CN101229353A - Medicine compounds for treating rheumatoid and atrophic arthritis - Google Patents
Medicine compounds for treating rheumatoid and atrophic arthritis Download PDFInfo
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- CN101229353A CN101229353A CNA2008101012316A CN200810101231A CN101229353A CN 101229353 A CN101229353 A CN 101229353A CN A2008101012316 A CNA2008101012316 A CN A2008101012316A CN 200810101231 A CN200810101231 A CN 200810101231A CN 101229353 A CN101229353 A CN 101229353A
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Abstract
The invention provides a drug combination for curing rheumatism and rheumatoid arthritis, which is a preparation prepared by the following raw materials by weight ratio: 1-9 portions of turmeric and 9-1 portions of cassia bark. The invention also provides a preparation method of the drug combination and an application thereof. The drug combination of the invention can cure the rheumatism and rheumatoid arthritis with precise efficacy; furthermore, the turmeric and the cassia bark are used compatibly, which improves the function of lucrative synergies and provides a new choice for the clinical application.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition for the treatment of rheumatoid arthritis, particularly, is to be the pharmaceutical composition that feedstock production forms with Rhizoma Curcumae Longae, Cortex Cinnamomi.Belong to the field of Chinese medicines.
Background technology
(Rheumatism Arthritis RA) is a kind of autoimmune disease based on the chronic progressive external arthropathy to rheumatoid arthritis, is symmetric polyarthritis, gets involved the most common with both hands, wrist, elbow, knee joint, ankle and joints of foot.Rheumatoid arthritis can show effect repeatedly, and delay finally causes joint deformity and afunction for many years.Rheumatoid arthritis is a worldwide disease, is distributed in all race and ethnic origin, and prevalence is 0.4%～1.0%, and prevalence has black race to be higher than white people, the occidentals is higher than Japanese tendency.Rheumatoid arthritis can occur in any age, but along with the age increases, its prevalence also increases thereupon, and the age occurred frequently is 40～60 years old.Sex and rheumatoid arthritis morbidity have much relations, and data shows that women's sickness rate is about 3 times of male.According to the 15th international arthritis in 1994 and autoimmune disease meeting coverage, the prevalence of China's rheumatoid arthritis is about 0.3%.Show according to SFDA south medication economics institute survey data, nearly 2 years, in the three major types medicine of China's treatment rheumatoid arthritis, NSAID (non-steroidal anti-inflammatory drug) is the main medication classification of rheumatoid medicine always, the market share nearly two of slow-acting drug and Chinese patent medicine increases every year to some extent simultaneously, illustrates that the scope of application of this two classes medicine enlarges.Thoroughly effect a radical cure because the rheumatoid arthritis disease has chronic, long-term, difficulty, needs of patients is taken medicine for a long time, and many ill old patients for many years are by medication experience of self and doctor's prescription, and turns to the retail market to purchase medicine voluntarily.Show that by SFDA south institute survey data the medicine of hospital market and retail market uses general layout difference to some extent.The market share that NSAID (non-steroidal anti-inflammatory drug) is occupied in the hospital market is the highest, secondly is to do medication slowly, and be Chinese patent medicine at last.And also be that the shared market share of non-steroidal anti-inflammatory medicine is the highest in the retail market, secondly be Chinese patent medicine, be to do medication slowly at last.2003, national nonsteroidal rheumatism medicine was still based on the COX-2 non-steroid antiinflammatory, and the market share of such medicine further rises, and wherein ten thousand networks of the celecoxib of Pfizer and Merck have occupied NSAID (non-steroidal anti-inflammatory drug) 47% the market share nearly; Slowly do in the medication, the Ai Ruohua of the Suzhou Long March-Xin Kai (leflunomide) is though Time To Market is not long, but it is very fast that its market share rises, the market share with 31.79% became the bellwether who does medication market slowly in 2003, the market of all the other brands is all very little, and, it is not formed threat than descending to some extent last year.And in the Chinese patent medicine market, the Pa Fulin of Yaan three nine-day periods after the winter solstice ranks first with the advantage of small scale, and competition situation is dispersive form, and the market share gap between the various brands is little, Market competition.
Rheumatoid arthritis belongs to Chinese medical ' arthralgia syndrome ' category.The traditional Chinese medical science is thought rheumatoid generation, and exopathogenic factor has factors such as diet, feelings will concurrently based on wind, cold, damp.Endogenous cause of ill is that the human body caused by liver and kidney deficiency makes cold-damp, blood stasis combine in meridians, muscle, causes the meridians plug to stagnate. the limbs atrophy distortion.Modern medicine thinks that rheumatoid arthritis belongs to autoimmune disease, and major lesions is chronic synovitis, and hypertrophy forms pannus.Invade articular cartilage, subchondral bone, ligament and flesh lower limb etc., cause articular cartilage, bone and joint capsule to destroy, finally cause joint deformity and afunction.Main clinical manifestation is arthroncus, pain, limitation of activity, morning stiff phenomenon.Later stage is caused ankylosis, deformity, afunction even maimed person.Chinese medicine is thought: rheumatism, the genus of arthromyodynia.Be positive QI-insufficiency, damp and hot dry take advantage of a weak point in opponent's defence of wind and cold and people cause limbs, joint, myalgia, are weighing, numbness, swelling, joint stuffiness, even joint deformity, or involve internal organs.This cause of disease void causes numbness, and because of numbness causes void, the exogenous pathogen expectorant stasis of blood is assorted extremely, and " obstructed ", " not flourish " are also seen.In view of clinical, medication is when promoting flow of QI and blood, promoting the flow of QI in the collateral by warming the meridian.
Rheumatic arthritis is a kind of allergic disease relevant with hemolytic streptococcal infection, inflammatory disorders with the whole body connective tissue is characteristics, after the streptococcal infection, streptococcic toxin and metabolite are antigen, body produces corresponding antibodies, antigen and antibody is in the connective tissue combination, make it to be inflamed degeneration and destruction, thus form rheumatic arthritis.
Leflunomide untoward reaction incident that French Sanofi-Aventis produced that takes place at the beginning of 2007 and the ten thousand networks incident of recalling has caused bigger impact for NSAID (non-steroidal anti-inflammatory drug) and slow-acting drug market, but meanwhile also brought development opportunity to Chinese patent medicine, Chinese patent medicine will occupy bigger share with little, the safe characteristics of its toxicity on market, market position will further promote, and the market structure for the treatment of rheumatoid arthritis medicine also will change thereupon.
Still there is not at present the relevant report that separately Chinese crude drug Rhizoma Curcumae Longae, Cortex Cinnamomi compatibility is used for the treatment of rheumatism, rheumatoid arthritis.
Summary of the invention
Technical scheme of the present invention relates to a kind of pharmaceutical composition for the treatment of rheumatism, rheumatoid arthritis.The present invention also provides this preparation of drug combination method and purposes.
The invention provides a kind of pharmaceutical composition for the treatment of rheumatism, rheumatoid arthritis, it is the preparation that is prepared from by the following weight proportion raw material:
Rhizoma Curcumae Longae 1-9 part, Cortex Cinnamomi 9-1 part.
