CN102895348A

CN102895348A - Pharmaceutical compositions for treating rheumatic joint disease, preparation method thereof and use thereof

Info

Publication number: CN102895348A
Application number: CN2012104439080A
Authority: CN
Inventors: 徐世军
Original assignee: Chengdu University of Traditional Chinese Medicine
Current assignee: Chengdu University of Traditional Chinese Medicine
Priority date: 2012-11-08
Filing date: 2012-11-08
Publication date: 2013-01-30
Anticipated expiration: 2032-11-08
Also published as: CN102895348B

Abstract

The invention provides pharmaceutical compositions for treating rheumatic joint disease, a preparation method thereof and application thereof. The pharmaceutical compositions mainly consist of the following raw materials in parts by weight: 10-70 parts of silky ant, 10-50 parts of astragalus mongholicus, 5-40 parts of pawpaw, 5-40 parts of salted aconite root and 2-20 parts of pseudo-ginseng. The invention further provides a preparation method of the pharmaceutical compositions and the use of the pharmaceutical compositions. The experiment improves that the pharmaceutical compositions provided by the invention have the effects of deficiency tonifying, consolidating basis, eliminating evil and smoothening numbness, not only can be used for effectively treating and relieving the arthralgia, the morning stiffness, the numbness and the bad flexibility caused by the rheumatism and the rheumatoid arthritis, but also can be used for preventing, treating and relieving the kidney function harm caused by the rheumatism, have the functions for treating the pathological changes such as arthrocele, pain, inhibited bending and stretching and the like, and can be particularly used for the rheumatic arthritis, the chronic infectious arthritis, the joint synovitis and the rheumatoid renal damage.

Description

A kind of pharmaceutical composition and preparation method and purposes for the treatment of rheumatic joint disease

Technical field

The present invention relates to a kind of pharmaceutical composition, particularly relate to a kind of pharmaceutical composition that is formed by crude drug Formica fusca, Radix Aconiti Lateralis Preparata, the Radix Astragali, Fructus Chaenomelis and Radix Notoginseng, belong to technical field of Chinese medicines.

Background technology

Rheumatoid arthritis (Rheumatoid Arthritis, RA) belongs to " arthromyodynia " category in motherland's medical science, and sickness rate is high, between twenty and fifty in the majority with 25～55 years old of morbidity, and the women falls ill and is higher than the male, and men and women's ratio is 1:4, and the whole world has more than one hundred million patients.According to statistics, the external prevalence of RA is 1～2%, and indivedual areas are up to 5%; China's sickness rate is about 0.74%, existing 1,500 ten thousand people left and right sides patients; The primary disease disability rate is higher, and the patient with rheumatoid arthritis of in time diagnosis and treatment 50%, the three year disability rate that disabled in 2 years does not reach 70%.And the patient who has suffered from rheumatoid arthritis, average life shortens 10～15 years.Discuss from course of disease length, fall ill disability rate approximately 20% in 1 year, can reach about 40% more than 2 years, the heavy damage work capacity, very big to human health risk, cause very big burden for society, family, seriously influence also for patient's physical and mental health and quality of life, the title of " not dead cancer " is therefore arranged.

The definite mechanism of RA is not very clear and definite, but modern study thinks that RA is that a kind of a large amount of T cellular infiltration is that main chronic synovitis is the autoimmune disease of feature at present, and crucial immunological abnormality comprises abnormal activation, the especially CD of the imbalance of T cell subsets and T cell ₄ ⁺The T cell has participated in exciting of RA and has continued.RA patient's pathological study result shows, patient's synovial membrane is take synovial cell's tumor sample propagation, blood vessel hyperplasia and inflammatory cell infiltration as main feature, and in the inflammatory cell that infiltrates with T cell especially CD ₄ ⁺The T cell subsets is main, in addition, and CD in the RA patient T cell subsets ₄ ⁺T cell proportion and clonal expansion ability all change to some extent, prompting T lymphocyte, especially CD ₄ ⁺T has extremely important status in RA occurs and develops.The T cell gathers and activates in the synovial membrane of inflammation, contacts with the direct of IL-17 and cell-cell by secretion of gamma-IFN, has brought into play important function in the RA inflammatory reaction, has promoted the infringement of RA bone by relevant the drawing together inducible factor of TNF in addition.RA patient is owing to existing CD ₄ ⁺The increase of T cell quantity or CD ₈ ⁺The decline of T quantity makes CD ₄ ⁺T/CD ₈ ⁺The rising that compares of T, relatively hyperfunction weaken relative with the Ts cell function of Th cell function, thus cause that the B cell function is hyperfunction, immunoglobulin expression is out of control.It is believed that in the past RA seldom involves kidney, even the common renal amyloidosis of renal damage occurs or the membranous nephropathy that caused by golden preparation or penicillamine and the interstitial nephritis relevant with on-steroidal AID (NSAIDs) treatment.Just because of the deficiency on the understanding, so that formed for a long time the wrong views that RA itself seldom causes nephropathy.Day by day deep along with the extensive use of kidney Biopsy and immunology research in recent years, people recognize that gradually RA not only can cause renal damage, and infringement is 100%; Research finds that the RA renal damage mainly is mesangial proliferative nephritis (RA-MsPGN), accounts for 30.1%～75.0% (also being reported as 25%-50%) of RA constitutional renal damage.

RA there is no specific short at present, and clinical treatment mainly is anti symptom treatment.World rheumatism alliance will have antirheumatic now and be divided into two large classes, namely improve the antirheumatic of symptom and the antirheumatic of control disease, the former is still present clinical common medicine, so far without a kind of antirheumatic of real control disease, clinical normal drug combination is to reaching the purpose of control disease, but with regard at present obtained in the recent period, with regard to the late result, the result can not be satisfactory; Although carried out in recent years Biotherapeutics, eventually because of expensive, Orally active is poor, can not limit its application in shortcomings such as target tissues by selectively acting; As if gene therapy can overcome the part defective of Biotherapeutics in theory, but in more than 300 clinical research in the world, 3000 many cases are the patient of receptor gene treatment, does not have an example clearly to show clinical improvements.Existing clinical application such as salicylic acid and other NSAID (non-steroidal anti-inflammatory drug), antimalarial, penicillamine, Tripterygium Preparations, golden preparation even 17-hydroxy-11-dehydrocorticosterone, its therapeutic effect is all undesirable, and side effect is large.The traditional Chinese medical science has accumulated rich experience in clinical practice in several thousand; quickening along with the surging of back to nature tide and modernization of Chinese medicine step; seek Chinese medicine means and medicine and become the emphasis of global concern and the focus of research; especially be accompanied by the understanding of RA target organ damage is deepened and attention; (dosage is little in developmental research " three is little "; toxicity is little; side effect is little) triple effect is (efficiently; quick-acting; long-acting) five convenience (take medicine; produce; transportation; carry; storage); both had good anti rheumatism action, the main target organ (lung that again RA is damaged; kidney; bone etc.) medicine that has a protective effect becomes the common focus of being concerned about of Chinese and western medicine.

Summary of the invention

First purpose of the present invention is to provide a kind of pharmaceutical composition for the treatment of rheumatic joint disease;

Second purpose of the present invention is to provide the preparation method of this pharmaceutical composition;

The 3rd purpose of the present invention is to provide the application of this pharmaceutical composition in preparation treatment and alleviation rheumatic arthropathy and rheumatic renal damage medicine.

The objective of the invention is to be achieved through the following technical solutions:

A kind of pharmaceutical composition for the treatment of rheumatic joint disease, the crude drug of this pharmaceutical composition consists of:

Formica fusca 10-70 part, Radix Astragali 10-50 part, Fructus Chaenomelis 5-40 part, Radix Aconiti Lateralis Preparata 5-40 part, Radix Notoginseng 2-20 part;

Further, its crude drug consists of:

Formica fusca 15-60 part, Radix Astragali 15-45 part, Fructus Chaenomelis 10-35 part, Radix Aconiti Lateralis Preparata 10-30 part, Radix Notoginseng 3-15 part;

Further, its crude drug consists of:

Formica fusca 15-50 part, Radix Astragali 15-40 part, Fructus Chaenomelis 10-30 part, Radix Aconiti Lateralis Preparata 10-30 part, Radix Notoginseng 3-15 part;

Further, its crude drug consists of:

Formica fusca 20-40 part, Radix Astragali 18-30 part, Fructus Chaenomelis 12-20 part, Radix Aconiti Lateralis Preparata 10-20 part, Radix Notoginseng 4-10 part;

Further, its crude drug consists of:

Formica fusca 25-40 part, Radix Astragali 18-30 part, Fructus Chaenomelis 12-20 part, Radix Aconiti Lateralis Preparata 10-20 part, Radix Notoginseng 5-10 part;

Further, its crude drug consists of:

30 parts of Formica fuscas, 20 parts of the Radixs Astragali, 15 parts of Fructus Chaenomeliss, 12 parts of Radix Aconiti Lateralis Preparata, 6 parts of Radix Notoginseng;

Or, 25 parts of Formica fuscas, 30 parts of the Radixs Astragali, 12 parts of Fructus Chaenomeliss, 20 parts of Radix Aconiti Lateralis Preparata, 5 parts of Radix Notoginseng;

Or, 40 parts of Formica fuscas, 18 parts of the Radixs Astragali, 20 parts of Fructus Chaenomeliss, 10 parts of Radix Aconiti Lateralis Preparata, 10 parts of Radix Notoginseng.

Pharmaceutical composition of the present invention can be prepared as follows:

Get in proportion five tastes crude drug, be prepared from water or with organic solvent extraction that water dissolves each other;

Or, get in proportion five tastes crude drug, wherein Formica fusca, the Radix Astragali, Fructus Chaenomelis, Radix Aconiti Lateralis Preparata merge with water or with organic solvent extraction that water dissolves each other and get extract; Radix Notoginseng is pulverized, with Radix Notoginseng powder join above-mentioned extract obtained in, mix homogeneously forms.

