CN111514193A - Application of rhizoma corydalis pain-relieving dropping pill in treatment of knee osteoarthritis - Google Patents
Application of rhizoma corydalis pain-relieving dropping pill in treatment of knee osteoarthritis Download PDFInfo
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Abstract
The invention belongs to the technical field of medicines, and particularly relates to a new application of a rhizoma corydalis pain relieving dropping pill. The inventor surprisingly finds that the corydalis tuber pain relieving dropping pill can inhibit inflammatory factors, has the effects of inhibiting cartilage degradation, promoting chondrocyte proliferation, promoting proteoglycan synthesis and the like, and has the effect superior to that of a diclofenac sodium sustained-release capsule singly and a diclofenac sodium sustained-release capsule and a corydalis tuber pain relieving dropping pill jointly used; the inventor finds that the corydalis tuber pain relieving dropping pill used alone in clinical level can remarkably relieve joint pain and joint stiffness and promote the recovery of joint mobility, has good clinical treatment effect on KOA, has the effect remarkably superior to that of diclofenac sodium, can remarkably reduce adverse reactions such as gastrointestinal tract irritation and the like compared with the diclofenac sodium, and has higher safety after being taken for a long time.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to an application of a corydalis tuber pain relieving dropping pill in treating knee osteoarthritis.
Background
The Corydalis tuber pain-relieving dropping pill consists of Corydalis tuber prepared by traditional Chinese medicine vinegar and angelica dahurica, wherein the Corydalis tuber of the monarch drug in the prescription is a dried tuber of Corydalis tuber of Papaveraceae, namely Corydalis yanhusuo W.T.Wang, and the pungent-warm-natured drug is good medicine for promoting qi, activating blood and relieving pain and is good for treating various pains on the upper and lower parts of the whole body; the ministerial drug radix Angelicae Dahuricae is dry root of Angelica dahurica (Fisch. ex Hoffm.) Benth. et hook. f. or Angelica dahurica (Fisch. ex Hoffm.) Benth. et hook. f. var. fortmosana (Boiss.) Shann et Yuan of Angelica dahurica of Umbelliferae, and can be used for dispelling pathogenic wind and cold, eliminating dampness arthralgia, and promoting flow of qi and blood to remove headache and body pain. The two medicines are mutually reinforced, have the effects of regulating qi, promoting blood circulation and relieving pain, and are used for treating stomachache, headache, costalgia and dysmenorrhea caused by qi stagnation and blood stasis. The prescription has the advantages of refinement, definite curative effect and wide clinical application. At present, pharmacological research shows that the corydalis tuber analgesic prescription has obvious pharmacological effects of easing pain, relieving smooth muscle spasm and the like.
Knee Osteoarthritis (KOA), abbreviated as knee osteoarthritis, is a chronic, progressive disease occurring in the active joints, characterized mainly by disintegration of the joint matrix and significant decrease of chondrocytes. Knee osteoarthritis is also called knee proliferative arthritis, degenerative arthritis, hypertrophic arthritis, degenerative osteoarthropathy and the like, is a frequently chronic progressive osteoarthropathy and is a common clinical disease in orthopedics. The disease is characterized by degeneration of knee joint cartilage as a main pathological feature. With the increasing aging population in the world in recent years, the incidence rate of knee osteoarthritis is on the trend of rising year by year in the global scope, the daily life and work of middle-aged and elderly people are seriously affected, and the incidence rate and disability rate are very high. The existing research shows that the pathological characteristics of the cartilage repair and regeneration are changed into progressive degeneration and disappearance of articular cartilage tissues, formation of articular marginal osteophytes and reactivity change of subchondral bone, and the degeneration speed exceeds the repair and regeneration speed. Primary or secondary degenerative changes of articular cartilage occur at the early stage of onset, and subchondral bone destruction and hyperosteogeny are accompanied, so that joints are gradually destroyed and malformations are generated. The entire course of its pathology affects not only the knee cartilage, but also the meniscus, subchondral bone, ligaments, joint capsule, synovium and periarticular muscles. The clinical manifestations are mainly progressive and chronic developed joint swelling and pain, stiffness and limited movement, and X-ray shooting suggests formation of knee joint bony spur.
