CN1626215A - Chinese traditional medicine for treating rheumatoid arthritis, and preparing technique - Google Patents

Chinese traditional medicine for treating rheumatoid arthritis, and preparing technique Download PDF

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CN1626215A
CN1626215A CNA2004100417158A CN200410041715A CN1626215A CN 1626215 A CN1626215 A CN 1626215A CN A2004100417158 A CNA2004100417158 A CN A2004100417158A CN 200410041715 A CN200410041715 A CN 200410041715A CN 1626215 A CN1626215 A CN 1626215A
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rheumatoid arthritis
chinese medicine
extract
powder
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CN1254264C (en
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濮存海
李辉
王波
王军花
金顺福
刘美慧
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NANJING ZHONGSHAN PHARMACEUTICAL FACTORY
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NANJING ZHONGSHAN PHARMACEUTICAL FACTORY
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Abstract

A Chinese medicine for treating rheumatoid arthritis is prepared from 6 Chinese-medicinal materials including ant, astragalus root, notoginseng, homalomena rhizome, etc. Its preparing process is also disclosed. Its advantages are high curative effect and low by-effect.

Description

A kind of Chinese medicine and preparation technology thereof who treats rheumatoid arthritis
Technical field
Field of traditional Chinese medicine pharmacy of the present invention particularly relates to a kind of Chinese medicine for the treatment of rheumatoid arthritis, the invention still further relates to the preparation technology of this medicine.
Background technology
Rheumatoid arthritis (rheumatoid arthritis) is a kind of clinical frequently-occurring disease, commonly encountered diseases, be a kind of be the chronic systemic autoimmune disease of feature with the articular synovitis.Synovitis is outbreak repeatedly lastingly, the destruction that can cause intraarticular cartilage and bone, and joint function disturbance, in addition maimed.The vasculitis pathological changes is involved each organ of whole body, so primary disease is called rheumatoid disease again.About 80% patient's age of onset was many at 20~45 years old with person between twenty and fifty, and men and women's ratio is 1: 2~4.Clinical arthralgia, the morning deadlock that mainly shows as, severe patient can cause joint deformity.Primary disease is relatively more difficult in treatment, clinical nonsteroidal antiinflammatory drug and the immunosuppressant of adopting treated more, severe patient need add with hormone medicine and can alleviate, but these medicines mostly are symptomatic treatment, and toxic and side effects is big, unsatisfactory curative effect, the patient often delays many decades and can not take a turn for the better, and finally shows as joint deformity more, loses self care ability, the more patient of joint involvement is unable to stir any more and angor especially all day not from bedding.The Chinese medicine that a few days ago lacks the treatment rheumatoid arthritis of energy treating both the principal and secondary aspects of a disease, good effect, few side effects on the market.
Summary of the invention
The Chinese medicine that the purpose of this invention is to provide the little treatment rheumatoid arthritis of a kind for the treatment of both the principal and secondary aspects of a disease, good effect, side effect.
Another object of the present invention provides the preparation technology of above-mentioned Chinese medicine.
Technical scheme of the present invention is the clear superiority that utilizes motherland's medical science to have in primary disease.The organic compatibility of Chinese medicine compound by multiple medicine, treating both the principal and secondary aspects of a disease has more superiority than simple chemical compound and biological preparation, and raw material of Chinese medicine is natural product, and toxic and side effects is little, and drug safety more can be accepted by the patient.
Theory of Chinese medical science thinks that arthromyodynia is that wet three gas of wind and cold are assorted extremely, closes and is numbness, and its migratory BI-syndrome caused mainly by pathogenic wind, BI-syndrome caused mainly by pathogenic cold being called painful BI, the dampness victor is a damp arthralgia, the many persons of yang-energy are pyretic arthralgia.The institute of numbness gives birth to, be to wet more, the wet YIN pathogen that belongs to, itself and wind and cold heresy are harmonious, and anemofrigid-damp arthralgia takes place, its pyretic arthralgia also suffers cloudy institute owing to YIN pathogen makes sun, the damp and hot numbness of above wind and cold is equivalent to common rheumatic arthritis and rheumatoid arthritis, as for the described rheumatoid arthritis of modern medicine, is the systemic disease based on the infringement joint, its pathogenesis is for suffering from a deficiency of the kidney, irritability is uncomfortable to be reached, and spleen the moon is depressed, and it is attacked by the cold and evil is gone into stomach, meridian qi and blood is not all right, the joint is puckery to be closed, and muscles and bones mistake is supported, gradually to clonic spasm of the muscle bone pine, joint deformity must not be stretched in the wrong.The cause of disease of the deficient one-tenth numbness of a large amount of clinical practice proof Liver and kidney is main, the kidney generating marrow and dominating bone, liver governing tendons, spleen governing muscles, it is the endogenous cause of ill of rheumatoid arthritis that kidney liver spleen three deficiency of five ZANG-organs decrease, and occupies an leading position, wind and cold is wet to be exopathogenic factor, so rheumatoid arthritis belongs to deficient property disease category.