Further, the described organic solvent that dissolves each other with water is selected from any one in methanol, ethanol, the acetone; Further be preferably the ethanol that concentration is 30%-80%;

Used extracting method comprises any one mode that decocts in extraction, reflux, extract,, immersion extraction, supersound extraction or the percolation extraction, the perhaps combination of Different Extraction Method.

Further, above-mentioned preparation method Raw medicine also can be purified, refining after extracting, as crossing macroporous resin column, and further routinely preparation process is made the acceptable any conventional dosage form of pharmaceutics, comprises granule, tablet, capsule, drop pill, oral liquid, suspension, emulsion, injection.

Pharmaceutical composition of the present invention also can adopt: get in proportion five tastes crude drug crude drug and directly pulverize, be mixed clinical acceptable dosage form;

Described pulverizing is preferably: through making the super fine below the particle diameter 100 μ m after the micronizing; Further preferably be prepared as the following super fine of 80 μ m; Further preferably be prepared as the following super fine of 70 μ m; Further preferably be prepared as the following super fine of 60 μ m; Further preferably be prepared as the following super fine of 50 μ m; Further preferably be prepared as the following super fine of 40 μ m; Further preferably be prepared as the following super fine of 30 μ m; Further preferably be prepared as the following super fine of 20 μ m; Further preferably be prepared as the following super fine of 10 μ m; Further preferably be prepared as the following super fine of 8 μ m;

Further, crude drug is ground into first coarse powder (crossing 24 mesh sieves) before the described micronizing, and makes moisture be lower than 4% through dried.

For above-mentioned dosage form can be realized, need when these dosage forms of preparation, to add the acceptable adjuvant of pharmacy, such as: filler, disintegrating agent, lubricant, suspending agent, binding agent, sweeting agent, correctives, antiseptic, substrate etc.Filler comprises: starch, pregelatinized Starch, lactose, mannitol, chitin, microcrystalline Cellulose, sucrose etc.; Disintegrating agent comprises: starch, pregelatinized Starch, microcrystalline Cellulose, carboxymethyl starch sodium, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose etc.; Lubricant comprises: magnesium stearate, sodium lauryl sulphate, Pulvis Talci, silicon dioxide etc.; Suspending agent comprises: polyvinylpyrrolidone, microcrystalline Cellulose, sucrose, agar, hydroxypropyl emthylcellulose etc.; Binding agent comprises, starch slurry, polyvinylpyrrolidone, hydroxypropyl emthylcellulose etc.; Sweeting agent comprises: saccharin sodium, Aspartane, sucrose, cyclamate, enoxolone etc.; Correctives comprises: sweeting agent and various essence; Antiseptic comprises: parabens, benzoic acid, sodium benzoate, sorbic acid and its esters, benzalkonium bromide, acetic acid chloroethene are decided, the Folium eucalypti globueli (Eucalyptus globulus Labill.) wet goods; Substrate comprises: PEG6000, PEG4000, insect wax etc.For making above-mentioned dosage form can realize pharmacy of Chinese materia medica, need when these dosage forms of preparation, to add acceptable other adjuvant of pharmacy (adjuvant of each dosage form record among the Fan Biting " pharmacy of Chinese materia medica ", Shanghai Science Press December in 1997 the 1st edition).

The pharmaceutical composition for the treatment of rheumatic joint disease of the present invention is except the form that feeds intake with Formica fusca, the Radix Astragali, Fructus Chaenomelis, Radix Aconiti Lateralis Preparata and Radix Notoginseng crude drug, can also adopt the form that feeds intake with Formica fusca, the Radix Astragali, Fructus Chaenomelis, Radix Aconiti Lateralis Preparata and Radix Notoginseng extract (effective site), therefore the present invention further discloses the pharmaceutical composition for the treatment of rheumatic joint disease:

A kind of pharmaceutical composition for the treatment of rheumatic joint disease, the raw material of this pharmaceutical composition consists of:

Formica fusca extract 10-70 part, Radix Astragali extract 10-50 part, Fructus Chaenomelis extract 5-40 part, Radix Aconiti Lateralis Preparata extract 5-40 part, Radix Notoginseng extract 2-20 part;

Further, its raw material consists of:

Formica fusca extract 20-50 part, Radix Astragali extract 15-40 part, Fructus Chaenomelis extract 10-30 part, Radix Aconiti Lateralis Preparata extract 10-30 part, Radix Notoginseng extract 3-15 part;

Further, its raw material consists of:

Formica fusca extract 25-40 part, Radix Astragali extract 18-30 part, Fructus Chaenomelis extract 12-20 part, Radix Aconiti Lateralis Preparata extract 10-20 part, Radix Notoginseng extract 5-10 part;

Further, its raw material consists of:

30 parts of Formica fusca extracts, 20 parts of Radix Astragali extracts, 15 parts of Fructus Chaenomelis extract, 12 parts of Radix Aconiti Lateralis Preparata extracts, 6 parts of Radix Notoginseng extracts;

Or, 25 parts of Formica fusca extracts, 30 parts of Radix Astragali extracts, 12 parts of Fructus Chaenomelis extract, 20 parts of Radix Aconiti Lateralis Preparata extracts, 5 parts of Radix Notoginseng extracts;

Or, 40 parts of Formica fusca extracts, 18 parts of Radix Astragali extracts, 20 parts of Fructus Chaenomelis extract, 10 parts of Radix Aconiti Lateralis Preparata extracts, 10 parts of Radix Notoginseng extracts.

Formica fusca extract of the present invention, Radix Astragali extract, Fructus Chaenomelis extract, Radix Aconiti Lateralis Preparata extract, Radix Notoginseng extract are respectively the water extract of Formica fusca, the Radix Astragali, Fructus Chaenomelis, Radix Aconiti Lateralis Preparata, Radix Notoginseng or the extractive with organic solvent that dissolves each other with water; The refining thing that further obtains through refining purification process behind the organic solvent extraction that perhaps dissolves each other through water or with water for Formica fusca, the Radix Astragali, Fructus Chaenomelis, Radix Aconiti Lateralis Preparata, Radix Notoginseng is as crossing macroporous resin column.

Further, the described organic solvent that dissolves each other with water is selected from any one in methanol, ethanol, the acetone; More preferably concentration is the ethanol of 30%-80%;

Used extracting method can be any one mode that decocts in extraction, reflux, extract,, immersion extraction, supersound extraction or the percolation extraction, the perhaps combination of Different Extraction Method.

Pharmaceutical composition of the present invention can also use with the other drug compatibility, and described other drug is for the medicine in relevant or similar field, such as rheumatic, antirheumatic, immunoregulation medicament, analgesic drug product etc.

Pharmaceutical composition of the present invention can be used for treatment and alleviates rheumatic arthropathy, and described rheumatic arthropathy is rheumatic arthritis, rheumatoid arthritis, articular synovitis and rheumatic renal damage.

Formica fusca of the present invention records for " Guangxi Chinese crude drug standard " second (1996), is the dry body of Formicidae animal bitooth multi-ant Polyrhachis dives Smith; The described Radix Astragali, Radix Aconiti Lateralis Preparata, Fructus Chaenomelis, Radix Notoginseng are 2010 editions " Chinese medicine that the Chinese pharmacopoeia First records or its processed products.

Ingredients of the present invention is prescription under traditional Chinese medical science QI and blood essence dynamic circulation theoretical direction, forms through the clinical basis of repeatedly verifying for many years and optimizing.This theory think gas, blood, smart three under physiological status mutual promotion, mutually transform; Influence each other under the pathological state, jointly cause a disease; Rheumatoid arthritis be because the extraneous inducement effect therapeutic method to keep the adverse QI flowing downwards hemospermia balance sysmte process that is broken and rebuilds, the multiple pathological product that the QI and blood essence produces in the Jianping weighing apparatus process again is mutually cementing, and influencing each other is to cause the main cause that disease is complicated and treatment is thorny; The basic pathogenesis of RA is that QI and blood essence is all empty, and the dynamic equilibrium of QI and blood essence is in low-level reconstructions, expectorant stasis of blood water cementing being at a stop in joint tissue of wetting, and the normal circulation of obstruction QI and blood essence causes vicious cycle.With Formica fusca, Radix Aconiti Lateralis Preparata QI invigorating hemospermia, rouse oneself vigour in the prescription, promote QI and blood essence blood circulation to transform to physiological status, be aided with its medicine and reach treating both the principal and secondary aspects of a disease, the effect for the treatment of must aim at the pathogenesis of disease; The circulation of qi promoting of Radix Astragali QI invigorating reaches qi-supplementing, blood-engendering, and the gas promoting the circulation of blood is moving, recovers to physiological level thereby drive the QI and blood fine balance; The blood of building up one's health by taking tonic such as Radix Notoginseng nourishes blood, thereby reaches the logical purpose of mending of essence and blood; Formica fusca is the worm medicine, and benefaction has promoting blood circulation to remove obstruction in the collateral, and the effect of stasis-dispelling and pain-killing is aided with the effect of invigorating blood circulation of Radix Notoginseng, reaches promoting tissue regeneration by removing blood stasis, promotes the purpose of joint function recovery, and the Fructus Chaenomelis relaxing muscles and tendons and activating QI and blood in the collateral is for clinical cardinal symptom; Radix Aconiti Lateralis Preparata is hot salty flat in this prescription, and Gan Wen returns the spleen kidney channel, gets its dispelling cold and removing dampness, the justice of warming YANG collateral dredging; The salty kidney of returning, salty energy softening the hard mass, the joint caused cellulose sample precipitation of softening RA, according to modern medical theory, Radix Aconiti Lateralis Preparata can improve again body Na+ concentration, changes the body inner penetration and presses, and dewatering by permeability reaches the effect of eliminating inflammatory exudate.The medicines such as Formica fusca, tepor, little salty, sour sweet enters the liver,spleen,kidney warp, dispelling wind collateral dredging, nourishing muscle and tendon blood stasis dispelling, anti-inflammatory analgesic.Sour in taste acting on the liver, liver governing tendons, the logical bone of acid, thus can easing joint movement, softening distortion joint prevents or alleviates the joint distortion, salty flavor entering the kidney, the kidney generating marrow and dominating bone, sweet flavour enters the spleen, spleen are source of generating QI and blood, thus can nourishing muscle and tendon, bone growth promoting is mended marrow.All medicines share, and amount to invigorating deficiency and tonifying vital QI, and the effect of eliminating evil blood stasis dispelling promotes QI and blood essence physiological equilibrium's recovery, reaches the purpose for the treatment of.