The knee osteoarthritis has a plurality of treatment methods, including physical therapy, western medicine therapy, surgical therapy, traditional Chinese medicine treatment and the like, the physical therapy only can relieve pain for patients and can not cure diseases, and the physical therapy is only suitable for auxiliary treatment; the operation treatment cost is high, the postoperative recovery is slow, the treatment risk is large, and the use is not recommended; at present, western medicine for treating the gonitis mainly comprises symptom control, disease improvement, cartilage protection, local external application and the like, and mainly aims at relieving or eliminating pain. The traditional Chinese medicine composition mainly comprises non-steroidal anti-inflammatory drugs, glucocorticoids, anti-inflammatory drugs, analgesic drugs, anxiolytic drugs and the like in clinic, mainly comprises the non-steroidal anti-inflammatory drugs, is mainly applied to glucosamine hydrochloride in recent years, can relieve inflammation and pain, but cannot change the pathological change of osteoarthritis fundamentally, namely only treats the symptoms, is difficult to treat due to long-term application of antipyretic analgesic and hormone drugs, has large harm to the body and multiple side effects, and has obvious gastrointestinal adverse reactions. Therefore, no particularly effective treatment for the disease is available in western medicine.
The research of the traditional Chinese medicine in the field is gradually increased, and good effects are obtained. The traditional Chinese medicine for treating knee osteoarthritis mainly aims at relieving joint pain, relieving joint swelling and the like. For example, chinese patent CN102327380B discloses a Chinese medicinal composition for treating knee osteoarthritis, which can relieve joint pain; chinese patent CN102846751B discloses a hyperplasia collateral-activating pill for treating knee osteoarthritis, which can relieve pain and shorten the treatment time of patients; chinese patent CN103520654B discloses a traditional Chinese medicine composition for treating knee osteoarthritis, which has an obvious effect on relieving knee pain.
At present, the treatment of knee osteoarthritis mainly comprises operation puncture combined medicine and Chinese and western medicine combined treatment, wherein a document (Yanyanling, lissening. curative effect observation of treating knee osteoarthritis by the knee puncture combined rhizoma corydalis pain relieving dropping pill [ J ] mathematical and pharmacology medicine journal, 2019,32(04):100 and 101.) discloses that the knee puncture combined rhizoma corydalis pain relieving dropping pill can relieve joint pain; the literature (Wangliang corydalis tuber analgesic dropping pill for treating acute gouty arthritis 55 cases [ J ]. Chinese traditional medicine science and technology 2015,022(006):716.) discloses that the corydalis tuber analgesic dropping pill and diclofenac sodium can obviously improve the treatment efficiency of the acute gouty arthritis, but the diclofenac sodium has serious gastrointestinal adverse reactions. The inventor surprisingly finds that the corydalis tuber pain relieving dropping pill can inhibit inflammatory factors, has the effects of inhibiting cartilage degradation, promoting chondrocyte proliferation, promoting proteoglycan synthesis and the like, and has the effect superior to that of a diclofenac sodium sustained-release capsule singly and a diclofenac sodium sustained-release capsule and a corydalis tuber pain relieving dropping pill jointly used; the inventor finds that the corydalis tuber pain relieving dropping pill used alone in clinical level can remarkably relieve joint pain and joint stiffness and promote the recovery of joint mobility, has good clinical treatment effect on KOA, has the effect remarkably superior to that of diclofenac sodium, can remarkably reduce adverse reactions such as gastrointestinal tract irritation and the like compared with the diclofenac sodium, and has higher safety.
Disclosure of Invention
The invention aims to provide an application of a rhizoma corydalis pain-relieving dropping pill in preparing a medicine for inhibiting generation of an inflammatory factor IL-1 alpha, wherein the rhizoma corydalis pain-relieving dropping pill consists of vinegar-processed rhizoma corydalis and radix angelicae in a weight ratio of 1:1-3: 1.
The invention also aims to provide an application of the corydalis tuber pain relieving dropping pill in preparing a medicine for inhibiting cartilage degradation, wherein the corydalis tuber pain relieving dropping pill consists of corydalis tuber processed with vinegar and dahurian angelica root in a weight ratio of 1:1-3: 1.
The invention also aims to provide application of the corydalis tuber analgesic dropping pill in preparing a medicine for promoting generation of inflammatory factor TGF-beta, wherein the corydalis tuber analgesic dropping pill consists of corydalis tuber processed with vinegar and dahurian angelica root in a weight ratio of 1:1-3: 1.