Further preferably, it is the medicament that is prepared from by the following weight proportion raw material:
Rhizoma Curcumae Longae 1-5 part, Cortex Cinnamomi 1-2 part.
Still more preferably, it is the medicament that is prepared from by the following weight proportion raw material:
1 part of Rhizoma Curcumae Longae 1-5 part, Cortex Cinnamomi.
Still more preferably, it is the medicament that is prepared from by the following weight proportion raw material:
2 parts in Rhizoma Curcumae Longae, 1 part of Cortex Cinnamomi.
Pharmaceutical composition of the present invention is to be active component by Rhizoma Curcumae Longae, cinnamomic water or extractive with organic solvent, adds the medicament that acceptable accessories or complementary composition are prepared from.
Wherein, described medicament is: capsule, tablet, pill, oral liquid or granule.
Wherein, every preparation unit contains curcumin (C in the described medicament
21H
80O
6) weight percentage for being no less than 7.0%.
The present invention also provides a kind of method for preparing this pharmaceutical composition, and it comprises the steps:
A, get it filled material Rhizoma Curcumae Longae, Cortex Cinnamomi;
B, Rhizoma Curcumae Longae add ethanol extraction, and concentration of alcohol is 〉=65%; Cortex Cinnamomi is adopted steam distillation, gets volatile oil, merges two kinds of extracts, adds acceptable accessories or complementary composition and is prepared into medicament pharmaceutically commonly used.
Wherein, the described concentration of alcohol of b step is: 70% ethanol, extracting method is: the ethanol percolation method.
The invention provides the purposes of this pharmaceutical composition in the medicine of preparation treatment rheumatoid arthritis.
The present invention also provides the purposes of this pharmaceutical composition in the medicine of preparation treatment rheumatic arthritis.
The arduous temperature of Rhizoma Curcumae Longae is logical in the medicine material of the present invention, the special promoting flow of QI and blood pain relieving of merit, the hot temperature of Cortex Cinnamomi is loose, but the promoting the flow of QI in the collateral by warming the meridian pain relieving, two medicines are with using, can make cold blood stasis removing logical, QI and blood passes unimpeded, and then all pains can be ended, conform to the traditional Chinese medical science " rheumatism ", " arthromyodynia " pathogenesis, so can be used for the treatment of rheumatism, rheumatoid arthritis, and drug effect is clear and definite, has synergistic function.
The specific embodiment
The preparation of embodiment 1 medicine of the present invention
Rhizoma Curcumae Longae 2000g Cortex Cinnamomi 1000g
More than two the flavor raw medicinal materials make 1000 of capsules altogether.
More than two the flavor, curcuma powder is broken into coarse powder, (appendix IO of Chinese Pharmacopoeia version in 2005) makes solvent with 70% ethanol according to percolation under fluid extract and the extractum item, carry out diafiltration after soaking into half an hour, the filtrate of waiting reaches 12000ml, stop diafiltration, decompression filtrate recycling ethanol, being concentrated into relative density is the clear paste of 1.35～1.38 (60 ℃); Cortex Cinnamomi is cut into thick material, adds 5 times of amounts of water, and water vapour distillation 5 hours is collected volatile oil.Extractum, volatile oil are added in the PEG400, load soft capsule, make 1000, promptly.
The preparation of embodiment 2 medicines of the present invention
Rhizoma Curcumae Longae 9000g Cortex Cinnamomi 1000g
More than two the flavor raw medicinal materials make 1000 of capsules altogether.
More than two the flavor, curcuma powder is broken into coarse powder, (appendix IO of Chinese Pharmacopoeia version in 2005) makes solvent with 65% ethanol according to percolation under fluid extract and the extractum item, carry out diafiltration after soaking into half an hour, the filtrate of waiting reaches 12000ml, stop diafiltration, decompression filtrate recycling ethanol, being concentrated into relative density is the clear paste of 1.35～1.38 (60 ℃); Cortex Cinnamomi is cut into thick material, adds 5 times of amounts of water, and water vapour distillation 5 hours is collected volatile oil.Extractum, volatile oil are added in the PEG400, load soft capsule, make 1000, promptly.
The preparation of embodiment 3 medicines of the present invention
Rhizoma Curcumae Longae 1000g Cortex Cinnamomi 9000g
More than two the flavor, curcuma powder is broken into coarse powder, (appendix IO of Chinese Pharmacopoeia version in 2005) makes solvent with 80% ethanol according to percolation under fluid extract and the extractum item, carry out diafiltration after soaking into half an hour, the filtrate of waiting reaches 12000ml, stop diafiltration, decompression filtrate recycling ethanol, being concentrated into relative density is the clear paste of 1.35～1.38 (60 ℃); Cortex Cinnamomi is cut into thick material, adds 5 times of amounts of water, and water vapour distillation 5 hours is collected volatile oil.Extractum, volatile oil are waved and are closed, and incapsulate in the agent, make 1000 capsules, promptly.
The preparation of embodiment 4 medicines of the present invention
Rhizoma Curcumae Longae 1000g Cortex Cinnamomi 1000g
More than two the flavor, curcuma powder is broken into coarse powder, (appendix IO of Chinese Pharmacopoeia version in 2005) makes solvent with 90% ethanol according to percolation under fluid extract and the extractum item, carry out diafiltration after soaking into half an hour, the filtrate of waiting reaches 12000ml, stop diafiltration, decompression filtrate recycling ethanol, being concentrated into relative density is the clear paste of 1.35～1.38 (60 ℃); Cortex Cinnamomi is cut into thick material, adds 5 times of amounts of water, and water vapour distillation 5 hours is collected volatile oil.Volatile oil mixes with extractum through cyclodextrin inclusion compound, adds adjuvant, and tabletting gets 1000.
The preparation of embodiment 5 medicines of the present invention
Rhizoma Curcumae Longae 5000g Cortex Cinnamomi 2000g
More than two the flavor, curcuma powder is broken into coarse powder, (appendix IO of Chinese Pharmacopoeia version in 2005) makes solvent with 95% ethanol according to percolation under fluid extract and the extractum item, carry out diafiltration after soaking into half an hour, the filtrate of waiting reaches 12000ml, stop diafiltration, decompression filtrate recycling ethanol, being concentrated into relative density is the clear paste of 1.35～1.38 (60 ℃); Cortex Cinnamomi is cut into thick material, adds 5 times of amounts of water, and water vapour distillation 5 hours is collected volatile oil.Extractum, volatile oil mix, and are prepared into oral liquid, and 1000, every 1ml.
The preparation of embodiment 6 medicines of the present invention
Rhizoma Curcumae Longae 5000g Cortex Cinnamomi 1000g
Be prepared into soft capsule by embodiment 1 described method.
The method of quality control of embodiment 7 medicines of the present invention
Curcumin is measured according to high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2005).
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Isopropyl alcohol: water: glacial acetic acid (20: 27: 48: 5) be mobile phase; The detection wavelength is 420nm.Theoretical cam curve is calculated with the curcumin peak should be not less than 2000.
The preparation precision of reference substance solution takes by weighing at 4 hours curcumin reference substance of 60 ℃ of drying under reduced pressure an amount of, adds methanol and makes the solution that every 1ml contains 15 μ g, promptly.