In an embodiment of the present invention, the pharmaceutical composition of the present invention that has provided different proportion is used for the experimentation of anti-model of adjuvant arthritis in rats, thereby draws the ratio range of the comparatively preferred crude drug of crude drug compositions of the present invention.

In other embodiment of the present invention, the extract that has provided the more excellent proportioning of primary raw material medicine of the present invention is used for the pharmacological evaluation of anti-dimethylbenzene mice ear, Ovum Gallus domesticus album rat paw edema, thermostimulation pain, chemical stimulation pain, adjuvant-induced arthritis, rheumatic renal damage (RA-MsPGN), proves that pharmaceutical composition of the present invention can be used for rheumatic arthritis, rheumatoid arthritis, rheumatic MsPGN.

In the following experimental example, used laboratory animal is not clearly indicated, and is: the KM mice, body weight 20 ± 2g, SD rat, body weight 200 ± 20g, provide the animal quality certification number by Sichuan Academy of Medical Sciences institute of lab animals: real moving pipe matter SCXK (river) 2004-16 in river.Experimental site is three grades of laboratorys of Chengdu University of Traditional Chinese Medicine of State Administration of Traditional Chinese Medicine herbal pharmacology, numbering: TCM2032043.Animal is raised under the light and shade cycle 12h/12h condition all at room temperature 22-24 ℃, freely drinks water and ingests.

Experimental example 1 different compatible composition antalgic and inflammation relieving proportioning ratio research

1 material

1.1 medicine and reagent

Formica fusca, Radix Aconiti Lateralis Preparata, Radix Notoginseng, the Radix Astragali, Fructus Chaenomelis are identified by the Ma Yuntong of Chengdu University of Traditional Chinese Medicine available from the large pharmacy of Tongrentang.Tramadol hydrochloride is produced (lot number: 0406245) by the Beijing Sihuan Medicine Science and Technology Co., Ltd; The dexamethasone acetate injection is produced (lot number: 66040099) by Xinan Pharmaceutical Co., Ltd..

1.2 laboratory animal

KM kind white mice, cleaning level, male and female dual-purpose, body weight (20 ± 2) g; Provided by Sichuan Academy of Medical Sciences institute of lab animals, the laboratory animal quality certification number is: the SCXK(river) 2004-16.

2 methods and result

2.1, the setting of Experimental agents proportioning ratio

Table 1 Formica fusca, the Radix Astragali, Fructus Chaenomelis, Radix Aconiti Lateralis Preparata and Radix Notoginseng proportioning ratio (g)

The experiment number	Formica fusca	The Radix Astragali	Fructus Chaenomelis	Radix Aconiti Lateralis Preparata	Radix Notoginseng
						1	10	10	5	5	2
2	20	15	10	8	4
						3	30	20	15	12	6
4	40	25	20	15	8
						5	50	30	25	20	10

Get respectively the crude drug of recipe quantity by table 1, Formica fusca, Radix Aconiti Lateralis Preparata, the Radix Astragali, Fructus Chaenomelis and Radix Notoginseng powder are broken into coarse powder, and adding distil water soaked after 30 minutes, and add 6 times of water gagings and fry in shallow oil three times, each 1 hour, filter, get 4 ℃ of Refrigerator stores of filtrate for subsequent use.

70 of 2.2 the impact on pain reaction---writhing method mices, male and female half and half, by being divided at random 7 groups after the body weight layering, i.e. blank group, positive controls (tramadol group) and 5 dosage ratio groups, 10 every group, every day, 1 continuous gastric infusion was 3 days.The results are shown in Table 2.

The different composition of prescription of table 2 are on the impact of mouse writhing reaction

Annotate: compare with the blank group, ^*P＜0.05; ^*P＜0.01; ^{* *}P＜0.001

As can be seen from Table 2, the prescription of proportion compatibility all can make mice prolongation of latency and the minimizing of writhing number of times of writhing response occur within the scope of the present invention, with the blank group significant statistical significance (P＜0.05 or P＜0.01 or P＜0.001) is arranged relatively, to the suppression ratio of mouse writhing number of times all greater than 60%, but Formica fusca, the Radix Astragali, Fructus Chaenomelis, Radix Aconiti Lateralis Preparata and Radix Notoginseng proportioning ratio be 30,20,15,12 and during 6g effect the most remarkable.2.3 70 of mice caused by dimethylbenzene xylene ear swelling test mices are complete male, by being divided at random 7 groups after the body weight layering, i.e. blank group, positive controls (dexamethasone acetate) and and 5 dosage ratio groups, 10 every group.Except positive controls in test same day intraperitoneal injection, the continuous gastric infusion of all the other every treated animals 3 days.The results are shown in Table 3.

The different composition of prescription of table 3 are on the impact of mice auricle swelling

Group	N(only)	Dosage (g/kg)	Ear swell poor (mg)	Suppression ratio (%)
					The blank group	10	Equal-volume	14.4±1.6	?
Positive controls	10	0.005	4.3±1.1 ^***	70.14
					1	10	10.95	7.2±2.7 ^*	50.00
2	10	10.95	8.5±2.7 ^*	40.97
					3	10	10.95	6.8±2.2 ^***	52.78
4	10	10.95	7.3±1.8 ^**	49.31
					5	10	10.95	9.3±1.7 ^*	35.42

Annotate: compare with the blank group, ^*P＜0.05; ^*P＜0.01; ^{* *}P＜0.001

As can be seen from Table 3, the mice ear that the prescription xylol of different proportion compatibilities causes has obvious inhibitory action, with the blank group obvious statistical significance (P＜0.05) is arranged relatively.And Formica fusca, the Radix Astragali, Fructus Chaenomelis, Radix Aconiti Lateralis Preparata and Radix Notoginseng proportioning ratio be 30,20,15,12 and 6g time effect the most remarkable.

3 conclusions

By antiinflammatory and analgesia research, the result show Formica fusca, the Radix Astragali, Fructus Chaenomelis, Radix Aconiti Lateralis Preparata and Radix Notoginseng proportioning ratio be 30,20,15,12 and during 6g effect antiinflammatory and analgesic activity all the most remarkable.

The experimental study of experimental example 2 drug particles analgesic and anti-inflammatory effects of the present invention

1 material

1.1 medicine and reagent

Exempt from arthralgia eliminating granule (abbreviation granule), press the preparation of embodiment 1 method; Tramadol hydrochloride is produced (lot number: 0406245) by the Beijing Sihuan Medicine Science and Technology Co., Ltd; The dexamethasone acetate injection is produced (lot number: 66040099) by Xinan Pharmaceutical Co., Ltd.; Glucosidorum Tripterygll Totorum is produced (lot number: 20040503) by Xieli Pharmaceutical Co., Ltd., Hunan; The cortisone acetate sheet is produced (lot number: 2,004,021 3) by Henan Province's Luohe City the second pharmaceutical factory.The before use fresh configuration of normal saline of all medicines, gastric infusion, 1 times/day.Freund's complete adjuvant (FCA) (Sigma company product).

1.2 laboratory animal

KM kind white mice, cleaning level, male and female dual-purpose, body weight (20 ± 2) g; The healthy SD rat, male, cleaning level, body weight (200 ± 20) g; Provide by Sichuan Academy of Medical Sciences institute of lab animals, the laboratory animal quality certification number is: the SCXK(river) 2004-16.

2 methods and result

2.1 analgesic activity

2.1.1 granule is on 50 of the impacts of pain reaction-hot plate method mice, entirely female, by being divided at random 5 groups after the body weight layering, be blank group, positive controls and high, medium and low 3 dosage groups of grains (32.4,16.2,8.1g crude drug in whole/kg), every group 10, every day, 1 continuous gastric infusion was 3 days.The results are shown in Table 4.

Table 4 granule is on the impact of hot plate method latency of pain response

Annotate: compare with the blank group, ^*P＜0.05; ^*P＜0.01; ^{* *}P＜0.001

As can be seen from Table 4, granule and tramadol hydrochloride all can the incubation period that pain is reacted occur by the significant prolongation mice in the 2h after administration, with the blank group significant statistical significance (P＜0.05 or P＜0.01) is arranged relatively, 4～6h also is improved the trend of latency of pain response after administration.

2.1.2 granule is on the impact of pain reaction---50 of writhing method mices, male and female half and half, grouping and the same 2.1.1 of administration the results are shown in Table 5.

The impact of table 5 Granules on Mouse writhing response

Annotate: compare with the blank group, ^*P＜0.05; ^*P＜0.01; ^{* *}P＜0.001

As can be seen from Table 5, prolongation of latency and writhing number of times that granule can make mice writhing response occur reduce, with the blank group significant statistical significance (P＜0.05 or P＜0.01 or P＜0.001) is arranged relatively, to the suppression ratio of mouse writhing number of times all greater than 50%.

2.2 antiinflammatory action

2.2.1 50 of mice caused by dimethylbenzene xylene ear swelling test mices, complete male, by being divided at random 5 groups after the body weight layering, i.e. blank group, the groups of grains of positive controls and high, medium and low 3 dosage (32.4,16.2,8.1g crude drug in whole/kg), 10 every group.Except positive controls in test same day intraperitoneal injection, the continuous gastric infusion of all the other every treated animals 3 days.The results are shown in Table 6.