The present invention is made up of Six-element Chinese medicines such as Formica fusca, the Radix Astragali, Radix Notoginseng, Rhizoma Paridis, Herba Erodii, Rhizoma Homalomenaes, Formica fusca is a monarch drug in the side, salty in the mouth is flat, Compendium of Material Medica claims that Formica fusca is an XUANJU, profound genus black, " black is into kidney, and coltfoal belongs to pony also ", go into the Liver and kidney warp, have the effect of nourishing the liver and kidney, bone and muscle strengthening, dispelling wind and removing obstruction in the collateral; The Radix Astragali, Radix Notoginseng are ministerial drug, and Radix Astragali sweet in the mouth is warm in nature, go into lung, spleen channel, invigorating QI to consolidate the body surface resistance, diuresis poison holding; The Radix Notoginseng sweet in the mouth, little bitterness temperature is gone into liver, stomach warp, dissipating blood stasis hemostasis, subduing swelling and relieving pain; Assistant is with Rhizoma Paridis, Herba Erodii, and the Rhizoma Paridis bitter in the mouth is cold in nature, goes into Liver Channel, reducing swelling and alleviating pain, arresting convulsion pain relieving, heat-clearing and toxic substances removing; Geranium is arduous, and property is flat, goes into the liver,kidney,spleen warp, muscle reinforcing and bone strengthening wind-damp dispelling, collateral dredging arteries and veins, heat-clearing and toxic substances removing; Make with Rhizoma Homalomenae, acrid in the mouth is warm in nature, goes into liver, lung meridian, the liver and the kidney tonifying, wind-damp dispelling, strengthening bone and muscle, alleviating pain and detumescence.
In sum, we to use Formica fusca nourishing the liver and kidney, strengthening the tendons and bones, dispelling wind and removing obstruction in the collateral be monarch; The Radix Astragali, Radix Notoginseng are share and can set upright by benefiting QI for strengthening the superficies, and the dissipating blood stasis analgesic therapy is minister; Herba Erodii, Rhizoma Paridis share the energy removing toxic substances and promoting subsidence of swelling, and removing obstruction in the collateral to relieve pain is for assisting a ruler in governing a country; The strong muscle of Rhizoma Homalomenae wind dispelling, the through disease of medicine-carried is done and is made again.All medicines cooperate, and have the effect of nourishing the liver and kidney, promoting blood circulation to remove obstruction in the collateral, expelling wind and removing dampness, reducing swelling and alleviating pain, strengthening the tendons and bones, strengthening vital QI to eliminate pathogenic factors, reach the purpose for the treatment of both the principal and secondary aspects of a disease.
Purpose of the present invention can realize by following measures:
A kind of Chinese medicine for the treatment of rheumatoid arthritis comprises following bulk drugs:
Formica fusca 8-10 part, Radix Astragali 2-3 part, Radix Notoginseng 1-2 part, Rhizoma Paridis 1-2 part, Herba Erodii 0.8-1.2 part, Rhizoma Homalomenae 0.8-1.2 part.
The Chinese medicine of described treatment rheumatoid arthritis, wherein each bulk drugs is preferred:
Formica fusca 8.5-9.0 part, Radix Astragali 2.0-2.5 part, Radix Notoginseng 1.0-1.5 part, Rhizoma Paridis 1.5-2.0 part, 1 part of Herba Erodii, 1 part of Rhizoma Homalomenae.
The Chinese medicine of described treatment rheumatoid arthritis, its medicament are said dosage forms on any pharmaceutics.
The Chinese medicine of described treatment rheumatoid arthritis, its dosage form can be pill, tablet, powder, granule, capsule, drop pill, syrup, medicated wine, oral solutions, injection.
A kind of preparation technology who treats the Chinese medicine of rheumatoid arthritis comprises the following step:
A. get astragalus membranaceus powder by prescription and be broken into fine powder, standby;
B. getting Formica fusca, Radix Notoginseng, Rhizoma Paridis, Herba Erodii, Rhizoma Homalomenae by prescription adds 5-7 and doubly measured the 20-80% soak with ethanol 1-3 hour, little then boiling reflux, extract, 2-4 hour, emit extracting solution after the cooling, doubly measure by 3-5 once more and add 50-70% ethanol, little boiling reflux, extract, 2-3 hour emitted extracting solution after the cooling, repeat to extract 2-3 time, merge extractive liquid,, leave standstill supernatant;
Relative density is 1.20 to 1.25 during c. with supernatant concentration to 40~50 ℃, thick paste:
D. add standby astragalus membranaceus powder,,, get dry extract in 60-65 ℃ of drying with gained thick paste mix homogeneously;
E. pulverize, sieve, add appropriate amount of auxiliary materials, mixing, conventional method is made required dosage form.
Supernatant concentration can adopt concentrating under reduced pressure among the described preparation technology, and temperature is controlled at 40-70 ℃, and concentrating under reduced pressure vacuum is 400-700mmHg, is 730-750mmHg when closely going out cream.
Advantage of the present invention:
Pharmacodynamic experiment of the present invention:
The experiment medicine: the present invention presses embodiment 1 preparation; Hydrocortisone injection, Harbin No.3 Pharmaceutical Factory production, concentration is 5mg/ml; Indometacin, the powder that Lik-Sang pharmaceutical factory in Tianjin provides is mixed with the suspension that concentration is 1mg/ml with 1% mucilago tragacanthae before test.
