WO2021042276A1

WO2021042276A1 - Combination drug for treating osteoarthritis

Info

Publication number: WO2021042276A1
Application number: PCT/CN2019/104251
Authority: WO
Inventors: 张贵民; 李元森; 程国良
Original assignee: 鲁南制药集团股份有限公司
Priority date: 2019-09-03
Filing date: 2019-09-03
Publication date: 2021-03-11
Also published as: CN114340650A

Abstract

A combination drug for treating osteoarthritis, relating to the field of medicine. The combination drug comprises celecoxib, and one of vein-dredging pills or vein-dredging granules. The vein-dredging pills or vein-dredging granules are prepared by radix astragali, flos lonicerae, cortex phellodendri, rhizoma atractylodis, semen coicis, radix scrophulariae, radix angelicae sinensis, radix paeoniae alba, radix glycyrrhizae, hirudo, scolopendra, scorpio, and other medicinal materials. Animal and clinical experiments show that the combination drug has a good therapeutic effect on joint diseases, particularly osteoarthritis, can obviously reduce inflammatory factors, reduce inflammatory response, obviously improve clinical symptoms, and improve the quality of life of patients, and is suitable for further promotion and use.

Description

A combined medicine for treating osteoarthritis

Technical field

The invention belongs to the field of traditional Chinese medicine, and specifically relates to a combined medicine for treating osteoarthritis.

Background technique

Osteoarthritis (OA), also known as proliferative osteoarthritis, osteoproliferation, degenerative arthropathy, senile arthritis, hypertrophic arthritis, is due to the degeneration of the cartilage, intervertebral discs, ligaments and other soft tissues that make up the joints. Degeneration, formation of bone spurs on the edges of the joints, hypertrophy of the synovial membrane and other changes, and bone destruction, causing secondary bone hyperplasia, leading to joint deformation, and when subjected to abnormal loads, a disease that causes symptoms such as joint pain and restricted mobility , There are two kinds of primary and secondary. Bone hyperplasia is a frequently-occurring and common disease, and it is a disease that causes joint pain.

The main purpose of treating osteoarthritis is to relieve pain, improve function, and improve the quality of life. Treatment options include various formulations of non-steroidal anti-inflammatory drugs (NSAIDs) (emulsions, ointments, patches, etc.), general pain medications, supplementation of glucosamine chondroitin, local injection of sodium hyaluronate to lubricate joint pain, acupuncture and severe cases Perform joint replacement surgery, etc.

With the continuous development of traditional Chinese medicine and the in-depth study of osteoarthritis, compared with western medicine, traditional Chinese medicine has a definite curative effect in the treatment of osteoarthritis with less toxic and side effects. Various treatment methods and other advantages. Modern pharmacology also shows that the treatment of osteoarthritis with traditional Chinese medicine can effectively reduce inflammation, improve microcirculation in joints, promote cartilage repair, significantly improve clinical symptoms, improve quality of life, and reduce economic burden.

Chinese patent CN1201787C discloses a Chinese medicinal composition for the treatment of thrombophlebitis, which comprises astragalus, honeysuckle, cork, atractylodes, coix seed, scrophulariaceae, angelica, white peony root, licorice, leeches, centipede, whole scorpion 12 Taste medicinal materials, the Chinese medicinal composition has the functions of clearing away heat and detoxification, removing blood stasis and dredging collaterals, diminishing swelling and swelling. It has a good clinical effect in the treatment of thrombophlebitis, and at the same time, it also has certain prevention and treatment of thromboangiitis obliterans Therapeutic effect. The product based on this patent has been put on the market. The product is called "Mailuo Shutong Granules/Pills". It is mainly used clinically for thrombotic superficial phlebitis caused by damp heat and stasis blocking the veins, and lower limbs caused by deep vein thrombosis in the non-acute stage. Swelling, pain, dark red complexion, or accompanied by cords.

technical problem

Relying on CN1201787C patented technology, the "Mailuoshutong" series of products have been produced. On this basis, the present invention is a further new use development and research on the patented traditional Chinese medicine composition, that is, the "Mailuoshutong" product.

Technical solutions

One of the objectives of the present invention is to provide the use of a combined medicine of Celecoxib and Mailuoshutong Pills or Mailuoshutong granules in the preparation of medicines for treating joint diseases.