The impact of table 6 Granules on Mouse auricle edema

Group	N(only)	Dosage (g/kg)	Ear swell poor (mg)	Suppression ratio (%)
					The blank group	10	Equal-volume	14.8±1.8	?
Dexamethasone group	10	0.005	6.3±1.7 ^***	57.4
					The granule high dose group	10	32.4	12.1±2.1 ^*	1?8.2
Dosage group in the granule	10	16.2	8.5±2.7 ^***	42.6
					The granule low dose group	10	8.1	1?1.9±2.17 ^*	19.6

Annotate: compare with the blank group, ^*P＜0.05; ^*P＜0.01; ^{* *}P＜0.001

As can be seen from Table 6, the mice ear that the granule xylol causes has obvious inhibitory action, with the blank group obvious statistical significance (P＜0.05) is arranged relatively.

2.2.2 acetic acid causes the hyperfunction experiment grouping of mouse peritoneal capillary permeability and the same 2.2.1 of administration, the results are shown in Table 7.

The impact of table 7 ant Granules on Mouse abdominal cavity capillary permeability

Group	N(only)	Dosage (g/kg)	The OD value
				The blank group	10	Equal-volume	1.5±.50
Dexamethasone	10	0.005	0.7±0.6 ^***
				The granule high dose group	10	32.4	1.0±0.4 ^**
Dosage group in the granule	10	16.2	0.8±0.3 ^***
				The granule low dose group	10	8.1	0.7±0.4 ^***

Annotate: compare with the blank group, ^*P＜0.05; ^*P＜0.01; ^{* *}P＜0.001

As can be seen from Table 7, the mouse peritoneal capillary permeability that granule causes glacial acetic acid is hyperfunction to have obvious inhibitory action, with the blank group significant statistical significance (P＜0.01 or P＜0.001) is arranged relatively.

2.2.3 Ovum Gallus domesticus album causes the experiment of rat paw edema and gets 50 of healthy male SD rats, body weight 1 80～220g.Be divided at random 5 groups, it is the blank group, the groups of grains of positive controls and high, medium and low 3 dosage (25.2,12.6,6.3g crude drug in whole/kg), except positive controls in test intraperitoneal injection on the same day, the continuous gastric infusion of all the other every treated animals 5 days.The results are shown in Table 8

The impact of table 8 granules in rats Ovum Gallus domesticus album foot swelling

Annotate: compare with the blank group, ^*P＜0.05; ^*P＜0.01; ^{* *}P＜0.001

() represents the foot swelling inhibition percentage

As can be seen from Table 8, the rat paw edema that granule causes Ovum Gallus domesticus album has obvious inhibitory action, with the blank group significant statistical significance (P＜0.05 or P＜0.01) is arranged relatively.

2.2.4 the impact on chronic inflammation model-mice granuloma induced by implantation of cotton pellets

Get 50 of healthy male mices, be divided at random 5 groups by body weight, the same 2.2.1 that divides into groups, successive administration 7 days, outside positive group intraperitoneal injection every day, all the other are gavage, the results are shown in Table 9.

The impact of table 9 Granules on Mouse granuloma induced by implantation of cotton pellets

Group	N(only)	Dosage (g/kg)	Granulation dry weight (mg)	The granulation index
					The blank group	10	Equal-volume	1?0.6±2.6	4.7±1.1
Dexamethasone group	10	0.005	4.9±1.3 ^***	2.3±0.6 ^***
					The granule high dose group	10	32.4	7.5±0.9 ^***	3.4±0.5 ^***
Dosage group in the granule	10	16.2	7.7±0.8 ^***	3.4±0.5 ^***
					The granule low dose group	10	8.1	7.0±0.8 ^***	3.1±0.5 ^***

Annotate: compare with the blank group, ^*P＜0.05; ^*P＜0.01; ^{* *}P＜0.001

As can be seen from Table 9, granule is to the significant inhibitory action of being formed with of granulation, and granulation dry weight and granulation index and blank group more all have extremely significant statistical significance (P＜0.001).

2.2.5 the inhibitory action to adjuvant-induced arthritis

Get 50 of rats, be divided at random 5 groups by body weight: (1) matched group; (2) granule prevention group; (3) granule therapy group; (4) cortisone prevention group; (5) cortisone treatment group, 10 every group.Rat under etherization, be injected in the right back foot pad with FCA0.1ml, it is the prevention group that injection adjuvant namely began administration the same day, beginning administration in the 8th day is treatment group, and be administered once every day, granule 12.6g/kgd, cortisone 25mg/kgd, matched group gavages isopyknic normal saline, continuous 21 days, extremely cuts open animal on the 22nd day.Injection adjuvant before and after 3 hours and every one fix the date each survey about sufficient sole of the foot volume once, the difference of volume is swelling before and after the adjuvant in giving with the parapodum sole of the foot, and observes Mus ear erythema, afterbody tuberosity etc. and situation occurs.

Preventative and the therapeutic administration of granule all can obviously suppress Earlier period of inflammation reaction and the once again swelling after 12 days of injection site, can suppress again the foot swelling that another hind leg delayed hypersensitivity causes, action intensity is similar to cortisone, the results are shown in Table 10.Each administration group rat ear's erythema and afterbody tuberosity and normal saline group more obviously alleviate.

Table 10 granule is on the impact of adjuvant arthritis rats pedal swelling

Annotate: compare with the normal saline group, ^*P＜0.05; ^*P＜0.01; ^{* *}P＜0.001

As can be seen from Table 10, granule is preventative all to have significantly inhibitory action with the therapeutic administration to adjuvant arthritis rats constitutional and Secondary cases foot swelling, with the blank group significantly statistical significance (P＜0.05 or P＜0.01 or P＜0.001) is arranged more all.

3. result

This experiment has good analgesic activity by hot plate method and acetic acid twisting method experiment confirm granule; Resist into rat Ovum Gallus domesticus album foot swelling experiment confirm granule acute exudative inflammation all being had preferably antagonism by mice dimethylbenzene ear swelling, glacial acetic acid abdominal cavity capillary permeability; Experimental results show that by the mice granuloma induced by implantation of cotton pellets granule also has preferably antagonism to chronic inflammatory disease; By adjuvant-induced arthritis experiment confirm granule the immunologic injury inflammation is had significant antagonism, result of study prompting granule has significant analgesia and antiinflammatory action.

Experimental example 3 drug particles of the present invention are on the impact of adjuvant arthritis rats synovial tissue pathomorphology

1, material

1.1 medicine and reagent

Exempt from arthralgia eliminating granule (abbreviation granule), press the preparation of embodiment 1 method;

Glucosidorum Tripterygll Totorum is produced (lot number: 20040503) by Xieli Pharmaceutical Co., Ltd., Hunan;

Freund's complete adjuvant (FCA) (Sigma company product);

1.2 key instrument

Microscope BH-2, Olympus;

1.3 laboratory animal

The healthy SD rat, the SPF level, male, body weight (200 ± 20) g is provided by Sichuan Academy of Medical Sciences institute of lab animals, and the laboratory animal quality certification number is: the SCXK(river) 2004-16.

2, method

2.1 group technology

60 SD rats are divided into 6 groups after by the body weight layering at random, be dosage group (middle dosage group) and granule low dose group (low dose group) in Normal group (blank group), model control group (model group), Radix Tripterygii Wilfordii positive controls (positive group), granule high dose group (high dose group), the granule, every group 10, gastric infusion once a day.Except normal group, respectively organize rat all by the modeling method modeling.

2.2 modeling method

In the subcutaneous inserting needle of the right back toes of modeling Mus to ankle joint, injection Freund adjuvant 0.1ml/ only induces arthritic generation with Freund's complete adjuvant.

2.3 medication

The high, medium and low dosage group of granule gavages that medicinal liquid is respectively 25.2,12.6g and 6.3 crude drug in whole/(kgd); The Radix Tripterygii Wilfordii group gavages medicinal liquid 5mg/ (kgd), and normal group and model group gavage isopyknic normal saline, and modeling beginning in the 14th day gastric infusion is until experiment finishes.

2.4 the drawing materials and prepare of specimen

The rat fasting was put to death rat after 24 hours after testing last administration in the 32nd day, take off right ankle joint on the aseptic working platform, the perfusion of 1 0% neutral formalin articular cavity is fixedly after 6-8 hour, separate synovial tissue, conventional film-making, HE dyeing is marked to cell infiltration, synovial cell proliferation and synovial membrane proliferation of fibrous tissue, presses 5 grades of point systems of lymphocyte of adjurant arthritis rat pathology ^[2](cell infiltration, 0: without inflammatory cell infiltration; 1:1～5/HP; 2:6～10/HP; 3:11～15/HP; 4: form microabscess.Synovial cell proliferation degree: 0: without infiltrating; 1: swelling hypertrophy (many); 2: increase continuous; 3: increase bilayer; More than the 4:3 layer.Synovial membrane proliferation of fibrous tissue degree: 0: without hypertrophy; 1: hypertrophy accounts for 1/3HP; 2: hypertrophy accounts for 1/2HP; 3: hypertrophy accounts for 1HP; 4: hypertrophy accounts for〉1HP), the morphologic change of tissues observed under the light microscopic.