Laboratory animal: Kunming mouse, body weight 18-22g, male and female half and half; The SD rat, body weight 120-140g, male and female half and half; The Wistar rat, body weight 150-180g, male and female half and half, laboratory animal room provides by Tianjin Inst. of Materia Medica.
The normal saline group all gives isometric normal saline and contrasts in the experiment.
One, antiinflammatory action of the present invention
1, the present invention is to the influence of mice capillary permeability
70 of mices, be divided into 7 groups at random, every group 10, male and female half and half, ig (filling stomach) administration respectively, every day 1 time, successive administration 4 days, after last administration 30 minutes, give every mice iv (intravenous injection) ivens blue solution (1.0% concentration) 0.08ml respectively, simultaneously ip (lumbar injection) glacial acetic acid solution (0.5% concentration) 0.4ml, put to death animal after 20 minutes, the dyestuff of cutting open the belly and oozing out with 5ml normal saline (NS) flushing abdominal cavity blood capillary is collected eluent, does blank with normal saline, survey trap at 722 spectrophotometer 580nm wavelength places, average and the matched group comparison, carry out statistical test, the results are shown in Table 1.The result shows that oral administration of the present invention is very obvious to the inhibitory action of mouse peritoneal capillary permeability, illustrates that the effect of anti-experimental character peritonitis of the present invention is very strong.
Table 1 the present invention is to the influence of mouse peritoneal capillary permeability (n=10, X ± SD)
Medicine Dosage (g crude drug/kg * d) Number of animals (only) Trap
????NS ????10 ????0.167±0.058
The present invention ????40×4 ????10 ????0.064±0.034***
The present invention ????20×4 ????10 ????0.092±0.024**
The present invention ????10×4 ????10 ????0.104±0.040*
The present invention ????5×4 ????10 ????0.110±0.034*
The present invention ????2.5×4 ????10 ????0.159±0.079
Hydrocortisone ????20mg/kg×4 ????10 ????0.110±0.026*
Annotate: *P<0.05, *P<0.01, * *P<0.001
2, the present invention is to the influence of Mus dropsy of ear
70 of mices are divided into 7 groups at random, 10 every group, male and female half and half, ig administration respectively, every day 1 time, successive administration 4 days after last administration 30 minutes, is coated with proinflammatory agent (2% Oleum Tiglii for respectively every mice left side ear, 73% ether, 20% dehydrated alcohol, 5% distilled water), dosage is 4/ear, to cause the Mus dropsy of ear, auris dextra compares, and puts to death mice after 2 hours, with the card punch of 9mm diameter, lay circular auricle at same position respectively, on torsion balance, weigh.Heavily deducting auris dextra sheet recast with left auricle is Mus dropsy of ear degree, averages and the comparison of normal saline matched group, carries out statistical test, the results are shown in Table 2.The result shows that the present invention has the inhibitory action of highly significant to the Mus dropsy of ear, and useful effect dosage is wide, illustrates that the present invention has very strong anti-experimental character edema effect.
Table 2 the present invention is to the influence of mouse ear edema
Medicine Dosage (g crude drug/kg * d) Number of animals (only) Trap (X ± SD, mg)
????NS ????10 ????17.567±5.742
The present invention ????40×4 ????10 ????5.750±4.293***
The present invention ????20×4 ????10 ????10.125±4.197**
The present invention ????10×4 ????10 ????10.401±3.798**
The present invention ????5×4 ????10 ????6.419±3.992***
The present invention ????2.5×4 ????10 ????9.838±4.906**
Hydrocortisone ????20mg/kg×4 ????10 ????4.170±2.195***
Annotate: *P<0.05, *P<0.01, * *P<0.001
3, the present invention is to the bullate influence of rat foot
50 of SD rats are divided into 5 groups at random, 10 every group, ig administration respectively, every day 1 time, successive administration 4 days, after last administration 30 minutes, give every ankle joint direction SC of rat left hind foot pad portion (subcutaneous injection) carrageenin (concentration is 1.0% suspension) 0.005ml respectively, cause edema.Different time before administration and after the administration, with the left and right sides, 0.5cm place limb diameter (amplifying about 6 times) under the photoelectricity projector measurement left hind ankle joint, deduct administration with diameter after the administration before diameter as the swelling degree.Average and the matched group comparison, carry out statistical test, the results are shown in Table 3.The result shows the swollen inhibitory action that highly significant is arranged of rat foot that on Carrageenan of the present invention causes.Antiinflammatory action of the present invention shows as the edema degree that alleviates the aseptic inflammation that is caused by carrageenin on this model, postpones the generation of inflammation and promotes disappearing of inflammation, and its antiinflammatory action is suitable with the hydrocortisone effect.
