CN1846719A - Rheumatism treating medicine and its prepn process - Google Patents
Rheumatism treating medicine and its prepn process Download PDFInfo
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- CN1846719A CN1846719A CN 200610033752 CN200610033752A CN1846719A CN 1846719 A CN1846719 A CN 1846719A CN 200610033752 CN200610033752 CN 200610033752 CN 200610033752 A CN200610033752 A CN 200610033752A CN 1846719 A CN1846719 A CN 1846719A
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Abstract
The present invention is one kind of rheumatism treating medicine and its preparation process. The rheumatism treating medicine is prepared with tripterygium in 1-7 weight portions and himalayan teasel in 1 weight portions; and the preparation process includes the following steps: soaking tripterygium, decocting tripterygium for 3.5-7 hr, adding himalayan teasel before further decoction of other 0.5-1 hr, filtering and further treatment to obtain the preparation in required form. The present invention has high curative effect on RA, AS, SLE, OA and other type of rheumatism, less toxic side effect, and simple preparation process.
Description
Technical field
The present invention relates to treat rheumatismal medicine and preparation method thereof.
Technical background
Rheumatism is the disease that a class relates to BJM and soft tissue thereof.Wherein, rheumatoid arthritis (Rheumatoid Arthritis, RA), ankylosing spondylitis (Ankylosing Spondilitis, AS), systemic lupus erythematosus (sle) (systemic lupus erythematosus, SLE) and osteoarthritis (Osteoarthritis, OA) be modal several rheumatism, muscle is all arranged, muscles and bones, clinical manifestation such as arthralgia and arthroncus, just affecting the hundreds of millions of population of all races of the whole world, cause the individual, the massive losses of family and society, countries in the world are all for seeking specific therapy and medicine effort.The nonsteroidal anti inflammatory medicine (as indometacin etc.) be the various rheumatismal line medicines of treatment, but improving the state of an illness, suppressing not have obvious effect aspect the destruction of joint, and its toxic and side effects that causes aspects such as digestive tract ulcer is also of common occurrence.In the medicine that improves the rheumatism state of an illness, methotrexate (MTX) is one of the most frequently used, that curative effect is the most definite Western medicine, MTX can slow down bone destruction and control active rheumatism, but can not stop the forfeiture of lasting cartilage and bone fully, and it has toxic and side effects such as bone marrow depression, hepatic injury, forces a part of patient's therapy discontinued.The Chinese medicine rheumatism is with a long history, has obtained clinical efficacy preferably, and wherein, tripterygium plant and effective ingredient thereof are generally acknowledged, one of effective wind resistance damp disease Chinese medicine.Extensively applying at present the clinical effect component preparation that mainly includes, is representative with the Tripterygium glycosides; Single pharmaceutical preparation is representative with the Tripterygium hypoglaucum; Compound preparation is representative with two rattan blood stasis dispelling mixture (by Celastrus orbiculatus Thunb. and Caulis Spatholobi composition of prescription).Studies show that, these three kinds of Radix Tripterygii Wilfordii pharmaceutical preparatioies can obviously alleviate arthralgia, eliminate arthroncus, but it is still dissatisfied to improving joint function disturbance, destruction of joint and lopsided effect, it suppresses gonad function, and the side effect of aspects such as gastrointestinal reaction and liver function injury has also influenced further application.
Summary of the invention
Purpose one of the present invention provides a kind for the treatment of both the principal and secondary aspects of a disease, good effect, rheumatismal medicines such as treatment RA, AS, SLE and OA that toxic and side effects is little.
Purpose two of the present invention provides manufacturing method for above mentioned medicine.
Technical scheme of the present invention is based on the traditional Chinese medical science on the rheumatismal dialectical basis, adopt two kinds of drug matchings, treating both the principal and secondary aspects of a disease is treated, and has rapid-actionly than single medicinal material or effective components of Chinese medicinal preparation, and effect is strong, the advantage that toxic and side effects is little, and raw material is natural plants, and it is wide, cheap to distribute, drug safety is convenient to the patient and is taken for a long time.