The above-mentioned joint diseases are mainly manifested as one or more of joint pain and tenderness, joint stiffness, joint swelling, limited joint movement, and joint deformities.

The above-mentioned joint diseases mainly refer to osteoarthritis.

The aforementioned osteoarthritis is primary osteoarthritis or secondary osteoarthritis.

Preferably, the secondary osteoarthritis mainly refers to one or more secondary to including but not limited to meniscus injury, intra-articular or peri-articular fracture, joint ligament injury, femoral head necrosis, congenital deformity or joint infection Osteoarthritis caused by this disease.

Preferably, the osteoarthritis is mainly manifested as one or more of articular cartilage degeneration and injury, articular cartilage stripping, reactive hyperplasia of joint edges and subchondral bone, bone hyperplasia, meniscus injury, and synovitis .

Preferably, the onset of osteoarthritis includes but is not limited to one or more of the hands, knees, hips, feet, and spine.

The weight ratio of celecoxib to Mailuoshutong pills in the combined drug is 1:180; the weight ratio of celecoxib to Mailuoshutong granules in the combined drug is 1:300.

The second object of the present invention is to provide the composition of the Mailuoshutong Pills or Mailuoshutong granules, that is, the Mailuoshutong Pills or Mailuoshutong granules are prepared from the following components:

300-1000 parts by weight of Astragalus, 300-1000 parts by weight of Honeysuckle, 100-500 parts by weight of Phellodendron

100-500 parts by weight of Coix seed 300-1000 parts by weight of Scrophulariaceae 300-1000 parts by weight

Angelica 100-500 parts by weight, White peony 100-500 parts by weight, licorice 50-150 parts by weight

180-500 parts by weight of leech, 10-40 parts by weight of centipede, 50-150 parts by weight of scorpion;

Preferably, the Mailuoshutong pill or Mailuoshutong granule is prepared from the following components:

Astragalus 500-850 parts by weight Honeysuckle 500-850 parts by weight Phellodendron 250-450 parts by weight

Cangzhu 250-450 parts by weight Coix seed 500-850 parts by weight Scrophulariaceae 500-850 parts by weight

Angelica 250-450 parts by weight, White peony 250-450 parts by weight, licorice 50-150 parts by weight

250-450 parts by weight of leech, 10-40 parts by weight of centipede, 50-150 parts by weight of scorpion.

Preferably, the Mailuoshutong pill is prepared from the following components:

Astragalus 833 parts by weight Honeysuckle 833 parts by weight Phellodendron 417 parts by weight

Atractylodes 417 parts by weight Coix seed 833 parts by weight Scrophulariaceae 833 parts by weight

417 parts by weight of Angelica 417 parts by weight of white peony 417 parts by weight of licorice 138 parts by weight

417 parts by weight of leech, 33 parts by weight of centipede, 138 parts by weight of scorpion;

Preferably, the Mailuoshutong granules are prepared from the following components:

Astragalus 500 parts by weight Honeysuckle 500 parts by weight Phellodendron 250 parts by weight

250 parts by weight of coix seed 500 parts by weight of Scrophulariaceae 500 parts by weight

Angelica 250 parts by weight, white peony 250 parts by weight, licorice 83 parts by weight

250 parts by weight of leech, 20 parts by weight of centipede, 83 parts by weight of scorpion.

The third object of the present invention is to provide a method for preparing the above-mentioned Mailuoshutong granules or Mailuoshutong pills, and the specific operations are as follows:

1) Take prescription amounts of honeysuckle, atractylodes, Scrophulariaceae, Angelica, Radix Paeoniae Alba, soak in water and distill to extract the volatile oil for use; the distilled water solution and medicine residue are for use;

2) Take the prescription amount of astragalus, phellodendron, coix seed, licorice, 1/2 prescription amount of leech, centipede, whole scorpion and mix the distilled medicinal residue obtained in step 1), add water and decoct twice, combine the decoction, spare;

3) Take the decoction obtained in step 2) and mix with the distilled aqueous solution in step 1), filter, and concentrate the filtrate to a clear paste with a relative density of 1.10-1.20 (80°C). Add ethanol to make the alcohol content reach 60%. Place, filter, recover ethanol under reduced pressure and concentrate to a clear paste with a relative density of 1.10 to 1.18 (80°C) or a thick paste with a relative density of 1.30 to 1.35 (80°C), dry, and pulverize into fine powder to obtain extract powder ,spare;