3 results

Adjuvant Arthritis Model in Rats synovium of joint cell infiltration, hypertrophy are obvious, and especially hypertrophy is remarkable, and the pathological change of each administration group synovium of joint of granule is light than model group.The results are shown in Table 11

Table 11 synovium of joint pathological evaluation (HE dyeing, scoring method)

Group	N (only)	Dosage (g/kg)	Cell infiltration	Synovial cell proliferation	The synovial membrane fibrous tissue increases
						Normal group	1?0	Equal-volume	0.30±48 ^***	0.20±0.42 ^***	0.1?0±0.32 ^***
Model group	8	Equal-volume	2.88±0.99	2.25±1.04	2.13±0.99
						The Radix Tripterygii Wilfordii group	9	0.005	0.78±0.67 ^***	1.22±0.67 ^**	1.22±0.44 ^**
High dose group	9	25.2	1.44±0.88 ^***	1.44±0.88 ^*	1.33±0.50 ^**
						Middle dosage group	9	12.6	1.11±0.60 ^***	1.33±0.50 ^**	1.22±0.44 ^**
Low dose group	9	6.3	2.00±1.00 ^*	1.56±0.53 ^*	1.44±0.53 ^*

Annotate: compare with model group, ^*P＜0.05; ^*P＜0.01; ^{* *}P＜0.001

Experimental example 4 drug particles of the present invention are on the impact on adjuvant arthritis rats T cell subsets

1 material

1.1 medicine and reagent

Exempt from arthralgia eliminating granule (abbreviation granule), press the preparation of embodiment 1 method; Glucosidorum Tripterygll Totorum is produced (lot number: 20040503) by Xieli Pharmaceutical Co., Ltd., Hunan; The before use fresh configuration of normal saline of all medicines, gastric infusion, 1 time/d; Freund's complete adjuvant (FCA) (Sigma company product); The Mus FITC-CD of the Chinese People's Anti-Japanese Military and Political College ₃/ PE-CD ₄Two mark monoclonal antibodies, the Mus FITC-CD of the Chinese People's Anti-Japanese Military and Political College ₃/ PE-CD ₈Two mark monoclonal antibodies, hemolysin lysing solution (BD company product).

1.2 key instrument

BECTON DICKINSON FACSCAN flow cytometer;

XH-B type vortex mixer, the healthy medical apparatus company limited in Jiangyan City;

CENTRIFVGE MODEU 0412-7 centrifuge, Shanghai Surgical Operation Equipment Factory;

1.3 laboratory animal

The healthy SD rat, the SPF level, male, body weight (200 ± 20) g is provided by Sichuan Academy of Medical Sciences institute of lab animals, and the laboratory animal quality certification number is: the SCXK(river) 2004-16.All animals are all tested after the animal housing of constant temperature and humidity raised for 1 week.

2 methods

2.1 group technology

40 SD rats are divided into 5 groups after by the body weight layering at random, be Normal group (normal group), model control group (model group), Radix Tripterygii Wilfordii positive controls (Radix Tripterygii Wilfordii group), granule high dose group (high dose group), granule low dose group (low dose group), every group 8, dosage sees Table 9.Except normal group, respectively organize rat all by the modeling method modeling.

2.2 modeling method

2.3 medication

The granule high dose group gavages medicinal liquid 12.6g crude drug in whole/(kgd), and the granule low dose group gavages medicinal liquid 6.3g crude drug in whole/(kgd); The Radix Tripterygii Wilfordii group gavages medicinal liquid 5mg/ (kgd), and normal group and model group gavage isopyknic normal saline, and modeling beginning in the 14th day gastric infusion is until experiment finishes.

2.4 the drawing materials and prepare of specimen

Tested after the last administration in the 32nd day the rat fasting 24 hours, the femoral artery sacrificed by exsanguination.(100 μ/ml) collect blood with the heparinization test tube.After getting anticoagulation 100 μ l adding mensuration pipe, add corresponding antibodies 10 μ l, the whirlpool mixing, the room temperature lucifuge is hatched 30min, add hemolysin 1ml, mixing is hatched 10min again, add PBS washing 1000rpm/min, each 5min, continuous three times, the adjustment cell number is 106/ml, upper machine is collected 30000 cells and analysis with cellquest software; The negative control pipe is respectively FITC-IgG1 and PE-IgG2, all the other time-and-motion study pipes except the corresponding antibodies that adds.

3 results

Table 12 is respectively organized the comparison that rat peripheral blood T cells subgroup positive cell changes

Annotate: compare with model group, ^*P＜0.05 ^*P＜0.01

As shown in Table 12, model group rat CD ₄ ⁺The T cell compares not statistically significant (P＞0.05), CD with blank group ₈ ⁺The T cell presents significantly low (P＜0.05), CD ₄ ⁺/ CD ₈ ⁺Ratio extremely significantly increases (P＜0.01), and Radix Tripterygii Wilfordii group, high dose group and low dose group all have significant regulating action to the T cell subsets of disorder.

Granule has good regulating action to the disorder of T cell subsets, and its mechanism may be in the positive selection of T cell at thymus, the specific raising of granule CD ₃ ⁺CD ₈ ⁺Two positive cells are combined with thymic cortex surface epithelial cell mhc class i molecule, make CD ₈ ⁺The generation of cell increases, thereby so that the Th/Ts balance of imbalance recovered, thereby the performance therapeutical effect, this may be one of approach of granule performance therapeutical effect.

Experimental example 5 medicine super fines of the present invention are on the impact of RA-MsPGN Renal Function in Rats

1 material

1.1 Experimental agents

Super fine (abbreviation micropowder) is pressed the preparation of embodiment 2 methods; Tripterygium wilfordii Polyglycosidium Tablets is produced (lot number: 20040503) by Xieli Pharmaceutical Co., Ltd., Hunan.The before use fresh configuration of normal saline of all medicines, gastric infusion, 1 times/day.

1.2 reagent and instrument

Freund's complete adjuvant (FCA), incomplete Freunds adjuvant (FIA), LPS (E.Coli O111:B4) and bovine serum albumin (N-BSA) are U.S. Sigma company; Holland prestige figure biochemical instruments.

1.3 laboratory animal

The healthy SD rat, male, SPF level, body weight (200 ± 20) g; Provided by Sichuan Academy of Medical Sciences institute of lab animals, the laboratory animal quality certification number is: the SCXK(river) 2004-16.

2 experimental techniques

2.1 the reconstruction animal model [Xu Shijun, Shen Yingjun, Eurasian dragon, etc.The attached super fine of ant is on the impact of RA-MsPGN rat model renal function.China's combination of Chinese and Western medicine nephropathy magazine, 2007; 8 (7): 391～393]

(1) pre-immunity: other group rat except Normal group adds 3mg bovine serum albumin (N-BSA) in the right sufficient lift hemostasis complete Freund's adjuvant 0.1ml of experimental mouse, after this respectively at strengthening 1 time at 1 weekend, 2 weekends, the simultaneously subcutaneous branch injection in back incomplete Freund's adjuvant 0.1ml includes 3mgBSA; 3 weekends, continuous 4 the injection BSA in abdominal cavity, interval 1h, injected dose is respectively every 0.5mg, 1.0mg, 1.5mg, 3.0mg; Strengthen morning next day 1 time (2.0mg/ only).

(2) formal immunity: other group rat N-BSA tail vein injection and abdominal cavity multiple spot subcutaneous injection except Normal group hocket every other day, and tail vein injection dosage increases 0.5mg, till 2.5mg at every turn from every 0.5mg.The lumbar injection amount is 1 times of tail vein injection amount.Tail vein injection escherichia coli endotoxin 200ng/ only after 2 weeks of immunity.Formal immunity is totally 7 weeks.

(3) model evaluation: from the 4th week of modeling, choose at random two model group rats per weekend and do synovium of joint and Pathological inspection, whether successful with evaluation model.

2.2 grouping and administration:

73 rats are divided into 6 groups at random, and namely blank group (blank group) is 13,20 of model control group (model group); Positive controls (Radix Tripterygii Wilfordii group), the high, medium and low dosage group of micropowder (high, medium and low dosage group), every group each 10, the free diet of animal, lower minute cage of equal conditions fed.After 3 weeks of modeling, gastric infusion once a day, blank group and model group give the equal-volume normal saline; Positive group gives Radix Tripterygii Wilfordii suspension 5mg/kg; The medicinal liquid of high, medium and low dosage group difference 25.2,12.6 and 6.3g crude drug in whole/kg is to 10 weekends.

Prepare with specimen 2.3 draw materials

Water is can't help in fasting after the last administration, adopts the metabolism of rat cage to collect twenty-four-hour urine liquid, adopts biuret method to measure urine protein quantitation; Femoral artery sacrificed by exsanguination rat is collected blood, and separation of serum is measured serum urea nitrogen and creatinine; Asepticly win left kidney, 10% formaldehyde is fixed, and paraffin embedding is cut 2～3um thin slice, HE dyeing, om observation.

3 statistical method

Measurement data adopts one factor analysis of variance, relatively adopts the t check between group; Ranked data adopt Ridit to analyze.

4 results

4.1 animal model:

Animal injection complete Freund's adjuvant right sufficient obvious tumefaction next day adds the peak that weighs day by day, then alleviates gradually, occurs afterwards for the second time swelling on the 10th day, the 12nd day offside hind leg, the swelling of forelimb secondary, and " rheumatism tuberosity " appears in the 3rd all afterbodys; The 4th all pathomorphology inspection synovium of joint see that typical adjuvant-induced arthritis changes, and the kidney mesentery is slightly bred simultaneously, to the remarkable hypertrophy of the 6th all kidney mesenterys, the pathological change of typical mesentery appreciation nephritis occurs.This model modeling factor and pathogenic process meet the characteristics of RA mesentery appreciation nephritis substantially, pathological change also proves that rat not only has typical arthritic characteristics, the characteristics that have simultaneously MsPGN illustrate this model modeling success, can be used for the research of RA mesentery appreciation nephritis.

