CN114340650A - Combined medicine for treating osteoarthritis - Google Patents

Combined medicine for treating osteoarthritis Download PDF

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CN114340650A
CN114340650A CN201980031449.5A CN201980031449A CN114340650A CN 114340650 A CN114340650 A CN 114340650A CN 201980031449 A CN201980031449 A CN 201980031449A CN 114340650 A CN114340650 A CN 114340650A
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张贵民
李元森
程国良
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Lunan Pharmaceutical Group Corp
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Abstract

A combined medicine for treating osteoarthritis belongs to the field of medicines, and comprises celecoxib and one of Mailuoshutong pills or Mailuoshutong granules. The MAILUOSHUTONG pill or MAILUOSHUTONG granule is prepared from radix astragali, flos Lonicerae, cortex Phellodendri, rhizoma Atractylodis, Coicis semen, radix scrophulariae, radix Angelicae sinensis, radix Paeoniae alba, Glycyrrhrizae radix, Hirudo, Scolopendra, and Scorpio. Animal and clinical tests show that the combined medicament has good treatment effect on joint diseases, particularly osteoarthritis, can obviously reduce inflammatory factors, reduce inflammatory response, obviously improve clinical symptoms, improve life quality of patients, and is suitable for further popularization and application.

Description

Combined medicine for treating osteoarthritis Technical Field
The invention belongs to the field of traditional Chinese medicines, and particularly relates to a combined medicine for treating osteoarthritis.
 Background
Osteoarthritis (OA), also known as proliferative osteoarthritis, hyperosteogeny, degenerative joint disease, senile arthritis, hypertrophic arthritis, is a disease characterized by the occurrence of bone destruction, secondary hyperosteogeny, joint deformation, joint pain, limited movement and other symptoms when abnormal load is applied, due to degeneration and degeneration of soft tissues such as cartilage, intervertebral disc, ligament and the like constituting the joint, bony spur formation at the joint margin, synovial pachynsis and other changes, which are classified into primary and secondary types. Hyperosteogeny is a frequently encountered disease, a common disease, and a disease causing arthralgia.
The main purpose of treating osteoarthritis is to relieve pain, improve function and improve quality of life. The treatment options include various dosage forms (emulsion, paste, patch, etc.) of non-steroidal anti-inflammatory drugs (NSAIDs), full-blown pain preparation, glucosamine chondroitin, local injection of sodium hyaluronate for lubrication of joints to relieve pain, acupuncture and moxibustion, and joint replacement surgery in severe cases.
With the continuous development of traditional Chinese medicines and the intensive research on osteoarthritis, compared with western medicines, the traditional Chinese medicine for treating osteoarthritis has the advantages of definite curative effect and small toxic and side effects. Various treatment methods and the like. Modern pharmacology also indicates that the traditional Chinese medicine for treating osteoarthritis can effectively reduce inflammatory reaction, improve microcirculation in joints, promote cartilage repair, obviously improve clinical symptoms, improve life quality and reduce economic burden.
Chinese patent CN1201787C discloses a Chinese medicinal composition for treating thrombophlebitis, which comprises 12 medicinal materials of astragalus, honeysuckle, phellodendron, rhizoma atractylodis, semen coicis, radix scrophulariae, angelica, radix paeoniae alba, liquorice, leech, centipede and scorpion, and the Chinese medicinal composition has the functions of clearing away heat and toxic materials, removing blood stasis, dredging collaterals, inducing diuresis and reducing edema, has better curative effect on clinical treatment of thrombophlebitis, and also has certain prevention and treatment effects on thromboangiitis obliterans. The product based on the patent is marketed and is named as Mailuoshutong granules/pills, and is mainly used for treating superficial thrombophlebitis caused by damp-heat stasis in veins, and lower limb swelling, pain, dark red skin color or accompanied with cord-like substances caused by non-acute deep vein thrombosis.