Rheumatism belongs to the category of " arthromyodynia " in motherland's medical science, numbness is the obstructed meaning of impatency.The cause of disease has endogenous cause of ill, two aspects of exopathogenic factor, interior be deficiency of both the liver and kidney, insufficiency of vital energy and blood, the space between skin and muscles inanition, outside by wind, cold, wet, pathogenic heat invasion and attack human body, say as " element is asked the numbness opinion " " wet three gas of wind and cold are assorted extremely, close and be numbness also." deficiency of the liver and kindey, wind-cold damp pathogen is attacked the generation that human body has caused arthromyodynia in an opponent's defence.The rheumatisant often has soreness of the waist and knees, arthralgia, swelling, localized pain or be the whole body migration, tuberosity or skin ecchymosis around the joint, or with spiritlessness and weakness, amenorrhea, dysmenorrhea, purplish tongue has petechia, deep-slow pulse, or hold concurrently puckery or knot generation, be deficiency of the liver and kindey, the intrusion of pathogenic wind-cold-dampness human body, numbness hinders due to joint, muscle and the meridians.Therefore, no matter from pathogen and pathology of tcm, still from analysis of clinical symptom, deficiency of the liver and kindey, the anemofrigid-damp arthralgia resistance all is very close with rheumatismal relation, this is an expelling wind and removing dampness, promoting blood circulation and stopping pain, the liver and kidney tonifying method applies to rheumatismal treatment theoretical foundation is provided.
The present invention is made by Tripterygium hypoglaucum and Radix Dipsaci two flavor drug matchings, and Tripterygium hypoglaucum has another name called powder back of the body Radix Tripterygii Wilfordii, Colquhounia coccinea Wall. var. mollis (Schlecht.) Prain, Celastrus orbiculatus Thunb., belong to Celastraceae, bitter in the mouth, warm in nature, has expelling wind and dampness, the promoting flow of QI and blood pain relieving, and the effect of subduing swelling and detoxicating (the new medical college in Jiangsu is compiled. Chinese medicine dictionary, the 1st edition, the Shanghai People's Press, 1977:1567).Radix Dipsaci bitter in the mouth suffering, tepor has invigorating the liver and kidney, reuniting the fractured tendons and bones, (the new medical college in Jiangsu is compiled Chinese medicine dictionary, the 1st edition, the Shanghai People's Press to the effect of blood circulation regulating, 1994:2268), two medicine compatibilities have the effect of expelling wind and removing dampness, promoting blood circulation and stopping pain and liver and kidney tonifying, reach the purpose for the treatment of both the principal and secondary aspects of a disease.
The present invention takes following bulk drugs to make: 1~7 part of Tripterygium hypoglaucum, 1 part of Radix Dipsaci.
The present invention preferably adopts following bulk drugs to make: 2 parts of Tripterygium hypoglaucumes, 1 part of Radix Dipsaci.
The Chinese medicine Tripterygium hypoglaucum is used as medicine with exsiccant usually, find that through experiment the exsiccant stem of Tripterygium hypoglaucum has identical drug effect with exsiccant of Tripterygium hypoglaucum (promptly common alleged Chinese medicine Tripterygium hypoglaucum), can substitute exsiccant of the Tripterygium hypoglaucum (promptly common alleged Chinese medicine Tripterygium hypoglaucum) of identical weight fully.Its preparation technology is constant.
Tripterygium hypoglaucum of the present invention can adopt the Radix Tripterygii Wilfordii of equivalent to replace.Preparation technology is constant.
The rheumatismal medicine of treatment of the present invention, its medicament are said dosage forms on any pharmaceutics.
Rheumatismal medicine of the present invention, its dosage form can be pill, tablet, powder, granule, capsule, drop pill, syrup, medicated wine, oral solutions, injection.
The preparation method of medicine of the present invention comprises the following steps: that getting Tripterygium hypoglaucum by prescription adds water to submerge, decocted 3.5-7 hour, and added Radix Dipsaci again, fried in shallow oil altogether 0.5-1 hour, filter, filtrate concentrates, and adds 0.1% ethyl hydroxybenzoate, 0.3% sodium benzoate stirring and dissolving, put cold, adjust medicinal liquid to full dose, filter, inspect qualified back packing by ready samples.Be prepared into oral liquid (mixture).
The preparation method of medicine of the present invention is after Tripterygium hypoglaucum, Radix Dipsaci aqueous extract filter, and filtrate can further concentrate, and extractum is made in oven dry, further is processed into capsule, granule or interpolation adjuvant and makes dosage forms such as tablet, syrup, drop pill; Also can adopt the routine techniques in present technique field further to be processed into other peroral dosage form or injection type.
The preparation method of medicine of the present invention can further add water and extract 1~2 time again after Tripterygium hypoglaucum, Radix Dipsaci aqueous extract filter, and filters merging filtrate, reconcentration.Further be processed into various dosage forms.
The adult uses dosage of the present invention for be equivalent to 10~30 gram Chinese crude drugs, every day 2~3 times at every turn.
