CN101780154A - Chinese traditional medicine composition for preventing and curing gouty arthritis and application thereof - Google Patents

Abstract

The invention belongs to the technical fields of Chinese traditional medicines and natural medicines and discloses a Chinese traditional medicine composition for preventing and curing gouty arthritis and an application thereof. In the invention, the Chinese traditional medicine composition for preventing and curing gouty arthritis comprises the following crude medicine components in parts by weight: 9-15 parts of radix saposhnikoviae, 6-9 parts of atractylodes rhizome, 12-15 parts of angelica, 15-30 parts of tarragon, 9-12 parts of stephania tetrandra, 6-9 parts of notopterygium root, 15-30 parts of giant knotweed, 6-9 parts of radix angelicae pubescentis, 12-15 parts of grifola and 9-12 parts of crude licorice. The preparation prepared from the Chinese traditional medicine composition of the invention has exact effect on curing acute gouty arthritis; the clinical experiment and the animal experiment prove that the preparation has the functions of resisting inflammations, easing pain and resisting acute gouty attack; and the preparation does not have obvious toxic side effects by toxicity studying.

Description

A kind of Chinese medicine composition and application thereof that is used to prevent and treat gouty arthritis

Technical field

The invention belongs to Chinese medicine and natural medicine technical field, be specifically related to a kind of Chinese medicine composition and preparation and application that prevents and treats gouty arthritis.

Background technology

Gout is that purine metabolic disturbance and/or urate excretion reduce caused one group of disease, its clinical characters is a hyperuricemia, the acute arthritis that characteristic is shown effect repeatedly, tophus deposition, tophus chronic arthritis and joint deformity, the later stage often involves kidney and causes the formation of chronic interstitial nephritis and uric acid salt renal calculus.In recent years, China's gout sickness rate is the trend of remarkable rising: a routine gout is not found in the investigation that Fang Qi in 1980 etc. carry out in Beijing, Shanghai, 502 adults in Guangzhou; 1997-1998, Dai Shengming etc. find that in the investigation of Shanghai City Yangpu District the sickness rate of gout is 0.22%; 2002, this numeral of reports such as Shi Fang reached 0.28%.

The clinical treatment of gouty arthritis, principle are summarized and are mainly contained 2 points: the one, alleviate its acute attack rapidly and effectively; The 2nd, reduce blood uric acid, prevent it to show effect repeatedly.Modern medicine treatment gouty arthritis acute stage mainly contains three class medicines: colchicine, nonsteroidal antiinflammatory drug and glucocorticoid, though clinical efficacy is reliable, prolonged application has big toxic and side effects.Colchicine often has gastrointestinal reactions such as stomachache, diarrhoea, vomiting, can cause during heavy dose of the application that bone marrow depression, hepatocyte destroy and neural toxicity, and its therapeutic dose and toxic dose are very approaching, are easy to take place toxicity.As for nonsteroidal antiinflammatory drug (NSAIDs), to be that a class has well analgesic, the medicine of analgesia and antiinflammatory action.Traditional NSAIDs reduces the generation of prostaglandin (PGs) by suppressing the activity of Cycloxygenase (COX), thereby brings into play analgesic, analgesia and antiinflammatory action.But its non-selectivity suppresses the activity of COX-1 and COX-2, and therefore, side effect of digestive tract is more to be seen.Former times dry goods (coxibs) medicines such as celecoxib that went on the market in succession in 1999 and rofecoxib can suppress COX-2 specifically, and the activity of COX-1 is not influenced or seldom influence, clinical osteoarthritis, the rheumatoid arthritis of being used for the treatment of, compare with traditional NSAIDs, its gastrointestinal side effect obviously reduces.Yet because rofecoxib has serious cardiovascular adverse effects (comprising heart attack and myocardial infarction), Merck ﹠ Co., Inc. initiatively withdrew from market with rofecoxib in 2004.New clinical data shows that other dry goods medicine also has this type of reaction former times, and the ground former times cloth that cuts down of Pfizer is also required to withdraw from market by FDA.As for glucocorticoid, it causes that easily a series of untoward reaction such as osteoporosis, digestive tract ulcer, metabolism disorder, immunosuppressant have been well-known, only fail to respond to any medical treatment or produce untoward reaction or have heavier General Symptoms just to consider to use, clinically not as a line choice drug in said medicine.In the catabasis of gouty arthritis, the main purpose of treatment is to reduce blood uric acid, and mainly containing of clinical practice at present suppresses the synthetic and promotion urate excretion two big class medicines of uric acid, and the former is representative with the allopurinol, and the latter is representative with the benzbromarone.The both has definite clinical efficacy, but all exist some tangible untoward reaction or toxic and side effects, limited its clinical practice, might bring out the generation of acute gouty arthritis as the both, allopurinol might cause fatal exfoliative dermatitis, and benzbromarone then may cause the patient who merges renal calculus renal colic etc. takes place.