 Technical problem
Based on the CN1201787C patent technology, a series of Mailuoshutong products are produced, and the invention further develops and researches new application of the traditional Chinese medicine composition in the patent, namely the Mailuoshutong product on the basis of the series of Mailuoshutong products.
 Technical solution
The invention aims to provide application of combined medicine of celecoxib and Mailuoshutong pills or Mailuoshutong granules in preparing medicines for treating joint diseases.
The joint diseases are mainly characterized by one or more of joint pain and tenderness, joint stiffness, joint swelling, joint movement limitation and joint deformity.
The joint diseases are mainly referred to as osteoarthritis.
The osteoarthritis is primary osteoarthritis or secondary osteoarthritis.
Preferably, the secondary osteoarthritis is osteoarthritis which mainly refers to osteoarthritis generated secondarily from one or more diseases including but not limited to meniscus injury, intra-articular or periarticular fracture, joint ligament injury, femoral head necrosis, congenital malformation or joint infection.
Preferably, the osteoarthritis is mainly manifested by one or more of articular cartilage degeneration injury, articular cartilage denudation, joint margin and subchondral bone reactive hyperplasia, hyperosteogeny, meniscus injury and synovitis.
Preferably, the site of onset of osteoarthritis includes, but is not limited to, one or more of the hands, knees, hips, feet, spine.
The weight ratio of the celecoxib to the Mailuoshutong pills in the combined medicament is 1: 180; the weight ratio of the celecoxib to the Mailuoshutong granules in the combined medicament is 1: 300.
The second purpose of the invention is to provide the composition of the Mailuoshutong pill or the Mailuoshutong granule, namely the Mailuoshutong pill or the Mailuoshutong granule is prepared from the following components:
1000 parts of 300 astragalus membranaceus, 300 parts of 300 honeysuckle and 500 parts of 100 parts of cortex phellodendri
100 parts of rhizoma atractylodis, 500 parts of coix seed, 300 parts of coix seed, 1000 parts of figwort, 300 parts of figwort root
100 portions of angelica, 500 portions of white peony root, 100 portions of licorice, 50 to 150 portions
Leech 180 and centipede 500 weight portions 10-40 weight portions and scorpion 50-150 weight portions;
preferably, the venation dredging pill or the venation dredging granule is prepared from the following components:
500 portions of astragalus root, 850 portions of 500 portions of honeysuckle, 250 portions of phellodendron, and 450 portions of
250 parts of rhizoma atractylodis, 850 parts of 500 parts of coix seed, 850 parts of 500 parts of figwort root, 850 parts of
250 portions of angelica sinensis, 450 portions of white paeony root, 250 portions of white paeony root, 450 portions of liquorice and 50 to 150 portions of
Leech 250 and centipede 450 weight portions and scorpion 50-150 weight portions.
Preferably, the Mailuoshutong pill is prepared from the following components:
astragalus 833 weight parts honeysuckle 833 weight parts phellodendron 417 weight parts
Rhizoma atractylodis 417, coix seed 833, figwort 833
417 parts of Chinese angelica root, 417 parts of white peony root, 138 parts of licorice root
Leech 417 parts by weight, centipede 33 parts by weight, scorpion 138 parts by weight;
preferably, the mailuoshutong granules are prepared from the following components:
500 parts by weight of astragalus membranaceus, 500 parts by weight of honeysuckle and 250 parts by weight of golden cypress
250 parts of rhizoma atractylodis, 500 parts of semen coicis, 500 parts of radix scrophulariae
250 parts of angelica sinensis, 250 parts of white peony root, 83 parts of liquorice
250 parts of leech, 20 parts of centipede and 83 parts of scorpion.
