CN102697887A - Traditional Chinese medicine composition for treating rheumatoid arthritis - Google Patents
Traditional Chinese medicine composition for treating rheumatoid arthritis Download PDFInfo
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- CN102697887A CN102697887A CN2012102114101A CN201210211410A CN102697887A CN 102697887 A CN102697887 A CN 102697887A CN 2012102114101 A CN2012102114101 A CN 2012102114101A CN 201210211410 A CN201210211410 A CN 201210211410A CN 102697887 A CN102697887 A CN 102697887A
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Abstract
The invention discloses a traditional Chinese medicine composition for treating rheumatoid arthritis. The composition is prepared from the following traditional Chinese medicines in parts by weight: 8-45 parts of radix angelicae pubescentis, 2-10 parts of radix clematidis and 0.2-2 parts of curcumin. Shown by pharmacological researches, the traditional Chinese medicine composition is better in anti-inflammation and antalgic action, and moreover, an obvious treatment effect is shown on experimental arthritis model animals. Compared with the prior art, the traditional Chinese medicine composition disclosed by the invention is good in curative effect and is safe and reliable, so that the traditional Chinese medicine composition is good in application prospect.
Description
Technical field
The invention belongs to the field of Chinese medicines, be specifically related to a kind of Chinese medicine composition of treating rheumatoid arthritis.
Background technology
Rheumatoid arthritis (Rheumatoid arthritis; RA) be a kind of be the chronic systemic autoimmune disease of characteristic with the articular synovitis; Synovitis continues outbreak repeatedly; The destruction that can cause intraarticular cartilage and bone, the amyotrophy on every side of joint in late period, the tetanic even permanent disability of diseased joints generation deformity property.
RA sickness rate worldwide is about 0.5%-1% at present, and RA has tangible disability rate, greatly reduces people's quality of life, has increased family and burden on society.Yet because pathogenesis is fuzzy, RA still belongs to a kind of refractory disease at present.The medicine of treating RA clinically mainly contains four big types: NSAID, glucocorticoid, act on antirheumatic and biological preparation slowly.The characteristics of NSAID are can alleviate the symptom of RA but the development that can not control RA, and have side effect such as gastrointestinal tract, liver, kidney, blood system.Glucocorticoid has stronger antiinflammatory action and certain immunosuppressive action, except that the symptom of improving RA, can also change the course of disease of RA.Yet such medicine has stronger side effect, and long-term prescription can cause osteoporosis, osteonecrosis, adrenal cortex atrophy, serious complication such as secondary infection.Slowly act on antirheumatic and comprise again and improve state of an illness medicine and immunosuppressant, their common feature also is can relieve clinical symptoms, can change the course of disease of RA again.Medicine commonly used has: leflunomide, methotrexate, sulfasalazine, anti-malarial agents, golden preparation, penicillamine, cyclophosphamide, ciclosporin, Radix Tripterygii Wilfordii etc.In recent years; Gold preparation, penicillamine etc. are big because of DeGrain, toxic and side effects; It is used gradually and reduces, and the use of methotrexate, the sharp Radix Tripterygii Wilfordii of sulfasalazine then is and increases trend gradually, but these medicines also exist obvious toxic and side effects; Not only have genotoxicity like the Radix Tripterygii Wilfordii preparation, also can produce serious adverse liver, kidney, immune system, blood and heart etc.The application of biological preparation makes the treatment of RA get into the targeted therapy stage; But it has also exposed a lot of shortcomings gradually in process of clinical application; Not only can increase the sickness rate of tumor like the TNF-alpha inhibitor, also possibly bring out other immune disease such as systemic lupus erythematosus (sle) etc.In addition, biological preparation is because price comparison is expensive, and it is used and has also received very big restriction.
RA belongs to Chinese medical ' arthralgia syndrome ' category, " element is asked the numbness opinion " record " wet three gas of wind and cold are assorted extremely, close and be numbness ", and think that meridians are inaccessible, QI and blood is obstructed to be its pathogenesis.Chinese traditional treatment RA is with a long history; Treatment to RA is main with wind-damp dispelling pain relieving and blood circulation promoting and blood stasis dispelling; The monomer of part Chinese medicine, effective site and compound recipe have obtained application clinically, but the popularization in not ideal enough or toxic and side effects fails greatly to obtain in a big way owing to curative effect.
Summary of the invention
The object of the present invention is to provide a kind of Chinese medicine composition of treating rheumatoid arthritis safely and effectively.
The Chinese medicine composition of treatment rheumatoid arthritis provided by the present invention is to be that feedstock production forms with Radix Angelicae Pubescentis, Radix Clematidis and curcumin, and the weight portion proportioning of each component is: Radix Angelicae Pubescentis 8-45 part, Radix Clematidis 2-10 part, curcumin 0.2-2 part.