Because gout is present to be non-radical-ability disease, might be throughout one's life all outbreaks repeatedly, so the control of primary disease is the process of a long-term and even lifelong participation, and the shortcoming of said medicine has all limited its prolonged application clinically.

Summary of the invention

The purpose of this invention is to provide the generation of gouty arthritis is write out a prescription and preparation and application with the drug matching that development has obvious treatment and preventive effect.

The invention provides a kind of Chinese medicine composition of preventing and treating gouty arthritis, this Chinese medicine composition contains the crude drug component of following weight portion:

Radix Saposhnikoviae (Saposhnikovia divaricata (Turcz.) Schischk.) 9～15

Rhizoma Atractylodis (Rhizoma Atractylodis) 6～9

Radix Angelicae Sinensis (Angelica sinensis (Oliv.) Diels) 12～15

Herba Artemisiae Scopariae (Artemisia capillaris Thunb.) 15～30

Radix Stephaniae Tetrandrae (Stephania tetrandra S.Moore) 9～12

Rhizoma Et Radix Notopterygii (Rhizoma Notopterygii) 6～9

Rhizoma Polygoni Cuspidati (Reynoutria japonica Houtt.) 15～30

Radix Angelicae Pubescentis (Araliafargesii Franch) 6～9

Polyporus (Polyporus) 12～15

Radix Glycyrrhizae (Radix Glycyrrhizae) 9～12

Further, the invention also discloses a kind of Chinese medicine extract, for being that the raw material effective component extracting makes with above-mentioned Chinese medicine composition.

Among the present invention, the prescription of crude drug is the most key, after knowing the crude drug prescription, those skilled in the art can adopt the Chinese medicine extraction process of effective component of various routines to extract its effective ingredient, as the decoction of routine, decoction and alcohol sedimentation technique, ethanol extract from water precipitation, salting out method etc., because the said extracted method all can obtain the main pharmacodynamics composition in the aforementioned Chinese medicine preparation, therefore all can have certain curative effect to gouty arthritis.

Can be again behind the described Chinese medicine composition effective component extracting through the step of routine concentrate, purification or the dry Chinese medicine extract that obtains.Wherein spissated method includes but not limited to: atmospheric evaporation, reduction vaporization, thin film evaporation, multiple-effect evaporation, the method of purification includes but not limited to: the purification of saltouing, the macroporous resin adsorption purification, the ethanol precipitation purification, ion-exchange resin purification, the flocculation sediment purification, membrane separation purification, the polyamide adsorption and purification, silica gel adsorption chromatography purification etc., exsiccant method includes but not limited to: oven drying method, the drum-type seasoning, the belt drying method, the hygroscopic desiccation method, fluid-bed drying, spray drying method, hypobaric drying method, freeze-drying, infrared drying, micro-wave drying method etc.

Chinese medicine composition of the present invention or Chinese medicine extract can be used for preparing the medicine of preventing and treating gouty arthritis.

The present invention also further provides a kind of Chinese medicine preparation, comprises aforementioned Chinese medicine extract and one or more conventional acceptable accessories for the treatment of effective dose.

Acceptable accessories comprises (but being not limited to): medicine acceptable carrier, diluent, filler, bonding agent and other excipient.Known treatment of branch art personnel inert inorganic or organic carrier in this area includes, but is not limited to lactose, corn starch or derivatives thereof, Talcum, vegetable oil, wax, fat, polyol for example Polyethylene Glycol, water, sucrose, ethanol, glycerol, like that, various antiseptic, lubricant, dispersant, correctives.Wetting agent, antioxidant, sweeting agent, coloring agent, stabilizing agent, salt, buffer is like that also can add wherein, and these materials are used to help the stability of filling a prescription as required or help to improve activity or its biological effectiveness or produce acceptable mouthfeel or abnormal smells from the patient under oral situation.Chinese medicine preparation such as granule and unguentum can be prepared by conventional method.Pharmaceutical composition of the present invention also can use with the other treatment agent.

Preferably, described Chinese medicine preparation is an oral formulations, includes but not limited to granule, pill, tablet, capsule, syrup, spray etc.

Behind the effective ingredient in extracting Chinese medicine composition, can adopt conventional pharmaceutic adjuvant and the aforementioned pharmaceutical composition of additive preparation.

The dose therapeutically effective of pharmaceutical composition of the present invention is that in the gross weight of raw medicinal material, oral safe and effective amount is generally 1.69-2.54 gram/kg body weight.Certainly, concrete dosage also should be considered factors such as route of administration, patient health situation, and these all are within the skilled practitioners skill.