The invention also aims to provide a preparation method of the Mailuoshutong granules or the Mailuoshutong pills, which comprises the following specific operations:
1) soaking honeysuckle, rhizoma atractylodis, figwort, angelica and white paeony root in water according to the prescription amount, and distilling to extract volatile oil for later use; distilling to obtain water solution and residue;
2) mixing the astragalus, the phellodendron, the coix seed, the liquorice, the leech, the centipede and the scorpion according to the prescription amount of 1/2 and the distilled medicine residue obtained in the step 1), adding water and decocting twice, and combining decoction for later use;
3) mixing the decoction obtained in the step 2) with the aqueous solution distilled in the step 1), filtering, concentrating the filtrate to obtain a clear paste with a relative density of 1.10-1.20 (80 ℃), adding ethanol to ensure that the ethanol content reaches 60%, standing, filtering, recovering ethanol under reduced pressure, concentrating to obtain a clear paste with a relative density of 1.10-1.18 (80 ℃) or a thick paste with a relative density of 1.30-1.35 (80 ℃), drying, and crushing into fine powder to obtain extract powder for later use;
4) pulverizing the rest 1/2 prescription amount of Hirudo, Scolopendra, and Scorpio into powder;
5) adding cyclodextrin into the volatile oil obtained in the step 1) to prepare an inclusion compound, uniformly mixing the inclusion compound with the extract powder obtained in the step 3), the medicinal powder obtained in the step 4) and celecoxib, and preparing a clinically acceptable dosage form directly or by adding pharmaceutically acceptable excipients through conventional procedures;
or mixing the extract powder obtained in step 3), the medicinal powder obtained in step 4) and celecoxib uniformly, granulating, spraying the volatile oil obtained in step 1) and mixing uniformly, and preparing into clinically acceptable dosage forms directly or by adding pharmaceutically acceptable excipients through conventional procedures.
 Advantageous effects
The invention has the following beneficial effects:
the combined medicine has obvious treatment effect. Animal experiments show that the combined drug can effectively reduce the content of inflammatory factors such as IL-1 beta, TNF-alpha, MMP-3 and the like in the serum of knee osteoarthritis rats, reduce inflammatory reaction, has the effect obviously superior to that of single drug, has the drug dosage less than that of single drug, and improves the drug safety; clinical tests show that the total effective rate of the combined medicine is 92.9 percent, which is obviously superior to 88.1 percent of the Mailuoshutong pill group and 83.3 percent of the celecoxib group, the contents of inflammatory factors IL-1 beta, TNF-alpha and MMP-3 of a patient are obviously reduced after treatment, the pain of the patient is relieved, and the life quality of the patient is improved.
 Modes for carrying out the invention
Example 1 preparation of Mailuoshutong pills
The formula is as follows:
Figure 248176DEST_PATH_IMAGE001
the preparation method comprises the following steps:
(1) pulverizing Hirudo, Scolopendra, and Scorpio (1/2 prescription amount) into fine powder;
(2) soaking honeysuckle, rhizoma atractylodis, figwort, angelica and white paeony root in the formula according to the prescription amount in water, distilling and extracting volatile oil, and adding cyclodextrin into the volatile oil to prepare an inclusion compound for later use; the distilled water solution and the medicine dregs are reserved;
(3) mixing radix astragali, cortex Phellodendri, Coicis semen, Glycyrrhrizae radix, Hirudo, Scolopendra, Scorpio and distilled residues, decocting with water twice, and mixing decoctions; mixing the decoction with the distilled water solution, filtering, concentrating the filtrate to obtain fluid extract with relative density of 1.10-1.20 (80 deg.C), adding ethanol to make ethanol content reach 60%, standing, filtering, recovering ethanol under reduced pressure, concentrating to obtain fluid extract with relative density of 1.10-1.18 (80 deg.C), and spray drying to obtain fine powder of extract;
(4) and (3) mixing the fine powder obtained in the step (1), the inclusion compound obtained in the step (2) and the extract fine powder obtained in the step (3), adding starch, uniformly mixing, granulating, drying, preparing 1000g, and filling into capsules to obtain the capsule.