4.2 micropowder the results are shown in Table 13. to the impact of Rat 24 h urine protein quantitation, creatinine (BUN) and blood urea nitrogen (Crea)

Table 13 super fine is on the impact of rat urine protein quantification, creatinine and blood urea nitrogen

Annotate: compare with model group, ^*P＜0.05; ^*P＜0.01, ^{* *}P＜0.001

4.3 micropowder is on the impact of rat mesangial cell in vitro, extracellular matrix pathological change

Wang Shi [Wang Jun, Zheng Jiaxin, Sun Ruitao are adopted in the observation of rat kidney pathological change.The former capsule of kidney is to the pathology effects of MsPGN rat model.China's combination of Chinese and Western medicine nephropathy magazine, the grade scale of 2002,3 (3) 6:346-347..That is: (1)+slight: each mesangial region contains 3 nucleus; Extracellular matrix slightly increases, and capillary lumen is not squeezed and is open shape, and hypertrophy mesentery width is no more than the diameter of blood capillary.(2) ++ moderate: each mesangial region contains 4 nucleus; The extracellular matrix moderate increases, and be less than 50% Capillary loops and be squeezed, the tube chamber mild stenosis, the mesentery width of hypertrophy surpasses the diameter of blood capillary, and capillary lumen presents the extruding phenomenon that weight does not wait.(3) +++severe: each mesangial region contains 5 or more nucleus; Extracellular matrix severe increases, and the capillary loops more than 50% is squeezed, and the mesentery of tube chamber severe stenosis or inaccessible hypertrophy is on the basis that diffusivity finger-like distributes, being block assembles, the extracellular matrix showed increased, at the position that the lumps hypertrophy is assembled, capillary structure is destroyed blood vessel and is disappeared.Concrete data see Table 14.

Table 14 micropowder is on the impact of rat mesangial cell in vitro, extracellular matrix pathological change

Annotate: the pathology degree relatively compares with model group, ^*P＜0.05; ^*P＜0.01

5. conclusion

Result of study shows, model group compared with normal group twenty-four-hour urine amount, urine protein quantitation and serum creatinine be significantly rising (p＜0.05 or p＜0.001) all, blood urea nitrogen is without significant change (P＞0.05), and each dosage group of the attached super fine of Tripterygium wilfordii Polyglycosidium Tablets and ant all can make twenty-four-hour urine amount, urine protein quantitation and serum creatinine, and it significantly reduces (p＜0.05 or p＜0.01); Each dosage group of the attached super fine of ant and Tripterygium wilfordii Polyglycosidium Tablets group be zero difference (P＞0.05) relatively; Match with the pathology testing result, illustrate that super fine has preferably protective effect to the renal function injury due to the RA, the hypertrophy of mesangial cell and extracellular matrix is also had suppress preferably to do.

Experimental example 6 drug powders of the present invention are on the impact of adjuvant arthritis rats foot swelling and T cell subsets

1. material is in method:

1.1 trial drug: super fine, press the preparation of embodiment 2 methods.Hydrocortisone injection, Xinan Pharmaceutical Co., Ltd.'s product, lot number: 66040099.

1.2, experimental animal: the SD rat, body weight 1 80～220g is the SPF level, and the animal quality certification number is provided by Sichuan Academy of Medical Sciences institute of lab animals: real moving pipe matter SCXK (river) 2004-16 in river.Experiment is carried out at Chengdu University of Traditional Chinese Medicine's herbal pharmacology laboratory (three grades of herbal pharmacology laboratorys of State Administration of Traditional Chinese Medicine, certificate number is TCM-03.043).

1.3, reagent and instrument:

1.3.1 reagent: complete Freund's adjuvant, Sigma company product; The two mark of the Mus FITC-CD3/PE-CD4 of Chinese People's Anti-Japanese Military and Political College monoclonal antibody, the two mark of the Mus FITC-CD3/PE-CD8 of Chinese People's Anti-Japanese Military and Political College monoclonal antibody, hemolysin lysing solution (U.S. company BD).

13.2 key instrument: Becton Dickinson Facscan flow cytometer (U.S. Block Scientific company).

1.4, method:

1.4.1, grouping and administration: 60 SD rats are divided into 6 groups at random by body weight, be dosage group, super fine low dose group in Normal group (normal group), model control group (model group), cortisone matched group (cortisone group), super fine high dose group, the super fine, 10 every group.Except normal group, respectively organize rat all by the modeling method modeling.Modeling began administration, the corresponding medicinal liquid 10mlkg of each administration treated animal ig the same day ^-1, normal group and model group ig10 mlkg ^-1Normal saline, every day 1 time, successive administration 21 days, the grouping and dosage see Table 15.

1.4.2, model preparation: in the subcutaneous inserting needle of the right back toes of modeling Mus to ankle joint, injection Freund adjuvant 0.1ml/ only induces arthritic generation with Freund's complete adjuvant (FCA).

1.4.3, measuring:

1) on the impact of adjuvant arthritis rats foot volume: the right back ankle joint of each Mus is marked before the experiment, sufficient sole of the foot volume once about each was surveyed at regular intervals after the injection front 3h of FCA and the injection, the difference that gives adjuvant front and back volume with the parapodum sole of the foot is swelling, the results are shown in Table 12

2) impact of human peripheral blood T cell subgroup: rat fasting 24h after the last administration, femoral artery sacrificed by exsanguination.Every group choose at random 8 for detection of.With heparinization test tube (100Uml ^-1) collection blood.After getting anticoagulation 100 μ l adding mensuration pipe, add corresponding antibodies 10 μ l, the whirlpool mixing, the room temperature lucifuge is hatched 30min, adds hemolysin 1ml again, and mixing is hatched 10min, adds PBS washing 1 * 10 ³Rpmmin ^-1, each 5min, continuous three times, adjusting cell number is 10 ⁶Cellml ^-1, upper machine collects 3 * 10 with Cellquest software ⁴Individual cell is also analyzed; The negative control pipe is respectively FITC-IgG1 and the PE-IgG2 except the corresponding antibodies that adds, and all the other operations are with measuring pipe.The results are shown in Table 13

1.4.4, statistical procedures: use the SPSS15.0 statistical software, data represent with X ± S, and each is organized data and is normal distribution and carries out one factor analysis of variance (one-wayANOVA), and nonnormal distribution is carried out the K-W check.

2. result

2.1 the impact on adjuvant arthritis rats foot volume:

The results are shown in Table 15.By table as seen, compare with model group, the positive group of cortisone after modeling 1,3h, and 3,5,8,12,15, the foot swelling value of 18d all is starkly lower than model group (P＜0.01), high, medium and low three the dosage groups of super fine after modeling 1,3h, and 3,5,8,12,15, the foot swelling value of 18d and significantly reductions (P＜0.05 or P＜0.01) of model group, show preferably antiphlogistic effects.

Table 15 super fine is on the impact of adjuvant arthritis rats pedal swelling

Annotate: compare with model control group, ^*P＜0.05; ^*P＜0.01

2.2 the impact of human peripheral blood T cell subgroup:

The results are shown in Table 16.

The comparison of table 16 super fine t lymphocyte subsets of peripheral blood impact

Annotate: compare with model group, ^*P＜0.05; ^*P＜0.01

By table as seen, compare with model group, high, medium and low three the dosage groups of super fine can significantly reduce CD ₄ ⁺/ CD ₈ ⁺Ratio (P＜0.05 or P＜0.01); High, the middle dosage group of super fine can significantly reduce CD ₄ ⁺% value (P＜0.01), the low dose group performance is not obvious; Super fine shows preferably antiphlogistic effects.

3. conclusion

This experimental result shows, each dosage of super fine all has and alleviates preferably the rat model foot swelling and reduce CD ₄ ⁺T value.

Experimental example 7 drug particles of the present invention and the comparative study of super fine anti-inflammatory and analgesic effect

1 material

1.1 trial drug super fine (abbreviation micropowder) is pressed the preparation of embodiment 2 methods; Exempt from arthralgia eliminating granule (abbreviation granule), press the preparation of embodiment 1 method.The crude drug in whole consumption of two kinds of dosage forms is the dosage (micropowder be granule 1/12) of clinical identical multiple in the test.Tramadol hydrochloride is produced (lot number: 0406245) by the Beijing Sihuan Medicine Science and Technology Co., Ltd; The dexamethasone acetate injection is produced (lot number: 66040099) by Xinan Pharmaceutical Co., Ltd.; Tripterygium wilfordii Polyglycosidium Tablets is produced (lot number: 20040503) by Xieli Pharmaceutical Co., Ltd., Hunan.All medicines are used the fresh configuration of normal saline, gastric infusion, 1 times/day before use.

1.2 animal KM kind white mice, male and female dual-purpose, body weight (20 ± 2) g; The SD rat, the SPF level, male, body weight (200 ± 20) g; Provide by Sichuan Academy of Medical Sciences institute of lab animals, the laboratory animal quality certification number is: SOCK (river) 2004-16.

2 methods and result

2.1 xylol causes 80 of the male mices of the impact of mice auricle swelling, is divided into 8 groups by the body weight stratified random.High, medium and low 3 dosage of groups of grains are respectively 32.4,16.2,8.1 crude drug in whole/kg, and high, medium and low 3 dosage of micropowder group are respectively 2.7,1.35,0.675g crude drug in whole/kg.Except Dexamethasone group in test same day intraperitoneal injection, all the other every treated animal gastric infusions, every day 1 time, for three days on end.1h after the last administration evenly is applied to the wide two sides of mouse right ear with 2Oral dimethylbenzene and causes inflammation, left ear in contrast, cause scorching after 30min put to death animal, take off left and right sides auricle with the card punch of diameter 8mrn and weigh.As swelling, calculate the swelling inhibition percentage with left and right sides auricle weight difference, the results are shown in Table 17.