4) Crush the remaining 1/2 prescription amount of leech, centipede, and scorpion into powder;

5) Add the volatile oil obtained in step 1) to cyclodextrin to make an inclusion compound, mix it with the extract powder obtained in step 3), the powder and celecoxib obtained in step 4), and add it directly or pharmaceutically acceptable through conventional procedures. The excipients are made into clinically acceptable dosage forms;

Or mix the extract powder obtained in step 3), the medicinal powder obtained in step 4), and celecoxib, granulate, spray into the volatile oil obtained in step 1) and mix well, and add pharmaceutically acceptable excipients directly or by conventional procedures Made into a clinically acceptable dosage form.

Beneficial effect

The beneficial effects of the present invention are mainly reflected in:

The combined medicine of the present invention has obvious therapeutic effect. Animal experiments show that the combined drug of the present invention can effectively reduce the content of IL-1β, TNF-α, MMP-3 and other inflammatory factors in the serum of rats with knee osteoarthritis, reduce inflammation, and the effect is significantly better than that of monotherapy. In addition, the dosage of the drug is smaller than that of the single prescription, which improves the safety of the drug; clinical trials show that the total effectiveness of the combined drug of the present invention is 92.9%, which is significantly better than 88.1% of the Mailuoshutong pill group and 83.3% of the celecoxib group. After treatment, the levels of inflammatory factors IL-1β, TNF-α, and MMP-3 decreased significantly, which relieved the pain of the patient and improved the quality of life of the patient.

Embodiments of the present invention

Example 1 Preparation of Mailuoshutong Pills

Party:

Preparation:

(1) Take leeches, centipedes, and scorpions (1/2 prescription amount) in the recipe, crush them into fine powder, and set aside;

(2) Take honeysuckle, atractylodes, Scrophulariaceae, Angelica, Radix Paeoniae Alba in the prescription amount, soak in water and distill to extract the volatile oil. The volatile oil is added with cyclodextrin to make an inclusion compound for later use; the distilled aqueous solution and medicine residue are for later use ；

(3) Take the prescription amount of astragalus, phellodendron, coix seed, licorice, the remaining prescription amount of leech, centipede, scorpion, and the distilled medicinal residue and mix, add water and decoct twice, and combine the decoction; decoction; The liquid is mixed with the distilled aqueous solution, filtered, and the filtrate is concentrated to a clear paste with a relative density of 1.10 to 1.20 (80°C), and ethanol is added to make the alcohol content reach 60%. Let stand, filter, and recover the ethanol under reduced pressure and concentrate to a relative density. The cleansing cream with a density of 1.10-1.18 (80℃) is spray-dried into a fine powder, and the fine powder of the extract is obtained for use;

(4) Take the fine powder obtained in step (1), the inclusion compound obtained in step (2), and the fine powder extract obtained in step (3) and mix, add starch, mix and granulate, dry, make 1000g, and fill it into capsules. Got.

Example 2 Preparation of Mailuoshutong Granules

Party:

Preparation:

(2) Take honeysuckle, atractylodes, Scrophulariaceae, Angelica, Radix Paeoniae Rubra in the prescription amount, soak in water and distill to extract the volatile oil, the volatile oil is used as a reserve; the distilled aqueous solution and medicine residue are used as a reserve;

(3) Take the prescription amount of astragalus, phellodendron, coix seed, licorice, the remaining prescription amount of leech, centipede, scorpion, and the distilled medicinal residue and mix, add water and decoct twice, and combine the decoction; decoction; The liquid is mixed with the distilled aqueous solution, filtered, and the filtrate is concentrated to a clear paste with a relative density of 1.15 to 1.20 (80°C), and ethanol is added to make the alcohol content reach 60%. Let stand, filter, and recover the ethanol under reduced pressure and concentrate to a relative density. A thick paste with a density of 1.30 to 1.35 (80°C), vacuum-dried, pulverized into fine powder, and obtained fine powder of the extract for later use;

(4) Take the fine powder obtained in step (1) and mix the fine powder of the extract obtained in step (3), add the formula amount of β-cyclodextrin, aspartame, sodium carboxymethyl starch, and dextrin and mix well to prepare Granulate, dry, spray into the volatile oil obtained in step (2), mix well to make 1000g, and get it.