The present invention is through pharmacodynamics test: the AA rat is the classical model of acute arthritis disease, the anti-acute arthritis disease of the present invention rapid-action, and action intensity is better than single Tripterygium hypoglaucum and two rattan blood stasis dispelling mixture.Pathological examination shows that the present invention can obviously suppress the neutrophil infiltration of AA rat acute arthritis, synovial tissue's hypertrophy and pannus hypertrophy.The CIA rat is the model of classical chronic autoimmunity arthritis, and the present invention can suppress twice inflammation peak of CIA rat after administration, with Tripterygium glycosides and MTX relatively, the present invention suppresses that the effect of chronic arthritis disease is rapid-action, effect is strong.On pathology, the present invention can obviously suppress CIA rat inflammatory cell infiltration, synovial tissue's hypertrophy and proliferation of fibrous tissue, the protection cartilage is stronger than Tripterygium glycosides and MTX effect.In the protection joint, suppress the bone destruction aspect, effect of the present invention also is better than Tripterygium glycosides and MTX.
Toxic and side effects is observed and to be shown, in the acute arthritis experiment, it is smooth-going that the present invention irritates behind the stomach hair diet of rat, and glossy and normal group be no significant difference relatively, and diet is normal.Two rattan blood stasis dispelling mixture groups, indometacin group and Tripterygium hypoglaucum group the hair pine occurs disorderly, and onyx is pale, the phenomenon of loss of appetite.Ovary and testis pathological examination show that the present invention does not have obvious influence for ovary and testis.
Experimental results show that, the drug effect that the present invention suppresses acute arthritis disease is better than Tripterygium hypoglaucum and ERTENG TONGBILING HEJI, the drug effect that suppresses chronic arthritis disease and destruction of joint is better than Tripterygium glycosides, and have treating both the principal and secondary aspects of a disease, characteristics that toxic and side effects is little, can be used for treating rheumatisms such as RA, AS, SLE and OA.
The invention will be further described below in conjunction with the drawings and the specific embodiments.
Description of drawings
Fig. 1 is Freund's complete adjuvant modeling rat (AA rat, an acute arthritis model) hind leg paw swelling time plot.Wherein be divided into six groups, i.e. normal group, modeling+normal saline group (modeling matched group), modeling+indometacin group (MTX group), modeling+of the present invention group, modeling+Tripterygium hypoglaucum group, modeling+two rattan blood stasis dispelling mixture groups.
Fig. 2 is cattle II Collagen Type VI modeling rat (chronic arthritis model) hind leg paw swelling time plot, wherein be divided into six groups, modeling+normal saline group (modeling matched group), modeling+indometacin group (MTX group), modeling+of the present invention group, modeling+Tripterygium hypoglaucum group, modeling+two rattan blood stasis dispelling mixture groups.
The instantiation mode
The invention will be further described by the following examples, and these embodiment are further concrete statements that summary of the invention of the present invention is done, but not to any restriction of embodiment of the present invention.
Embodiment 1
Prescription: Tripterygium hypoglaucum 40kg, Radix Dipsaci 20kg.
Preparation method (mixture): Tripterygium hypoglaucum is added water to submerge, be decocted first 3.5-7 hour, add Radix Dipsaci again with frying in shallow oil 0.5-1 hour, filter, filtrate is concentrated into about 90,000 milliliters, add 0.1% ethyl hydroxybenzoate, 0.3% sodium benzoate stirring and dissolving is put coldly, adjusts medicinal liquid to full dose, filter, inspect qualified back packing by ready samples.Be prepared into 90,000 milliliters oral liquid (mixture).
Embodiment 2
Prescription: Tripterygium hypoglaucum 60kg, Radix Dipsaci 20kg.
Preparation method (capsule): Tripterygium hypoglaucum is added water to submerge, and is decocted first 3.5-7 hour, adds Radix Dipsaci again with frying in shallow oil 0.5-1 hour, filter, concentrating under reduced pressure, pressure are-0.08Mpa that temperature is 50 ℃-80 ℃, concentrate the clear paste of measuring relative density 1.18-1.20, in 65 ℃ of oven dry, get dry extract, pulverize, cross 60 mesh sieves, adorn capsule No. 0.Be prepared into capsule.
Embodiment 3
Prescription: Tripterygium hypoglaucum 20kg, Radix Dipsaci 20kg.
Preparation method (tablet): Tripterygium hypoglaucum is added water to submerge, and is decocted first 3.5-7 hour, adds Radix Dipsaci again with frying in shallow oil 0.5-1 hour, filters, concentrating under reduced pressure, pressure are-0.08Mpa that temperature is 50 ℃-80 ℃, concentrates the clear paste of measuring relative density 1.18-1.20, in 65 ℃ of oven dry, get dry extract, pulverize, cross 100 mesh sieves, weighing adds the proper proportion carboxymethyl starch sodium, mixing, alcohol granulation, drying, granulate is weighed, and adds the magnesium stearate of proper proportion, tabletting, bag water-soluble film clothing, package storage.Be prepared into tablet.