Be preferably: Radix Angelicae Pubescentis 12-30 part, Radix Clematidis 3-8 part, curcumin 0.5-1.5 part.
Further be preferably: Radix Angelicae Pubescentis 15-25 part, Radix Clematidis 4-6 part, curcumin 0.8-1.2 part.
Further be preferably: 20 parts of Radix Angelicae Pubescentiss, 5 parts of Radix Clematidis, 1 part of curcumin.
Chinese medicine composition of the present invention is to be active component with the extractive with organic solvent of Radix Angelicae Pubescentis, Radix Clematidis and curcumin, adds the pharmaceutical preparation that pharmaceutically acceptable various adjuvant is prepared from.
The method for preparing of Chinese medicine composition of the present invention may further comprise the steps:
1) Radix Angelicae Pubescentis is ground into coarse powder, with alcohol reflux 2-4 time, concentration of ethanol is >=40%, collects extracting solution, filters, and merging filtrate concentrates, drying, extract A;
2) Radix Clematidis is ground into coarse powder, the alcohol reflux of adding 30%-95% 2-4 time is collected extracting solution, filters, and merging filtrate concentrates, and drying gets extract B;
3) extract A and extract B are merged, pulverize, add curcumin, be prepared into dosage form pharmaceutically commonly used.
The consumption of ethanol of the concentration above-mentioned steps 1) >=40% is 4-10 a times of medical material weight, and each time of extracting is 1-3 hour;
Step 2) concentration described in is that the consumption of ethanol of 30%-95% is 5-12 a times of medical material weight, and each time of extracting is 1-3 hour.
To be said Chinese medicine composition be used for treating the application of the medicine of rheumatoid arthritis in preparation in application provided by the present invention.
Chinese medicine composition of the present invention is to be that feedstock production forms with Radix Angelicae Pubescentis, Radix Clematidis and curcumin; Radix Angelicae Pubescentis in the prescription is the dry root of the heavy peristome Radix Angelicae Sinensis of Umbelliferae herbaceous plant; Radix Clematidis is the dry root and rhizome of ranunculaceae plant Radix Clematidis, Cotton Gossypii Radix clematidis floridae or northeast clematis; The two all has the effect of expelling wind and removing dampness, arthralgia aggravated by cold pain relieving, is the common drug of Chinese traditional treatment rheumatoid arthritis.Research shows that Radix Angelicae Pubescentis has the anti-immunization of stronger antiinflammatory, and its main component of bringing into play anti-RA effect possibly be coumarin kind compound.As traditional wind-damp dispelling key medicine; Radix Clematidis is used for the with a long history of treatment " arthromyodynia ", and modern study shows that Radix Clematidis has obvious anti-inflammatory and analgesic effect; But the material base of its anti-inflammatory and antalgic is conclusive evidence also, possibly be the higher Radix Clematidis total glycosides of content wherein.
The pathogenesis of relevant RA, although not clear and definite fully as yet at present, the research of recent years shows that angiogenesis is one of characteristic of the early stage synovial membrane pathological change of RA, also is the principal element that produces and keep the RA pannus.RA patient's synovial hyperplasia, the increase of synovial fluid volume not only cause arthroncus, pain; The distance of synovial cell and adjacent blood vessel is increased; Thereby make synovial tissue's anoxia, hypoperfusion, and anoxia can be induced the formation of new vessels as the potential signal of angiogenesis.New vessels also makes more cytokine, inflammatory factor and macrophage etc. soak into synovial membrane when for synovial membrane a large number of nutrients being provided, and has further promoted the hypertrophy of synovial membrane and the formation of pannus, causes vicious cycle.Therefore, suppress the latent effect target spot that new vessels forms has become the RA treatment at present.Curcumin is a kind of phenols pigment that from the zingiberaceous plant Rhizoma Curcumae Longae, extracts, and also is present in other zingiberaceous plant such as Rhizoma Curcumae, the Radix Curcumae, and Rhizoma Curcumae Longae, Rhizoma Curcumae, Radix Curcumae are blood-activating and stasis-removing.Curcumin has multiple pharmacological effect such as antiinflammatory, antitumor, angiogenesis inhibitor, antioxidation, has therefore become the domestic and international research focus in recent years.The blood vessel formation against function of curcumin has obtained checking in multinomial experiment, and has research to think, the blood vessel formation against function of curcumin is that the activity through proteolytic enzyme in the angiogenesis realizes.