Clinical observation, drug effect and toxicological study result show, the effective ingredient of Chinese medicine composition of the present invention, can obviously alleviate acute gouty arthritis patient's arthralgia and swelling, improve function of joint, treatment group total effective rate reaches 95%, matched group (colchicine) total effective rate compares there was no significant difference (P＞0.05) for 94%, two group; Find that simultaneously this medical instrument has the reduction blood uric acid, increase the discharge of the acid of urinating, be better than matched group (P＜0.05), and obvious toxicity is not found in clinical research.Animal experiment study shows: compare with model group, can obviously reduce the writhing response number of times that acetic acid causes scorching mice, and can obviously improve the pain threshold (P＜0.05) of thermic pain mice; Can suppress the auricle edema of inflammation-causing substance induced mice and the pedal swelling of rat, reduce the quantity of leucocyte that causes in the scorching mice inflammatory exudate; Can suppress rat due to the uric acid sodium ankle swelling, reduce hypoxanthine and cause the serum uric acid level of hyperuricemia mice, and have and increase the trend that hyperuricemia mouse retention uric acid is discharged.Acute toxicity testing is the result show, observes 7 continuously after the administration, do not see the reaction of animal dead and overt toxicity.

In secular clinical practice, find, the preparation that adopts Chinese medicine composition of the present invention to make has definite curative effect for acute gouty arthritis, confirmed all that from clinical and zoopery aspect it has the effect of antiinflammatory, analgesia, the acute attack of antagonism gout, and toxicological study is not seen obvious toxic-side effects.

The mechanism of action of thing combined according to the invention and activity intensity thereof are expected to it is researched and developed into novel six kind new medicines of preventing and treating gouty arthritis.

The specific embodiment

Embodiment 1: the preparation of medicament composition granule agent

Prescription by table 1 takes by weighing crude drug.

In the table, the amount of getting of all material unit is kg.

Table 1

Prescription	??1	??2	??3	??4	??5	??6	??7	??8	??9
										Radix Saposhnikoviae	??12	??12	??9	??10	??14	??15	??9	??12	??15
Rhizoma Atractylodis	??8	??7	??6	??6	??7	??9	??9	??8	??6
										Radix Angelicae Sinensis	??14	??13	??12	??15	??12	??15	??14	??13	??12
Herba Artemisiae Scopariae	??23	??30	??15	??17	??21	??30	??16	??20	??18
										Radix Stephaniae Tetrandrae	??11	??10	??9	??11	??9	??12	??10	??9	??11
Rhizoma Et Radix Notopterygii	??8	??7	??6	??9	??6	??9	??8	??7	??9

Prescription	??1	??2	??3	??4	??5	??6	??7	??8	??9
										Rhizoma Polygoni Cuspidati	??23	??27	??15	??28	??20	??30	??21	??16	??18
Radix Angelicae Pubescentis	??8	??7	??6	??9	??7	??9	??8	??7	??6
										Polyporus	??14	??13	??12	??15	??13	??15	??13	??14	??12
Radix Glycyrrhizae	??11	??10	??9	??12	??9	??12	??10	??12	??11

Extract, concentrate: after checking each flavor prepared slices of Chinese crude drugs correctly by the prescription in the table 11, put into 1.0m ³In the multi-function extractor.Extract for the first time, add pure water and surpass three cun of powder, after boiling, 85 ℃ of insulation circulations were extracted 45 minutes, by infusion pump medicinal liquid were imported receiver, imported in the DN350 outer circulation single effect evaporator again and concentrated vacuum 0.02-0.04Mpa, vapour pressure 0.06-0.1Mpa.Extract for the second time, add pure water and surpass the powder one-inch, after boiling, 85 ℃ of insulation circulations were extracted 30 minutes.Medicinal liquid input receiver, import then in the outer circulation single effect evaporator and concentrate, be concentrated into relative density 1.20-1.23 (80 ℃ of heat are surveyed), wait to join.

System extractum: press recipe quantity in the medicinal liquid and add dextrin, antiseptic, mix thoroughly, dress is put into vacuum drying oven oven dry about 20 hours.Be dried to and beat powder, beat powder for degree.

Granulate: [prescription is formed] dry extract 730g

Dextrin 370g

95% alcoholic solution: 100ml

The about 1000g of the granule of making altogether

Fine-powdered extractum is added an amount of 95% ethanol, mixes thoroughly, put into oscillating granulator and granulate to certain humidity, put into circulation air draft baking oven be dried to moisture below 5%, granulate.Packing, labeling.

Other prescriptions are also adopted use the same method preparation extractum and granule.

Embodiment 2: granule causes the influence of rat pedal swelling to uric acid sodium

1. tried thing: granule: the granule of embodiment 1 prescription 1 preparation, the positive control medicine is a colchicine, Xishuangbanna pharmaceutical factory produces, 0.5mg/ sheet, lot number 020814.