Example 2 preparation of Mailuoshutong granules
The formula is as follows:
Figure 678152DEST_PATH_IMAGE002
the preparation method comprises the following steps:
(1) pulverizing Hirudo, Scolopendra, and Scorpio (1/2 prescription amount) into fine powder;
(2) soaking honeysuckle, rhizoma atractylodis, figwort, angelica and white paeony root in the formula according to the prescription amount in water, distilling and extracting volatile oil for later use; the distilled water solution and the medicine dregs are reserved;
(3) mixing radix astragali, cortex Phellodendri, Coicis semen, Glycyrrhrizae radix, Hirudo, Scolopendra, Scorpio and distilled residues, decocting with water twice, and mixing decoctions; mixing the decoction with the distilled water solution, filtering, concentrating the filtrate to obtain fluid extract with relative density of 1.15-1.20 (80 deg.C), adding ethanol to make ethanol content reach 60%, standing, filtering, recovering ethanol under reduced pressure, concentrating to obtain soft extract with relative density of 1.30-1.35 (80 deg.C), vacuum drying, and pulverizing into fine powder to obtain extract fine powder;
(4) and (3) mixing the fine powder obtained in the step (1) and the extract fine powder obtained in the step (3), adding beta-cyclodextrin, aspartame, sodium carboxymethyl starch and dextrin according to the formula ratio, uniformly mixing, granulating, drying, spraying the volatile oil obtained in the step (2), uniformly mixing, and preparing 1000 g.
Example 3 preparation of Mailuoshutong pills
The formula is as follows:
Figure 765056DEST_PATH_IMAGE003
the preparation method comprises the following steps: the same as in example 1.
Example 4 preparation of Mailuoshutong pills
The formula is as follows:
Figure 504342DEST_PATH_IMAGE004
the preparation method comprises the following steps: the same as in example 1.
Example 5 preparation of Mailuoshutong granules
The formula is as follows:
Figure 286485DEST_PATH_IMAGE005
the preparation method comprises the following steps: the same as in example 2.
Example 6 preparation of Mailuoshutong granules
The formula is as follows:
Figure 441522DEST_PATH_IMAGE006
the preparation method comprises the following steps: the same as in example 2.
 Industrial applicability
In order to verify the effect of the combination drug in treating joint diseases, the inventor carries out related animal and clinical tests, and it is worth to be noted that the following animal and clinical tests only take the knee joint in osteoarthritis as an example to carry out pharmacodynamic description, and for other joint diseases, the inventor also carries out research, and the research result shows that the combination drug of the invention can achieve the same or similar effect as that of treating knee osteoarthritis for other types of osteoarthritis and joint diseases. The following animal and clinical trials are not intended to limit the present invention.
The traditional Chinese medicine composition has the treatment effect on the osteoarthritis rats
1. Laboratory animal
Male SD-grade rats, weight 180-220 g, laboratory animal license number: SCXK (Shandong) 20140007, provided by Jinanpunyue laboratory animal Breeding Co., Ltd, was acclimatized prior to the experiment for one week.
2. Experimental drugs
Celecoxib capsules, the mailuoshutong pills obtained in example 1, and the mailuoshutong granules obtained in example 2.
3 grouping and molding method
3.1 grouping
Taking 70 rats, and dividing into blank group, model group, celecoxib group, vein relaxing pill group, vein relaxing granule group, combination 1 group and combination 2 group, wherein each group comprises 10 rats.
3.2 Molding method
The method comprises the following steps of establishing a knee osteoarthritis model of each group of rats by adopting an improved Hulth modeling method, and specifically operating as follows:
the left lower limb of the rat was subjected to a depilatory treatment 1 day before the operation. Before operation, the patient is fasted for 12 hours, and water is forbidden for 4 hours. After anesthetizing a rat, fixing the rat on a mouse board in a supine mode, after the left knee of the rat is disinfected conventionally, taking the inner side of the left knee joint of the rat as an operation point, cutting the left knee joint of the rat longitudinally from the side of the patellar tendon, wherein the range is about 1cm long, cutting an internal anterior cruciate ligament, removing an internal meniscus, carrying out drawer experiment examination, after the rat is positive, alternately washing the rat by using complex iodine and physiological saline for 2 times, cleaning blood liquid in a wound, infiltrating an operation field by using gentamicin sulfate injection to prevent intra-articular infection, then suturing the wound and wrapping, and ending the operation.