Table 3 the present invention is to the bullate influence of rat carrageenan foot
Medicine Dosage (g crude drug/kg * d) Different time is sufficient after the administration swells (X ± SD, cm)
0.5 hour 1 hour 2 hours 3 hours 6 hours
????NS ??0.143± ????0.756 ??1.271± ????0.957 ??2.129± ????1.004 ??2.814± ????0.790 ??2.786± ????0.636
The present invention ????10×4 ??0.140± ????0.551 ??0.271± ????0.235 ** ??0.814± ????0.474 * ??1.4856± ????0.652 ** ??1.943± ????1.192
The present invention ????5×4 ??0.143± ????0.214 ??0.343± ????0.251 ** ??1.143± ????0.551 * ??1.543± ????0.412 ** ??2.071± ????0.732 *
The present invention ????2.5×4 ??0.243± ????0.311 ??0.600± ????0.503 ??0.686± ????0.636 * ??1.443± ????0.613 ** ??1.714± ????0.567 **
Hydrocortisone ????20mg/kg×4 ??0.071± ????0.187 ??0.100± ????0.101 ** ??0.143± ????0.244 ??1.717± ????0.568 ** ??1.774± ????0.809 **
Annotate: *P<0.05, *P<0.01, * *P<0.001
4, the present invention is to the influence of adjuvant arthritis
Adjuvant preparation: the bacillus calmette-guerin vaccine of deactivation in advance is placed in the disinfectant agate glass breast cup, adds the incomplete freund adjuvant of sterilization in advance, grind and lead to the adjuvant that concentration is 10mg/ml.
Laboratory animal: male by the Wistar rat that Tianjin Inst. of Materia Medica laboratory animal room provides, 50, average weight 198.0 ± 10.4g is divided into 5 groups at random, 10 every group.
Cause scorching method: in the sufficient pad portion of the right hind of every rat, intradermal injection adjuvant 0.07ml/ only with the arthritic generation of inducing adjuvant, raises in the observation ward of band central air-conditioning.
1) to the influence of constitutional pathological changes
Yu Zhiyan preventative ig administration in preceding 3 days, once a day, control group administered physiological saline, after the last administration, began to cause inflammation in 30 minutes, observation causes the swelling degree at 0.5cm place under scorching back 18 hours to 12 days adjuvant injection side ankle joint, represents with the difference (amplifying 10 times cm) of photoelectricity projector measurement left and right sides hind leg diameter, takes the mean and the matched group comparison, carry out the statistics mapping, the results are shown in Table 4.The result shows that the present invention has the antiinflammatory action of highly significant to rat assist agent arthritis constitutional pathological changes, and presents rapid-action and the persistent characteristics of effect.
Table 4 the present invention is to the influence of rat assist agent arthritis constitutional pathological changes
Medicine Dosage (the g crude drug/kg) Different time is sufficient after the administration swells (X ± SD, cm)
18 hours The 4th day The 6th day The 8th day The 12nd day
??NS ??1.460± ????0.336 ??2.860± ????0.706 ??2.910± ????0.550 ??2.840± ????0.554 ??2.440± ????1.189
The present invention ????10 ??0.600± ????0.308 *** ??2.040± ????0.513 * ??1.560± ????0.876 *** ??1.400± ????0.600 *** ??1.160± ????0.826 *
The present invention ????5 ??0.680± ????0.313 *** ??1.930± ????0.797 * ??1.340± ????0.950 ** ??1.900± ????0.910 * ??1.630± ????0.701
The present invention ????2.5 ??0.640± ????0.336 *** ??1.600± ????1.020 ** ??1.040± ????0.422 ** ??1.060± ????0.740 *** ??1.400± ????0.961 *
Indometacin ????5mg/kg ??1.040± ????0.456 * ??1.140± ????0.378 ** ??1.770± ????0.424 ** ??1.200± ????0.758 *** ??1.880± ????0.572
Annotate: *P<0.05, *P<0.01, * *P<0.001
2) to the influence of Secondary cases pathological changes
The 8th day beginning ig administration after adjuvant causes inflammation, control group administered physiological saline, every day 1 time, successive administration to the 30 days is observed prevention and the therapeutical effect of the present invention to the Secondary cases pathological changes.The day of self administration of medication is counted, and, takes the mean and the matched group comparison as the index of Secondary cases pathological changes with miking left hind foot pad thickness (adjuvant injection offside swelling degree is represented with mm) in per 4 days, carries out statistical test, the results are shown in Table 5.The result shows that the present invention is swollen to parapodum to the adjuvant injection, and promptly the inhibitory action highly significant of rat delayed hypersensitivity illustrates that the present invention can alleviate or stop the generation of rat assist agent arthritis Secondary cases pathological changes.
Table 5 the present invention is to the influence of rat assist agent arthritis Secondary cases pathological changes
Medicine Dosage (the g crude drug/kg) Different time is sufficient after the administration swells (X ± SD, cm)
The 8th day The 12nd day The 16th day The 20th day The 24th day The 30th day
??NS ??4.700± ????0.480 ??5.780± ????0.140 ??5.760± ????0.560 ??5.520± ????0.330 ??5.880± ????0.578 ??5.860± ????0.360
The present invention ????5 ??4.790± ????0.360 ??4.970± ????0.340 *** ??5.050± ????0.270 ** ??4.940± ????0.310 *** ??5.000± ????0.210 ** ??5.550± ????0.260 *
The present invention ????2.5 ??4.660± ??4.700± ??5.190± ??5.030± ??5.100± ??5.610±
??0.350 ??0.440 *** ??0.400 ** ??0.370 *** ??0.490 ** ?0.210
The present invention ?1.25 ??4.470± ????0.290 ??5.070± ????0.340 *** ??5.150± ????1.130 * ??5.300± ????0.220 ??5.180± ????0.320 ** ?5.450± ???0.060 *
Indometacin ?5mg/kg ??4.700± ???0.330 ??5.000± ????0.350 *** ??4.690± ????0.120 *** ??4.640± ????0.610 ** ??4.680± ????0.470 *** ?4.850± ???0.670
Annotate: *P<0.05, *P<0.01, * *P<0.001
3) to the influence of general pathological changes
When observing the left back foot swelling degree of rat assist agent arthritis, the red and swollen situation of record forelimb, ear as the index of general pathological changes, is taken the mean and the matched group comparison by 5 grades of point systems, carries out statistical test, the results are shown in Table 6.The result shows that the present invention can stop the generation of rat assist agent arthritis general pathological changes.