The invention also aims to provide application of the corydalis tuber analgesic dropping pill in preparing a medicine for promoting proteoglycan synthesis, wherein the corydalis tuber analgesic dropping pill consists of corydalis tuber processed with vinegar and angelica dahurica in a weight ratio of 1:1-3: 1.
The invention also aims to provide application of the corydalis tuber pain relieving dropping pill in preparing a medicine for promoting chondrocyte proliferation, wherein the corydalis tuber pain relieving dropping pill consists of corydalis tuber processed with vinegar and angelica dahurica in a weight ratio of 1:1-3: 1.
The invention also aims to provide application of the corydalis tuber analgesic dropping pill in preparing a medicament for inhibiting inflammation, wherein the corydalis tuber analgesic dropping pill consists of corydalis tuber processed with vinegar and dahurian angelica root in a weight ratio of 1:1-3: 1.
The invention also aims to provide application of the corydalis tuber pain relieving dropping pill in preparation of a medicine for assisting in inhibiting knee osteoarthritis inflammation symptoms, wherein the corydalis tuber pain relieving dropping pill consists of corydalis tuber and angelica dahurica which are processed with vinegar in a weight ratio of 1:1-3: 1.
The invention also aims to provide application of the corydalis tuber pain relieving dropping pill in preparation of a medicine for promoting joint function recovery, wherein the corydalis tuber pain relieving dropping pill consists of corydalis tuber processed with vinegar and angelica dahurica in a weight ratio of 1:1-3: 1.
The invention also aims to provide an application of the corydalis tuber pain relieving dropping pill in preparing a medicine for relieving joint stiffness, wherein the corydalis tuber pain relieving dropping pill consists of corydalis tuber processed with vinegar and dahurian angelica root in a weight ratio of 1:1-3: 1.
The invention has the beneficial effects that: the inventor surprisingly finds that the corydalis tuber pain relieving dropping pill can inhibit inflammatory factors, has the effects of inhibiting cartilage degradation, promoting chondrocyte proliferation, promoting proteoglycan synthesis and the like, and has the effect superior to that of a diclofenac sodium sustained-release capsule singly and a diclofenac sodium sustained-release capsule and a corydalis tuber pain relieving dropping pill jointly used; the inventor finds that the corydalis tuber pain relieving dropping pill can remarkably relieve joint pain and joint stiffness and promote the recovery of joint mobility in clinical level, has good clinical treatment effect on KOA, has the effect remarkably superior to that of diclofenac sodium, can remarkably reduce adverse reactions such as gastrointestinal tract irritation and the like compared with the diclofenac sodium by singly using the corydalis tuber pain relieving dropping pill, and has good safety after long-term taking of the corydalis tuber pain relieving dropping pill (more than or equal to 2 weeks).
Detailed Description
The corydalis tuber analgesic dropping pill described in the following examples is prepared from corydalis tuber (processed with vinegar) and dahurian angelica root with auxiliary materials, and is prepared from Gansu Longshen-Ongfa pharmaceutical industry GmbH.
Example 1 animal experiments
1. Materials and methods
1.1 Experimental animals and groups
SPF female rats 40, body weight 200. + -.20 g. After adaptive feeding for 1 week, the animals are randomly divided into a blank group, a model group and a rhizoma corydalis pain relieving dropping pill group, and a diclofenac sodium sustained-release capsule and rhizoma corydalis pain relieving dropping pill group (combined medicine group), wherein each group comprises 10 animals.
1.2 reagents and instruments
Rhizoma corydalis pain-relieving dropping pill (Gansu Long Shenjon pharmaceutical industry GmbH), diclofenac sodium sustained-release capsule (pharmaceutical Co., Ltd., China), monoiodoacetate (MIA, Sigma Co., USA), ELISA kit of IL-1 alpha and TGF-beta (Beijing European North Biotechnology Co., Ltd.), full wavelength scanning enzyme-labeling instrument (Thermo Co., USA), and low temperature high speed centrifuge (Beckman Co., USA).