The preparation precision of need testing solution takes by weighing this product content 25mg, puts in the 100ml volumetric flask, adds dissolve with methanol, shakes up, and standardize solution is need testing solution.
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
Medicinal soft capsule content of the present invention contains curcumin (C
21H
80O
6) should be no less than 7.0%.
Below by pharmacodynamics test proof beneficial effect of the present invention.
1, experiment purpose and experimental design
Medicine of the present invention is by the modern compound preparation of being made up of Chinese medicines such as Rhizoma Curcumae Longaes, and effects such as energy cold expelling, dehumidifying, pain relieving are used for rheumatoid arthritis, rheumatic arthritis.Evaluating drug effect partly adopts the adjuvant-induced arthritis model (AA) that can better reflect the performance of RA symptom, and multiple acute and chronic inflammatory model, its effect of thoroughly evaluatings such as pain model.
2 medicines and reagent
The many tripterygium glycosideses of Radix Tripterygii Wilfordii: river pharmaceutical factory is washed in Hubei, lot number: 060422.
Rotundine Tablets: the accurate word of traditional Chinese medicines: H51021203.Specification: 30mg/ sheet, 100 slices/bottle.Jianjiang Pharmaceutical Factory, lot number: 050602.
Dexamethasone tablet: the accurate word of traditional Chinese medicines: H4424469.Specification: 0.75mg/ sheet, 100 slices/bottle.Guangdong Huanan Pharmaceutical Factory, lot number: 030501.
Glacial acetic acid: analytical pure, 500ml/ bottle (525g), Chengdu long connection chemical reagent company limited, lot number: 20050321.
Dimethylbenzene: analytical pure, 500ml/ bottle.Chengdu chemical reagent factory, lot number: 20001206.
Phenol: specification: 500g/ bottle.The Long Huagongshijichang of Chengdu section, lot number: 20040202.
Shuttle methylcellulose: specification: 500g/ bag.The Long Huagongshijichang of Chengdu section, lot number: 20031201.
Pentobarbital sodium: specification: 25g/ bottle.The chemical plant is known in last sea-run, SERVA import packing.Lot number: 921019.
Cyclophosphamide for injection: the accurate word H32020857 of traditional Chinese medicines.Specification: 0.2g/ bottle, 5 bottle/boxes.Hengrui Medicine Co., Ltd., Jiangsu Prov. produces, lot number: 06030412,
India ink: specification: 50ml/ bottle.Chemical plant in the west, Beijing, lot number: 980331
Normal saline (0.9% sodium chloride injection): the accurate word H51021158 of traditional Chinese medicines.Sichuan Kelun Large Pharmaceutical Factory Co. Ltd's product
Lyophilizing scarification bacillus calmette-guerin vaccine: Shanghai Vaccine and Serum Institute
Many two of Radix Tripterygii Wilfordii: produce the accurate word 243020138 of traditional Chinese medicines by Xieli Pharmaceutical Co., Ltd., Hunan
The quantitative ELA test kit of rat tumor necrosis factor-alpha (import packing), the gloomy male company in Shanghai
The quantitative ELA test kit of rat tumor il-1 β (import packing), the gloomy male company in Shanghai
Superoxide dismutase (SOD) testing cassete: bio-engineering research institute is built up in Nanjing
Malonaldehyde (MDA) is measured test kit: Nanjing is built up bio-engineering research and is provided.
Nitric oxide (NO) is measured test kit: Nanjing is built up bio-engineering research and is provided.
Nitric oxide synthetase (NOS) is measured test kit: Nanjing is built up bio-engineering research and is provided
3 laboratory animals and environment
3.1 laboratory animal
Km (Kunming kind) mice, the cleaning level, SCXK (river) 2005-19 number is provided by the Traditional Chinese Medicine Research Institute, Sichuan Province Experimental Animal Center.
The SD rat, the cleaning level, SCXK (river) 2005-19 number is provided by the Traditional Chinese Medicine Research Institute, Sichuan Province Experimental Animal Center.
3.2 experimental situation
Experimental situation meets national mice, rat, Cavia porcellus, rabbit barrier system use facility standard (No. the 100th, Sichuan Province's management of laboratory animal meeting licence).
4, experimental apparatus
EB-3200D electronic balance (day island proper Tianjin);
JA1003A electronic balance (Shanghai Jingtian Electronic Instrument Co., Ltd.);
Goldspink board electronic stopclock (Shanghai No.5 Watch Factory);
Thermometer (HANNA instruments, H198501)
RF-5301 spectrofluorophotometer (day island proper Tianjin)
XZC-2B type autocontrol temperature hot-plate instrument, (by Shandong Academy of Medical Sciences maintenance of equipment supply station)
Electric heating constant temperature air dry oven (going up the grand experimental facilities company limited of Nereid)
PV-200 toes swelling instrument (Sichuan Tai Meng)
Microplate reader ZS-3 (Beijing boat firewood),
2500E type CO
2Incubator (Wuxi Kodak)
Test example 1 medicine material compatibility screening test of the present invention (different proportion compatibility combinations are to the influence of mouse dimethylbenzene ear expanding)
90 of Kunming mouses, male and female half and half, body weight 18～22g is divided into 9 groups at random by body weight, 10 every group.First group is model control group (irritating the stomach salad oil), and (benorylate, 5g/dl), three to nine groups are the different proportion compatibility combinations of medicine of the present invention, dosage 8g (crude drug in whole)/kg to second group of positive matched group.Irritating the stomach volume is the 0.1ml/10g body weight, every day 1 time, for three days on end.40min after the last administration, dimethylbenzene (0.015ml/ only) evenly is applied in the mouse right ear tow sides causes inflammation (except the negative control group), put to death after 20 minutes, cut two ears along the auricle baseline,, calculate and respectively organize inhibitory rate of intumesce (%) as swelling degree (mg) with the difference of two auricle weight.
Swelling degree (mg)=auris dextra sheet weight-left auricle is heavy
Show by following table 1 experimental result, (Rhizoma Curcumae Longae: Cortex Cinnamomi=9: 1～1: 9) all the xylol ear swelling has inhibitory action (p＜0.05～0.01) or inhibitory action trend (p＞0.05), and suppression ratio is between 11.54～33.40% in medicine Different Weight proportion compatibility combination of the present invention.With Rhizoma Curcumae Longae (1-5): Cortex Cinnamomi (1-2) compatibility is the optimum ratio scope, and further preferred Rhizoma Curcumae Longae: Cortex Cinnamomi is 2: 1 o'clock, and it is the strongest that xylol causes the mice auricle swelling inhibitory action, has remarkable antiinflammatory action.