2. laboratory animal: the SD rat, all available from Hunan College of Traditional Chinese Medicine's Experimental Animal Center, the animal quality certification number: moving word 20-002 number (rat) of Hunan doctor.

3. instrument and equipment: slide gauge, Wuhan Educational Instrument Factory produces.

4. experimental technique: get 50 of body weight 200～250g male SD rats, every group 10, be divided at random: 1. distilled water group, 2. groups of grains, 3. groups of grains, 4. groups of grains, 5. totally six groups of the 0.5mg/kg colchicine groups of 6.4g/kg embodiment 1 of 3.2g/kg embodiment 1 of 1.6g/kg embodiment 1.Every Mus gastric infusion every day 20ml/kg, the distilled water group is given isopyknic distilled water, every day 1 time, continuous 7 days.Measured the right back sufficient sufficient sole of the foot thickness of every Mus on the 7th day earlier, after the administration 1 hour, in the right back whole plantar subcutaneous injection uric acid sodium of rat (100mg/ml) suspension 0.1ml/ only, and measure the right back whole sole of the foot thickness of rat when causing scorching back the 0.5th, 1,2,3,4,5,6,7,8h, calculate swelling degree of the paw, swelling rate, the result carries out the T check, and calculates the inhibitory rate of intumesce of administration group.

5. the above dosage of granule 1.6g/kg of experimental result: embodiment 1, uric acid sodium is caused the rat pedal swelling obvious inhibitory action.Compare with the distilled water group, cause scorching back 1h to 7h and can reduce swelling degree of the paw (p＜0.05～p＜0.01).

6. experiment conclusion: the granule of Chinese medicine composition preparation of the present invention causes the effect of having clear improvement of rat pedal swelling to uric acid sodium.

Embodiment 3: granule is to the influence of experimental hyperuricemia mice serum uric acid level

1. tried thing: granule: the granule of embodiment 1 prescription 1 preparation, the positive control medicine is an allopurinol tablet, Guangdong Bidi Pharmaceutical Co., Ltd produces, 100mg/ sheet, lot number 20030203.

2. laboratory animal: the NIH mice, available from Hunan College of Traditional Chinese Medicine's Experimental Animal Center, the animal quality certification number: moving word 20-001 number (mice) of Hunan doctor.

3. instrument and equipment: BECKMAN CX9ALX full automatic biochemical apparatus.

4. experimental technique: get 60 of NIH mices, male and female half and half, body weight 18～22g is divided into 6 groups at random: the granule group of distilled water group, hypoxanthine+distilled water group, hypoxanthine+2.31g/kg granule group, hypoxanthine+4.62g/kg granule group, hypoxanthine+9.24g/kg embodiment 1, hypoxanthine+39mg/kg allopurinol group.Every Mus oral administration every day 40ml/kg, continuous 4 days.After the last administration 1 hour, the equal Intraperitoneal injection of hypoxanthine 1g/kg of all the other each treated animals causes the mice hyperuricemia model except that the distilled water group, capacity normal saline such as distilled water group injection.Injected back 30 minutes, each treated animal is plucked eyeball and is got blood, and the centrifugal 15min of 3000RPM gets serum and surveys the hematuria acid number.

5. experimental result: the 9.24g/kg granule can obviously reduce experimental hyperuricemia mice serum uric acid level, with hypoxanthine+distilled water group significant difference (p＜0.05) is arranged relatively, sees Table 1:

Table 1 granule to the influence of experimental hyperuricemia mice serum uric acid level (x ± SD, μ mol/ml, n=10)

6. experiment conclusion: granule of the present invention has certain reduction blood uric acid effect.

Embodiment 4: granule is to the influence of experimental hyperuricemia mouse retention uric acid level

1. tried thing: granule: the granule of embodiment 1 prescription 1 preparation, the positive control medicine is an allopurinol tablet, Guangdong Bidi Pharmaceutical Co., Ltd produces, 100mg/ sheet, lot number 20030203.

2. laboratory animal: the NIH mice, available from Hunan College of Traditional Chinese Medicine's Experimental Animal Center, the animal quality certification number: moving word 20-001 number (mice) of Hunan doctor.

3. instrument and equipment: BECKMAN CX9ALX full automatic biochemical apparatus.

4. experimental technique: get 60 of NIH mices, male and female half and half, body weight 18～22g, be divided into 6 groups at random, be respectively distilled water group, hypoxanthine+distilled water group, hypoxanthine+2.31g/kg granule group, hypoxanthine+4.62g/kg granule group, hypoxanthine+9.24g/kg granule group, hypoxanthine+39mg/kg allopurinol group, every Mus oral administration every day 40ml/kg, continuous 4 days.After the last administration 1 hour, except that the distilled water group, the equal Intraperitoneal injection of hypoxanthine 1g/kg of all the other each treated animals causes the mice hyperuricemia model, capacity normal saline such as distilled water group injection.Each treated animal of injection back all gavages the 1ml distilled water, injects back 1 hour, and the urine that begins to collect each treated animal is measured the acid number of urinating.Data are handled by statistics, the results are shown in Table 6.