Embodiment 4
Prescription: Tripterygium hypoglaucum 70kg, Radix Dipsaci 10kg
Preparation method (granule): Tripterygium hypoglaucum is added water to submerge, and is decocted first 3.5-7 hour, adds Radix Dipsaci again with frying in shallow oil 0.5-1 hour, filter, concentrating under reduced pressure, pressure are-0.08Mpa, temperature is 50 ℃-80 ℃, concentrate the clear paste of measuring relative density 1.18-1.20,, get dry extract in 65 ℃ of oven dry, pulverize, cross 100 mesh sieves, add suitable starch, Icing Sugar and ethanol, the trough-type mixture machine mix homogeneously.Granulation machine is granulated, package storage.Be prepared into granule.
Embodiment 5
Prescription: Tripterygium hypoglaucum 80kg, Radix Dipsaci 20kg.
Preparation method (syrup): Tripterygium hypoglaucum is added water to submerge, be decocted first 3.5-7 hour, and added Radix Dipsaci again, filter with frying in shallow oil 0.5-1 hour, filtrate is concentrated into about 80,000 milliliters, add 0.1% ethyl hydroxybenzoate, 0.3% sodium benzoate stirring and dissolving adds proper honey, put cold, adjust medicinal liquid to 100,000 milliliters of full doses, filter, inspect qualified back packing by ready samples.Be prepared into syrup.
Embodiment 6
Prescription: Tripterygium hypoglaucum 100kg, Radix Dipsaci 20kg
Preparation method (capsule): Tripterygium hypoglaucum is added water to submerge, be decocted first 3.5-7 hour, add Radix Dipsaci again with frying in shallow oil 0.5-1 hour, filter, further adding water extracts 1~2 time again, merging filtrate, concentrating under reduced pressure, pressure are-0.08Mpa, temperature is 50 ℃-80 ℃, concentrate to measure the clear paste of relative density 1.18-1.20, taking polyethylene glycol 6000 about 10kg in addition, heat dissolve and with the clear paste mixing, dropper with internal diameter 9.0mm, under 50 ℃ of insulations, splash in the liquid Paraffin liquid coolant below 10 ℃, be condensed into ball, promptly get drop pill.
With embodiments of the invention 1 is experiment material, carries out the pharmacodynamics test of embodiment 7, embodiment 8.
The effect experiment of example example 7 acute arthritis diseases
7.1 method
7.1.1 modeling: the purebred Wistar rat of no-special pathogen (SPF), female, body weight (110g ± 20g), available from No.1 Military Medical Univ.'s animal center, the animal quality certification number: 2002A041.Feeding environment: The First Affiliated Hospital of Guangzhou University of Traditional Chinese Med's cleaning level Animal House.Be divided into earlier modeling group and normal control group at random, modeling with Freund's complete adjuvant 0.2ml in the injection of rat root of the tail portion (every 0.2mL/ time).Be divided at random again after the modeling success: modeling+9 of normal saline groups (modeling matched group), 9 of modelings+indometacin group (MTX group), modeling+of the present invention group 10,10 of modelings+Tripterygium hypoglaucum group, 8 of modelings+two rattan blood stasis dispelling mixture groups.Be administration the sufficient swollen same day, and modeling matched group and normal control group are pressed 10mlkg
-1D
-1Irritate stomach with normal saline, indometacin is 1.6 times of clinical common dose, and other medicines dosage is 6.25 times of clinical common dose, indometacin 2gkg
-1D
-1, 5gkg of the present invention
-1D
-1, two rattan blood stasis dispelling mixture 5gkg
-1D
-1, Tripterygium hypoglaucum 3.75gkg
-1D
-1Put to death animal after with the etherization animal in administration after 7 days, get the fixedly HE dyeing of left front and right back the 2nd toes joint.
7.1.2 the measurement of paw swelling: volumetric method is measured the paw swelling of two hind legs.
7.1.3 the evaluation of toes joint HE pathology sheet: get left fore and right hind near-end the 3rd toes joint, fixing, section, HE dyeing is carried out blind method evaluation to neutral grain, lymphocyte and plasmocyte infiltrating, synovial cell proliferation.Point system: 1. neutrophil infiltration degree (acute inflammation situation), 0 minute: do not have and soak into; + 1-5/visual field (HP); 2 minutes: 6-10/HP; 3 minutes: 11-15/HP; 4 minutes: form microabscess.2. synovial cell proliferation degree, 0 minute: do not have and soak into; 1 minute: swelling hypertrophy (many); 2 minutes: increase continuous; 3 minutes: increase bilayer; 4 minutes: more than three layers.3. pannus, 0 minute: do not have and soak into; 1 minute: new vessels was invaded 1/3 place; 2 minutes: invade 1/2; 3 minutes: invade>1/2; 4 minutes: the both sides pannus merged mutually.