The present invention has following advantage:
Therefore 1, the prescription of Chinese medicine composition not only meets Chinese medical theory, has also used contemporary pharmacology to the pathogenetic up-to-date understanding of RA fully, has advantages such as prescription is reasonable, evident in efficacy.
2, the raw materials used equal safety non-toxic of Chinese medicine composition in treatment RA, can not produce obvious toxic and side effects, and cost is lower, and is cheap.
Through following experimental example curative effect of the present invention and safety are done further elaboration.
The analgesic activity of experimental example 1 Chinese medicine composition of the present invention
1. material
1.1 laboratory animal
A cleaning level ICR mice, male and female half and half, body weight 18～22g is provided by Yangzhou University comparative medicine center, the quality certification number: SCXK (Soviet Union) 2007-0001.
1.2 medicine
The preparation of Chinese medicine composition of the present invention: Radix Angelicae Pubescentis 1500g is pulverized, and the concentration that adds 8 times of amounts is 60% alcohol reflux 2 times, each 3 hours, collect extracting solution, filter, merging filtrate concentrates, drying, extract A; Radix Clematidis 900g is pulverized, and the concentration that adds 6 times of amounts is 70% alcohol reflux 2 times, 3 hours for the first time, 2 hours for the second time, collect extracting solution, filter, merging filtrate concentrates, drying, extract B; Extract A and extract B are merged, and pulverizing adds 85g curcumin mixing, faces with preceding to be made into needed respective concentration with carboxymethylcellulose sodium solution (0.5% CMC-Na solution).
Celecoxib capsule (Celecoxib Capsules): the pfizer inc import divides packing, lot number: 1000323, and specification: 0.2g, the CMC-Na that faces with preceding usefulness 0.5% is made into needed respective concentration.
2. method
Adopt glacial acetic acid to cause the mouse writhing reaction experiment; 50 of ICR mices; Male and female half and half are divided into 5 groups at random, 10 every group; Be respectively model group (giving 0.5% CMC-Na solution), positive controls (celecoxib, 60mg/kg), Chinese medicine composition high dose group (2.4g crude drug/kg), middle dose groups (1.2g crude drug/kg), low dose group (0.6g crude drug/kg).It is 0.2ml/10g that each group all adopts gastric infusion, capacity.
After each organized mice administration 1h, the glacial acetic acid 0.2ml of every mouse peritoneal injection 0.7%, record respectively organized time (latent time) and the interior number of times of turning round body of 15min that writhing response appears for the 1st time in mice.
3. result
Compare with model group; Chinese medicine composition object height (2.4g/kg), in (1.2g/kg) dose groups can obviously prolong time (P＜0.05 that occurs writhing response after the mice 0.7% glacial acetic acid modeling for the first time; P＜0.01); Chinese medicine composition object height (2.4g/kg), in (1.2g/kg), low (0.6g/kg) three dose groups all can significantly reduce occur in the 15min after the modeling turn round body number of times (P＜0.05; P＜0.01), shows that this Chinese medicine composition has analgesic activity preferably to glacial acetic acid induced mice pain reaction.The result sees table 1
Table 1 Chinese medicine composition is to the influence
of glacial acetic acid induced mice pain reaction
Compare with model group,
*P＜0.05,
*P＜0.01
The antiinflammatory action of experimental example 2 Chinese medicine compositions of the present invention
1. material
1.1 laboratory animal
A cleaning level ICR mice, male, body weight 18～22g is provided by Yangzhou University comparative medicine center, the quality certification number: SCXK (Soviet Union) 2007-0001; A cleaning level SD rat, male, body weight 180～200g is provided by Suzhou Industrial Park Ai Ermaite Science and Technology Ltd., the quality certification number: SCXK
(Soviet Union) 2009-0001.
1.2 medicine
The preparation of Chinese medicine composition of the present invention: with experimental example 1.
Celecoxib capsule (Celecoxib Capsules): the pfizer inc import divides packing, lot number: 1000323, and specification: 0.2g, the CMC-Na that faces with preceding usefulness 0.5% is made into required respective concentration.
Dexamethasone acetate tablets: Shandong Lukang Cisen Pharmaceutical Co., Ltd, specification: 0.75mg, the CMC-Na that faces with preceding usefulness 0.5% is made into required respective concentration.