1.3 Molding method and administration method
A moderate KOA rat model was prepared using the MIA method. 1mg of MIA was dissolved in 50mL of 0.9% sodium chloride solution. Rats were anesthetized by intraperitoneal injection with 1% sodium pentobarbital (0.6mL/100g), and then the rat hairs near the right knee were removed, and after the joint was flexed to the maximum, 50. mu.L of physiological saline solution containing 1mg of MIA was injected into the right knee cavity. The blank was infused with 50 μ L of saline once a week for four consecutive weeks. The obvious swelling of soft tissues and the unobvious superficial bony marks are seen, namely the molding is successful. Performing drug intervention at the 5 th week, performing intragastric administration on the corydalis tuber analgesic dropping pill group by using 0.4g/kg of corydalis tuber analgesic dropping pill solution (the corydalis tuber analgesic dropping pill medicinal powder is dissolved in 0.5% CMC-Na solution), performing intragastric administration on the diclofenac sodium sustained-release capsule group by using 0.009g/kg of diclofenac sodium sustained-release capsule solution (the diclofenac sodium sustained-release capsule medicinal powder is dissolved in 0.5% CMC-Na solution), and performing intragastric administration on the combined medicine group by using 0.4g/kg of corydalis tuber analgesic dropping pill and 0.009g/kg of diclofenac sodium sustained-release capsule mixed solution (the corydalis tuber analgesic dropping pill medicinal powder and the diclofenac sodium sustained-release capsule medicinal powder are dissolved in 0.5% CMC-Na solution); once a day for four consecutive weeks. The blank group and the model group were dosed with the same amount of 0.5% CMC-Na solution.
1.4 detection method
Rats were intraperitoneally injected with 1% pentobarbital (0.6mL/100g) for deep anesthesia and fixed supine on the operating table. After the abdomen is disinfected conventionally, the abdominal cavity is cut open along the median line of the abdomen by using an operation scissors, the abdominal aorta is fully exposed, 5-8 mL of blood is collected, the blood is kept stand for 2h, centrifuged for 15min at 3000r/min, and the supernatant is taken and stored in a refrigerator at minus 80 ℃. Absorbance values (OD values) were read at a wavelength of 450nm and concentrations were calculated using a standard curve, following the exact instructions of the relevant ELISA kit.
1.5 statistical methods
The statistical treatment adopts SPSS17.0 software, and the measured data are all calculated according to the mean value plus or minus standard deviation
And (4) showing. The difference is statistically significant with P < 0.05.
2. Results
As shown in Table 1, the IL-1 alpha and TGF-beta contents in the serum of each group of rats are increased (p is less than 0.05) and the TGF-beta contents in the serum of the model group of rats are all reduced (p is less than 0.05) compared with the blank group of rats; the content of IL-1 alpha in the blood serum of rats in the rhizoma corydalis pain-relieving pill group, the diclofenac sodium sustained-release capsule group and the combined drug group is reduced (P is less than 0.05) compared with that in the model group, and the effect of the rhizoma corydalis pain-relieving pill group is better than that of the combined drug group and the diclofenac sodium sustained-release capsule group; the content of TGF-beta of the rhizoma corydalis pain relieving pill group, the diclofenac sodium sustained-release capsule group and the combined drug group is higher than that of the model group (P is less than 0.05), and the rhizoma corydalis pain relieving pill group and the combined drug group have no difference, have equivalent effect and are superior to the diclofenac sodium sustained-release capsule group.
TABLE 1 comparison of groups of rats IL-1 α and TGF- β: (
ng/g，n＝10)
| Group of | IL-1α | TGF-β |
| Blank group | 48.6±9.4 | 108.4±18.5 |
| Model set | 89.3±11.2* | 63.1±13.6* |
| Rhizoma corydalis pain-relieving dropping pill group | 66.5±8.5# | 101.6±19.3# |
| Diclofenac sodium sustained-release capsule group | 72.1±10.4# | 96.3±21.9# |
| Combination drug group | 68.4±9.6# | 105.7±24.6# |
Note: comparison with blank group<0.05; in comparison with the set of models,#P＜0.05。
3. conclusion
IL-1 α promotes cartilage degradation and contributes to the production of other inflammatory substances, which also contribute to accelerated cartilage destruction; TGF-. beta.plays an important role in the regeneration and growth of articular cartilage by antagonizing TNF-. alpha.and by modulating inflammatory factors, stimulating proteoglycan synthesis and the proliferation of chondrocytes. The research result shows that the content of IL-1 alpha in serum of the model group is obviously higher than that of the normal group, and the content of IL-1 alpha of the rhizoma corydalis pain-relieving dropping pill group is obviously lower than that of the model group, so that the cartilage degradation of a patient with KOA can be inhibited; the content of TGF-beta in serum of the model group is obviously lower than that of TGF-beta in the normal group, and the content of TGF-beta in the rhizoma corydalis pain relieving pill group and the diclofenac sodium sustained-release capsule combined rhizoma corydalis pain relieving pill group is obviously higher than that of TGF-beta in the model group, can stimulate proteoglycan synthesis and chondrocyte proliferation of a KOA patient, and is beneficial to regeneration and growth of articular cartilage of the KOA patient. Therefore, the corydalis tuber analgesic dropping pill can improve the expression level of the anti-inflammatory factor in the KOA model, thereby delaying the progress of the KOA.