7.2 result
Shown in Fig. 1 and table 1, obvious swelling appears in the AA rat hindlimb after the modeling, and along with the prolongation of time, swelling increases the weight of gradually, peaks in the 7th day.Foot was respectively organized there was no significant difference (P>0.05) in swollen back first day.After the administration the 3rd day, the present invention was in relatively having significant difference (P<0.05) with the modeling group, and two rattan blood stasis dispelling mixture, Tripterygium hypoglaucum and modeling group be there was no significant difference (P>0.01) relatively.After the administration the 7th day, two rattan blood stasis dispelling mixture, Tripterygium hypoglaucum is in the modeling group significant difference (P<0.05) being arranged relatively.The present invention, indometacin and modeling group relatively have significant differences (P<0.01).
The swollen comparison sheet of table 1AA rat foot
Group | N | The 1st day (ml) | The 3rd day (ml) | The 7th day (ml) |
Normally+normal saline group modeling+normal saline group modeling+indometacin group | 6 9 9 | 0.19±0.02 * 0.26±0.10 0.24±0.04 | 0.19±0.02 ** 0.32±0.12 △△ 0.25±0.07 | 0.19±0.02 * 0.43±0.09 △△ 0.32±0.08 ** |
Modeling+two rattan blood stasis dispelling mixture group modeling+Tripterygium hypoglaucum group modelings+of the present invention group | 8 10 10 | 0.22±0.05 0.27±0.06 0.25±0.08 | 0.27±0.07 0.29±0.09 0.25±0.05 * | 0.34±0.10 * 0.34±0.12 * 0.29±0.09 ** |
Compare with the modeling group
*P<0.05,
*Compare with normal group P<0.01
△ △P<0.01 (down together).
Table 2 shows that the pathological examination of drawing materials in the 7th day after the modeling is that tangible neutrophil infiltration appears in modeling group toes joint, and synovial tissue's hypertrophy and pannus hypertrophy relatively have significant difference (P<0.01) with normal group; Indometacin, two rattan blood stasis dispelling mixture, Tripterygium hypoglaucum and the present invention all can obviously suppress the neutrophil infiltration of AA rat, synovial tissue's hypertrophy and pannus hypertrophy (P<0.01, P<0.05).The present invention and two rattan blood stasis dispelling mixture, Tripterygium hypoglaucum relatively has significant difference (P<0.01).
The score of table 2AA rat toes joint pathology
Group | N | Neutrophil cell soaks into | Synovial tissue's hypertrophy | Pannus |
Normally+and normal saline group modeling+normal saline group modeling+indometacin group modeling+two rattan blood stasis dispelling mixture group modeling+Tripterygium hypoglaucum group modelings+of the present invention group | 6 9 9 8 10 10 | 0±0 ** 1.83±0.75 △△ 0.25±0.71 ** 0.86±0.38 **□ 0.78±0.38 **□ 0.13±0.35 ** | 0±0 ** 2.67±0.52 △△ 1.38±0.74 ** 1.71±0.49 **□ 1.78±1.09 **□ 0.88±0.84 ** | 0±0 **2.33±0.82 △△1.13±0.99 **1.43±0.54 *□1.44±0.53 *□0.75±0.89 ** |
Compare with the modeling group
*P<0.05,
*Compare with normal group P<0.01
△ △P<0.01 is with of the present invention group of comparison P<0.05.
7.3 conclusion
The AA rat is the classical model of acute arthritis disease, and above experimental result shows, the anti-acute arthritis disease of the present invention rapid-action, and action intensity is better than single Tripterygium hypoglaucum and two rattan blood stasis dispelling mixture.Pathological examination shows that the present invention can obviously suppress the neutrophil infiltration of AA rat acute arthritis, synovial tissue's hypertrophy and pannus hypertrophy, and also than two rattan blood stasis dispelling mixture, the Tripterygium hypoglaucum effect is stronger.
Example example 8 chronic arthritis diseases and destruction of joint effect experiment
8.1 method
8.1.1 modeling: the purebred Wistar rat of no-special pathogen (SPF), female, body weight (110g ± 20g), available from No.1 Military Medical Univ.'s animal center, the animal quality certification number: 2002A041.Feeding environment: The First Affiliated Hospital of Guangzhou University of Traditional Chinese Med's cleaning level Animal House.Be divided into earlier modeling group and normal control group at random, be divided at random after the modeling success again: modeling+8 of normal saline groups (modeling matched group), modeling+MTX organizes (MTX group) 7,9 of modelings+TBL total alkali group.Modeling is dissolved in the 0.1mmoL/L acetic acid with cattle II Collagen Type VI, in the fully mixed emulsifying in 1: 1 of 2g/L ratio and adjuvant, in the injection of rat root of the tail portion (every 0.2mL/ time).Be administration the sufficient swollen same day, and modeling matched group and normal control group are pressed 10mlkg
-1D
-1Irritate stomach with normal saline, MTX dosage is 7.6mgkg
-1W
-1, Tripterygium glycosides is 45.5mgkg
-1D
-1, dosage is 30 times of clinical common dose, the present invention is 5gkg
-1D
-1, dosage is 6.25 times of clinical common dose.In administration after 35 days with behind the etherization animal, under the limbs vola mind-set, the instep adhesive tape that makes progress is fixed on the platform.Use breast molybdenum target machine (Italian Ji Te company product) to carry out the whole body X-ray photograph, condition is 30KV, 0.6mAs.After putting to death animal, get the fixedly HE dyeing of left front and right back the 2nd toes joint.
