period was statistically significant (time effect P < 0.05). There was no statistically significant difference in the joint swelling scores between the two groups of patients at each time point (P > 0.05).

In order to explore the safety of the Huyin analgesic prescription of the present invention in treating acute gouty arthritis, safety indicators were evaluated for both groups of patients. Safety indicators include vital signs, blood routine, urine routine, liver and kidney function, adverse events (including dizziness, drowsiness, nausea, vomiting, abdominal pain, dyspepsia, rash, dry mouth, and any other symptoms reported by patients), and serious adverse events (referring to adverse events requiring hospitalization). The baseline period and the fifth day of treatment were evaluated once each.

Experimental Results

The results are shown in Figure 4. There were no statistically significant differences in the vital signs (temperature, respiration, heart rate, blood pressure) between the groups and the changes in vital signs between the two groups at baseline, 5 days after treatment, and during the follow-up period (P>0.05).

The results are shown in Figure 5. After 5 days of treatment, the serum white blood cell counts and neutrophil counts of the two groups of patients decreased significantly, and the differences between the two groups were statistically significant (P < 0.05). After 5 days of treatment, the differences in the white blood cell counts and neutrophil counts before and after treatment between the two groups were not statistically significant (P > 0.05). Before and after treatment, there were no statistically significant differences in alanine aminotransferase, aspartate aminotransferase, urea nitrogen, serum creatinine and serum uric acid between the treatment group and the control group (P > 0.05).

The results are shown in Figure 6. A total of 16 cases of non-serious adverse events occurred in the two groups, 4 in the treatment group and 12 in the control group. The incidence rate in the treatment group was 4.44%, which was lower than 13.33% in the control group. The difference between the two groups was statistically significant (P < 0.05). The treatment group had significantly better tolerance to the drug than the control group. The adverse reactions in the treatment group were mainly gastrointestinal symptoms, while the symptoms in the control group included chest tightness, increased blood pressure, lower limb edema, liver function damage and gastrointestinal symptoms, which were consistent with foreign literature. The adverse reactions in both groups were mild. One case in the control group asked to withdraw from the trial due to stomach pain. All patients recovered from adverse reactions and no serious adverse events occurred.

In order to explore the mechanism of action of the Huyin analgesic prescription of the present invention in treating acute gouty arthritis and provide a theoretical basis for oral administration of the Huyin analgesic prescription, the following serum inflammatory factors were detected and analyzed:

1. Detection of serum inflammatory factors

(1) Fasting venous blood was collected from subjects at baseline (day 0) and in the morning of day 5, and serum was obtained by centrifugation. Serological indicators mainly included CRP, IL-1β, IL-6, IL-8, IL-17, SFRP5, Wnt5a, and β-catenin.

2. Data Statistical Analysis

SPSS24.0 and SAS9.4 software were used for statistical analysis. Repeated measurement data analysis of variance was used for data from multiple measurements of the same observation index of the same subject at different time points. Hypothesis tests uniformly used two-sided tests, and the test statistics and their corresponding P values were given. P<0.05 was considered statistically significant.

3. Experimental results

(1) Changes in the expression of inflammatory factors after treatment with Huyin Pain Relief Decoction

Elisa test analysis was used to obtain the expression levels of inflammatory factors in patients before and after treatment with Huyin Pain Relief Recipe. SPSS24.0 and SAS9.4 software were used for statistical analysis, and the results are shown in Figure 7. The statistical results showed that after 5 days of treatment, the serum CRP, IL-1β, IL-6, IL-8, IL-17, SFRP5, Wnt5a and β-catenin of the two groups of patients decreased significantly, and the intra-group differences were statistically significant (P < 0.05). After 5 days of treatment, the difference between the two groups of patients in CRP, IL-1β, IL-8, IL-17, SFRP5, Wnt5a and β-catenin before and after treatment was compared, and there was no statistically significant difference between the two groups (P > 0.05).