EXAMPLE 2 clinical trials
In this example, 60 patients with knee osteoarthritis were subjected to clinical tests.
1. Clinical trial
1.1 general data
The invention brings 60 patients with knee osteoarthritis together, and randomly distributes the patients to A group (n is 30) and B group (n is 30), and the two groups of patients have no statistical significance (P is more than 0.05) in age, sex, height, weight, BMI, disease part, X-ray stage, blood routine before treatment and blood biochemical index, and have comparability.
1.2 diagnostic criteria
Case selection was performed according to the diagnostic criteria "osteoarthritis diagnosis and treatment guidelines" published by the bone science division of the chinese medical society in 2007:
(1) recurrent knee joint pain in nearly 1 month;
(2) x-ray slices (standing or weight bearing) indicate narrowing of joint space, subchondral bone sclerosis and/or cystic change, joint marginal osteophyte formation;
(3) synovial fluid (at least 2 times) is clear, viscous, WBC < 2000/ml;
(4) middle-aged and elderly patients (more than or equal to 40 years old);
(5) morning stiffness is less than or equal to 3 min;
(6) when the patient moves, the patient feels bone friction sound.
Note: the diagnosis of OA of knee joint can be realized by combining clinical, laboratory and X-ray examination and according to the conditions of (1) + (2), or (1) + (3) + (5) + (6), or (1) + (4) + (5) + (6).
1.3 inclusion criteria
(1) Meets the diagnosis standard of knee osteoarthritis;
(2) age 40 to 75 years;
(3) a Visual Analogue Scale (VAS) of greater than 10mm and less than 60 mm;
(4) inclusion of disease into early first, second and third stages with reference to performance on X-ray;
(5) no drug treatment was received within the last 2 weeks.
1.4 exclusion criteria
(1) Those who have undergone knee joint surgery in the past;
(2) patients with traumatic osteoarthritis;
(3) pregnant women, lactating women;
(4) the follow-up person can not be participated in within one month;
(5) severe primary diseases such as liver, kidney, hematopoietic system, digestive system, cardiovascular and cerebrovascular diseases, etc. are complicated;
(6) patients with knee tuberculosis, knee deformity, and malignant tumor;
(7) patients with mental diseases and can not participate in the coordination;
(8) those with a history of opioid analgesics, sedative hypnotics, and alcohol abuse;
(9) patients with allergic history of the test drugs.
1.5 methods of treatment
Treatment groups: rhizoma corydalis pain-relieving dripping pill, and can be administered orally. 30 pills at a time, 3 times a day. The administration is carried out for 4 weeks;
control group: diclofenac sodium sustained-release capsules for oral administration. Once 100mg (2 grains), 1 time a day, or once 50mg (1 grain), 2 times a day. The composition is administered for 4 weeks.
1.6 Observation index
(1) General record items, biological indicators, diagnostic indicators;
(2) the curative effect index is as follows: WOMAC osteoarthritis index score (table 2), visual simulation score (VAS);
(3) the safety index is as follows: general examination items: heart rate, respiration, blood pressure, body weight, etc. recorded according to an observation table; routine examination of blood, once before and after treatment; performing blood biochemical examination, wherein the examination is performed once before and after treatment; performing electrocardiographic examination once before and after treatment; gastrointestinal symptom rating scale (GSRS, table 3);
(4) research evaluation indexes are as follows: combining medication, compliance, dropping and elimination;
(5) the specification of observation time points comprises follow-up objects, indexes and time points; before treatment, one week after treatment and after treatment, the clinical outcome index observation is carried out.