8.1.2 the measurement of paw swelling: volumetric method is measured the paw swelling of two hind legs.
8.1.3 the evaluation of toes joint HE pathology sheet: get left fore and right hind near-end the 3rd toes joint, fixing, section, HE dyeing is carried out blind method evaluation to neutral grain, lymphocyte and plasmocyte infiltrating, synovial cell proliferation.Point system: 1. neutrophil infiltration degree (acute inflammation situation), 0 minute: do not have and soak into; 1 minute: 1-5/visual field (HP); 2 minutes: 6-10/HP; 3 minutes: 11-15/HP; 4 minutes: form microabscess.2. lymphocytic infiltration degree, 0 minute: do not have and soak into; 1 minute: a small amount of existence; 2 minutes: sparse being dispersed in; 3 minutes: a large amount of existence; 4 minutes: a large amount of cells, and form lymph follicle.3. plasmocyte infiltrating degree, 0 minute: do not have and soak into; 1 minute: 1-5/HP; 2 minutes: 6-10/HP; 3 minutes: 11-15/HP; 4 minutes:>16/HP.4. synovial cell proliferation degree, 0 minute: do not have and soak into; 1 minute: swelling hypertrophy (many); 2 minutes: increase continuous; 3 minutes: increase bilayer; 4 minutes: more than three layers.5. synovial membrane proliferation of fibrous tissue degree, 0 no hypertrophy; + hypertrophy accounts for 1/3HP; ++ hypertrophy accounts for 1/2HP; +++hypertrophy accounts for 1HP; ++ ++ hypertrophy>1HP.6. articular cartilage is destroyed situation, and 0 does not have destruction; + special mess shape destroys<1/3; ++ 1/2 destroys; +++2/3 destroys; ++ ++ all destroy.
8.1.4 the evaluation of extremities joint X-ray sheet: the destruction of joint of every rat divides bone erosion (erosion) and joint space change, and (Joint spacenarrowing, JSN) two aspects are estimated.Bone erosion standards of grading: 0 minute: normal; 1 minute: suspicious or a small local lesion arranged; 2 minutes: two local lesions or focus total surface area≤50%; 3 minutes: the focus more than three or focus total surface area>50%:4 branch: articular surface destroyed fully, or bone occurred and dwindle.Joint space: 0 minute: normal; 1 minute: suspicious or a small local lesion arranged; 2 minutes: the joint occurred narrow; 3 minutes: ankylosis or joint space broadening.Bone erosion is totally 96 bones, comprising: far-end refers to a bone (16), and near-end refers to a bone (18), palm phalanx (18), and palm anklebone (16), anklebone (24): forelimb comprises central bone, magnum, unciform bone, navicular bone, semilunar bone, triquetrum.Hind leg comprises mesocuneiform bone, ectocuneiform bone, cuboid, os tarsi centrale, astragalus, calcaneus etc.), radius (2), ulna (2).Totally 100 of joint spaces comprise: DIPJ (16), proximal interphalangeal joint (18), palm toe joint (18), palm ankle joint (14), ankle joint (28), forelimb comprises polygonal-central bone joint, central authorities-magnum joint, head-unciform bone joint, hook-shaped-the triquetrum joint, central authorities-navicular bone joint, boat shape-semilunar bone joint, month shape-triquetrum joint.Hind leg comprises os tarsi centrale-mesocuneiform bone joint, mesocuneiform bone-ectocuneiform bone joint, ectocuneiform bone-cuboid joint, os tarsi centrale-astragalus joint, shank-cuboid joint, with-the cuboid joint, apart from-with the joint), oar, ankle joint (2), chi, ankle joint (2), shin-apart from the joint (2).Mark after readding sheet by the blind method of iconography doctor.
8.2 result
8.2.1 influence to CIA rat arthritis disease
Fig. 2 shows: hind leg the peak promptly occurs at the 7d that inflammation takes place, and disappears gradually then, reduces to the lightest at 17d, swelling gradually again then, and the 2nd inflammation peak appears in the 19th~25d.4~13d after hind leg swelling, forelimb also Secondary cases swelling can occur, disappear gradually in the 15~17d inflammation from beginning swelling, occur swelling behind the 19d once more, engender second inflammation peak.