Among these, the blank group was given a sham surgical treatment, with only the joint cavity opened, without damaging ligaments and meniscus, and the wound was sutured and bandaged.
The injured limb after operation is not fixed, so that the injured limb can move freely, gentamicin is injected into the rat after the operation for three consecutive days, and the wound is disinfected to prevent wound infection.
4. Administration of drugs
After 1 week of operation, all groups of rats survived, the wound has no red swelling and suppuration phenomena, the wound is basically healed, the response is sensitive, the excretion has no abnormality, and the forced movement of the rats is started, 1 time a day, 30min each time and 8 weeks continuously. The administration is performed simultaneously with the forced activity.
The celecoxib group, the example 1 group, the example 2 group, the combined drug 1 group and the combined drug 2 group are respectively administered with corresponding drugs; the model group and the blank group were given the same amount of physiological saline. The administration was continued by gavage for 8 weeks.
The doses administered were as follows:
celecoxib group: 18 mg/kg;
mailuoshutong pill group: 3.24 g/kg;
vein relaxing granule group: 5.4 g/kg;
combination drug 1 group: 9mg/kg of celecoxib and 1.62g/kg of Mailuoshutong pills;
combination drug 2 groups: 9mg/kg of celecoxib and 2.7g/kg of Mailuoshutong granules;
5. observation index
After the last administration, fasting water is carried out for 12 hours, abdominal aorta blood sampling is carried out on each group of rats after anesthesia, centrifugation is carried out, supernatant fluid is taken, and the contents of IL-1 beta, TNF-alpha and MMP-3 in the blood of the rats are detected by adopting an enzyme linked immunosorbent assay.
6. Results of the experiment
6.1 during the experiment period of the general conditions of the rats in each group, the rats in the blank group have good mental state and normal autonomic activity, diet, drinking water and defecation; the rats in the model group have reactions such as reduced autonomic activity, lying, laziness in movement and the like, and the drinking water and diet are reduced compared with the defecation in the blank group; with the increase of the administration time, the mental state of the rats in each administration group is gradually improved, the autonomous activity is obviously increased, and the drinking water and defecation are gradually increased.
6.2 serum IL-1 beta, TNF-alpha, MMP-3 content changes
TABLE 1 changes in the IL-1. beta., TNF-. alpha., MMP-3 content in the serum of rats of each group: (
Figure 710830DEST_PATH_IMAGE007
）
Figure 168487DEST_PATH_IMAGE008
Note: in contrast to the blank group,*P＜0.05， #p is less than 0.01; in contrast to the model set,@p is less than 0.01; compared with the group 1 of the combined medicine,&P＜0.01。
as can be seen from Table 1, the blank group comparison shows that the contents of IL-1 beta, TNF-alpha and MMP-3 in the serum of the rat in the model group are obviously higher, and the difference has statistical significance (P is less than 0.01); after the rats of each administration group are treated by the medicament, the contents of IL-1 beta, TNF-alpha and MMP-3 are increased, and the statistical significance is achieved when the differences of the contents are compared with that of a model group (P is less than 0.01); compared with the drug combination 1, except the drug combination 2 groups of rats, the other drug administration groups of rats have higher contents of IL-1 beta, TNF-alpha and MMP-3 in serum, and the difference has statistical significance (P is less than 0.01).
The results show that the combined medicine can effectively reduce the content of inflammatory factors such as IL-1 beta, TNF-alpha, MMP-3 and the like in the blood serum of knee osteoarthritis rats, and the effect is obviously superior to that of single medicine.