5. experimental result: the 9.24g/kg granule can obviously reduce experimental hyperuricemia mouse retention uric acid level, with hypoxanthine+distilled water group significant difference (p＜0.05) is arranged relatively.See Table 2:

Table 2 granule to the influence of experimental hyperuricemia mouse retention uric acid level (x ± SD, μ mol/ml, n=10)

6. experiment conclusion: granule has the effect of certain promotion urate excretion.

Embodiment 5: the granule xylol causes the influence of mice auricle swelling

1. tried thing: granule: the medicament composition granule agent of embodiment 1 prescription 1 preparation, the positive control medicine is an aspirin, Hunan Nan Guang pharmaceutcal corporation, Ltd, specification 500mg/ sheet, lot number 20010901.

2. laboratory animal: the NIH mice, available from Hunan College of Traditional Chinese Medicine's Experimental Animal Center, the animal quality certification number: moving word 20-001 number (mice) of Hunan doctor.

3. instrument and equipment: JD200-3 electronic balance, Longteng Electronic Weighing Instrument Co., Ltd., Shenyang.

4. experimental technique: get 50 of male mices, body weight 25～30g, be divided into 6 groups at random, be respectively distilled water group, 2.31g/kg granule group, 4.62g/kg granule group, 9.24g/kg granule group, 200mg/kg aspirin group, each organizes Mus gastric infusion 40ml/kg, once a day, continuous 5 days.Administration was after 30 minutes in the 5th day, ear is coated with 0.05ml/ caused by dimethylbenzene xylene inflammation in a mice left side, disconnected cervical vertebra is put to death mice after 30 minutes, cut two ears along the auricle baseline, strike bottom left, auris dextra disk with diameter 6mm card punch, on analytical balance, weigh, calculate every Mus ear swelling degree (swelling degree=left ear weight-auris dextra is heavy), data are carried out T check in groups, and calculate inhibitory rate of intumesce [inhibitory rate of intumesce=(distilled water group swelling degree meansigma methods-medicine group swelling degree meansigma methods)/distilled water group swelling degree meansigma methods].

5. experimental result: the above dosage xylol of granule 2.31g/kg causes mice auricle swelling obvious suppression effect (p＜0.05～p＜0.001), sees Table 3:

Table 3 granule xylol cause mice auricle swelling influence (x ± SD, n=10)

6. experiment conclusion: the granule xylol causes mice auricle swelling inhibitory action.

Embodiment 6: the granule on Carrageenan causes the influence of rat paw edema

1. tried thing: granule: the medicament composition granule agent of embodiment 1 prescription 1 preparation, the positive control medicine is an aspirin, Hunan Nan Guang pharmaceutcal corporation, Ltd, specification 500mg/ sheet, lot number 20010901.

2. laboratory animal: the SD rat, all available from Hunan College of Traditional Chinese Medicine's Experimental Animal Center, the animal quality certification number: moving word 20-002 number (rat) of Hunan doctor.

3. instrument and equipment: slide gauge, Wuhan Educational Instrument Factory produces.

4. experimental technique: get 50 of male rats, body weight 200～250g, every group 10 are divided at random: distilled water group, 1.6g/kg granule group, 3.2g/kg granule group, 6.4g/kg granule group, 100mg/kg aspirin group, every Mus gastric infusion every day 20ml/kg, the distilled water group is given isopyknic distilled water, every day 1 time, continuous 5 days.The 5th day earlier with the right back sufficient sufficient sole of the foot thickness of the every Mus of vernier caliper measurement, after the administration 30 minutes, only inject 1% carrageenin solution (sterile saline preparation) 0.1ml/ down in the right back sufficient plantar aponeurosis of rat, and measure the right back whole sole of the foot thickness of rat when causing scorching back the 0.5th, 1,2,3,4,5,6,7,8h, calculate the Mus pedal swelling rate of different periods of respectively organizing [swelling rate=(cause scorching metapedes sole of the foot thickness-cause scorching front foot sole of the foot thickness)/cause scorching front foot sole of the foot thickness], data are carried out T check in groups.

5. experimental result: the above dosage of granule 1.6g/kg, on Carrageenan causes the rat pedal swelling obvious inhibitory action.Compare with the distilled water group, 1.6g/kg, 3.2g/kg dosage 1h to 6h after causing inflammation can reduce swelling degree of the paw (p＜0.05～p＜0.01), and 6.4g/kg dosage 0.5h to 8h after causing inflammation all can reduce swelling degree of the paw (p＜0.05～p＜0.001).