2. method
2.1 mice caused by dimethylbenzene xylene auricle edema experiment
50 of ICR mices; Be divided into 5 groups at random; Every group 10, be respectively model group (0.5% CMC-Na solution), positive controls (celecoxib, 60mg/kg), Chinese medicine composition high dose group (2.4g crude drug/kg), middle dose groups (1.2g crude drug/kg), low dose group (0.6g crude drug/kg).It is 0.2ml/10g that each group all adopts gastric infusion, capacity, every day 1 time, successive administration 7 days.Behind last administration 1h, xylene 0.02ml is uniformly coated on the wide two sides, front and back of mouse right ear causes inflammation, do contrast with left auricle.After causing scorching 1h mice is taken off cervical vertebra execution, cut two ears, respectively get an auricle with the card punch of 9mm in same position and weigh along the auricle baseline.Calculate swelling degree and inhibitory rate of intumesce (%):
Swelling degree (mg)=cause scorching auricle weight-control sides auricle to weigh,
Inhibitory rate of intumesce (%)=[(the average swelling degree of the model group-average swelling degree of medication group)/average swelling degree of model group] * 100%
2.2 cotton balls is induced the experiment of rat granuloma
2.2.1 animal divides into groups
50 of SD rats; Be divided into 5 groups at random; Every group 10, be respectively model group (0.5% CMC-Na solution), positive controls (dexamethasone, 0.4mg/kg), Chinese medicine composition high dose group (1.8g crude drug/kg), middle dose groups (0.9g crude drug/kg), low dose group (0.45g crude drug/kg).It is 0.8ml/100g that each group all adopts gastric infusion, capacity.
2.2.2 cotton balls preparation
The preparation diameter is the rayon balls of 6.5～8.5mm; Quality is 10 ± 1mg/; Above-mentioned cotton balls is immersed in the lmin that sterilizes in 75% ethanol, takes out cotton balls, on each cotton balls, add 1mg penicillin sodium/0.1ml normal saline again in 50 ℃ of stove-dryings; 50 ℃ of stove-dryings are accurately weighed behind the natural cooling.
2.2.3 cotton balls heeling-in and administration
Rat is with 10% urethane (9ml/kg) intraperitoneal injection of anesthesia, and it is subcutaneous that the cotton balls of having weighed is implanted rat both sides axillary fossa respectively, immediately skin suture.Operation began administration the same day, every day 1 time, continuous 7 days, rat was taken off cervical vertebra in the 8th day to put to death, take out cotton balls in 60 ℃ of oven for drying to constant weight, deduct the raw cotton QIUJING and heavily be granuloma weight (representing) with the mg/100g body weight.Respectively organize granuloma weight and calculate suppression ratio (%):
Suppression ratio=[(the granulomatous average weight of the model group-granulomatous average weight of medication group)/granulomatous average weight of model group] * 100%
2.3 statistical procedures
Experimental data is represented with
; Adopt one factor analysis of variance to carry out date processing, relatively adopt the t check between group.
3. result
3.1 the Chinese medicine composition xylol causes the influence of mice auricle swelling
Compare with model group, Chinese medicine composition object height (2.4g/kg), in (1.2g/kg), low (0.6g/kg) dose groups all can significantly suppress mice auricle swelling (P＜0.05, P＜0.01), and dosage is big more, suppression ratio is high more.The result sees table 2
Table 2 Chinese medicine composition xylol causes the influence
of mice auricle swelling
Compare with model group,
*P＜0.05,
*P＜0.01
3.2 Chinese medicine composition is to the granulomatous influence of the inductive rat of cotton balls
Cotton balls is implanted and to be begun administration the same day, and successive administration 7 days took off cervical vertebra with rat on the 8th day to put to death, and won the cotton balls the axillary fossa of rat both sides under, in 60 ℃ of oven for drying to constant weight, accurately weighing, the observation Chinese medicine composition is to the granulomatous influence of the inductive rat of cotton balls.The result sees table 3
Table 3 Chinese medicine composition is to the bullate influence of rat granuloma
Compare with model group,
*P＜0.05,
*P＜0.01
Visible by table 3, Chinese medicine composition object height (1.8g/kg), in the granuloma weight of (0.9g/kg), low (0.45g/kg) dose groups be starkly lower than model group (P＜0.05, P＜0.01).Each dose groups of Chinese medicine composition all has inhibitory action in various degree to the inductive rat granuloma of cotton balls, and suppression ratio raises with the increase of dosage.
Experimental example 3 Chinese medicine compositions of the present invention are to the therapeutical effect of adjuvant arthritis rats
1. material
1.1 laboratory animal
A cleaning level SD rat, male, body weight 130～160g is provided by Suzhou Industrial Park Ai Ermaite Science and Technology Ltd., the quality certification number: SCXK (Soviet Union) 2009-0001.
1.2 medicine and reagent
The preparation of Chinese medicine composition of the present invention: with experimental example 1.
Leflunomide tablet (Leflunomide Tables), Suzhou ChangZheng-Xinkai Pharmaceutical Co.,Ltd, lot number: 100520, specification: 10mg, the CMC-Na that faces with preceding 0.5% is made into desired concn.