Secondly, the clinical trial research of the traditional Chinese medicine composition
1 data and method
1.1 general data
Selecting 126 cases of knee osteoarthritis patients who are treated by an orthopedic outpatient service from 2016 to 2018 in 8 months, and randomly dividing the patients into a celecoxib group, a venation dredging group and a combined group according to different treatment methods, wherein each group comprises 42 patients; wherein the celecoxib groups were 19 men, 23 women, aged 56-78 years, averaged 66.7 ± 13.5 years, 26 single knees, 16 double knees, according to the Kellgren-Lawrence classification criteria [6 ]: 19 cases of I stage, 15 cases of II stage and 8 cases of III stage; in the choroid sutong group, 17 men and 25 women, aged 56-79 years, averaged 67.5 ± 14.2 years, 23 single knees and 19 double knees, according to the Kellgren-Lawrence classification: 20 cases of I grade, 15 cases of II grade and 7 cases of III grade; combination groups of 20 men, 22 women, age 55-79, mean 64.8 ± 14.8, 25 single knees, 17 double knees, according to the Kellgren-Lawrence classification criteria: 18 cases of I stage, 16 cases of II stage and 6 cases of III stage. The general data differences of sex, age and disease grade of two groups of patients are not statistically significant (P > 0.05), and are comparable.
Inclusion criteria were: the diagnosis standard of knee joint osteoarthritis is met, wherein the diagnosis standard of osteoarthritis diagnosis and treatment guidelines for osteoarthritis (2007 edition) is the bone science division of the Chinese medical society; the X-ray film shows that the joint clearance is narrowed, and the articular cartilage is hardened or cystic change; the knee joint repeatedly feels pain for more than one month and has friction sound during movement; signing an informed consent. Exclusion criteria: combining rheumatic arthritis and rheumatoid arthritis; ② patients with liver and kidney function deficiency, serious cardiovascular and cerebrovascular diseases or drug allergy; ③ those aged more than 80 years who have communication disorder and are unconscious.
1.2 methods of treatment
Celecoxib (celecoxib, fevery pharmaceuticals ltd., national drug standard: J20120063) is administered in the celecoxib group at 0.2g per day; mailuoshutong pills (Lunan Kaiping Co., Ltd., specification: 12 g/bottle, national Standard: Z19991025) are taken in the Mailuoshutong pill group, one bottle each time and three times a day; the combination group is combined with the Mailuoshutong pills for combination treatment on the basis of oral celecoxib, and the dosage is the same as above. Three groups of patients were treated continuously for 4 weeks.
2 determination of therapeutic Effect
Changes in the levels of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and Matrix Metalloproteinases (MMPs) in the synovial fluid were observed before and after treatment in three groups of patients. Extracting 1.5mL of joint fluid from knee and eye of affected limb, injecting into silicified test tube, centrifuging at high speed for 10min, collecting supernatant, and detecting by ELISA method, wherein the kit is selected from Wuhan doctor De bioengineering Co., Ltd, and the operation is strictly performed according to kit instructions.
The clinical efficacy is evaluated according to the guidelines of clinical research on new drugs in traditional Chinese medicine and the international WOMAC scale score [7-8 ]. The WOMAC scale scoring content comprises three items of arthralgia, stiffness and functional activity, scoring is carried out in a question-asking mode, 24 questions are asked, each question is 0-4 points, and the higher the WOMAC score is, the more serious the symptom is. The clinical curative effect evaluation comprises the following steps: the symptoms such as arthralgia disappear, joint movement is normal, the WOMAC score is reduced by more than or equal to 95 percent, X-ray examination shows that the joint is normal, the obvious effects are that the symptoms such as arthralgia are obviously relieved, the joint movement is not limited, the WOMAC score is reduced by more than or equal to 70 percent and is less than 95 percent, X-ray examination shows that the joint is obviously improved, the effects are that the symptoms such as arthralgia are relieved, the joint movement is slightly limited, the WOMAC score is reduced by more than or equal to 30 percent and is less than 70 percent, X-ray examination shows that the joint is improved, the effects are not effective, the symptoms such as arthralgia and the joint movement are not obviously improved, the WOMAC score is reduced by less than 30 percent, and the X-ray examination is not changed. Total effective rate = cure rate + significant efficiency + effective rate.