Table 6 the present invention is to the influence of rat assist agent arthritis general pathological changes
Medicine Dosage (g crude drug/kg * d) Animal (only) Morbidity animal (only) Scoring (X ± SD)
??NS ????10 ????8 ??2.900±0.341
The present invention ????5 ????10 ????4 ??1.000±1.414**
The present invention ????2.5 ????10 ????4 ??1.200±1.304*
The present invention ????1.25 ????10 ????6 ??1.600±1.516
Indometacin ????5mg/kg ????10 ????6 ??1.400±1.312*
Annotate: *P<0.05, *P<0.01, * *P<0.001
Conclusion: rat assist agent arthritis is a kind of inflammatory model of immunity, its etiopathogenesis and change of illness state process and people's rheumatoid arthritis is similar, the present invention all has the inhibitory action of highly significant to constitutional pathological changes, Secondary cases pathological changes and general pathological changes on this model, and its antiinflammatory action is not second to the positive control drug indometacin.
Two, anti-allergy action of the present invention
1, the present invention is to the influence of mice delayed hypersensitivity
Get 50 of mices, be divided into 5 groups at random, every group 10, respectively at every mice left hind foot pad SC of portion (subcutaneous injection) 10% chicken red blood cell (CRBC) normal saline suspension 50 μ l sensitization, begin the ig administration simultaneously, administration every day 1 time, successive administration 6 days, after last administration, attack at the CRBC of the right back sufficient pad SC of portion equivalent immediately and cause delayed hypersensitivity, sufficient mat thickness (amplifying 6 times) about usefulness photoelectricity projector is measured after 24 hours is represented the swelling degree with two sufficient mat thickness differences, averages and the matched group comparison, carry out statistical test, the results are shown in Table 7.The result shows that the mouse DTH that the present invention causes CRBC has the inhibitory action of highly significant, and its action intensity and hydrocortisone are suitable.
The influence of the mouse DTH that table 7 the present invention causes CRBC
Medicine Dosage (g crude drug/kg * d) Animal (only) The footpad swelling degree (X ± SD, cm)
??NS ????10 ????0.860±0.188
The present invention ????10×6 ????10 ????0.380±0.215***
The present invention ????5×6 ????10 ????0.410±0.197***
The present invention ????2.5×6 ????10 ????0.590±0.362*
Hydrocortisone ????20mg/kg×6 ????10 ????0.340±0.171**
Annotate: *P<0.05, *P<0.01, * *P<0.001
2, the present invention is to the influence of mice contact dermatitis
Get 50 of mices, be divided into 5 groups at random, every group 10, each treated animal in administration on the same day, in dinitrochlorobenzene (DNCB) the acetone soln 20 μ l sensitization of every mouse carotid back part SC7.0%, successive administration 11 days, attack at the DNCB solution 15 μ l that mice left side ear is coated with same concentrations after 30 minutes in last administration, put to death mice after 16 hours, take off auricle with the 9mm card punch and weigh, difference with left and right sides auricle weight is represented the swelling degree, the results are shown in Table 8.The result shows that the present invention can significantly suppress the inductive tardy property mice contact dermatitis by DNCB, and its effect is better than hydrocortisone, and low dose of effect is stronger.
The influence of the mouse DTH that table 8 the present invention causes DNCB
Medicine Dosage (g crude drug/kg * d) Animal (only) Mouse ear swollen (X ± SD, mg)
??NS ????10 ????24.125±6.334
The present invention ????10×6 ????10 ????19.625±8.123
The present invention ????5×6 ????10 ????12.556±7.148**
The present invention ????2.5×6 ????10 ????9.500±6.481***
Hydrocortisone ????20mg/kg×6 ????10 ????15.124±9.299*
Annotate: *P<0.05, *P<0.01, * *P<0.001
Three, the present invention is to the influence of rat liver lipid peroxide (LPO) generation
Male rat is got its liver after putting to death, and makes 10% liver homogenate with 4 ℃ of normal saline.Get the 1.0ml liver homogenate, add diluent 0.05ml of the present invention (contrast adds normal saline) incubation 1 hour in 37 ℃ of air bath oscillators, taking-up adds 20% TCA solution 1.0ml (contrast and add TCA before incubation), with the 1.0ml normal saline, left standstill behind the mixing 10 minutes, get supernatant 2.5ml, add 0.67% TBA solution 1.0ml, boiling water bath heating 10 minutes, the cooling back is in 722 spectrophotometer 532nm place colorimetrics, each concentration is done 3 pipes, experiment repeats 2 times, calculates the lipid peroxide growing amount, takes the mean and compares, calculate the generation suppression ratio, the results are shown in Table 9.The result shows that the present invention has obvious inhibitory action to the generation of rat liver lipid peroxide, illustrate that the present invention can suppress the generation of LPO, prevent that free radical from making body inner cell film unsaturated fatty acid generation peroxidation generate lipid peroxide, cause cell membrane damage, thereby improve permeability of cell membrane.