To

Example 3 Preparation of Mailuoshutong Pills

Party:

Preparation method: the same as in Example 1.

Example 4 Preparation of Mailuoshutong Pills

Party:

Preparation method: the same as in Example 1.

Example 5 Preparation of Mailuoshutong Granules

Party:

Preparation method: the same as in Example 2.

Example 6 Preparation of Mailuoshutong Granules

Party:

Preparation method: the same as in Example 2.

Industrial applicability

In order to verify the effect of the combined drugs of the present invention in the treatment of joint diseases, the inventors conducted relevant animal and clinical trials. It is worth noting that the following animal and clinical trials only take the knee joint in osteoarthritis as an example. Pharmacodynamics description, the inventor has also conducted research on other joint diseases, and the research results show that the combined drug of the present invention can achieve the same treatment as knee osteoarthritis for other types of osteoarthritis and joint diseases. Or a similar effect. The following animal and clinical trials cannot limit the present invention.

1. Therapeutic effect of the traditional Chinese medicine composition of the present invention on osteoarthritis rats

1. Laboratory Animals

Male SD rats, weighing 180-220g, experimental animal license number: SCXK (Lu) 2014 0007, provided by Jinan Pengyue Experimental Animal Breeding Co., Ltd., were bred adaptively for one week before the experiment.

2. Experimental drugs

Celecoxib capsules, Mailuoshutong pills obtained in Example 1, and Mailuoshutong granules obtained in Example 2.

3 Grouping and modeling methods

3.1 Group

Seventy rats were divided into blank group, model group, celecoxib group, Mailuoshutong pill group, Mailuoshutong granule group, combined medication 1 group, combined medication 2 groups, each with 10 rats.

3.2 Modeling method

Each group of rats used the modified Hulth modeling method to establish a rat knee osteoarthritis model. The specific operations are as follows:

One day before the operation, the left lower limb of the rat was depilated. Fasting for 12 hours before surgery and water for 4 hours. After the rat is anesthetized, lie supine and fixed on the rat board. After routine disinfection of the rat’s left knee, take the inner side of the rat’s left knee joint as the operating point and make a longitudinal incision from the side of the patellar tendon. The range is about 1cm. The cross is cut before the internal test. The ligament, the internal meniscus was removed, and the drawer test was performed. After the test was positive, rinsed with complex iodine and saline alternately twice to clean the bloody fluid in the wound, and then infiltrate the surgical field with gentamicin sulfate injection to prevent Intra-articular infection, then the wound is sutured and bandaged, and the operation is over.

Among them, the blank group was treated with sham operation, only the joint cavity was opened, the ligaments and meniscus were not damaged, and the wound was sutured and bandaged.

After the operation, the injured limbs were not fixed and allowed to move freely. For three consecutive days, each rat was injected with gentamicin intramuscularly, and the wound was disinfected to prevent wound infection.

4. Administration

One week after the operation, the rats in each group were alive. There was no redness, swelling or suppuration in the wound. The wound was basically healed, and the reaction was sensitive, and there was no abnormal excretion. The rats were forced to move once a day for 30 minutes each time for 8 weeks. Give the drug while compulsive activity.

The celecoxib group, the example 1 group, the example 2 group, the combination medicine group 1 and the combination medicine group 2 were given corresponding drugs respectively; the model group and the blank group were given the same amount of normal saline. The intragastric administration was continued for 8 weeks.

The dosage is as follows:

Celecoxib group: 18mg/kg;

Mailuoshutong pill group: 3.24g/kg;

Mailuoshutong granules group: 5.4g/kg;

Combination medication group 1: Celecoxib 9mg/kg + Mailuoshutong pill 1.62g/kg;

Combination medication group 2: Celecoxib 9mg/kg + Mailuoshutong granules 2.7g/kg;

5. Observation indicators

After the last administration, fasting with water for 12 hours. After anesthesia, blood was collected from the abdominal aorta of each group of rats, centrifuged, and the supernatant was taken. The enzyme-linked immunosorbent assay was used to detect IL-1β, TNF-α, and TNF-α in the rat’s blood. MMP-3 content.