The different proportion compatibility combinations of table 1 medicine material of the present invention are to the influence of mouse dimethylbenzene ear expanding
| Group | Number of animals (only) | Dosage (g/kg * d) | Swelling degree (ml) | Swelling suppresses (%) |
| The model control group benorylate is according to organizing Rhizoma Curcumae Longae 9: Cortex Cinnamomi 1 Rhizoma Curcumae Longae 5: Cortex Cinnamomi 1 Rhizoma Curcumae Longae 2: Cortex Cinnamomi 1 Rhizoma Curcumae Longae 1: Cortex Cinnamomi 1 Rhizoma Curcumae Longae 1: Cortex Cinnamomi 2 Rhizoma Curcumae Longaes 1: Cortex Cinnamomi 5 Rhizoma Curcumae Longaes 1: Cortex Cinnamomi 9 | 10 10 10 10 10 10 10 10 10 | - 0.005×3 8×3 8×3 8×3 8×3 8×3 8×3 8×3 | 41.32±6.23 19.35±5.42 *** 36.22±6.72 * 34.41±5.47 ** 27.52±6.21 *** 29.25±8.23 ** 33.25±6.27 ** 36.55±6.29 * 35.25±8.35 * | - 53.17 12.34 16.72 33.40 29.21 19.53 11.54 14.69 |
Compare with model group:
*P＞0.05
*P＜0.05;
* *P＜0.01.
Test example 2 different proportion compatibility combination Dichlorodiphenyl Acetate induced mice are turned round the influence of body number of times
90 of Kunming mouses, male and female have concurrently, body weight 18～22g, be divided into 9 groups at random by body weight, 10 every group, first group of negative matched group (irritating the stomach salad oil), second group of positive matched group (Rotundine Tablets, 0.08g/kg), three to nine groups are the different proportion compatibility combinations of medicine of the present invention, dosage 8g (crude drug in whole)/kg.Regularly irritate the stomach mice once every day, for three days on end.After the last administration 40 minutes, 0.75% acetic acid is all injected in each Mus abdominal cavity, and 0.2ml/ only.Observe to inject and respectively organize the number of times that writhing response (the abdominal part indent stretches hind leg, and buttocks is raised) occur in back 20 minutes.
Show by following table 2 experimental results, the different proportion compatibility combination of medicine of the present invention (Rhizoma Curcumae Longae: Cortex Cinnamomi=(9: 1)～(1: 9)) all the mouse writhing number of times is had inhibitory action (p＜0.05～0.01) or inhibitory action trend (p＞0.05), with Rhizoma Curcumae Longae: Cortex Cinnamomi: (1-5): in the time of (1-2), compatibility is the optimum ratio scope, more preferably: Rhizoma Curcumae Longae: Cortex Cinnamomi: (1-2): 1, wherein with Rhizoma Curcumae Longae: Cortex Cinnamomi is 2: 1 o'clock, inhibitory action is the strongest, and the large tracts of land deep pain that the acetic acid lumbar injection is caused has remarkable antagonism.
The different proportion compatibilities combination of table 2 medicine material of the present invention Dichlorodiphenyl Acetate to the influence of mouse writhing number of times
| Group | Number of animals (only) | Dosage (g/kg *d) | Turn round the body number of times |
| Model group rotundine group Rhizoma Curcumae Longae 9: Cortex Cinnamomi 1 Rhizoma Curcumae Longae 5: Cortex Cinnamomi 1 Rhizoma Curcumae Longae 2: Cortex Cinnamomi 1 Rhizoma Curcumae Longae 1: Cortex Cinnamomi 1 Rhizoma Curcumae Longae 1: Cortex Cinnamomi 2 Rhizoma Curcumae Longaes 1: Cortex Cinnamomi 5 Rhizoma Curcumae Longaes 1: Cortex Cinnamomi 9 | 10 10 10 10 10 10 10 10 10 | - 0.08×3 8×3 8×3 8×3 8×3 8×3 8×3 8×3 | 31.2±5.3 5.1±1.4 *** 25.7±6.2 ** 20.4±5.8 *** 18.6±6.7 *** 23.1±7.2 *** 22.6±5.1 *** 26.7±8.2 * 28.7±6.1 * |
Compare with model group:
*P＞0.05
*P＜0.05;
* *P＜0.01.
Conclusion: take all factors into consideration above 2 experimental results, illustrate that Rhizoma Curcumae Longae, Cortex Cinnamomi compatibility use, brought into play the effect of Synergistic, wherein with Rhizoma Curcumae Longae: Cortex Cinnamomi is that 2: 1 compatibility group antiinflammatory actions, analgesic activity are the strongest, is best proportion compatibility group.
The antiinflammatory action of test example 3 medicines of the present invention
The medicine of the present invention that following test is used, the 1g extract is equivalent to crude drug in whole 7.78g, is prepared from by embodiment 1.Lot number: 2006043; Clinical consumption: 0.4g (crude drug in whole)/kg (body weight).Be made into 80%, 40%, 20% 3 concentration solution, dosage is respectively 8,4,2g (crude drug in whole)/kg, is equivalent to 20,10,5 times of clinical dosage.Usage: oral, 1ml/100g (BW).
1, to the influence of mouse dimethylbenzene ear expanding
(1) purpose: smear certain density dimethylbenzene for the mice auricular concha and can cause and bring out mice auricular concha acute inflammation edema.This model can be observed medicine of the present invention to the early stage antagonism of inflammation.
(2) method: 50 of Kunming mouses, male and female half and half, body weight 18～22g is divided into 5 groups at random by body weight, 10 every group.First group is model control group (irritating the stomach salad oil), and (benorylate, 5g/dl), three to five groups are the large, medium and small dosage group of medicine of the present invention to second group of positive matched group.Irritating the stomach volume is the 0.1ml/10g body weight, every day 1 time, for three days on end.40min after the last administration, dimethylbenzene (0.015ml/ only) evenly is applied in the mouse right ear tow sides causes inflammation (except the negative control group), put to death after 20 minutes, cut two ears along the auricle baseline,, calculate and respectively organize inhibitory rate of intumesce (%) as swelling degree (mg) with the difference of two auricle weight.
Swelling degree (mg)=auris dextra sheet weight-left auricle is heavy
(3) experimental result: by table 3, the heavy dose of group of medicine of the present invention mice auricle swelling degree all significantly is lower than model contrast (p＜0.05), so it is inhibited to think that medicine xylol of the present invention causes mice auricle swelling.
Table 3 medicine of the present invention is to the influence of mouse dimethylbenzene ear expanding
| Group | Number of animals (only) | Dosage (g/kg*d) | Swelling degree (ml) | Swelling suppresses (%) |
| The benorylate of model control group medicine group of the present invention medicine group of the present invention medicine group of the present invention is according to group | 10 10 10 10 10 | - 8×3 4×3 2×3 0.005×3 | 39.63±9.26 29.65±10.22** 31.40±15.54* 39.25±16.32* 20.33±11.24*** | - 25.74 15.3 10.4 42.89 |
Compare with model group: * p＞0.05 * * p＜0.05; * * p＜0.01.
2, to the influence of rat carrageenan foot pawl swelling
(1) purpose: be chosen in the effect proinflammatory agent carrageenin local injection that injects 2～4 hours swelling peakings in back and bring out rat foot claw swelling, the characteristics of this model are to cause the synthetic increase of scorching local PG, and bring out edema with vaso-active substance and kassinin kinin class.Cause the antiinflammatory action that medicine of the present invention is observed in the volumetrical variation of scorching front and back rat paw edema by measurement.