The influence that table 9 the present invention generates rat liver lipid peroxide (LPO)
Medicine Concentration (%) The LPO growing amount (nm/g * 10, X ± SD) LPO generates suppression ratio (%)
??NS ????19.116±2.158 ????0
The present invention ??10 ????2.963±0.290 *** ????84.500
The present invention ??5 ????3.800±0.260 *** ????80.120
The present invention ??1 ????16.970±3.920 * ????11.230
Procaine ??2 ????12.018±3.773 * ????37.130
Annotate: *P<0.05, *P<0.01, * *P<0.001
Four, analgesic activity of the present invention
1, the influence that mouse writhing is reacted
Get 50 of mices, be divided into 5 groups at random, 10 every group, male and female half and half, ig administration respectively, every day 1 time, administration is 3 times altogether, after the 3rd administration 2 hours, giving every ip in mice concentration is that 0.6% acetum 0.2ml causes pain, writes down to second mouse writhing number of times in 10 minutes behind the chemical algogen with register, average and matched group relatively, carry out statistical test, the results are shown in Table 10.The result shows that the present invention has the analgesic activity of highly significant, and heavy dose of analgesic effect and indometacin are suitable.
Table 10 the present invention is to the influence of mice acetic acid twisting reaction
Medicine Dosage (g crude drug/kg * d) Animal (only) On average turn round body number (X ± SD)
??NS ????10 ????42.100±18.351
The present invention ????40×3 ????10 ????6.200±9.319 ***
The present invention ????20×3 ????10 ????15.100±11.567 ***
The present invention ????10×3 ????10 ????29.40±5.835
Indometacin ??10mg/kg×3 ????10 ????8.830±9.806***
Annotate: *P<0.05, *P<0.01, * *P<0.001
Toxicological experiment of the present invention:
One, acute toxicity test of the present invention
Get 60 of Kunming mouses, body weight 18-22g, be divided into 6 groups at random, 10 every group, male and female half and half, an ig gives 1.0ml/ of the present invention only (200g crude drug/2 administrations of Kg component in 50-200g crude drug/Kg dosage range, the 1st 1.0ml/ only only gave 0.33ml/ in 2 hours again), observe a week behind the medicine, write down each dosage group dead animal number, the results are shown in Table 11.
Table 11 the present invention is to acute toxicity test in mice
Dosage (the g crude drug/kg) Animal (only) Dead animal (only) Death toll (%) Mortality rate probability (P)
????200 ????10 ????10 ????100 ????98.81
????150 ????10 ????9 ????90 ????86.36
????125 ????10 ????6 ????60 ????64.04
????100 ????10 ????2 ????20 ????29.38
????75 ????10 ????1 ????10 ????4.41
????50 ????10 ????0 ????0 ????0.04
After heavy dose of group (more than 125g crude drug/kg) animal ig administration 30 minutes, the obvious suppression symptom appears, show as and do not like to move, lie prostrate down, breathe and slow down etc., the beginning in 4-5 hour after administration of 200g crude drug/kg dosage treated animal is dead, with death in the 2nd day after the administration at most, postmortem does not find that internal organs are unusual.According to table 11 data, with the Bliss method calculate an ig administration of the present invention to LD50=114.361 (102.207-127.95) g crude drug/kg of mice, the present invention is about as much as clinical consumption 520 times (everyone 13.2g every day crude drugs of the maximum dosage of being grown up) to the mice median lethal dose(LD 50), and the result proves that the present invention is relatively safe drugs.
Two, long term toxicity test of the present invention
160 of SD rats, average weight 140.49 ± 10.31g, be divided into 4 groups at random, every group 40, male and female half and half are mixed in free choice feeding administration in an amount of feedstuff by 20g crude drug/kg, 10g crude drug/kg, 5g crude drug/kg, 0g crude drug/kg dosage with medicine respectively, and every morning is administered once, successive administration 6 months is observed growth promoter, hematology, urine particularization index, blood particularization index and hepatic and renal function.The result shows that to remove high dose group and middle dosage group male rat 2 months beginning body weight gains after the administration slack-off, outside 3 months total serum proteins and urea nitrogen content increase after the administration, do not find obvious toxic reaction, the every index of small dose group rat is all normal, it is safe and effective that the result proves that 5g crude drug/kg takes for a long time, is equivalent to 22.5 times of clinical adult's consumption (13.2g crude drug/60Kg body weight).
The present invention can bring into play therapeutical effect on the basis of body-building, but early stage clinical cure, mid-term can disease controlling, and late period can relief of symptoms, and late result is more satisfactory.
The specific embodiment
By the following examples the present invention is further illustrated.
Embodiment 1
Prescription: Formica fusca 687.5g, the Radix Astragali (life) 187.5g, Radix Notoginseng 95g, Rhizoma Paridis 125g, Herba Erodii 77.5g, Rhizoma Homalomenae 77.5g.