Adjuvant is used bacillus calmette-guerin vaccine: Beijing Biological Product Inst., and lot number: 20100413, specification: 60mg/ props up.
Liquid paraffin: Shanghai Ling Feng chemical reagent company limited, lot number: 080512.
Benzalkonium bromide solution (Xin Guer goes out): the Jiangxi moral becomes pharmaceutical Co. Ltd, lot number: 20100902.
Modified form RPMI-1640 culture medium: Sai Mo flies generation that biochemistry goods (Beijing) company limited, lot number: NVL0333.
Calf serum: Hangzhou Sijiqing Biological Engineering Material Co., Ltd.'s product, packing behind 56 ℃ of water-bath deactivation 30min ,-20 ℃ of preservations.
3-(4,5 dimethyl-thiazole-2)-2,5 diphenyl tetrazole bromine salt (MTT): the Sigma Company products, face with preceding with PBS (0.01M PH7.4) is made into the MTT solution of 5mg/ml, the filtering with microporous membrane degerming, 4 ℃ keep in Dark Place.
Dimethyl sulfoxide (DMSO): Shanghai Ling Feng chemical reagent company limited provides lot number: 080413.
Concanavalin A, Con A (ConA): the Sigma Company products, use D-Hank ' s liquid to be made into the storing solution that concentration is 2.5mg/ml.
Lipopolysaccharide (LPS): Sigma Company products, lot number: 029K4023.Use D-Hank ' s liquid to be made into the storing solution that concentration is 2.5mg/ml.
D-Hank ' s solution: take by weighing NaCl 8.00g, KCl 0.40g, Na
2HPO
412H
2O 0.12g, KH
2PO
40.06g, NaHCO
30.35g be dissolved in the 1000ml tri-distilled water autoclaving, 4 ℃ of preservations.
TNF-α, IL-1 β, IL-6 enzyme-linked immunologic detecting kit: Nanjing is built up bio-engineering research and is provided.
1.2 instrument
YLS-7B type toes volumetric measurement appearance: the Jinan benefit is prolonged development in science and technology company limited product.
SW-CJ-2F clean bench: SuZhou Antai Air Tech Co., Ltd..
CO
2Cell culture incubator: U.S. Thermo electron product.
XDS-1B type inverted microscope: Chongqing optical instrument head office.
DG5031 type enzyme-linked immunosorbent assay instrument: medical equipment Co., Ltd of East China Electronics Co., Ltd group.
0412-1 table-type low-speed centrifuge: Shanghai Medical Appliance (Group) Co., Ltd. Surgical Instruments Factory.
HH-S type electric-heated thermostatic water bath: Dongtai City, Jiangsu Province electrical apparatus factory.
KH-600DB type numerical control supersonic washer: Kunshan standing grain wound ultrasonic instrument company limited.
DGX-914B-1 electric drying oven with forced convection: Shanghai good fortune agate testing equipment company limited.
2. method
2.1 the foundation of rat assist agent arthritis (AA) model
With 80 ℃ of water-bath 1h of bacillus calmette-guerin vaccine deactivation, fully grind mixing with autoclaved liquid paraffin, be mixed with the Emulsion that concentration is 10g/L, be Freund's complete adjuvant (Freund ' s complete adjuvant, FCA).Except that the normal control group, cause inflammation in every the left back toes intradermal injection of rat 0.1ml FCA, cause and be designated as d0 the scorching same day.
2.2 divide into groups and administration
Cause scorching back d14; The rat that modeling is successful is divided into 5 groups at random; Every group 10, be respectively model group, leflunomide group (Lef, 5mg/kg), Chinese medicine composition high dose group (1.8g crude drug/kg), middle dose groups (0.9g crude drug/kg), low dose group (0.45g crude drug/kg).D14 begins administration, successive administration 16 days.Each administration group adopts gastric infusion, and every day 1 time, the administration capacity is 0.6ml/100g; Irritate normal control group and model group every day stomach for 1 time and give 0.5% CMC-Na solution of equivalent.
2.3 the mensuration of sufficient pawl swelling degree and the scoring of sufficient pawl
Before the Yu Zhiyan (d0) and cause scorching back d14, d18, d22, d26, d30 and measure with toes volumetric measurement appearance and respectively organize the right back sufficient pawl volume of rat, obtain swelling degree (Δ mm=causes the scorching preceding volume of scorching back volume-cause).Simultaneously, cause scorching back d14, d18, d22, d26, d30 and respectively rat is carried out sufficient pawl scoring, standards of grading are: by the scoring of 0～4 Pyatyi, 0=does not have redness; The 1=toe joint is red and swollen; 2=toe joint and toes swelling; Sufficient pawl swelling below the 3=ankle joint; 4=comprises the whole sufficient pawl swelling of ankle joint.The scoring sum of all the other 3 the sufficient pawls except that left back sufficient pawl is the arthritis index of this rat, and (arthritic index, AI), peak is 12.