Two kinds of dosage forms of table 17 are on the impact of mice auricle swelling

Group	Mus number (only)	Dosage (g/kg)	The ear method of double differences (mg)	Suppression ratio (%)
					Matched group	10	?	14.8±1.8	?
Dexamethasone	10	0.005	6.32±1.7 ^**	57.4
					The granule high dose group	10	32.40	12.12±2.1 ^*	1?8.2
Dosage group in the granule	10	16.20	8.47±2.7 ^**	42.6
					The granule low dose group	10	8.1?0	11.85±2.17 ^*	19.6
The micropowder high dose group	10	2.70	1?1.43±3.6 ^**	23.0
					Dosage group in the micropowder	10	1.35	9.98±3.3 ^**	32.4
The micropowder low dose group	10	0.675	11.52±3.9 ^**	22.3

Compare with matched group ^*P＜0.05, ^*P＜0.01 (lower same)

Table 17 result demonstration, the granule of 3 dosage and micropowder xylol cause mice ear all obvious inhibitory action, and two kinds of dosage forms compare not statistically significant under the clinical identical multiple consumption.

2.2 Dichlorodiphenyl Acetate cause the mouse peritoneal capillary permeability hyperfunction affect grouping and administration with 2.1,1h after the last administration, mouse tail vein injection 1% azovan blue 0.1M1/10g body weight, lumbar injection 0.6% acetum 0.2ml/ is only simultaneously.Put to death mice behind the 20min, with 5ml distilled water flushing abdominal cavity, collect flushing liquor, centrifugal, get supernatant in spectrophotometer 590nm colorimetric, judge the permeability of mouse peritoneal blood capillary with absorbance (OD) value.The results are shown in Table 18.

The impact that two kinds of dosage forms of table 18 are hyperfunction on the mouse peritoneal capillary permeability

Group	Mus number (only)	Dosage (g/kg)	The OD value
				Matched group	1?0	?	1.45±0.50
Dexamethasone	1?0	0.05	0.66±0.6 ^**
				The granule high dose group	1?0	32.40	0.96±0.4 ^**
Dosage group in the granule	1?0	16.20	0.83±0.3 ^**
				The granule low dose group	1?0	8.10	0.74±0.4 ^**
The micropowder high dose group	1?0	2.70	0.52±0.1 ^**
				Dosage group in the micropowder	1?0	1.35	0.39±0.2 ^**
The micropowder low dose group	1?0	0.675	0.54±0.2 ^**

Table 18 result shows, the granule of 3 dosage and super fine Dichlorodiphenyl Acetate cause that the mouse peritoneal capillary permeability is hyperfunction all an extremely significant inhibitory action, two kinds of dosage forms not statistically significants relatively under the identical multiple consumption.

2.3 on the foot swelling of rat Ovum Gallus domesticus album affect 60 of rats, be divided into 6 groups by the body weight stratified random.Except dexamethasone in test same day intraperitoneal injection.All the other every treated animal gastric infusions, every day 1 time, continuous 5 days.Mark at the right back ankle joint of each Mus before the experiment, measure twice of each Mus foot volume with sufficient volume measuring apparatus.Average as the normal foot volume.30min after the last administration, every subcutaneous inserting needle of Rat Right metapedes sole of the foot section is near the subcutaneous injection lO～X ankle joint, the clear solution 0.1ml of Fresh Egg causes inflammation, respectively at cause scorching after 30,60,120,240,360min measures and causes scorching sufficient volume, calculate each rat and cause the right back sufficient sole of the foot volume-variation value in scorching front and back, represent the anti-inflammatory effect of medicine with paw swelling and the swollen inhibition percentage of foot, the results are shown in Table 19.

Two kinds of dosage forms of table 19 are on the impact of rat Ovum Gallus domesticus album foot swelling

() interior data are that foot swelling suppresses percentage

Table 19 result demonstration, the granule of high and low dose all has extremely significant inhibitory action with micropowder to the rat paw edema due to the Ovum Gallus domesticus album. and two kinds of dosage forms compare not statistically significant under the clinical identical multiple consumption.

2.4 the impact grouping same 2.1 on the mice granuloma induced by implantation of cotton pellets.Administration same day is implanted the sterilization cotton balls in the mouse armpit subcutaneous operation, and (10mg ± 0.5mg), gastric infusion is 7 days continuously, the Dexamethasone group intraperitoneal injection.Put to death mice after 7 days.Peel off granulation tissue, in 60 ℃ of baking ovens, dry, weigh, calculate granuloma and heavily reach the granulation index, the results are shown in Table 20.Two kinds of dosage forms of table 20 are on the impact of mice granuloma induced by implantation of cotton pellets

Group	Mus number (only)	Dosage (g/kg)	Granulation dry weight (mg)	The granuloma index
					Matched group	10	?	10.60±2.6	4.70±1.1
Dexamethasone	10	0.005	4.92±1.3 ^**	2.26±0.6 ^**
					The granule high dose group	10	32.40	7.52±0.9 ^**	3.42±0.5 ^**
Dosage group in the granule	10	16.20	7.65±0.8 ^**	3.44±0.5 ^**
					The granule low dose group	10	8.1?0	6.99±0.8 ^**	3.14±0.5 ^**
The micropowder high dose group	10	2.70	8.30±1.3 ^**	3.62±0.5 ^**
					Dosage group in the micropowder	10	1.35	9.30±1.5 ^**	3.88±0.7 ^*
The micropowder low dose group	10	0.675	8.80±1.8 ^**	4.03±1.0 ^*

Table 20 result demonstration, the granule of 3 dosage and micropowder all have significant inhibitory action to the formation of granulation, and two kinds of dosage forms compare not statistically significant under the clinical identical multiple consumption.

2.5 hot plate dolorimeter temperature is regulated in the impact of hot plate method test mice pain reaction, constant in 55 ± 0.5 ℃, put take female mice and to begin in people's dolorimeter to clock to occurring licking metapedes required time (5) as pain week value. screen pain threshold 80 of the mices of asking of 5～30s, be divided into 8 groups by the body weight stratified random, matched group and each administration group are 10 mices, measure respectively every group every the wealthy value of mice pain 2 times, every minor tick 5min averages as normal pain threshold (being the front pain threshold of administration).Then be subjected to reagent or equal volume normal saline 0.1ml/10g.Every day 1 time, for three days on end, after the last administration 30,60,120,240,360min measure respectively organize mice bitterly the value of closing as administration after gate of a village value bitterly, pain threshold greater than 60s person in 60s.The results are shown in Table 21.

Two kinds of dosage forms of table 21 are on the impact of hot plate method test mice pain reaction

Table 21 result demonstration, the micropowder of 3 dosage, granule and tramadol hydrochloride all can significantly improve pain threshold after administration, and two kinds of dosage forms compare not statistically significant under the clinical same amount multiple.

2.6 Dichlorodiphenyl Acetate writhing method mice pain reaction affect 80 male and female half and half of mice, grouping and administration be with 2.1, the normal saline 0.1ml/l0g of gastric infusion merit equal volume, behind the administration 30min, lumbar injection 0.6% glacial acetic acid solution 0.2ml/ is only.Writhing response number of times in 1 5min behind the observation injection acetic acid, and calculate the analgesia rate, the results are shown in Table 22.

The impact of two kinds of dosage form Dichlorodiphenyl Acetates of table 22 writhing method mice pain reaction

Prolongation of latency and writhing number of times that table 22 result demonstration, the micropowder of 3 dosage and granule can both make mice writhing response occur reduce, and two kinds of dosage forms compare not statistically significant under the clinical identical multiple consumption.

3 results

Result of study shows, the granule consumption is 12 times of micropowder under clinical identical multiple dosage, but the antalgic and inflammation relieving effect basic simlarity of two kinds of dosage forms.Prompting is under same or analogous therapeutic effect, and the consumption of micropowder only is 1/12 of granule.

The specific embodiment

Embodiment 1

The prescription crude drug forms: Formica fusca 3000g, Radix Astragali 2000g, Fructus Chaenomelis 1500g, Radix Aconiti Lateralis Preparata 1200g, Radix Notoginseng 600g

Get the crude drug of recipe quantity, Formica fusca, Radix Aconiti Lateralis Preparata, the Radix Astragali and papaya powder are broken into coarse powder, and adding distil water soaked after 30 minutes, add 6 times of water gagings and fry in shallow oil three times, and each 1 hour, filtration, filtrate was concentrated into relative density 1.07(60 ℃) clear paste, for subsequent use; Other gets the Radix Notoginseng of recipe quantity, pulverizes, and crosses 120 mesh sieves, gets the Radix Notoginseng impalpable powder, and with the clear paste mix homogeneously of Radix Notoginseng impalpable powder and said extracted gained, acceptable adjuvant is according to the routine techniques of this area preparation, granulation agent in the adding pharmacy.

The every gram of granule of the present invention is equivalent to 6 gram crude drug.

Embodiment 2

Get the crude drug of the present invention of recipe quantity, Formica fusca, Radix Aconiti Lateralis Preparata, the Radix Astragali, Radix Notoginseng and Fructus Chaenomelis are pulverized, and cross 24 mesh sieves, get the raw material coarse powder; The raw material coarse powder placed 60 ℃ drying in oven 5h, take out, guarantee that pan feeding moisture should be lower than 4%; Coarse powder after the oven dry is carried out micronizing, and grinding time is 20min, gets particle diameter and is about 8 μ m super fines.

The every gram of super fine of the present invention is equivalent to 1 gram crude drug.

Embodiment 3

The prescription crude drug forms: Formica fusca 2500g, Radix Astragali 3000g, Fructus Chaenomelis 1200g, Radix Aconiti Lateralis Preparata 2000, Radix Notoginseng 500g

Get the crude drug of the present invention of recipe quantity, Formica fusca, Radix Aconiti Lateralis Preparata, the Radix Astragali, Radix Notoginseng and Fructus Chaenomelis are pulverized, and cross 24 mesh sieves, get the raw material coarse powder, add the alcohol reflux three times of 10 times of amounts 70%, and each 1.5 hours, filter, merging filtrate, Recycled ethanol is to without the alcohol flavor; Filtrate is used first 5 times of water gaging eluting by macroporous resin, and eluent is abandoned or adopted, and with adding 70% ethanol elution, collects eluent again, and decompression recycling ethanol is to nothing alcohol flavor; Add again in the pharmacy acceptable adjuvant and make tablet according to the routine techniques of this area preparation.