(2) method: get 50 of rats, complete male, body weight 100～120g is divided into 5 groups at random by body weight, 10 every group.First group of negative matched group (irritating the stomach salad oil), (benorilate tablet, 0.6g/kg), three to five groups are the large, medium and small dosage group of medicine of the present invention to second group of positive matched group.Regularly irritate the stomach mice once every day, for three days on end.Preceding 1 day of last medication is done a labelling with marking pen around the rat right hind leg ankle joint, measure every rat right hind leg normal foot sole of the foot volume with drainage.Behind the last administration 30min, only cause inflammation at rat right hind leg foot plantar subcutaneous injection 1% carrageenin suspension 0.05ml/ respectively.Respectively at causing inflammation back 1,2,4,6,8h, 5 time points are all respectively surveyed right hind foot sole of the foot volume one time, observe causing the sufficient volume-variation in scorching front and back, and calculate the swelling rate.
(3) experimental result: by table 4 as seen, medicine heavy dose group of the present invention 1,2 hour in extremely scorching back, the dosage group was at extremely scorching back 1 hour in the medicine of the present invention, and sufficient corpus unguis amasss significantly less than model group.So can think that medicine on Carrageenan local injection of the present invention brings out rat swelling and has obvious inhibitory action, mainly act on the carrageenin local injection after sufficient pawl swelling in 1 hour form the phase.
Table 4 medicine of the present invention causes the influence of rat paw edema to chondrus ocellatus Holmes
| Group | Dosage (g/kg*d) | Number of animals (only) | Cause scorching preceding (ml) | Cause scorching back different time swelling rate (%) | ||||
| 1h | 2h | 4h | 6h | 8h | ||||
| The medicine benorylate of the present invention of model edition with parallel text invention medicine medicine of the present invention | - 8×3 4×3 2×3 0.6×3 | 10 10 10 10 10 | 14.58±0.94 14.16±0.83 * 14.66±1.05 * 14.13±1.01 * 14.83±0.97 * | 26.15±7.55 20.88±7.21 ** 22.30±4.39 ** 25.91±8.03 * 17.75±3.97 *** | 33.51±7.71 26.31±8.39 ** 34.77±9.63 * 35.61±15.29 * 20.14±10.42 ** | 38.18±9.76 32.21±8.08 * 34.82±4.41 * 38.03±7.85 * 28.74±5.89 *** | 34.48±9.15 31.52±9.02 * 31.65±8.47 * 36.37±9.75 * 24.95±6.64 ** | 28.86±14.37 25.25±9.53 * 26.99±5.48 * 24.43±11.45 * 18.98±7.72 * |
Compare with model group: * p＞0.05 * * p＜0.05; * * p＜0.01.
3, to the influence of mice granuloma induced by implantation of cotton pellets
(1) purpose: it is subcutaneous that autoclaved cotton balls is implanted little groin, can produce and the similar connective tissue proliferation of inflammation later stage pathology.This model can be observed medicine of the present invention to anti-inflammatory later stage connective tissue proliferation function.
(2) method: 60 of mices, male and female half and half, body weight 18～22g is divided into 5 groups at random by body weight, 12 every group.First group is model control group (irritating the stomach salad oil), and (dexamethasone, 15mg/dl), three to five groups are the large, medium and small dosage group of medicine of the present invention to second group of positive matched group.Lumbar injection pentobarbital sodium 30mg/kg anesthetized mice, it is fixing to lie on the back, iodine tincture, alcohol disinfecting hypogastric region skin, cut off along ventrimeson and to be about the 0.5cm otch, with 2 sterilization cotton balls (each cotton balls 10mg) autoclavings, drip each 0.05ml of 800u/ml penicillin and 650u/ml respectively, 50 ℃ of oven dry) to implant the left and right strange portion of mice respectively subcutaneous.Postoperative began to adopt not isoconcentration medicinal liquid gastric infusion of isometric(al), every day 1 time, continuous 7 days the same day.Animal is put to death in 1h cervical vertebra displacement after the last administration, and cotton balls is taken out together with connective tissue on every side, rejects fatty tissue, places 55 ℃ of baking oven 24hr oven dry, weighs after the cooling.Dry weight deducts the raw cotton ball weight, promptly gets granulation tissue weight.Granuloma weight is with mg (granuloma)/10g (body weight) expression.
(3) experimental result: by table 5, medicine of the present invention heavy dose of group granulation weight and granulation index so this medicine can suppress the formation of cotton balls granulation tissue, have certain inhibitory action to chronic inflammatory disease significantly less than model control group different (p＜0.05).
Table 5 medicine of the present invention is to the influence of mice granuloma induced by implantation of cotton pellets
| Group | Number of animals (only) | Dosage (g/kg*d) | Granulation weight (mg) | Granulation weight (mg/10g body weight) |
| Model control group medicine of the present invention medicine of the present invention medicine Dexamethasone group of the present invention | 12 12 12 12 12 | - 8×7 4×7 2×7 0.015×7 | 23.65±10.58 19.95±7.22 ** 23.00±3.94 * 24.25±4.17 15.5±4.12 *** | 7.28±2.66 5.86±1.13 ** 6.54±2.13 * 7.24±1.44 * 4.23±1.03 *** |
Compare with model group: * p＞0.05 * * p＜0.05; * * p＜0.01.
4, to the influence of intraperitoneal mouse capillary permeability
(1) purpose: adopt low-concentration acetic acid to make pro-inflammatory cytokine, cause the abdominal cavity acute inflammatory reaction.Inject dyestuff ivens orchid from the tail vein again, what of inflammatory exudation are the penetrating amount of measuring the abdominal cavity dyestuff can represent.Judge the antiphlogistic effects of medicine by the OD value of spectrophotometric determination administration pneumoretroperitoneum dyestuff
(2) experimental technique: get 60 of mices, 18～22g, male, be divided into 5 groups at random by body weight, 12 every group, first group is model control group (irritating the stomach salad oil), (aspirin, 0.02g/kg), three to five groups are the large, medium and small dosage group of medicine of the present invention to second group of positive matched group.Regularly irritate stomach once every day, for three days on end.40min after the last administration, the blue 0.1ml/10g of tail vein injection 1% ivens, lumbar injection 0.6% acetic acid 0.2ml/ only simultaneously, sacrificed by decapitation behind the 20min, wash the abdominal cavity repeatedly with the 5ml normal saline after cutting off the abdominal cavity, draw the abdominal cavity eluate, add normal saline at last and be settled to 10ml with suction pipe, the centrifugal 10min of 3000r/min gets supernatant 3ml and surveys absorbance A in spectrophotometer 590nm place.
(3) experimental result: by table 6 as seen, heavy dose of group of medicine of the present invention and middle dosage group absorbance A value are starkly lower than model group (P＜0.05).Event can think that medicine of the present invention can reduce by 0.6% acetic acid institute to the mouse peritoneal capillary permeability.