6. Experimental results

6.1 General conditions of rats in each group During the experiment, the rats in the blank group were in good mental state, and their autonomous activities, diet and drinking, and defecation were normal; the rats in the model group showed reactions such as decreased autonomous activities, lying and lazy movements, and no diet, drinking, and defecation. Compared with the group, the rats in each administration group gradually improved their mental state, increased their autonomous activities, and gradually increased their diet, drinking, and defecation with the increase of the administration time.

6.2 Changes in serum levels of IL-1β, TNF-α, and MMP-3

Table 1 Changes in the levels of IL-1β, TNF-α and MMP-3 in serum of rats in each group (

)

Note: Compared with the blank group, ^* P＜0.05, ^# P＜0.01; compared with the model group, ^@ P＜0.01; compared with the combination group 1 group, ^& P＜0.01.

It can be seen from Table 1 that compared with the blank group, the serum levels of IL-1β, TNF-α, and MMP-3 in the model group were significantly higher, and the difference was statistically significant (P<0.01); After drug treatment, the levels of IL-1β, TNF-α, and MMP-3 increased, and the difference was statistically significant compared with the model group (P<0.01); compared with combination medication 1, except for combination medication group 2 rats, The levels of IL-1β, TNF-α, and MMP-3 in serum of rats in the other treatment groups were relatively high, and the difference was statistically significant (P<0.01).

The above results show that the combined drug of the present invention can effectively reduce the content of IL-1β, TNF-α, MMP-3 and other inflammatory factors in the serum of rats with knee osteoarthritis, and the effect is significantly better than single medication.

2. Clinical trial study of the Chinese medicine composition of the present invention

1 Materials and methods

1.1 General information

A total of 126 patients with knee osteoarthritis admitted to the orthopedic clinic from June 2016 to August 2018 were selected and randomly divided into celecoxib group, mailuoshutong group and combination group according to different treatment methods, each with 42 People; 19 males and 23 females in the celecoxib group, aged 56-78 years old, with an average age of 66.7±13.5 years, 26 cases of one knee, 16 cases of double knees, according to Kellgren-Lawrence grading standard [6]: Grade I 19 cases, 15 cases of grade Ⅱ, 8 cases of grade Ⅲ; Mailuoshutong group 17 males, 25 females, aged 56-79 years, an average of 67.5±14.2 years, 23 cases of one knee, 19 cases of double knees, according to Kellgren- Lawrence grading standard: 20 cases of grade Ⅰ, 15 cases of grade Ⅱ, 7 cases of grade Ⅲ; combined group: 20 males, 22 females, aged 55-79 years, average 64.8±14.8 years, 25 cases with one knee, 17 cases with double knees According to the Kellgren-Lawrence grading standard: 18 cases of grade I, 16 cases of grade II, and 6 cases of grade III. There was no statistically significant difference in general data such as gender, age, and disease classification between the two groups (P>0.05), and they were comparable.

Inclusion criteria: ①Comply with the diagnostic criteria for knee osteoarthritis in the "Guidelines for the Diagnosis and Treatment of Osteoarthritis (2007 Edition)" of the Orthopedic Branch of the Chinese Medical Association; ②X-rays show narrowing of the joint space, hardening of articular cartilage or cystic degeneration; ③Knee Joint pain for more than one month and friction sound when moving; ④Sign informed consent. Exclusion criteria: ①Combined with rheumatism and rheumatoid arthritis; ②Patients with insufficient liver and kidney function, severe cardiovascular and cerebrovascular diseases, or drug allergies; ③Patients ≥80 years old, with communication disorders, and unconsciousness.

1.2 Treatment methods

The celecoxib group took celecoxib (celecoxib, Pfizer Pharmaceutical Co., Ltd., National Medicine Standard: J20120063), 0.2g per day; the Mailuoshutong pill group took the Mailuoshutong pill (Lunan Houpe Pharmaceutical Co., Ltd., specifications : 12g/bottle, Standard Chinese Medicine: Z19991025), one bottle each time, three times a day; the combined group was treated with Mailuoshutong pills on the basis of oral celecoxib, and the dosage was the same as above. Three groups of patients were treated continuously for 4 weeks.