Table 2 WOMAC score scale
TABLE 3 GSRS rating Scale
2. Results
2.1 clinical efficacy assessment based on VAS scores
2.1.1 differential test analysis of VAS scores before and after treatment in two groups of patients
The results are shown in table 4, where the differences between the VAS scores of both groups of patients were not statistically significant (P > 0.05) after one week of treatment and four weeks of treatment; and the VAS score of two groups of patients is obviously reduced after one week and four weeks of treatment compared with that of the same group before treatment (P is less than 0.05). The results show that the corydalis tuber pain-relieving dropping pill and the diclofenac sodium sustained-release capsule can better relieve the pain of the patient with the KOA.
TABLE 4 comparison of VAS scores before and after treatment in two groups of patients
Note: the comparison between the groups at each time point,*p is more than 0.05; compared with the treatment before the same group of treatment,#p is less than 0.05; compared with the treatment of the same group for one week,&P＜0.05。
2.1.2 non-adverse test analysis of VAS scores before and after treatment in two groups of patients
The results are shown in Table 5, where the differences between the VAS reduction values were not statistically significant in both groups after one and four weeks of treatment (P > 0.05). The non-inferiority threshold was 2 mm/4 mm for one week, the values were all less than 0.025 as shown by the one-sided t-test, and H0 was rejected. 95% CI shows: the interval lies entirely within the range of [ -2, ∞ ]/[ -4, ∞ ]. In summary, both groups are considered to be non-inferior in terms of efficacy, i.e. the effect of the corydalis tuber analgesic drop pills on pain relief in KOA patients is not inferior to that of the diclofenac sodium sustained release capsules, at the examination level of α ═ 0.025 (unilateral), either one week or four weeks after treatment.
TABLE 5 comparison of VAS reduction before and after treatment for two groups of patients
Note: d1One week of treatment VAS-pre-treatment VAS; d2Treatment with four weeks VAS-pre-treatment VAS; p: d value difference detection and comparison of two groups;
two groups of d values are compared by non-inferiority check.
2.2 clinical efficacy assessment of WOMAC Scale before and after treatment in two groups of patients
2.2.1 differential test analysis of WOMAC scores before and after treatment in two groups of patients
The results are shown in table 6, where both groups of patients had no statistical significance for the WOMAC total score and differences between the fractions after one week of treatment, four weeks of treatment (P > 0.05); the total WOMAC score and each item of the two groups of patients are obviously reduced after one week and four weeks of treatment compared with the same group of patients before treatment (P is less than 0.05). The results show that the corydalis tuber pain relieving dropping pill and the diclofenac sodium sustained-release capsule can better relieve the pain and the stiffness of the patient with the KOA and promote the recovery of the joint function.
TABLE 6 comparison of WOMAC Total score and score at each time point for two groups of patients: (
/(M,IQR))
Note: the comparison between the groups at each time point,*p is less than 0.05; compared with the treatment before the same group of treatment,#p is less than 0.05; compared with the treatment of the same group for one week,&P＜0.05。
2.2.2 non-inferiority test analysis of WOMAC scores before and after treatment in two groups of patients
The results are shown in Table 7, where no statistical significance was observed in the difference between the WOMAC score reduction values of the two groups of patients after one or four weeks of treatment (P > 0.05). The non-inferiority threshold was 3.51 mm/four weeks 3.74mm for one week, and the one-sided t-test results showed values less than 0.025, rejecting H0. 95% CI shows: the interval lies entirely within the range of [ -3.51, ∞ ]/[ -3.74, ∞ ]. In summary, the therapeutic effect of the treatment group is considered to be non-inferior to that of the control group, i.e., the pain relieving effect of the corydalis tuber analgesic dropping pill on the pain relieving, stiffness relieving and joint function recovering of KOA patients is not inferior to that of the diclofenac sodium sustained-release capsule, no matter whether the treatment is carried out for one week or four weeks, at the examination level of α ═ 0.025 (unilateral).
TABLE 7 comparison of WOMAC degradation before and after treatment for two groups of patients
Note: d1WOMAC-pre-treatment WOMAC for one week; d2Treatment with four weeks WOMAC-pretreatment WOMAC;
p: d value difference detection and comparison of two groups;
two groups of d values are compared by non-inferiority check.
2.3 comparison of the mean values of the scores based on the WOMAC Scale
2.3.1 comparison of pain scores in WOMAC scores at each time point of treatment in two groups of patients
The results are shown in Table 8, with comparisons P > 0.05 between the time points; compared with the prior treatment, the P of the same group is less than 0.05 after one week of treatment and four weeks of treatment, which indicates that the corydalis tuber pain-relieving dropping pill and the diclofenac sodium sustained-release capsule can better relieve the pain of the patient with KOA.