2.4 splenic lymphocytes
D31 sacrificed by decapitation rat after modeling cleans up the rat of putting to death earlier with 0.1% bromo geramine solution, put into 75% alcoholic solution immersion 10min again with sufficiently sterilised.The aseptic spleen of getting is put into gauze (200 order); And gauze put into the plate of containing D-Hank ' the s liquid contain 10% calf serum; Reject fat and connective tissue, the spleen tissue that is cut into small pieces is twisted into pieces with the syringe nook closing member gently, individual cells is got in D-Hank ' the s liquid through gauze.Solution is moved in the centrifuge tube, and the centrifugal 5min of 1500r/min inhales and abandons supernatant, uses D-Hank ' s liquid washed cell 3 times, adds to contain the RPMI RPMI-1640 2ml suspension cell of 10% calf serum and make cell counting, and the adjustment cell concentration is 1 * 10
10/ L.
Every hole adds 100 μ l splenocyte suspensions (final concentration is 5 * 10 on 96 well culture plates
9/ L), adding the RPMI1640 culture fluid that 100 μ l contain ConA (final concentration is 5mg/L, inducer T lymphocyte propagation) or LPS (final concentration is 6mg/L, induces bone-marrow-derived lymphocyte propagation) again, whole volume is 200 μ l, respectively establishes 3 multiple holes.Put 37 ℃, 5%CO
2Cultivate 48h in the incubator; The every hole of 4h adds the MTT solution 20 μ l of 5mg/ml before stopping cultivation, continues to cultivate 4h, cultivates careful suction the in end back and abandons supernatant; Every hole adds DMSO100 μ l; Fully concussion is dissolved crystallization fully, measures absorbance (A) value in ELIASA 490nm wavelength, and the result is with the equal value representation of 3 multiple hole A.
2.5AA TNF-α, IL-1 β and IL-6 Determination on content in the rat blood serum
D30 takes a blood sample to each group rat eye socket rear vein beard after modeling, with the centrifugal 15min of blood 3000r/min, and separation of serum ,-20 ℃ of preservations.The mensuration of TNF-α, IL-1 β and IL-6 adopts the ELISA method in the serum, presses the operation of test kit description.
2.6 statistical procedures
Experimental data is represented with
; Adopt one factor analysis of variance to carry out date processing, relatively adopt the t check between group.
3. result
3.1 Chinese medicine composition is to the influence of AA rat foot claw swelling degree
D19 after the modeling, the non-sufficient pawl of scorching side (right back) that causes of part rat begins to occur Secondary cases swelling.Tangible secondary inflammation has all appearred in most of rat during d14, shows as right back foot and front foot and obvious swelling occurs, the movable minimizing, and allergic pannus etc. appears in eyes.The rat random packet that d14 is successful with modeling also begins administration, successive administration 16 days.And measure respectively in d14, d18, d22, d26, d30 and to organize respectively that rat is non-to cause scorching parapodum pawl volume, the result sees table 4
Table 4 Chinese medicine composition is to the influence
of AA rat foot claw swelling degree
Compare with the normal control group,
#P＜0.05,
##P＜0.01; Compare with model group,
*P＜0.05,
*P＜0.01
Visible by table 4, to compare with the normal control group, model group rat foot claw swelling degree obviously increases (P＜0.01); Chinese medicine composition administration group begins to bring into play curative effect from causing scorching back d22; Compare with model group; Chinese medicine composition high dose group (1.8g/kg), middle dose groups (0.9g/kg), low dose group (0.45g/kg) all can obviously suppress AA rat Secondary cases foot swelling (P＜0.05, P＜0.01).
3.2 Chinese medicine composition is to the exponential influence of AA rat arthritis
Cause scorching back d14 and begin each group rat to be carried out sufficient pawl scoring in per 4 days, visible by table 5, to compare with model group, each dose groups of Chinese medicine composition all can significantly reduce the AI (P＜0.05, P＜0.01) of AA rat.
Table 5 Chinese medicine composition is to the exponential influence of AA rat arthritis
Compare with model group,
*P＜0.05,
*P＜0.01
3.3 Chinese medicine composition is to the influence of ConA, the inductive rat splenic lymphocytes of LPS
The result is as shown in table 6; With compared with normal; The all obviously risings (P＜0.01) of the inductive splenic lymphocytes of the sharp LPS of model group rat ConA; Chinese medicine composition object height, middle dose groups all have obvious suppression effect (P＜0.05, P＜0.01) to the splenic lymphocytes that the AA rat raises.