6. experiment conclusion: the granule on Carrageenan causes the effect of having clear improvement of rat inflammation.

Embodiment 7: granule is to the swollen influence that generates of rat granuloma

1. tried the medicament composition granule agent of thing: embodiment 1 prescription 1 preparation, the positive control medicine is the prednisolone acetate injection, and the lake northing likes that hundred pharmaceutcal corporation, Ltds (former Hubei Pharmaceutic Works) produce, and specification 125mg/ props up, lot number 20020609

2. laboratory animal: the SD rat, all available from Hunan College of Traditional Chinese Medicine's Experimental Animal Center, the animal quality certification number: moving word 20-002 number (rat) of Hunan doctor.

3. instrument and equipment: ES-C600 electronics sky, instrument balance equipment factory in Hunan, Hunan produces.

4. experimental technique: get 50 of SD male rats, body weight 150～180g.Fixing with pentobarbital sodium 40mg/kg anesthesia back, in abdominal scissors one osculum, expand subcutaneous tissue with mosquito forceps, imbed a sterilization cotton balls (weight 50mg at the left and right groin of rat place, drip 1 of ampicillin injection 1mg/0.1ml before putting into), sew up, postoperative is divided into 5 groups at random with rat, every group 10, be respectively distilled water group, 1.6g/kg granule group, 3.2g/kg granule group, 6.4g/kg granule group, 9mg/kg prednisolone acetate group, and intramuscular injection PNC (1,600,000 u/100ml) 0.4ml/ only, and continuous 2 days in case infect.Preceding 4 groups of equal gastric infusion 20ml/kg, prednisolone acetate group intramuscular injection 9mg/kg, every day 1 time, continuous 7 days.Administration after weighing in the 7th day, and after administration, the disconnected cervical vertebra of rat put to death in 1 hour, take out the granulation cotton balls, shell clean fatty tissue, in 60 ℃ of baking boxs, weigh after dry 12 hours, calculate every 100g body weight granulation tissue weight [every 100g body weight granulation tissue weight=(granulation cotton balls dry weight-cotton balls weight)/body weight * 100], data are carried out statistical procedures

5. experimental result: the above dosage of granule 1.6g/kg, promptly swollen generation of rat granuloma there is very obvious suppression effect, with distilled water group ratio significant differences (p＜0.01～p＜0.001) is arranged, see Table 4:

Table 4 granule to the swollen influence that generates of rat granuloma (x ± SD, n=10)

6. experiment conclusion: granule has very obvious suppression effect to swollen generation of rat granuloma.

Embodiment 8: granule causes the influence (hot plate method) of pain mice to thermal source

1. tried the medicament composition granule agent of thing: embodiment 1 prescription 1 preparation, the positive control medicine is a pethidine hydrochloride, Shenyang No. 1 Pharmaceutical Factory, and specification 100mg/ props up, lot number 021109-2.

2. laboratory animal: the NIH mice, available from Hunan College of Traditional Chinese Medicine's Experimental Animal Center, the animal quality certification number: moving word 20-001 number (mice) of Hunan doctor.

3. instrument and equipment: mechanical stopwatch, diamond plate MC, stopwatch factory in Shanghai produces.

4. experimental technique: get body weight 18～22g NIH female mice, screen 50 of mices that lick metapedes in 30 seconds, be divided into 5 groups at random by pain threshold, be distilled water group, 2.31g/kg granule group, 4.62g/kg granule group, 9.24g/kg granule group, 20mg/kg pethidine hydrochloride group, 10 every group.Mice placed on 55 ± 0.5 ℃ the constant temperature hot plate, measures pain threshold before the administration (beginning to the time of licking for the first time till the metapedes) twice from the contact hot plate, with meansigma methods as administration before pain threshold.Every Mus administration 20ml/kg, the 30th minute, the 45th minute, the 60th minute, the 90th minute, the 120th minute, the 150th minute, the 240th minute measurement mice pain threshold (person takes out not lick the metapedes in 60 seconds in measuring behind the medicine, and calculated by 60 seconds the threshold of pain) after administration.Data are carried out t check in groups.

5. experimental result: the above dosage of granule 2.31g/kg can obviously prolong the mice pain threshold, increases the threshold of pain and improves percentage rate, with the distilled water group significant difference (P＜0.05～P＜0.001) is arranged relatively.

6. experiment conclusion: granule has certain analgesic activity to thermal source induced mice pain.

Embodiment 9: granule causes the influence (writhing method) of pain mice to glacial acetic acid

1. tried the medicament composition granule agent of thing: embodiment 1 prescription 1 preparation, the positive control medicine is an aspirin, Hunan Nan Guang pharmaceutcal corporation, Ltd, specification 500mg/ sheet, lot number 20010901.