2 Judgment of curative effect

The changes in the levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and matrix metalloproteinases (MMPs) in the synovial fluid of the three groups of patients before and after treatment were observed. Extract 1.5 mL of synovial fluid from the knees and eyes of the affected limb, inject it into a siliconized test tube, centrifuge at high speed for 10 minutes, take the supernatant, and detect by ELISA. The kit is selected from Wuhan Boster Bioengineering Co., Ltd. The operation is strictly in accordance with the kit instructions get on.

According to the "Guiding Principles for Clinical Research of New Chinese Medicines" and the International Knee Osteoarthritis WOMAC scale score, the clinical efficacy is evaluated [7-8]. The WOMAC scale includes three items: joint pain, stiffness, and functional activity. The score is based on questioning. There are 24 questions in total, each with a score of 0 to 4. The higher the WOMAC score, the more severe the symptoms. Evaluation of clinical efficacy: ①Healed: joint pain and other symptoms disappeared, joint movement was normal, WOMAC score reduced ≥ 95%, X-ray examination showed normal; significant effect: joint pain and other symptoms were significantly relieved, joint movement was not restricted, 70%≤WOMAC score Decrease <95%, X-ray examination shows obvious improvement; Effective: Joint pain and other symptoms are relieved, joint movement is slightly restricted, 30%≤WOMAC score reduction <70%, X-ray examination shows improvement; Ineffective: Joint pain and other symptoms And no significant improvement in joint activities, WOMAC The score decreased by <30%, and the X-ray examination did not change. Total effective rate = recovery rate + apparent rate + effective rate.

The international DOA scoring standard—Leguesne Index 4 is used for scoring. The scoring content includes knee joint rest pain, exercise pain, tenderness, joint mobility, morning stiffness and walking ability. The higher the score, the more severe the symptoms [9].

3 Statistical methods

Use software SPSS19.0 to perform statistical analysis on all experimental data. All measurement data are expressed as variance, using t test, counting data using X2 test, and all comparative data P<0.05 are statistically significant.

4 results

4.1 Comparison of inflammatory factor levels

The results of the levels of inflammatory factors in the three groups of patients before and after treatment are shown in Table 2. It can be seen from Table 2 that there was no significant difference in the levels of IL-1β, TNF-α, and MMP-3 in the three groups before treatment (P>0.05); after treatment, the levels of IL-1β, TNF-α and MMP-3 in the three groups were more significant. The levels of IL-1β, TNF-α, and MMP-3 in the combined group decreased significantly before treatment. The levels of IL-1β, TNF-α, and MMP-3 were lower than those in the celecoxib group and the Mailuoshutong group. The difference between the elecoxib group and the Mailuoshutong group was statistically significant (P＜0.05), and the difference in the levels of the factors between the celecoxib group and the Mailuoshutong group after treatment was also statistically significant (P＜0.05) ; The differences in the levels of each factor before and after treatment in the three groups were statistically significant (P<0.05).

Table 2 Comparison of changes in the levels of inflammatory factors in the three groups (x±`s, mg/ml)

4.2 Comparison of clinical efficacy

The results of the clinical efficacy evaluation of the three groups of patients are shown in Table 3. It can be seen from Table 3 that 11 cases (26.2%) in the celecoxib group were cured, which was similar to the Mailuoshutong group (28.6%) and lower than the combination group (35.7%); at the same time, the total effective rate in the celecoxib group was 83.3% The total effective rate of the Mailuoshutong group was 88.1%, while the total effective rate of the combined group reached 92.9%, which was higher than that of the single-drug group. In addition, the inefficiency of the combined group was only 7.1%, while the single-drug group was higher than 10%. The efficiency was higher than that of the combined group, and the difference between the three groups was not statistically significant (P>0.05).

Table 3 Comparison of clinical efficacy among the three groups of patients (n,%)

4.3 Comparison of DOA scores of clinical signs

The DOA score results of the clinical signs of the three groups of patients before and after treatment are shown in Table 4. It can be seen from Table 4 that there was no statistically significant difference in the clinical sign scores of the three groups before treatment (P>0.05); the clinical sign scores after treatment were significantly lower than those before treatment, and the sign scores of the combined group were significantly lower than Mailuoshu after treatment. The score difference between the three groups after treatment was statistically significant (t=3.577, P＜0.05) in the Tong group and the celecoxib group; the difference before and after treatment in the combined group was statistically significant (t=8.315, P＜0.05), Mailuoshu The difference before and after treatment in the Tong group was statistically significant (t=3.264, P＜0.05), and the difference in the celecoxib group before and after treatment was also statistically significant (t=3.662, P＜0.05). There was no significant difference in the scores of the signs in the Lecoxib group (P>0.05).