Preparation technology's (capsule):
1, get astragalus membranaceus powder by prescription and be broken into fine powder, cross 100 mesh sieves, standby, Formica fusca is worn into coarse powder, crosses 60 mesh sieves, and Radix Notoginseng is about the Semen phaseoli radiati size for coarse powder, and all the other are decoction pieces;
2, get Formica fusca, Radix Notoginseng, Rhizoma Paridis, Herba Erodii, Rhizoma Homalomenae by prescription, total amount is that 1.0625Kg adds 6 times of amount 60% ethanol 6.375Kg, soaked 1 hour, little then reflux, extract, 3 hours of boiling is emitted extracting solution after the cooling, add 60% ethanol 4.25Kg by 4 times of amounts for the second time, little reflux, extract, 2 hours of boiling is emitted extracting solution after the cooling, extract operation for the third time with for the second time, merge three times extracting solution, leave standstill supernatant;
3, with the supernatant concentrating under reduced pressure, temperature is controlled at 60 ℃, and concentrating under reduced pressure vacuum is 650mmHg, is 740mmHg when closely going out cream, and relative density is 1.20 when being concentrated into 50 ℃, gets thick paste;
4, add standby astragalus membranaceus powder 187.5g and 90g dextrin,,, get dry extract in 65 ℃ of oven dry with gained thick paste mix homogeneously;
5, pulverize, cross 60 mesh sieves, adorn capsule No. 0, explosive payload is a 0.4g medicated powder, package storage.
Preparation method (tablet): with above-mentioned step 1-3, get the thick paste that obtains under 3 then and add standby astragalus membranaceus powder 187.5g,, get dry extract in 65 ℃ of oven dry.It is ground into fine powder, crosses 100 mesh sieves, weigh, add the carboxymethyl starch sodium of proper proportion, mixing is used alcohol granulation, drying, and granulate is weighed, and adds the magnesium stearate of proper proportion, tabletting, 0.4 gram/sheet, bag water-soluble film clothing, package storage.
Preparation method (granule): with above-mentioned step 1-3, get the thick paste that obtains under 3 then and add standby astragalus membranaceus powder 187.5g,, get dry extract in 65 ℃ of oven dry.It is ground into fine powder, crosses 100 mesh sieves, add Icing Sugar, dextrin and the ethanol of proper proportion, mix homogeneously in trough-type mixture machine.Granulate with oscillating granulator, get granule, package storage.
Embodiment 2
Prescription: Formica fusca 700g, the Radix Astragali (life) 165g, Radix Notoginseng 100g, Rhizoma Paridis 120g, Herba Erodii 75g, Rhizoma Homalomenae 77g.
Preparation technology's (capsule):
1, get astragalus membranaceus powder by prescription and be broken into fine powder, cross 100 mesh sieves, standby, Formica fusca is worn into coarse powder, crosses 60 mesh sieves, and Radix Notoginseng is about the Semen phaseoli radiati size for coarse powder, and all the other are decoction pieces;
2, get Formica fusca, Radix Notoginseng, Rhizoma Paridis, Herba Erodii, Rhizoma Homalomenae by prescription, total amount is 1.072Kg, adds 7 times of amount 50% ethanol 7.504Kg, soaks 1 hour, little then reflux, extract, 3 hours of boiling, emit extracting solution after the cooling, for the second time add 60% ethanol 4.288Kg, little reflux, extract, 2 hours of boiling by 4 times of amounts, emit extracting solution after the cooling, extract operation for the third time with for the second time, merge three times extracting solution, leave standstill supernatant;
3, with the supernatant concentrating under reduced pressure, temperature is controlled at 60 ℃, and concentrating under reduced pressure vacuum is 600mmHg, is 740mmHg when closely going out cream, and relative density is 1.25 when being concentrated into 50 ℃, gets thick paste;
4, add standby astragalus membranaceus powder 165g and 90g dextrin,,, get dry extract in 60 ℃ of oven dry with gained thick paste mix homogeneously;
5, pulverize, cross 60 mesh sieves, adorn capsule No. 0, explosive payload is a 0.4g medicated powder, package storage.
Preparation method (tablet): with above-mentioned step 1-3, get the thick paste that obtains under 3 then and add standby astragalus membranaceus powder 165g,, get dry extract in 60 ℃ of oven dry.It is ground into fine powder, crosses 100 mesh sieves, weigh, use alcohol granulation, drying, granulate is weighed, and adds carboxymethyl starch sodium, the micropowder silica gel of proper proportion, mixing, tabletting, 0.4 gram/sheet, bag water-soluble film clothing, package storage.
Preparation method (granule): with above-mentioned step 1-3, get the thick paste that obtains under 3 then and add standby astragalus membranaceus powder 165g,, get dry extract in 60 ℃ of oven dry.It is ground into fine powder, crosses 100 mesh sieves, add Icing Sugar, starch and the ethanol of proper proportion, mix homogeneously in trough-type mixture machine.Granulate with oscillating granulator, get granule, package storage.
Embodiment 3
Prescription: Formica fusca 750g, the Radix Astragali (life) 180g, Radix Notoginseng 110g, Rhizoma Paridis 120g, Herba Erodii 80g, Rhizoma Homalomenae 80g.