TABLE 8 comparison of pain scores before and after treatment for two groups of patients
2.3.2 comparison of stiffness scores in WOMAC scores at each time point of treatment in two groups of patients
The results are shown in Table 9, with comparisons P > 0.05 between the time points; compared with the same group which is treated for one week and four weeks, the P is less than 0.05, which shows that the corydalis tuber pain relieving dripping pill and the diclofenac sodium sustained-release capsule can better relieve the joint stiffness of the KOA patient.
TABLE 9 comparison of stiffness scores before and after treatment for two groups of patients
2.3.3 comparison of Activity difficulty scores in the WOMAC score at each time point of treatment for two groups of patients
The results are shown in table 10, where P is <0.05 compared to the same group after one week of treatment and four weeks of treatment, and the difficulty of activity score of the experimental group is lower than that of the control group after one week of treatment compared to the control group. Namely, compared with the diclofenac sodium sustained-release capsule, the corydalis tuber analgesic dropping pill can more quickly promote the recovery of the joint movement function of the patient with the KOA.
TABLE 10 comparison of WOMAC Activity difficulty scores before and after treatment in two groups of patients
2.3.4 comparison of Total score scores in WOMAC scores at each time point of treatment in two groups of patients
The results are shown in Table 11, with comparisons P > 0.05 between the time points; p is less than 0.05 compared with P after one week of treatment and four weeks of treatment in the same group. The results show that the corydalis tuber pain relieving dropping pill and the diclofenac sodium sustained-release capsule can better relieve the pain and the stiffness of the patient with the KOA and promote the recovery of the joint function.
TABLE 11 comparison of WOMAC Total scores before and after treatment in two groups of patients
2.4 safety evaluation before and after treatment of two groups of drugs
2.4.1 comparison of blood routine indices before and after treatment
The results are shown in table 12, and the differences between the blood routine groups after four weeks of treatment of two groups of patients and before the treatment of the same group have no statistical significance, which indicates that the blood routine of KOA patients before and after the treatment of the corydalis tuber analgesic dripping pills has no influence (P is more than 0.05).
TABLE 12 comparison of blood routine indices before and after treatment
Note: compared with the treatment before the same group of treatment,#P＜0.05。
2.4.2 comparison of biochemical indices of blood before and after treatment
The results are shown in Table 13, and the differences between the biochemical blood indicators of the two groups of patients after four weeks of treatment have no statistical significance (P is more than 0.05) compared with the biochemical blood indicators of the same group before treatment, which indicates that the biochemical blood indicators of the KOA patients before and after the treatment of the corydalis tuber pain-relieving drop pills have no influence.
TABLE 13 Biochemical index comparison of blood before and after treatment: (
/(M,IQR))
2.4.3 Security evaluation based on GSRS Scale
The results are shown in Table 14, where the differences between the two groups of patients treated for one and four weeks were statistically significant (P <0.05) compared to the same group before treatment; after treatment, the GSRS score of the patients in the test group is obviously reduced compared with that before treatment, and after treatment, the GSRS score of the patients in the control group is obviously improved compared with that before treatment. The result shows that when the diclofenac sodium sustained-release capsule is used for treating the KOA, the adverse reaction of the gastrointestinal tract is larger, and when the corydalis tuber analgesic dropping pill is used for treating the KOA, the adverse reaction of the gastrointestinal tract is basically not generated, the safety is better, and the diclofenac sodium sustained-release capsule is suitable for long-term administration.
TABLE 14 comparison of GSRS scores at each time point for two groups of patients (M, IQR)
Note:*p: comparing the time points among groups;#p: compared to the same group before treatment;&p: compared with the same group at one week of treatment.
2.4.4 two sets of mean comparisons based on GSRS scores
Results as shown in table 15, the differences in GSRS scores in the experimental group compared to the control group were statistically significant (P <0.05) after one and four weeks of treatment. The result shows that when the diclofenac sodium sustained-release capsule is used for treating the KOA, the adverse reaction of the gastrointestinal tract is larger, and when the corydalis tuber analgesic dropping pill is used for treating the KOA, the adverse reaction of the gastrointestinal tract is basically not generated, the safety is better, and the diclofenac sodium sustained-release capsule is suitable for long-term administration.