Embodiment 4

The prescription crude drug forms: Formica fusca 4000g, Radix Astragali 1800g, Fructus Chaenomelis 2000g, Radix Aconiti Lateralis Preparata 1200g, Radix Notoginseng 1000g

Get the crude drug of the present invention of recipe quantity, Formica fusca, Radix Aconiti Lateralis Preparata, the Radix Astragali and Fructus Chaenomelis were soaked after 30 minutes, adding 6 times of water gagings fries in shallow oil three times, each 1 hour, filter, filtrate is concentrated into relative density 1.07(60 ℃) clear paste, (inlet temperature is decided to be spray drying: 170～1 80 ℃, leaving air temp is decided to be: 90～1 00 ℃), collect the dry extract powder; Radix Notoginseng is pulverized, and crosses 120 mesh sieves, gets the Radix Notoginseng impalpable powder, with above-mentioned dry extract powder mix homogeneously, adds in the pharmacy acceptable adjuvant again and makes capsule according to the routine techniques of this area preparation.

Embodiment 5

The prescription crude drug forms: Formica fusca 2000g, Radix Astragali 1500g, Fructus Chaenomelis 1000g, Radix Aconiti Lateralis Preparata 800g, Radix Notoginseng 400g;

Get the recipe quantity crude drug, Formica fusca, Radix Aconiti Lateralis Preparata, the Radix Astragali, Radix Notoginseng and Fructus Chaenomelis are pulverized, cross 24 mesh sieves, get the raw material coarse powder, add 8 times of amount methanol supersound extraction three times, front twice each 40min, 20min filters merging filtrate for the third time, filtrate decompression is concentrated into relative density 1.1 5(60 ℃) clear paste, for subsequent use; Extracting resulting clear paste adds in the pharmacy acceptable adjuvant again and makes drop pill according to the routine techniques of this area preparation.

Embodiment 6

The prescription crude drug forms: Formica fusca 6000g, Radix Astragali 2000g, Fructus Chaenomelis 3000g, Radix Aconiti Lateralis Preparata 1000g, Radix Notoginseng 1500g;

Get the crude drug of the present invention of recipe quantity, Formica fusca, Radix Aconiti Lateralis Preparata, the Radix Astragali and Fructus Chaenomelis add 8 times of water gaging dipping 6h, percolation 24h, flow velocity 2L/h.Collect percolate, centrifugal, upper macroporous adsorptive resins, wash with water first, use again 70% ethanol elution, collect ethanol elution, filtrate is concentrated into relative density 1.07(60 ℃) clear paste, spray drying (inlet temperature is decided to be: 170～1 80 ℃, leaving air temp is decided to be: 90～1 00 ℃) is collected the dry extract powder; Radix Notoginseng is pulverized, and crosses 120 mesh sieves, gets the Radix Notoginseng impalpable powder, with above-mentioned dry extract powder mix homogeneously, adds in the pharmacy acceptable adjuvant according to the routine techniques granulation agent of this area preparation again.

Embodiment 7

The prescription crude drug forms: Formica fusca 2000g, Radix Astragali 4000g, Fructus Chaenomelis 1000g, Radix Aconiti Lateralis Preparata 3000g, Radix Notoginseng 500g;

Get the recipe quantity crude drug, Formica fusca, Radix Aconiti Lateralis Preparata, the Radix Astragali, Radix Notoginseng and Fructus Chaenomelis are pulverized, and cross 24 mesh sieves, get the raw material coarse powder, add 12 times of water gaging reflux, extract, three times, each 1.5h, filter, merging filtrate, acceptable adjuvant is made oral liquid according to the routine techniques of this area preparation in the adding pharmacy.

Embodiment 8

The prescription raw material forms: Formica fusca extract 6000g, Radix Astragali extract 2000g, Fructus Chaenomelis extract 3000g, Radix Aconiti Lateralis Preparata extract 1000g, Radix Notoginseng extract 1500g;

Described Formica fusca extract, Radix Astragali extract, Fructus Chaenomelis extract, Radix Aconiti Lateralis Preparata extract, Radix Notoginseng extract are respectively the extract that Formica fusca, the Radix Astragali, Fructus Chaenomelis, Radix Aconiti Lateralis Preparata, Radix Notoginseng prepare through 60% alcohol reflux.It is fine powder that the said extracted thing is pulverized, and mixing adds conventional adjuvant according to the routine techniques granulation agent of this area preparation.

Embodiment 9

The prescription raw material forms: Formica fusca extract 3000g, Radix Astragali extract 2000g, Fructus Chaenomelis extract 1500g, Radix Aconiti Lateralis Preparata extract 1200g, Radix Notoginseng extract 600g;

Described Formica fusca extract, Radix Astragali extract, Fructus Chaenomelis extract, Radix Aconiti Lateralis Preparata extract, Radix Notoginseng extract are respectively the extract that Formica fusca, the Radix Astragali, Fructus Chaenomelis, Radix Aconiti Lateralis Preparata, Radix Notoginseng prepare through the acetone reflux, extract.It is fine powder that the said extracted thing is pulverized, and mixing adds conventional adjuvant and makes powder according to the routine techniques of this area preparation.

Embodiment 10

The prescription raw material forms: Formica fusca extract 2500g, Radix Astragali extract 3000g, Fructus Chaenomelis extract 1200g, Radix Aconiti Lateralis Preparata extract 2000, Radix Notoginseng extract 500g;

Described Formica fusca extract, Radix Astragali extract, Fructus Chaenomelis extract, Radix Aconiti Lateralis Preparata extract, Radix Notoginseng extract are respectively Formica fusca, the Radix Astragali, Fructus Chaenomelis, Radix Aconiti Lateralis Preparata, Radix Notoginseng through the standby extract that obtains of decocting boiling.It is fine powder that the said extracted thing is pulverized, and mixing adds conventional adjuvant and makes tablet according to the routine techniques of this area preparation.

Claims

1. pharmaceutical composition for the treatment of rheumatic joint disease is characterized in that the crude drug of described pharmaceutical composition consists of:

Formica fusca 1 0-70 part, the Radix Astragali 1 0-50 part, Fructus Chaenomelis 5-40 part, Radix Aconiti Lateralis Preparata 5-40 part, Radix Notoginseng 2-20 part.

2. pharmaceutical composition as claimed in claim 1 is characterized in that the crude drug of this pharmaceutical composition consists of:

5 parts of Formica fusca 15-60 parts, Radix Astragali 15-45 part, Fructus Chaenomelis 10-35 part, Radix Aconiti Lateralis Preparata 10-30 part, Radix Notoginseng 3-1;

3. pharmaceutical composition as claimed in claim 2 is characterized in that the crude drug of this pharmaceutical composition consists of:

5 parts of Formica fusca 15-50 parts, Radix Astragali 15-40 part, Fructus Chaenomelis 10-30 part, Radix Aconiti Lateralis Preparata 10-30 part, Radix Notoginseng 3-1;

The preferred feedstock medicine consists of: 0 part of Formica fusca 20-40 part, Radix Astragali 18-30 part, Fructus Chaenomelis 12-20 part, Radix Aconiti Lateralis Preparata 1 0-20 part, Radix Notoginseng 4-1;

More preferably crude drug consists of: 0 part of Formica fusca 25-40 part, the Radix Astragali 1 8-30 part, Fructus Chaenomelis 1 2-20 part, Radix Aconiti Lateralis Preparata 1 0-20 part, Radix Notoginseng 5-1.

4. pharmaceutical composition for the treatment of rheumatic joint disease is characterized in that the raw material of this pharmaceutical composition consists of:

Formica fusca extract 10-70 part, Radix Astragali extract 10-50 part, Fructus Chaenomelis extract 5-40 part, Radix Aconiti Lateralis Preparata extract 5-40 part, Radix Notoginseng extract 2-20 part.

5. pharmaceutical composition as claimed in claim 4 is characterized in that the raw material of this pharmaceutical composition consists of:

Formica fusca extract 25-40 part, Radix Astragali extract 18-30 part, Fructus Chaenomelis extract 12-20 part, Radix Aconiti Lateralis Preparata extract 10-20 part, Radix Notoginseng extract 5-10 part.

6. such as the preparation method of the arbitrary pharmaceutical composition of claim 1-3, it is characterized in that the method comprises:

A, get five tastes crude drug in proportion, with water or the organic solvent extraction that dissolves each other with water; Or, get in proportion five tastes crude drug, wherein Formica fusca, the Radix Astragali, Fructus Chaenomelis, Radix Aconiti Lateralis Preparata merge with water or with organic solvent extraction that water dissolves each other and get extract; Radix Notoginseng is pulverized, with Radix Notoginseng powder join above-mentioned extract obtained in, mix; Or get in proportion five tastes crude drug crude drug and directly pulverize, mix;

B, make clinical acceptable dosage form.

7. preparation method as claimed in claim 6 is characterized in that the described organic solvent that dissolves each other with water is any one or two kinds in methanol, ethanol or the acetone; Described extraction is any one mode or its combination that decocts in extraction, reflux, extract,, immersion extraction, supersound extraction or the percolation extraction.

8. preparation method as claimed in claim 6, it is characterized in that described micronizing before crude drug pulverize first, cross 24 mesh sieves and get the crude drug coarse powder, and make moisture be lower than 4% through dried.

9. such as the application in the arbitrary described pharmaceutical composition preparation treatment of claim 1-5 and alleviation rheumatic arthropathy or the rheumatic renal damage medicine.

10. application as claimed in claim 9 is characterized in that described rheumatic arthropathy is rheumatic arthritis, rheumatoid arthritis or articular synovitis.