2. laboratory animal: the NIH mice, available from Hunan College of Traditional Chinese Medicine's Experimental Animal Center, the animal quality certification number: moving word 20-001 number (mice) of Hunan doctor.

3. instrument and equipment: mechanical stopwatch, diamond plate MC, stopwatch factory in Shanghai produces.

4. experimental technique: get 50 of body weight 18～22gNIH mices, male and female half and half, be divided into 5 groups at random, be respectively: distilled water group, 2.31g/kg granule group, 4.62g/kg granule group, 9.24g/kg granule group, 200mg/kg aspirin group, each organizes Mus administration 20ml/kg respectively.Administration is the equal lumbar injection 0.6% glacial acetic acid 0.1ml/10g of each Mus after 30 minutes, turns round the body number of times in incubation period and 30 minutes that the reaction of observation mouse writhing takes place, and data are carried out t check in groups.

5. experimental result: the result shows that the 9.24g/kg granule can obviously prolong the incubation period that glacial acetic acid causes the reaction of pain mouse writhing, all can reduce the number of times of turning round body in 30 minutes more than the granule 4.62g/kg.Compare with the distilled water group, have significant difference (p＜0.05～p＜0.01), see Table 5:

Table 5 granule to glacial acetic acid cause the pain mice influence (x ± SD, n=10)

6. experiment conclusion: granule has certain analgesic activity to glacial acetic acid induced mice pain.

Embodiment 10: the granule animal acute toxicity test

1. tried the medicament composition granule agent of thing: embodiment 1 prescription 1 preparation.

2. laboratory animal: white mice, body weight 18～22g, male and female half and half are provided by Hunan College of Traditional Chinese Medicine's Experimental Animal Center, and the animal quality certification number is: moving word 20-001 number of Hunan doctor.Animal places cleaning level air conditioning labor to raise 20～25 ℃ of room temperatures, relative humidity 55～70%.

3. experimental technique: through prerun, the oral LD that can not ask ₅₀So, measure its maximum tolerated dose (MTD).Get 40 of NIH mices, male and female half and half, body weight 18～22g, after conforming, be divided into 2 groups at random, 20 every group, water is can't help in fasting 12 hours, and the administration group is pressed the granule extractum liquid that the 0.4ml/10g body weight is irritated stomach 70%, matched group is irritated the isopyknic distilled water of stomach, the same day 2 times, 8 hours at interval, the conventional raising after the administration, observed 7 days continuously, record dead mouse, diet, activity, hair and two be situation just.

4. experimental result: irritate stomach visible medicine sample feces after 8 hours, movable normal.Observe continuously in one week, animal behavior activity, diet, drinking-water are normal, hair color light, eye, mouth, nose, vagina, the no abnormal secretions of anus, none death.Medicine group body weight gain is compared there was no significant difference (P＞0.05) with matched group, put to death animal and dissection on the 8th day, organs and tissues such as the perusal heart, liver, spleen, lung, kidney, uterus, and two treated animals there is no obvious pathological changes.Mice dosis tolerata on the 1st is 56g extractum/kg, is equivalent to 224 times of 70kg adult per kilogram of body weight 1 consumption per day 0.25g extractum/kg.

5. experiment conclusion: this result of the test shows, the MTD of mice oral granular formulation is that (386.4g crude drug/kg) is equivalent to a 70kg clinical consumption per day 0.25g extractum/kg (224 times of 1.73g crude drug/kg) of being grown up to 56g extractum/kg.All are normal for animal, none death, and the prompting granule does not have tangible acute toxic reaction, disposable administration basic security in the clinical dosage scope of recommending.

Embodiment 11: the granule long-term toxicity test for animals

1. tried the medicament composition granule agent of thing: embodiment 1 prescription 1 preparation.

2. laboratory animal: the SD rat, body weight 50～90g, male and female half and half are provided by Hunan College of Traditional Chinese Medicine's Experimental Animal Center, and the animal quality certification number is: moving word 20-002 number of Hunan doctor.Animal places cleaning level air conditioning labor to raise 20～25 ℃ of room temperatures, relative humidity 55～70%.

3. instrument and equipment: BECKMAN CX9ALX full automatic biochemical apparatus, KX-21 cellanalyzer.