Scoring with an international DOA scoring standard, Leguesines index 4, the scoring including knee joint rest pain, movement pain, tenderness, joint mobility, morning stiffness and walking ability, the higher the score the more severe the symptoms [9 ].
3 statistical methods
Statistical analysis was performed on all experimental data using software SPSS19.0, with all measures represented as variances, using the t test, and counts using the X2 test, and all comparisons P <0.05 were statistically significant.
4 results
4.1 comparison of inflammatory factor levels
The results of the inflammatory factor levels before and after treatment in three groups of patients are shown in table 2. As can be seen from Table 2, there was no statistical difference in the levels of IL-1. beta., TNF-. alpha., and MMP-3 in the first three groups before treatment (P > 0.05); the IL-1 beta, TNF-alpha and MMP-3 levels of the three groups of patients are reduced compared with those before treatment after treatment, wherein the reduction trend of the combined group is obvious, the IL-1 beta, TNF-alpha and MMP-3 levels are lower than those of the celecoxib group and the choroid dredging group, the difference of the level values of all factors of the combined group after treatment compared with the celecoxib group and the choroid dredging group has statistical significance (P is less than 0.05), and the difference of the level values of all factors of the celecoxib group and the choroid dredging group after treatment also has statistical significance (P is less than 0.05); the difference of the level values of the factors before and after the three groups of treatments has statistical significance (P is less than 0.05).
TABLE 2 comparison of the level changes of inflammatory factors in three groups (x ±'s, mg/ml)
Figure 828138DEST_PATH_IMAGE009
4.2 comparison of clinical efficacy
The results of the clinical efficacy evaluations of the three groups of patients are shown in table 3. As can be seen from table 3, the celecoxib group healed 11 cases (26.2%), with results similar to those of the vena cava-relaxing group (28.6%) lower than those of the combination group (35.7%); meanwhile, the total effective rate of the celecoxib group is 83.3 percent, the total effective rate of the venation dredging group is 88.1 percent, and the total effective rate of the combined group reaches 92.9 percent and is higher than that of the single medicine group; in addition, the combined group has the inefficiency of only 7.1 percent, while the single drug group is higher than 10 percent, the inefficiency is higher than that of the combined group, and the difference of the three groups has no statistical significance (P is more than 0.05).
TABLE 3 comparison of clinical efficacy of three groups of patients (n,%)
Figure 645922DEST_PATH_IMAGE010
4.3 DOA score comparison of clinical signs
The DOA score results for clinical signs before and after treatment in three groups of patients are shown in table 4. As can be seen from Table 4, the difference in the scores of the clinical signs before the three groups of treatments was not statistically significant (P > 0.05); the scores of all clinical signs after treatment are obviously reduced compared with the scores before treatment, wherein the scores of all the signs after the treatment of the combination group are obviously lower than those of the choroid smooth group and the celecoxib group, and the score difference of the three groups after the treatment has statistical significance (t =3.577, P is less than 0.05); the differences between the pre-treatment and the post-treatment of the combination group are statistically significant (t =8.315, P < 0.05), the differences between the pre-treatment and the post-treatment of the choroid dredging group are statistically significant (t =3.264, P < 0.05), the differences between the pre-treatment and the post-treatment of the celecoxib group are also statistically significant (t =3.662, P < 0.05), and the differences between the scores of the signs of the choroid dredging group and the celecoxib group are not statistically significant (P > 0.05).