Table 6 Chinese medicine composition is to the influence
of AA rat splenic lymphocytes
Compare with the normal control group,
#P＜0.05,
##P＜0.01; Compare with model group,
*P＜0.05,
*P＜0.01
3.4 Chinese medicine composition is to the influence of TNF-α, 1L-1 β and IL-6 level in the AA rat blood serum
The result is as shown in table 7, compares all obviously risings (P＜0.01) of the content of TNF-α, IL-1 β and IL-6 in the model group rat blood serum with the normal control group; And the content of the high, medium and low dose groups TNF-α of Chinese medicine composition, IL-1 β and IL-6 is compared all significantly reduction (P＜0.05, P＜0.01) with model group.
Table 7 Chinese medicine composition is to the influence
of TNF-α, IL-1 β and IL-6 level in the AA rat blood serum
Compare with the normal control group,
#P＜0.05,
##P＜0.01; Compare with model group,
*P＜0.05,
*P＜0.01
Experimental example 4 Chinese medicine compositions of the present invention are to the acute toxicity test of mice
1. material
1.1 laboratory animal
A cleaning level ICR mice, male and female half and half, body weight 18～22g is provided by Yangzhou University comparative medicine center, the quality certification number: SCXK (Soviet Union) 2007-0001.
1.2 receive the reagent thing
The preparation of Chinese medicine composition of the present invention: with experimental example 1.
2. method
Because the toxicity of this Chinese medicine composition is less, difficulty is measured LD
50So the maximum dosage-feeding experiment is adopted in this experiment.Get 30 of mices; Dosage gastric infusion by maximum dosage 60g (crude drug)/kg; This dosage is pressed 66 times that are about adult's bio-occlusion pharmaceutical quantities after the system number conversion, and capacity is 0.4ml/10g, activity of close observation mice and death condition in 4 hours behind the disposable gastric infusion; After this every day at the upper and lower noon respectively observes 1 time, observes continuously 7 days.
3. result
None death in 4 hours after 30 mice administrations, most of mice is movable normal, wherein only 2 the mental status to occur not good, the movable minimizing, and recover normal after 1 day.In subsequently 7 days dead mouse does not appear, mice hair color gloss, the equal no abnormality seen of activity and diet.After 7 days, all mices are put to death, dissect and perusal, do not see that internal organs are arranged is unusual.
In sum, Chinese medicine composition of the present invention can prolong after the mice modeling and the time of writhing response occurs for the first time, and can obviously reduce occur in the 15min after the modeling turn round the body number of times; Can significantly reduce the mice auricle swelling due to the xylene; Can obviously suppress the inductive rat granulation tissue hyperplasia of cotton balls; Secondary inflammation to the AA rat has the obvious suppression effect; Can obviously reduce the sharp sufficient pawl scoring score value of AA rat foot claw swelling degree; AA Rats Spleen T, bone-marrow-derived lymphocyte propagation can be obviously strengthened, and the level of TNF-α in its serum, IL-1 β and IL-6 can be significantly reduced; Acute toxicity test demonstration said composition does not have obvious toxic and side effects.Therefore, Chinese medicine composition anti-inflammatory and analgesic effect of the present invention is good, and safe and reliable.
The specific embodiment
Through following examples the method for preparing of Chinese medicine composition of the present invention is done further explanation, but protection scope of the present invention is not limited.
Embodiment 1
Prescription: Radix Angelicae Pubescentis 1200g, Radix Clematidis 300g, curcumin 60g.
Radix Angelicae Pubescentis is ground into coarse powder, and the concentration that adds 5 times of amounts is 60% alcohol reflux 3 times, each 2 hours, collect extracting solution, filter, merging filtrate concentrates, drying, extract A; Radix Clematidis is ground into coarse powder, and the concentration that adds 8 times of amounts is 95% alcohol reflux 2 times, each 1.5 hours, collect extracting solution, filter, merging filtrate concentrates, drying, extract B; Extract A and extract B are merged, pulverize,, adds an amount of mannitol again with the curcumin mixing, 50% alcoholic solution system soft material, the granulation of 14 mesh sieves, 40 ℃ of dryings 3 hours, dried granule is crossed 14 mesh sieve granulate, promptly makes granule.
Embodiment 2
Prescription: Radix Angelicae Pubescentis 2100g, Radix Clematidis 420g, curcumin 95g.