Table 3 shows, there was no significant difference is given in each treatment in the 1st day of the swollen back of foot, of the present invention group promptly began to occur suppressing the effect of CIA rat arthritis disease on the 7th day after administration, relatively has significant difference (P<0.05) with modeling group and other treatment group, Tripterygium glycosides group and Tripterygium hypoglaucum group after after the administration the 19th day with modeling group comparing difference highly significant (P<0.01), MTX is 19 days and modeling group comparing difference remarkable (P<0.05) behind the group medicine, after the administration the 35th day, the present invention, Tripterygium glycosides group and MTX group and modeling group be difference significantly (P<0.05) relatively all.
Table 3CIA rat foot is relatively swollen
Group | N | The 1st day (ml) | The 7th day (ml) | The 19th day (ml) | The 35th day (ml) |
Normally+and normal saline group modeling+normal saline group modeling+MTX group modeling+Tripterygium glycosides group modeling+of the present invention group | 8 8 7 10 10 | 0.25±0.02 * 0.34±0.04 △△ 0.35±0.06 0.35±0.04 0.33±0.02 | 0.32±0.02 *0.52±0.13 △△0.48±0.14 □0.52±0.13 □0.40±0.10 * | 0.33±0.02 * 0.52±0.09 △△ 0.44±0.08 * 0.38±0.78 ** 0.35±0.05 ** | 0.34±0.01 ** 0.51±0.20 △△ 0.38±0.02 △△ 0.35±0.05 ** 0.35±0.07 ** |
Compare * P<0.05 with the modeling group, compare with normal group * * P<0.01
△ △P<0.01 (down together),
With of the present invention group of comparison P<0.05.
8.2.2 influence to CIA rat joint pathology
Table 4 shows that administration is after 35 days, and tangible neutrophil infiltration appears in CIA rat toes joint, lymphocytic infiltration, and plasmocyte infiltrating, synovial tissue's hypertrophy, proliferation of fibrous tissue and cartilage destruction relatively have significant difference (P<0.01) with normal group; The present invention has remarkable inhibitory action (P<0.01) to above index; Tripterygium glycosides and this MTX can obviously suppress synovial tissue's hypertrophy, proliferation of fibrous tissue and cartilage destruction (P<0.01, P<0.05).Tripterygium glycosides and MTX and the present invention compare, neutrophilic granulocyte, lymphocyte, plasmocyte infiltrating, and synovial tissue's hypertrophy, proliferation of fibrous tissue and cartilage destruction all have notable difference (P<0.01, P<0.05).
Table 4-1CIA rat joint chronic inflammatory disease pathological evaluation
Group | N | Neutrophil cell soaks into | Lymphocytic infiltration | Plasmocyte infiltrating |
Normally+and normal saline group modeling+normal saline group modeling+MTX group modeling+Tripterygium glycosides group modeling+of the present invention group | 8 8 7 10 10 | 0±0 ** 1.56±1.32 △△ 1.54±1.33 □ 1.62±1.04 □□ 0.7±1.26 ** | 0±0 ** 1.88±0.72 △△ 1.62±0.96 □□ 1.54±0.10 1.10±0.79 ** | 0±0 ** 1.25±0.93 △△ 0.92±0.86 □ 1.08±1.04 □□ 0.3±0.47 ** |
Table 4-2CIA rat joint chronic inflammatory disease pathological evaluation
Group | N | Synovial tissue's hypertrophy | Proliferation of fibrous tissue | Cartilage destruction |
Normally+and normal saline group modeling+normal saline group modeling+MTX group modeling+Tripterygium glycosides group modeling+of the present invention group | 8 8 7 10 10 | 0±0 ** 2.38±1.09 △△ 1.62±0.65 ** 1.69±0.63 ** 1.35±0.49 ** | 0±0 ** 3.38±1.41 △△ 2.62±1.12 *□□ 2.38±1.33 *□□ 1.05±1.23 ** | 0±0 ** 3.50±0.82 △△ 2.00±1.63 **□ 1.85±1.52 **□ 0.50±1.10 ** |
Compare * P<0.05 with the modeling group, compare with normal group * * P<0.01
△ △P<0.01 is with of the present invention group of comparison P<0.01.
8.2.3 influence to CIA rat destruction of joint
Table 5 shows that the present invention, MTX and Tripterygium glycosides all can suppress the erosion of CIA rat ossa articularia and the joint space changes (P<0.01 or P<0.05), compares with Tripterygium glycosides and MTX, and the present invention suppresses destruction of joint effect stronger (P>0.05).