4. experimental technique: get 96 of SD rats, body weight 50～90g, male and female half and half, be divided into 4 groups at random: blank group (distilled water), 3.5g/kg granule group (low dosage, 13.78 times of clinical equivalent amount), 7.0g/kg granule group (middle dosage, 27.56 times of clinical equivalent amount), 14.0g/kg granule group (high dose, clinical equivalent amount 55.12 times).Each organizes rat gastric infusion every day once, and volume is 20ml/kg, successive administration 3 months.The outward appearance sign of observed and recorded animal, behavioral activity, feces character etc. during the administration, the record food ration is weighed weekly once and is adjusted dosage.After the last administration, each organizes 10 animals of random process, and 2 all post processings are observed in the drug withdrawal of residue animal, and method is with first.Observe general signs (behavioral activity, hair color, the feces character, mucosa place secretions, food ration, body weight change), (erythrocyte is measured in blood sampling to blood cell analysis, leukocyte, leukocyte differential count, hemoglobin, platelet, clotting time), blood biochemical is learned check and (is got the determination of serum alanine aminotransferase, the amino acid conversion of Radix Asparagi enzyme, creatinine, blood urea nitrogen, total bilirubin, bilirubin direct, alkali phosphatase, glucose, T-CHOL, triglyceride, total protein, blood parameters such as albumin), system becomes celestial and histopathologic examination (cores, liver, spleen, lung, kidney, the uterus, ovary, testis, the adrenal gland, the thymus perusal is also weighed, and calculates organ coefficient; Except that thymus, above-mentioned organ is carried out histopathology observe).

5. experimental result: overview index: the gastric infusion granule is 3 months continuously, drug withdrawal recovers to observe 15 days, rat outward appearance sign, behavioral activity, feces character are all normal, and food ration and each dosage group body weight gain and blank group be no significant difference (p＞0.05) relatively.Hematological indices detects: administration phase and convalescent period, each dosage group rat was compared with the blank group, and every index of surveying does not have significant difference.Administration phase and convalescent period, each dosage group rat was compared with the blank group, every index of surveying there are no significant difference (p＞0.05).Organ coefficient: administration is measured its organ coefficient to two batches of animals of putting to death after 30 days and after 2 weeks of drug withdrawal, and the administration group is compared there was no significant difference (p＞0.05) with matched group.Histopathologic examination: the administration phase and convalescent period the rat when dissected through perusal, each internal organs there is no unusual or pathological changes, tissue such as the rat heart, liver, spleen, lung, kidney, testis, uterus, ovary, adrenal gland, stomach, small intestinal is through check pathological section, it is clear that the cardiac muscle cross striation of rat is respectively organized in matched group and experiment as a result, sarcoplasm is abundant, and the karyon chromatin is careful; Matter is normal between hepatocyte, lobules of liver, liver; Splenic white pulp, red pulp structure are normal; Bronchus, alveolar, interstitial lung are normal; Glomerule is evenly distributed, and the hair and blood pipe is clear, capsular space and renal tubules chamber inanition, and size is normal, and renal cells is normal; Each Qu Jingguan that organizes rat is full, and spermatogenic epithelium thickness and level are normal, and a matter is normal; Endometrium, flesh layer, placenta percreta are normal; Ovary follicles at different levels are normal; Adrenal cortex and medullary substance are normal; Stomach and mucous membrane of small intestine, tela submucosa, flesh layer, placenta percreta are all normal.

6. experiment conclusion: granule 3.5g/kg, 7.0g/kg, three dosage of 14g/kg recover two weeks to rat oral gavage administration three months and drug withdrawal continuously, observe the general situation of visible rat, outward appearance sign, hematology and blood parameters, main organs coefficient etc. all with matched group no significant difference (p＞0.05); Perusal and tectology are observed its heart, liver, spleen, lung, kidney, testis, uterus, ovary, adrenal gland, thymus, brain, stomach, small intestinal does not all have obvious pathological change.Prompting granule long-term prescription does not have obviously chronic and tardy property toxic reaction, and it is safe taking for a long time by adult's clinical medicine dose of present recommendation.

Claims (7)

1. Chinese medicine composition of preventing and treating gouty arthritis, this Chinese medicine composition contains the crude drug component of following weight portion:

Radix Saposhnikoviae 9～15

Rhizoma Atractylodis 6～9

Radix Angelicae Sinensis 12～15

Herba Artemisiae Scopariae 15～30

Radix Stephaniae Tetrandrae 9～12

Rhizoma Et Radix Notopterygii 6～9

Rhizoma Polygoni Cuspidati 15～30

Radix Angelicae Pubescentis 6～9

Polyporus 12～15

Radix Glycyrrhizae 9～12.

2. Chinese medicine composition is prevented and treated purposes in the medicine of gouty arthritis in preparation according to claim 1.

3. Chinese medicine extract is for being that the raw material effective component extracting makes with the described Chinese medicine composition of claim 1.

4. prevent and treat purposes in the medicine of gouty arthritis as Chinese medicine extract as described in the claim 3 in preparation.

5. a Chinese medicine preparation comprises the described Chinese medicine extract of the claim 3 for the treatment of effective dose and one or more acceptable accessories.

6. as Chinese medicine preparation as described in the claim 5, it is characterized in that described Chinese medicine preparation is an oral formulations.

7. as Chinese medicine preparation as described in the claim 6, it is characterized in that described oral formulations is granule, pill, tablet, capsule, syrup or spray.