Radix Angelicae Pubescentis is ground into coarse powder, and the concentration that adds 7 times of amounts is 95% alcohol reflux 4 times, each 1.5 hours, collect extracting solution, filter, merging filtrate concentrates, drying, extract A; Radix Clematidis is ground into coarse powder, and the concentration that adds 10 times of amounts is 40% alcohol reflux 3 times, each 3 hours, collect extracting solution, filter, merging filtrate concentrates, drying, extract B; Extract A and extract B are merged, pulverize; Add in the curcumin behind an amount of microcrystalline Cellulose mixing and the said mixture mix homogeneously, it is an amount of to add magnesium stearate, in the capsulae vacuus of packing into, promptly makes capsule again.
Embodiment 3
Prescription: Radix Angelicae Pubescentis 980g, Radix Clematidis 650g, curcumin 120g.
Radix Angelicae Pubescentis is ground into coarse powder, and the concentration that adds 8 times of amounts is 80% alcohol reflux 2 times, 3 hours for the first time, 2 hours for the second time, collect extracting solution, filter, merging filtrate concentrates, drying, extract A; Radix Clematidis is ground into coarse powder, and the concentration that adds 5 times of amounts is 60% alcohol reflux 4 times, each 1 hour, collect extracting solution, filter, merging filtrate concentrates, drying, extract B; Extract A and extract B are merged, pulverize; Add in the curcumin behind an amount of pregelatinized Starch mixing and the said mixture mix homogeneously, dry granulation adds an amount of magnesium stearate, Pulvis Talci mixing, and tabletting wraps film-coat, promptly makes tablet.
Claims (8)
1. Chinese medicine composition of treating rheumatoid arthritis; It is characterized in that this Chinese medicine composition is is that feedstock production forms with Radix Angelicae Pubescentis, Radix Clematidis and curcumin, the weight portion proportioning of each component is: Radix Angelicae Pubescentis 8-45 part, Radix Clematidis 2-10 part, curcumin 0.2-2 part.
2. the Chinese medicine composition of treatment rheumatoid arthritis according to claim 1 is characterized in that, the weight portion proportioning of each component is: Radix Angelicae Pubescentis 12-30 part, Radix Clematidis 3-8 part, curcumin 0.5-1.5 part.
3. the Chinese medicine composition of treatment rheumatoid arthritis according to claim 2 is characterized in that, the weight portion proportioning of each component is: Radix Angelicae Pubescentis 15-25 part, Radix Clematidis 4-6 part, curcumin 0.8-1.2 part.
4. the Chinese medicine composition of treatment rheumatoid arthritis according to claim 3 is characterized in that, the weight portion proportioning of each component is: 20 parts of Radix Angelicae Pubescentiss, 5 parts of Radix Clematidis, 1 part of curcumin.
5. according to the Chinese medicine composition of the arbitrary described treatment rheumatoid arthritis of claim 1-4; It is characterized in that; It is to be active component with the extractive with organic solvent of Radix Angelicae Pubescentis, Radix Clematidis and curcumin, adds the pharmaceutical preparation that pharmaceutically acceptable various adjuvant is prepared from.
6. according to the method for preparing of the Chinese medicine composition of the arbitrary described treatment rheumatoid arthritis of claim 1-5, it is characterized in that may further comprise the steps:
1) Radix Angelicae Pubescentis is ground into coarse powder, with alcohol reflux 2-4 time, concentration of ethanol is >=40%, collects extracting solution, filters, and merging filtrate concentrates, drying, extract A;
2) Radix Clematidis is ground into coarse powder, the alcohol reflux of adding 30%-95% 2-4 time is collected extracting solution, filters, and merging filtrate concentrates, and drying gets extract B;
3) extract A and extract B are merged, pulverize, add curcumin, be prepared into dosage form pharmaceutically commonly used.
7. the method for preparing of the Chinese medicine composition of treatment rheumatoid arthritis according to claim 6 is characterized in that, the consumption of ethanol of the concentration described in the step 1) >=40% is 4-10 a times of medical material weight, and each time of extracting is 1-3 hour;
Step 2) concentration described in is that the consumption of ethanol of 30%-95% is 5-12 a times of medical material weight, and each time of extracting is 1-3 hour.
8. be used for treating the application of the medicine of rheumatoid arthritis in preparation according to the arbitrary described Chinese medicine composition of claim 1-5.
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| CN105343791A (en) * | 2015-12-12 | 2016-02-24 | 杨献美 | Application of traditional Chinese medicine composition to preparation of drug for treating rheumatoid arthritis |
| CN105362949A (en) * | 2015-12-12 | 2016-03-02 | 杨献美 | Traditional Chinese medicine composition for treating rheumatoid arthritis |
| CN113413383A (en) * | 2021-06-17 | 2021-09-21 | 广州中医药大学(广州中医药研究院) | Novel application of Songcuoling |
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Application publication date: 20121003 |