Table 6 medicine of the present invention is to the influence of intraperitoneal mouse capillary permeability
| Group | Number of animals (only) | Dosage (g/kg) | The A value | Suppression ratio (%) |
| Dosage low dose in the model group aspirin heavy dose | 9 10 9 10 10 | 0.02×3 8×3 4×3 2×3 | 0.18±0.11 0.04±0.02 *** 0.05±0.04 *** 0.05±0.04 *** 0.12±0.09 * | 76.63 73.36 73.46 33.3 |
Compare with model group: * p＞0.05 * * p＜0.05; * * p＜0.01.
5, medicine of the present invention is to the influence of rat thoracic cavity leukoplania
(1) purpose: adopt carrageenin to make pro-inflammatory cytokine, cause the abdominal cavity acute inflammatory reaction.Measure total white blood cells in peritoneal exudate amount and the transudate, estimate the inhibitory action of medicine of the present invention inflammatory cell.
(2) experimental technique: 50 of SD rats, 100-120g, male and female have concurrently, be divided into 5 groups at random by body weight, first group is model control group (irritating the stomach salad oil), second group of positive matched group (aspirin, 0.02g/kg, be 10 times of clinical dosage), three to five groups are the large, medium and small dosage group of medicine of the present invention.Regularly irritate stomach once every day, and after the last administration 1 hour for three days on end, rat is used the ether light anaesthesia, face upward the position and be fixed on the operating-table, only go into 0.5% carrageenin 0.05ml/ from thoracic cavity, rat right side subscript.Sacrificed by decapitation rat after 5 hours is opened the chest at the tabula periphery, oozes out liquid measure with the measurement of syringe sucking-off pleural fluid, measures total white blood cells in the transudate with cell counter
(3) experimental result: by table 7 as seen, the big or middle dosage group of medicine of the present invention transudate total white blood cells significantly is lower than model group (p＜0.01), and the heavy dose of group of medicine of the present invention transudate volume significantly is lower than model group (p＜0.05).So can think, medicine of the present invention oozes out 0.5% carrageenin institute to the trip of rat thoracic cavity leukocyte and liquid inhibitory action.
Table 7 medicine of the present invention is to the influence of rat thoracic cavity leukoplania
| Group | Number of animals (only) | Dosage (g/kg*d) | Leukocyte number (cell/mm3) | Pleural fluid volume (ml) |
| Model edition with parallel text invention medicine medicine of the present invention medicine aspirin of the present invention | 10 10 10 10 10 | - 8×3 4×3 2×3 0.02*3 | 20.96±8.54 6.34±7.64 *** 8.12±7.88 *** 19.63±13.25 * 5.90±4.10 *** | 3.39±0.89 2.49±0.01 ** 3.20±0.57 * 3.30±0.81 * 2.00±0.68 *** |
Compare with model group: * p＞0.05 * * p＜0.05; * * p＜0.01.
The analgesic activity of test example 4 medicines of the present invention
1, the Dichlorodiphenyl Acetate induced mice is turned round the influence of body number of times
(1) purpose: inject certain density acetic acid to mouse peritoneal and can bring out mouse peritoneal deep large tracts of land and more persistent pain, cause mice to produce writhing response.This model can be observed the non-specific analgesic activity of medicine of the present invention.
(2) experimental technique: 50 of mices, male and female have concurrently, body weight 18～22g, be divided into 5 groups at random by body weight, 10 every group, first group of negative matched group (irritating the stomach salad oil), (Rotundine Tablets, 0.08g/kg), three to five groups are the large, medium and small dosage group of medicine of the present invention to second group of positive matched group.Regularly irritate the stomach mice once every day, for three days on end.
After the last administration 40 minutes, 0.75% acetic acid is all injected in each Mus abdominal cavity, and 0.2ml/ only.Observe to inject and respectively organize the number of times that writhing response (the abdominal part indent stretches hind leg, and buttocks is raised) occur in back 20 minutes.
(3) experimental result: by table 8, the big or middle dosage group of medicine of the present invention mouse writhing number of times is lower than the model control group mice, and significant difference (P＜0.05) is arranged.So can think that medicine of the present invention has antagonism to the large tracts of land deep pain that the acetic acid lumbar injection causes.
Table 8 medicine Dichlorodiphenyl Acetate of the present invention to the influence of mouse writhing number of times
| Group | Dosage (g/kg*d) | Number of animals (only) | Turn round the body number of times |
| Model group medicine group of the present invention medicine group of the present invention medicine group of the present invention rotundine group | - 8×3 4×3 2×3 0.04×3 | 10 10 10 10 10 | 30.4±5.89 18.6±16.97 ** 21.7±6.29 ** 26.6±13.10 * 2.9±1.45 ** |
Compare with model group: * p＞0.05 * * p＜0.05; * * p＜0.01.
2, to hot plate to the influence of mice pain reflection
(1) experimental technique: be divided into 5 groups at random by body weight, 10 every group.First group is normal control (irritate stomach salad oil), second group of positive matched group (Rotundine Tablets, 0.04g/kg are 10 times of clinical dosage), and three to five groups are the large, medium and small dosage group of medicine of the present invention.Regularly irritate the stomach mice once every day, for three days on end.Regulate hot-plate instrument in advance, make temperature constant at 60 ± 0.3 ℃, hot plate needs preheating 10 minutes.Screen qualified female mice and (put hot plate to the pain threshold of metapedes required time occurring adding as this Mus, all add the foot time less than 5 seconds or give it up greater than 30 seconds or leaper) 50, repeat to survey normal pain threshold, get two subnormal threshold of pain meansigma methodss, as the pain threshold before this Mus administration.Measure 30,60,90,120 minutes pain threshold of mice after the last administration.As 60 second mice still reactionless, mice is taken out, in order to avoid scald, calculated with 60 seconds its threshold of pain.
Experimental result: as seen by table 9, the heavy dose of group of medicine of the present invention is higher than normal control group mice pain threshold at 30min, 60min and middle dosage group 30min mice pain threshold, has significant difference (P＜0.05), so can think that non-specific pain has certain inhibitory action due to the medicine hot plate of the present invention.
Table 9 medicine of the present invention to hot plate to the influence of mice pain reflection
| Group | Number of animals (only) | Dosage (g/kg) | Different time mice pain threshold (s) | ||||
| Before the administration | 30min | 60min | 90min | 120min | |||
| Normal control | 10 | - | 14.51±2.36 | 17.61±6.14 | 22.82±5.69 | 23.91±9.92 | 28.01±5.33 |
| Positive control medicine of the present invention medicine of the present invention medicine of the present invention | 10 10 10 10 | 0.04 8 4 2 | 15.82±2.74 * 15.13±4.15 * 15.42±5.31 * 14.70±4.52 * | 36.12±2.60 *** 29.72±5.74 ** 32.70±4.24 ** 36.40±4.25 * | 37.91±5.29 *** 30.21±5.71 ** 36.92±5.3 * 32.13±7.75 * | 40.12±4.43 ** 35.92±7.25 * 39.81±6.25 * 39.63±5.03 * | 39.11±7.15 * 35.12±4.14 * 36.03±5.92 * 36.52±8.18 * |
Compare with the normal control group:
*P＞0.05;
*P＜0.05;
* *P＜0.01.