The score of table 5CIA destruction of joint X-ray sheet relatively
Group | N | Bone erosion | The joint space changes | Total points |
Normally+of the present invention group of normal saline group modeling+normal saline group MTX group Tripterygium glycosides group | 8 8 7 10 10 | 0±0 **190.38±86.39 △△118.29±31.43 *□91.10±45.72 **51.70±36.81 ** | 0±0 ** 147.66±44.48 △△ 98.86±30.71 *□ 86.10±35.82 **□ 52.40±27.51 ** | 0±0 **338.03±129.13 △△217.14±60.08 *□177.20±79.67 **□104.10±64.32 ** |
Annotate: the destruction of joint total points adds joint space variation mark by the bone erosion mark and the modeling group compares * P<0.05, and compare with normal group * * P<0.01
△ △P<0.01 is with of the present invention group of comparison P<0.05
8.3 conclusion
The CIA rat is the model of the chronic autoimmunity arthritis of classics, experimental result shows, administration of the present invention can suppress twice inflammation peak of CIA rat, compares with Tripterygium glycosides and MTX, and the present invention suppresses the effect of chronic arthritis disease and has characteristics rapid-action, that effect is strong.On pathology, the present invention can obviously suppress CIA rat inflammatory cell infiltration, synovial tissue's hypertrophy and proliferation of fibrous tissue, the protection cartilage is stronger than Tripterygium glycosides and MTX effect.In the protection joint, suppress the bone destruction aspect, effect of the present invention also is better than Tripterygium glycosides and MTX.
Experimental results show that, the drug effect that the present invention suppresses acute arthritis disease is better than Tripterygium hypoglaucum and ERTENG TONGBILING HEJI, the drug effect that suppresses chronic arthritis disease and destruction of joint is better than Tripterygium glycosides, and have treating both the principal and secondary aspects of a disease, characteristics that toxic and side effects is little, can be used for treating rheumatisms such as RA, AS, SLE and OA.
Claims (9)
1, the rheumatismal medicine of a kind of treatment is characterized in that being made by following bulk drugs: 1 part of Tripterygium hypoglaucum 1-7 part Radix Dipsaci.
2, medicine according to claim 1 is characterized in that: Tripterygium hypoglaucum and Radix Dipsaci weight ratio are 2: 1.
3, medicine according to claim 1 and 2 is characterized in that: Tripterygium hypoglaucum exsiccant replacement of Tripterygium hypoglaucum of equivalent.
4, medicine according to claim 1 and 2 is characterized in that: Tripterygium hypoglaucum replaces with the Radix Tripterygii Wilfordii of equivalent.
5, medicine according to claim 1 and 2 is characterized in that dosage form is said any dosage form on the pharmaceutics.
6, require described medicine according to right 4, it is characterized in that said dosage form is an oral liquid.
7, the preparation method of the rheumatismal medicine of the described treatment of claim 1, may further comprise the steps: get the Tripterygium hypoglaucum and the Radix Dipsaci of recipe quantity, Tripterygium hypoglaucum is added water to submerge and is decocted first 3.5-7 hour, adds Radix Dipsaci again with frying in shallow oil 0.5-1 hour, filter, further make required dosage form according to a conventional method.
8, the preparation method of medicine according to claim 6, after the preparation method that it is characterized in that oral liquid also comprised filtration, filtrate concentrated, add 0.1% ethyl hydroxybenzoate, 0.3% sodium benzoate stirring and dissolving is put cold, adjust medicinal liquid to full dose, filter, inspect qualified back packing by ready samples.
9, the preparation method of medicine according to claim 6, it is characterized in that Tripterygium hypoglaucum, Radix Dipsaci water extract filter after, further add water and extract again 1~2 time, merging filtrate is further made required dosage form according to a conventional method.
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CN105043837A (en) * | 2015-09-14 | 2015-11-11 | 国麒光电科技(天津)有限公司 | Automatic sample preparation system for laser-induced breakdown spectrometer |
CN107519237A (en) * | 2017-08-31 | 2017-12-29 | 广州中医药大学第附属医院 | A kind of pharmaceutical composition for preventing and treating rheumatoid arthritis |
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CN105043837A (en) * | 2015-09-14 | 2015-11-11 | 国麒光电科技(天津)有限公司 | Automatic sample preparation system for laser-induced breakdown spectrometer |
CN105043837B (en) * | 2015-09-14 | 2018-10-02 | 国麒光电科技(天津)有限公司 | A kind of automation sample-preparing system for laser induced breakdown spectrograph |
CN107519237A (en) * | 2017-08-31 | 2017-12-29 | 广州中医药大学第附属医院 | A kind of pharmaceutical composition for preventing and treating rheumatoid arthritis |
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