TABLE 4 comparison of DOA scores for clinical signs before and after treatment (x ±'s) for three groups of patients
Figure 254889DEST_PATH_IMAGE011
In conclusion, the venation dredging pill and the celecoxib can improve the cure rate of patients, reduce the level of inflammatory factors, relieve the pain of the patients, improve the life quality of the patients and is suitable for clinical application.

Claims (10)

  1. The use of celecoxib and Mailuoshutong pills or Mailuoshutong granules in the preparation of medicaments for treating joint diseases.
  2. The use according to claim 1, wherein the joint disease is manifested by one or more of joint pain and tenderness, joint stiffness, joint swelling, joint mobility limitation, or joint deformity.
  3. The use according to claim 1, wherein the joint disease is osteoarthritis.
  4. The use according to claim 3, wherein the osteoarthritis is primary osteoarthritis or secondary osteoarthritis.
  5. The use of claim 4, wherein secondary osteoarthritis is osteoarthritis secondary to one or more diseases including but not limited to meniscal injury, intra-or peri-articular fracture, joint ligament injury, femoral head necrosis, congenital malformations, or joint infection.
  6. The use according to claim 3, wherein the osteoarthritis is one or more of degenerative joint cartilage damage, articular cartilage exfoliation, reactive hyperplasia of joint margin and subchondral bone, hyperosteogeny, meniscus damage, synovitis.
  7. The use of claim 3, wherein the site of onset of osteoarthritis includes, but is not limited to, one or more of the hands, knees, hips, feet, spine.
  8. The use according to any one of claims 1 to 7, wherein the weight ratio of celecoxib to choroid rduton's pellets in the combination is 1: 180; the weight ratio of the celecoxib to the Mailuoshutong granules in the combined medicament is 1: 300.
  9. The use of claim 8, wherein the choroid soothing pill or particles are prepared from the following components:
    1000 parts of 300 astragalus membranaceus, 300 parts of 300 honeysuckle and 500 parts of 100 parts of cortex phellodendri
    100 parts of rhizoma atractylodis, 500 parts of coix seed, 300 parts of coix seed, 1000 parts of figwort, 300 parts of figwort root
    100 portions of angelica, 500 portions of white peony root, 100 portions of licorice, 50 to 150 portions
    Leech 180 and centipede 500 weight portions 10-40 weight portions and scorpion 50-150 weight portions;
    preferably, the venation dredging pill or the venation dredging granule is prepared from the following components:
    500 portions of astragalus root, 850 portions of 500 portions of honeysuckle, 250 portions of phellodendron, and 450 portions of
    250 parts of rhizoma atractylodis, 850 parts of 500 parts of coix seed, 850 parts of 500 parts of figwort root, 850 parts of
    250 portions of angelica sinensis, 450 portions of white paeony root, 250 portions of white paeony root, 450 portions of liquorice and 50 to 150 portions of
    Leech 250 and centipede 450 weight portions and scorpion 50-150 weight portions.
  10. The combination of claim 9, wherein the mailuoshutong pill is prepared from the following components:
    astragalus 833 weight parts honeysuckle 833 weight parts phellodendron 417 weight parts
    Rhizoma atractylodis 417, coix seed 833, figwort 833
    417 parts of Chinese angelica root, 417 parts of white peony root, 138 parts of licorice root
    Leech 417 parts by weight, centipede 33 parts by weight, scorpion 138 parts by weight;
    the Mailuoshutong granules are prepared from the following components:
    500 parts by weight of astragalus membranaceus, 500 parts by weight of honeysuckle and 250 parts by weight of golden cypress
    250 parts of rhizoma atractylodis, 500 parts of semen coicis, 500 parts of radix scrophulariae
    250 parts of angelica sinensis, 250 parts of white peony root, 83 parts of liquorice
    250 parts of leech, 20 parts of centipede and 83 parts of scorpion.
CN201980031449.5A 2019-09-03 2019-09-03 Combined medicine for treating osteoarthritis Pending CN114340650A (en)

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