Table 4 Comparison of DOA scores of clinical signs before and after treatment in the three groups of patients (x±`s)

In summary, Mailuoshutong pill combined with celecoxib can improve the cure rate of patients, reduce the level of inflammatory factors, relieve the pain of patients, and improve the quality of life of patients, which is suitable for clinical application.

Claims

A use of a combined medicine of celecoxib and Mailuoshutong pills or Mailuoshutong granules in the preparation of medicines for treating joint diseases.
The use according to claim 1, characterized in that the joint disease is mainly manifested as one or more of joint pain and tenderness, joint stiffness, joint swelling, restricted joint movement or joint deformity.
The use according to claim 1, wherein the joint disease is osteoarthritis.
The use according to claim 3, wherein the osteoarthritis is primary osteoarthritis or secondary osteoarthritis.
The use according to claim 4, wherein the secondary osteoarthritis refers to secondary osteoarthritis, including but not limited to meniscus injury, intra-articular or peri-articular fracture, joint ligament injury, femoral head necrosis, Osteoarthritis caused by one or more of congenital deformities or joint infections.
The use according to claim 3, wherein the osteoarthritis is articular cartilage degeneration injury, articular cartilage stripping, joint edge and subchondral bone reactive hyperplasia, bone hyperplasia, meniscus injury, synovial membrane One or more than two types of inflammation.
The use according to claim 3, wherein the onset of osteoarthritis includes but is not limited to one or more of the hands, knees, hips, feet, and spine.
The use according to any one of claims 1-7, wherein the weight ratio of Celecoxib to Mailuoshutong Pills in the combination drug is 1:180; and the combination drug contains Celecoxib in a weight ratio of 1:180. The weight ratio of cloth to Mailuoshutong granules is 1:300.
The use according to claim 8, wherein the Mailuoshutong pill or Mailuoshutong granule is prepared from the following components:

300-1000 parts by weight of Astragalus, 300-1000 parts by weight of Honeysuckle, 100-500 parts by weight of Phellodendron

100-500 parts by weight of Coix seed 300-1000 parts by weight of Scrophulariaceae 300-1000 parts by weight

Angelica 100-500 parts by weight, White peony 100-500 parts by weight, licorice 50-150 parts by weight

180-500 parts by weight of leech, 10-40 parts by weight of centipede, 50-150 parts by weight of scorpion;

Preferably, the Mailuoshutong pill or Mailuoshutong granule is prepared from the following components:

Astragalus 500-850 parts by weight Honeysuckle 500-850 parts by weight Phellodendron 250-450 parts by weight

Cangzhu 250-450 parts by weight Coix seed 500-850 parts by weight Scrophulariaceae 500-850 parts by weight

Angelica 250-450 parts by weight, White peony 250-450 parts by weight, licorice 50-150 parts by weight

250-450 parts by weight of leech, 10-40 parts by weight of centipede, 50-150 parts by weight of scorpion.
The combination medication according to claim 9, wherein the Mailuoshutong pill is prepared from the following components:

Astragalus 833 parts by weight Honeysuckle 833 parts by weight Phellodendron 417 parts by weight

Atractylodes 417 parts by weight Coix seed 833 parts by weight Scrophulariaceae 833 parts by weight

417 parts by weight of Angelica 417 parts by weight of white peony 417 parts by weight of licorice 138 parts by weight

417 parts by weight of leech, 33 parts by weight of centipede, 138 parts by weight of scorpion;

The Mailuoshutong granules are prepared from the following components:

Astragalus 500 parts by weight Honeysuckle 500 parts by weight Phellodendron 250 parts by weight

250 parts by weight of coix seed 500 parts by weight of Scrophulariaceae 500 parts by weight

Angelica 250 parts by weight, white peony 250 parts by weight, licorice 83 parts by weight

250 parts by weight of leech, 20 parts by weight of centipede, 83 parts by weight of scorpion.