The immunoregulation effect of test example 5 medicines of the present invention
1, medicine of the present invention is to the influence of the tardy paraphilia reaction of 2.4-dinitrochlorobenzene (DNCB) induced mice
(1) purpose: observe medicine of the present invention to the tardy allergic influence of mice, can reflect the regulating action of medicine to the reaction of body specific immune.
(2) experimental technique: get 50 of Kunming mouses, male and female half and half, 18-22g is divided into 5 groups at random by body weight.First group is model control group (irritate stomach salad oil), second group of positive matched group, and subcutaneous injection 0.015g/kg cyclophosphamide every other day, three to five groups are the large, medium and small dosage group of medicine of the present invention.All the other respectively organize administration every day 1 time, and gastric infusion is 7 days continuously.The DNCB preparation: sensitization or attack are preceding to be the fresh preparation of solvent with acetone and Oleum Sesami at 1: 1.Depilation 3 * 3cm in the every Mus of 3d back before the administration; Administration evenly was applied in mouse back with 50ul 1%DNCB solution the same day, strengthened 1 time next day again.Behind the sensitization 7d, 20ul1%DNCB solution evenly is applied in evenly is applied in every mouse right ear and attacks, take off neck behind the 24h and put to death animal, weigh, cut two ears along the auricle baseline and weigh, and get thymus, spleen is weighed.Difference with left and right sides auricle weight is represented the swelling degree, and calculates spleen index, thymus index.
(3) experimental result: by table 10, the heavy dose of group of medicine of the present invention swelling degree significantly less than model group to group (p＜0.05), so think that medicine of the present invention reacts the tardy paraphilia of DNCB induced mice inhibitory action is arranged.
Table 10 medicine of the present invention is to the influence of the tardy paraphilia reaction of 2.4-dinitrochlorobenzene induced mice
| Group | Number of animals (only) | Dosage (g/kg*d) | Thymus index (mg/10g) | Index and spleen index (mg/10g) | Swelling degree (mg) |
| Model control group medicine group of the present invention medicine group of the present invention medicine group of the present invention cyclophosphamide group | 10 10 10 10 10 | - 8×3 4×3 2×3 0.02×7 | 0.52±0.080 0.41±0.03** 0.47±0.09 * 0.49±0.11 * 0.31±0.16*** | 0.39±0.020 0.33±0.021 * 0.35±0.074 * 0.38±0.055 * 0.25±0.034*** | 47.22±10.30 35.56±11.14** 40.76±10.33 * 44.38±8.82 * 12.14±9.95*** |
Compare with model group: * p＞0.05 * * p＜0.05; * * p＜0.01.
2, to the effect of mice reticuloendothelial system phagocytic function
(1) purpose: observe the influence of medicine of the present invention, can reflect the regulating action of medicine to the reaction of body nonspecific immunity to mouse monokaryon macrophage system phagocytic function.
(2) method: 72 of Kunming mouses, male and female half and half, body weight 18～22g is divided into 6 groups at random by body weight and sex, 12 every group.First group is model control group (irritating the stomach salad oil), and (dexamethasone, 10mg/dl), three to five groups are the large, medium and small dosage group of medicine of the present invention to second group of positive matched group.Irritating the stomach volume is the 0.1ml/10g body weight, every day 1 time, continuous 7 days.After the last administration 1 hour, tail vein injection india ink (dilution in 1: 4) 0.1ml/10g body weight, injection back 30s and 10min get blood 50ul from the vena orbitalis posterior clump respectively, add 0.1%Na
2CO
3In the ml solution, shake up, 675nm wavelength colorimetric reads optical density A
30sAnd A
10min, be calculated as follows phagocytic index k and proofread and correct phagocytic index α.
(3) experimental result: each dosage group of medicine of the present invention all can reduce phagocytic index, and there were significant differences (p＜0.05) for heavy dose of group.This medicine has inhibitory action to the effect of mice reticuloendothelial system phagocytic function.
Table 11 medicine of the present invention is to the effect to mice reticuloendothelial system phagocytic function
| Group | Number of animals (only) | Dosage (g/kg*d) | Phagocytic index k | Proofread and correct phagocytic index α |
| Model control group medicine group of the present invention medicine group of the present invention medicine group of the present invention Dexamethasone group | 12 12 12 12 12 | - 8×7 4×7 2×7 0.010×7 | 2.023±0.219 0.309±0.063** 0.430±0.328 * 1.934±0.611 * 0.284±0.161*** | 2.07±0.50 1.25±0.16** 1.60±0.23 * 1.90±0.35 * 1.00±0.23** |
Compare with model group: * p＞0.05 * * p＜0.05; * * p＜0.01.
3, the influence that the mice hemolytic antibody is generated
(1) purpose: it is red thin to inject 5% chicken to mouse peritoneal, brings out producing antibody in the body, estimates the regulating action that medicine of the present invention reacts the body nonspecific immunity.
(2) experimental technique is got 60 of Kunming mouses, and male and female half and half are divided into 6 groups at random by body weight.Successive administration after 3 days every mouse peritoneal inject 5% chicken erythrocyte suspension 0.3ml/ and only carry out immunity.Give the equal-volume salad oil as the blank group for first group; Second group is cyclophosphamide; The 3rd group is the Radix Tripterygii Wilfordii group; The 3rd group the 4th to six group prop up irritate the high, medium and low concentration of stomach medicine of the present invention medicinal liquid as the administration group, successive administration 7 days.The cyclophosphamide group is respectively at 2.4.6 days subcutaneous injection cyclophosphamide 0.02g/kg, and immunity was promptly extractd eyeball in back 7 days and got blood and carry out hemolytic antibody and measure.The preparation of Sanguis Gallus domesticus cell: under the aseptic condition, get Sanguis Gallus domesticus in the sterilization conical flask that fills Alsever ' s solution, Sanguis Gallus domesticus and Alsever ' s solution proportion are 1: 5, mixing, and 4 ℃ of refrigerators are preserved.Wash 3 times preceding two times centrifugal speed 1000r/min, centrifugal 5min during use with normal saline, abandon supernatant and interface leukocytic cream, at last should be double centrifugal (1500r/min, 5min), constant until the packed cell volume value, be made into the red cell suspension of desired concn with normal saline by ratio.Immunity was promptly extractd eyeball in back 7 days and is got blood and carry out hemolytic antibody and measure.After getting the blood pact, the centrifugal 10min of 2000r/min, get serum 10 μ l and dilute 100 times with normal saline 1ml, get dilute serum 1ml then in vitro, mix with the fresh guinea pig serum 0.5ml after 5% chicken erythrocyte suspension 0.5ml and the dilution in 1: 10, mixing, put into 37 ℃ of thermostat water bath constant temperature 30min immediately, take out immediately then and put into the ice bath cessation reaction, centrifugal, get supernatant in 540nm place colorimetric, add 5% chicken erythrocyte suspension 0.5ml with the 1ml normal saline, 10% guinea pig serum 0.5ml measures absorbance (A) value respectively as blank.
(3) experimental result: by table 12 as seen, the heavy dose of group of medicine of the present invention optical density value significantly is lower than model control group (p＜0.05), shows that this medicine generates inhibited to the mice hemolytic antibody.