(2) Analysis of the efficacy of Huyin analgesic prescription

The results showed that both Huyin Pain Relief Recipe and etoricoxib could quickly relieve the joint symptoms of patients with acute gouty arthritis after intervention. The VAS scores of joint pain, tenderness of affected joints, and swelling scores all decreased significantly over the treatment time, and there was no difference between the two groups. Gout is an inflammatory joint disease caused by the deposition of sodium urate crystals. The key link in the initiation of inflammation depends on the activation of NLRP3 inflammasomes. Subsequently, activated caspase-1 cleaves the precursor IL-1β and secretes mature IL-1β. IL-1β is a key cytokine in the inflammatory process of acute gouty arthritis mediated by sodium urate. At the same time, the activation of the IL-1β signaling pathway can promote the production of proinflammatory mediators such as IL-6 and IL-8, and its expression is positively correlated with the degree of inflammation. Many interleukins, such as proinflammatory factors IL-1β, IL-6, IL-8, IL-17, and anti-inflammatory factors IL-10 and IL-37, play an important role in the inflammatory process of gout. Therefore, the study further detected the expression levels of CRP, IL-1β, IL-6, IL-8, and IL-17, which are closely related to the inflammatory process of acute gouty arthritis. The results showed that the inflammatory indicators of the two groups of patients decreased significantly after treatment, indicating that both drug interventions can effectively reduce the patients' joint inflammation response.

SFRP5 can participate in regulating the body's cell growth, lipid metabolism, inflammation, immunity and other processes by inhibiting the Wnt/β-catenin classical pathway and non-classical pathway signal transduction. This study found that both Huyin Pain Relief and Etoricoxib can reduce the expression of SFRP5, Wnt5a, and β-catenin in gout patients. Based on this, we speculate that SFRP5 plays a certain role in the treatment of AGA with Huyin Pain Relief, and whether this regulatory pathway is related to the downstream Wnt/β-catenin signaling pathway deserves further discussion.

The above is only a preferred embodiment of the present invention. It should be pointed out that ordinary technicians in this technical field can make several improvements and supplements without departing from the method of the present invention. These improvements and supplements should also be regarded as the scope of protection of the present invention.

Claims (4)

1. An oral Chinese medicine composition for treating acute gouty arthritis, characterized in that the Chinese medicine composition is made of the following raw materials in parts by weight: 7-11 parts of Notopterygium, 7-11 parts of Pubescent Angelica, 10-14 parts of Angelica Sinensis, 8-12 parts of Ligusticum chuanxiong, 10-14 parts of Atractylodes, 10-14 parts of Phellodendron, 10-14 parts of Achyranthes Bidentatae, 13-17 parts of Artemisia Capillaris, 13-17 parts of Polygonum Cuspidatum, 7-11 parts of Stephania Tetrandrae, 13-17 parts of Poria, and 13-17 parts of Cynanchum wilfordii. 2. The Chinese medicine composition according to claim 1 is characterized in that the Chinese medicine composition is made of the following raw materials in parts by weight: 8-10 parts of Notopterygium, 8-10 parts of Pubescent Angelica, 11-13 parts of Angelica Sinensis, 9-11 parts of Ligusticum chuanxiong, 11-13 parts of Atractylodes, 11-13 parts of Phellodendron, 11-13 parts of Achyranthes Bidentatae, 14-16 parts of Artemisia Capillaris, 14-16 parts of Polygonum Cuspidatum, 8-10 parts of Stephania Tetrandrae, 14-16 parts of Poria, and 14-16 parts of Cynanchum wilfordii. 3. The Chinese medicine composition according to claim 1 is characterized in that the Chinese medicine composition is made of the following raw materials in parts by weight: 9 parts of Notopterygium wilfordii, 9 parts of Angelica sinensis, 12 parts of Ligusticum chuanxiong, 12 parts of Atractylodes macrocephala, 12 parts of Phellodendron chinense, 12 parts of Achyranthes bidentata, 15 parts of Artemisia capillaris, 15 parts of Polygonum cuspidatum, 9 parts of Stephania tetrandra, 15 parts of Poria cocos, and 15 parts of Cynanchum wilfordii. 4. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a drug for treating acute gouty arthritis.