TABLE 15 comparison of GSRS scores (MIQR) at each time point for two groups of patients
Note:*p: comparing the time points among groups;#p: compared to the same group before treatment;&p: compared with the same group at one week of treatment.
In conclusion, the corydalis tuber analgesic dropping pill can adjust the expression level of the anti-inflammatory factor in the KOA model, can obviously relieve the inflammatory symptoms of a rat in the KOA model, reduce the content of the inflammatory factor IL-1 alpha, and can inhibit the cartilage degradation of a patient with KOA; promote TGF-beta secretion, can stimulate proteoglycan synthesis and chondrocyte proliferation of a KOA patient, and is helpful for regeneration and growth of articular cartilage of the KOA patient, thereby delaying the progress of the KOA; the corydalis tuber pain relieving dropping pill can obviously relieve the pain symptom of knee joints of patients with mild and moderate KOA, and the pain relieving effect is not weaker than that of a diclofenac sodium sustained-release capsule; the corydalis tuber analgesic dropping pill can effectively improve the functions of knee joints of patients with mild and moderate KOA, has obvious curative effects particularly in the aspects of stiffness, difficulty in joint movement, secretion of inflammatory factors and the like, and has no weak effect than that of a diclofenac sodium sustained-release capsule; the side effects of the gastrointestinal tract are low when the corydalis tuber pain-relieving dropping pill (more than or equal to 2 weeks) is taken for a long time, and the pill has good safety.
The above description is intended to describe in detail the preferred embodiments of the present invention, but the embodiments are not intended to limit the scope of the claims of the present invention, and all equivalent changes and modifications made within the technical spirit of the present invention should fall within the scope of the claims of the present invention.
Claims (10)
1. The application of the corydalis tuber analgesic dropping pill in preparing the medicine for inhibiting the generation of the inflammatory factor IL-1 alpha is that the corydalis tuber analgesic dropping pill consists of corydalis tuber processed by vinegar and angelica dahurica with the weight ratio of 1:1-3: 1.
2. The application of the corydalis tuber pain relieving dropping pill in preparing a medicine for inhibiting cartilage degradation comprises corydalis tuber processed with vinegar and angelica dahurica in a weight ratio of 1:1-3: 1.
3. The rhizoma corydalis pain-relieving dropping pill is applied to preparing a medicine for promoting generation of inflammatory factor TGF-beta, and consists of vinegar-processed rhizoma corydalis and radix angelicae in a weight ratio of 1:1-3: 1.
4. The application of the corydalis tuber analgesic dropping pill in preparing the medicine for promoting the synthesis of proteoglycan comprises corydalis tuber and angelica dahurica which are processed by vinegar and have the weight ratio of 1:1-3: 1.
5. The application of the corydalis tuber analgesic dropping pill in preparing the medicine for promoting the proliferation of the chondrocytes is that the corydalis tuber analgesic dropping pill consists of corydalis tuber processed by vinegar and angelica dahurica with the weight ratio of 1:1-3: 1.
6. The application of the rhizoma corydalis pain-relieving dropping pill in preparing a medicine for inhibiting inflammation comprises vinegar-processed rhizoma corydalis and radix angelicae in a weight ratio of 1:1-3: 1.
7. The rhizoma corydalis pain-relieving dropping pill is applied to the preparation of the medicine for assisting in inhibiting knee osteoarthritis inflammation symptoms, and consists of vinegar-processed rhizoma corydalis and radix angelicae in a weight ratio of 1:1-3: 1.
8. The application of the rhizoma corydalis pain-relieving dropping pill in preparing the medicine for treating knee osteoarthritis is that the rhizoma corydalis pain-relieving dropping pill consists of corydalis tuber and angelica dahurica which are processed by vinegar and have the weight ratio of 1:1-3: 1.
9. The application of the rhizoma corydalis pain-relieving dropping pill in preparing the medicine for promoting the joint function recovery comprises rhizoma corydalis and radix angelicae dahuricae which are processed by vinegar and have the weight ratio of 1:1-3: 1.
10. The application of the corydalis tuber pain relieving dropping pill in preparing the medicine for relieving the joint stiffness comprises corydalis tuber processed with vinegar and angelica dahurica in a weight ratio of 1:1-3: 1.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN116019856A (en) * | 2023-02-23 | 2023-04-28 | 河南福森药业有限公司 | New use of rhizoma corydalis pain relieving oral liquid |
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Application publication date: 20200811 |