The influence that table 12 pair mice hemolytic antibody generates
| Group | Number of animals (only) | Dosage (g/kg*d) | The A value |
| Model control group Radix Tripterygii Wilfordii group cyclophosphamide group medicine group of the present invention medicine group of the present invention medicine group of the present invention | 10 10 10 10 10 10 | - 0.002×7 0.02×7 8×7 4×7 2×7 | 0.428±0.052 0.382±0.040** 0.273±0.123*** 0.321±0.146** 0.420±0.038 0.424±0.022 |
Compare with model group: * p＞0.05 * * p＜0.05; * * p＜0.01.
Conclusion:
In sum, medicine gastric infusion of the present invention, xylol causes mice auricle swelling, the on Carrageenan local injection brings out rat foot claw swelling, rat thoracic cavity leukoplania, intraperitoneal mouse capillary permeability and mice granuloma induced by implantation of cotton pellets all obvious inhibitory action, shows that medicine of the present invention has antiinflammatory action.
Medicine gastric infusion of the present invention can significantly suppress the hot plate method induced mice and add sufficient number of times, the antagonism hot plate due to non-specific pain; Also can significantly suppress method of acetic acid and cause the mouse writhing number of times, the large tracts of land deep pain that the acetic acid lumbar injection is caused has antagonism.
Effect has obvious inhibitory action to medicine gastric infusion of the present invention to the normal mouse reticuloendothelial system phagocytic; DNCB is brought out DTH reaction and serum hemolysin antibody to be generated obvious inhibitory action is all arranged.
Medicine gastric infusion of the present invention causes rat arthritis (AA) primary affection and the secondary affection effect of having clear improvement to complete Freund's adjuvant, can alleviate multiple pathological changes such as synovial hyperplasia, proliferation of fibrous tissue, the multiple cell infiltration of minimizing.Can reduce nitric oxide (NO) in adjuvant arthritis rats (AA) serum, malonaldehyde (MDA) content, and nitric oxide synthetase (NOS) vigor; Improve superoxide dismutase (SOD) vigor.Show certain antioxidation.Can reduce inflammatory cytokine TNF-α, IL-β content in adjuvant arthritis rats (AA) serum.The mechanism of medicine resisting rheumatoid disease of the present invention or with antioxidation, to regulate inflammatory cytokine relevant.
To sum up, medicine of the present invention has antiinflammatory action, analgesic activity, and immunomodulating and antioxidation are to the effect of being significantly improved of adjuvant arthritis animal model, so can be used for treating rheumatism, rheumatoid arthritis treatment.
Claims (10)
1. pharmaceutical composition for the treatment of rheumatism, rheumatoid arthritis, it is characterized in that: it is the medicament that is prepared from by the following weight proportion raw material:
Rhizoma Curcumae Longae 1-9 part, Cortex Cinnamomi 9-1 part.
2. the pharmaceutical composition of treatment rheumatism according to claim 1, rheumatoid arthritis is characterized in that: it is the medicament that is prepared from by the following weight proportion raw material:
Rhizoma Curcumae Longae 1-5 part, Cortex Cinnamomi 1-2 part.
3. the pharmaceutical composition of treatment rheumatism according to claim 2, rheumatoid arthritis is characterized in that: it is the medicament that is prepared from by the following weight proportion raw material:
1 part of Rhizoma Curcumae Longae 1-5 part, Cortex Cinnamomi.
4. the pharmaceutical composition of treatment rheumatism according to claim 3, rheumatoid arthritis is characterized in that: it is the medicament that is prepared from by the following weight proportion raw material:
2 parts in Rhizoma Curcumae Longae, 1 part of Cortex Cinnamomi.
5. according to the pharmaceutical composition of each described treatment rheumatism of claim 1-4, rheumatoid arthritis, it is characterized in that: it is to be active component by Rhizoma Curcumae Longae, cinnamomic water or extractive with organic solvent, add the medicament that acceptable accessories or complementary composition are prepared from, described medicament is: capsule, tablet, pill, oral liquid or granule.
6. the pharmaceutical composition of treatment rheumatism according to claim 5, rheumatoid arthritis is characterized in that: described capsule is a soft capsule, and every contains curcumin C
21H
80O
6Weight percentage for being no less than 7.0%.
7. method for preparing the pharmaceutical composition of each described treatment rheumatism of claim 1-6, rheumatoid arthritis, it comprises the steps:
A, get it filled material Rhizoma Curcumae Longae, Cortex Cinnamomi;
B, Rhizoma Curcumae Longae add ethanol extraction, and concentration of alcohol is 〉=65%; Cortex Cinnamomi is adopted steam distillation, gets volatile oil, merges two kinds of extracts, adds acceptable accessories or complementary composition and is prepared into medicament pharmaceutically commonly used.
8. the pharmaceutical composition of treatment rheumatism according to claim 7, rheumatoid arthritis is characterized in that: the described concentration of alcohol of b step is: 70% ethanol, extracting method is: the ethanol percolation method.
9. the purposes of the described pharmaceutical composition of claim 1 in the medicine of preparation treatment rheumatoid arthritis.
10. the purposes of the described pharmaceutical composition of claim 1 in the medicine of preparation treatment rheumatic arthritis.
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| CN102697887A (en) * | 2012-06-26 | 2012-10-03 | 南京辰逸生物科技有限公司 | Traditional Chinese medicine composition for treating rheumatoid arthritis |
| CN102186489B (en) * | 2008-10-07 | 2013-10-02 | 特拉维夫大学拉玛特有限公司 | Use of cinnamon bark extract for treating amyloid-associated diseases |
| CN116270944A (en) * | 2023-04-10 | 2023-06-23 | 博凯药业有限公司 | Joint conditioning effervescent ball and preparation method and application thereof |
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| CN1166975A (en) * | 1997-04-15 | 1997-12-10 | 钱金宝 | High-efficiency liniment for bone injury and chilblain |
| CN1193786C (en) * | 2003-04-16 | 2005-03-23 | 王朝岭 | Preparation of Chinese herbal medicine for treating cold injury, various indurations and swelling, pain as well as its preparing method |
| CN100400095C (en) * | 2005-02-02 | 2008-07-09 | 冯上舒 | Rubber plaster for treating insufficient cold type chronic gstroentertis and rheumatic arthritis and preparation thereof |
| US8017162B2 (en) * | 2005-10-26 | 2011-09-13 | Oryza Oil & Fat Chemical Co., Ltd. | Anti-inflammatory agent |
| CN100342905C (en) * | 2006-04-21 | 2007-10-17 | 曾凡铜 | Medicinal powder for external application of treating rheumatism and spur |
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| CN102186489B (en) * | 2008-10-07 | 2013-10-02 | 特拉维夫大学拉玛特有限公司 | Use of cinnamon bark extract for treating amyloid-associated diseases |
| CN102697887A (en) * | 2012-06-26 | 2012-10-03 | 南京辰逸生物科技有限公司 | Traditional Chinese medicine composition for treating rheumatoid arthritis |
| CN116270944A (en) * | 2023-04-10 | 2023-06-23 | 博凯药业有限公司 | Joint conditioning effervescent ball and preparation method and application thereof |
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