Preparation technology's (capsule):
1, get astragalus membranaceus powder by prescription and be broken into fine powder, cross 100 mesh sieves, standby, Formica fusca is worn into coarse powder, crosses 60 mesh sieves, and Radix Notoginseng is about the Semen phaseoli radiati size for coarse powder, and all the other are decoction pieces;
2, get Formica fusca, Radix Notoginseng, Rhizoma Paridis, Herba Erodii, Rhizoma Homalomenae by prescription, total amount is 1.14Kg, adds 5 times of amount 60% ethanol 5.7Kg, soaks 1 hour, little then reflux, extract, 3 hours of boiling, emit extracting solution after the cooling, for the second time add 60% ethanol 4.56Kg, little reflux, extract, 2 hours of boiling by 4 times of amounts, emit extracting solution after the cooling, extract operation for the third time with for the second time, merge three times extracting solution, leave standstill supernatant;
3, with the supernatant concentrating under reduced pressure, temperature is controlled at 60 ℃, and concentrating under reduced pressure vacuum is 600mmHg, is 740mmHg when closely going out cream, and relative density is 1.25 when being concentrated into 40 ℃, gets thick paste;
4, add standby astragalus membranaceus powder 180g and 90g dextrin,,, get dry extract in 60 ℃ of oven dry with gained thick paste mix homogeneously;
5, pulverize, cross 60 mesh sieves, adorn capsule No. 0, explosive payload is a 0.4g medicated powder, package storage.
Preparation method (tablet): with above-mentioned step 1-3, get the thick paste that obtains under 3 then and add standby astragalus membranaceus powder 180g,, get dry extract in 60 ℃ of oven dry.It is ground into fine powder, crosses 100 mesh sieves, weigh, add the carboxymethyl starch sodium of proper proportion, mixing is used alcohol granulation, drying, and granulate is weighed, and adds the micropowder silica gel of proper proportion, tabletting, 0.4 gram/sheet, bag water-soluble film clothing, package storage.
Preparation method (granule): with above-mentioned step 1-3, get the thick paste that obtains under 3 then and add standby astragalus membranaceus powder 180g,, get dry extract in 60 ℃ of oven dry.It is ground into fine powder, crosses 100 mesh sieves, add the dextrin and the ethanol of proper proportion, mix homogeneously in trough-type mixture machine.Granulate with oscillating granulator, get granule, package storage.

Claims (6)

1, a kind of Chinese medicine for the treatment of rheumatoid arthritis is characterized in that comprising following bulk drugs:
Formica fusca 8-10 part, Radix Astragali 2-3 part, Radix Notoginseng 1-2 part, Rhizoma Paridis 1-2 part, Herba Erodii 0.8-1.2 part, Rhizoma Homalomenae 0.8-1.2 part.
2, the Chinese medicine of treatment rheumatoid arthritis according to claim 1 is characterized in that each bulk drugs is preferred:
Formica fusca 8.5-9.0 part, Radix Astragali 2.0-2.5 part, Radix Notoginseng 1.0-1.5 part, Rhizoma Paridis 1.5-2.0 part, 1 part of Herba Erodii, 1 part of Rhizoma Homalomenae.
3,, it is characterized in that said medicament is a said dosage form on any pharmaceutics according to the Chinese medicine of claim 1 or 2 described treatment rheumatoid arthritiss.
4,, it is characterized in that said medicament can be pill, tablet, powder, granule, capsule, drop pill, syrup, medicated wine, oral solutions, injection according to the Chinese medicine of the described treatment rheumatoid arthritis of claim 3.
5, a kind of preparation technology who treats the Chinese medicine of rheumatoid arthritis is characterized in that comprising the following step:
A. get astragalus membranaceus powder by prescription and be broken into fine powder, standby;
B. getting Formica fusca, Radix Notoginseng, Rhizoma Paridis, Herba Erodii, Rhizoma Homalomenae by prescription adds 5-7 and doubly measured the 20-80% soak with ethanol 1-3 hour, little then boiling reflux, extract, 2-4 hour, extracting solution is collected in the cooling back, doubly measure by 3-5 once more and add 50-70% ethanol, little boiling reflux, extract, 2-3 hour, extracting solution is collected in the cooling back, repeats to extract 2-3 time, merge extractive liquid,, leave standstill supernatant;
Relative density is 1.20 to 1.25 during c. with supernatant concentration to 40~50 ℃, thick paste;
D. add standby astragalus membranaceus powder,,, get dry extract in 60-65 ℃ of drying with gained thick paste mix homogeneously;
E. pulverize, sieve, add appropriate amount of auxiliary materials, mixing, conventional method is made required dosage form.
6, preparation technology according to claim 5 is characterized in that supernatant concentration can adopt concentrating under reduced pressure, and temperature is controlled at 40-70 ℃, and concentrating under reduced pressure vacuum is 400-700mmHg, is 730-750mmHg when closely going out cream.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101239159B (en) * 2008-03-17 2010-07-21 杨成德 Chinese medicinal composition for treating rheumatoild disease and preparation thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101239159B (en) * 2008-03-17 2010-07-21 杨成德 Chinese medicinal composition for treating rheumatoild disease and preparation thereof

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