CN1836685A - Use of catechu in preparing drug for treating hyperuricemia - Google Patents

Abstract

The present invention provides new use of catechu in preparing medicine for treating hyperuricemia, medicine composition containing catechu and its preparation process and use. The medicine of the present invention can lower uric acid content in blood and treat gouty arthritis and has less bad reaction and high safety.

Description

The purposes of catechu in the medicine of preparation treatment hyperuricemia

Technical field

The present invention relates to a kind of new purposes of medicine, particularly, is the purposes of catechu in the medicine of preparation treatment hyperuricemia, belongs to drug world.

Background technology

Hyperuricemia is because of the purine metabolism obstacle, uricopoiesis increases and/or urate excretion reduces, and make blood uric acid concentration surpass the normal value upper limit, normal person's blood uric acid concentration (serum, the uric acid enzyme process) fluctuation is in narrower scope, the male is 0.15-0.38mmol/L (2.4-6.4mg/dl), and Women was 0.1-0.3mmol/L (1.6-5.2mg/dl) in the past.Its value is near the male behind the Women.Epidemiological study prompting, blood uric acid are hyperuricemia when surpassing 0.42mmol/L (7.0mg/dl).Gout is because long-term purine metabolism obstacle, uricopoiesis increase and or the kidney releasing uric acid reduce uric acid sodium micro-crystallization deposition and the inflammatory reaction that causes.In recent years along with the improving constantly of China's living standards of the people, high purine, high protein, high-fat a large amount of absorptions, the sickness rate of hyperuricemia and gout increases sharply.Treatment to hyperuricemia at present mainly contains to suppress two big class Western medicine of uricopoiesis and promotion urate excretion.And the treatment of gout is except that the same with hyperuricemia, select for use and suppress outside uricopoiesis and the promotion urate excretion two big class medicines, gouty arthritis occurs during also according to the gout acute attack and select for use, as colchicine (colchicine), NSAID (non-steroidal anti-inflammatory drug) (NSAIDs) and adrenocortical hormone and thyroliberin (ACTH) class medicine at the gouty arthritis medicine.Promote urate excretion often to select probenecid clinically for use with the Western medicine that reduces blood uric acid; The Western medicine that suppresses uricopoiesis then is the representative medicine with the allopurinol.Colchicine is the specific drug of treatment acute gouty arthritis, this medicine uses with a long history, it is best to take curative effect in the 24h of gout acute attack, this medicine is a mitotic inhibitor, can combine with tubulin and form dimer, stop the formation of mitosis spindle, it is synthetic to suppress simultaneously tubulin, influencing born of the same parents' inner cell organ moves and substance transportation, the release of superization of the prevention factor and the distortion of cell and mobile, thereby the neutrophilic granulocyte that suppresses local organization, mononuclear cell discharges leukotriene B4, the glycoprotein chemokine, interleukin-1 inflammatory factors such as (IL-1), the distortion of inflammation-inhibiting cell and chemotactic are alleviated or the termination inflammatory reaction.But the effective dose of colchicine and toxic dose are very approaching, bigger untoward reaction is arranged, back 80% patient that takes medicine can have nausea and vomiting, diarrhoea stomachache, anorexia etc. before clinical symptoms is alleviated fully, and this medicine also can cause bone marrow depression performances such as leukopenia, thrombocytopenia and alopecia, hepatic and renal function injure, spirit depressing etc., serious adverse reactions such as ascending paralysis can appear in individual patient, respiration inhibition and cause death.Plain hormone of adrenal gland's skin or thyroliberin (ACTH) can suppress non-infectious inflammation, alleviate congestion and edema, and the inflammation-inhibiting cell moves to inflammation part, stops reactions such as inflammatory mediator such as kassinin kinin class, histamine, slow reacting substance; Suppress cytophagous phagocytic function, stablize lysosome membrane, stop complement to participate in inflammatory reaction; Also can influence immunoreactive too many levels and play immunosuppressive action; Reduce reticuloendothelial system and eliminate granule or cytosis; Can make lymphocytolysis; Reduce the autoimmune antibody level, to control inflammation alleviating pain.But such medical instrument has the untoward reaction of general cortex hormone, thereby only is used for acute gout and shows effect very seriously repeatedly, uses other drug to fail to respond to any medical treatment or can not anti-receptor, and occurs symptom " knock-on " phenomenon easily.(Nonsteroid anti-infiammatorydrugs, dominant mechanism NSAIDs) is arachidonic acid (arachidonic acid, AA) metabolic influence NSAID (non-steroidal anti-inflammatory drug).Can discharge AA during gouty arthritis urate crystal irritation cell film, produce a large amount of metabolites---prostaglandin through the Cycloxygenase effect, wherein PGE2 and PGE1 have stronger blood vessel dilating, reduce the antiotasis effect; Can improve vascular permeability, strengthen the edema that Kallidin I and histamine cause; Stimulate leukocytic chemotaxis; Anticoagulant; Stimulate T cell generation osteoclasosteoclast activating factor and stimulate bone resorption.Produce superoxide ion, hydroxy radical, epoxy free radical and hydrogen peroxide etc. simultaneously at the generation prostaglandin, cause tissue injury.In addition, AA is under the effect of lipoxidase, and neutrophil cell produces LTB4; Mononuclear cell and macrophage produce LTB4 and LTC4; Basophilic granulocyte, eosinophilic granulocyte and some mastocyte mainly produce leukotriene sulfuration polypeptide, and these materials all are very strong pro-inflammatory cytokines.Simultaneously, in the lipoxidase metabolic process, produce many hydrogen peroxide fatty acids, Cycloxygenase is had very strong stimulation and influences the metabolism of Cycloxygenase approach, strengthen the generation of inflammation.NSAIDs not only can suppress Cycloxygenase-1 (cycloxygenase-1, COX-1), (cycloxygenase-2 COX-2), but also can reduce the metabolic effect of lipoxidase, thereby reach its antiinflammatory action Cycloxygenase-2.But mostly NSAIDs is because of easily bringing out perforated ulcer and stronger gastric irritation, and can cause water, sodium retention and water breakthrough swells, hypertension, particularly can cause lethal aplastic anemia and agranulocytosis and to the obstacle of hepatic and renal function, as Phenylbutazone etc.Though excretory medicine third sulfanilamide of uricosuric can promote renal tubules excretion uric acid, to alleviate hyperuricemia, this product also has the side effect of general sulfa drugs.Though and xanthine inhibitor allopurinol can reduce the generation of uric acid in the body and synthetic,, the marrow function of inhibition is arranged and bigger gastrointestinal reaction is arranged and side effect such as anaphylaxis drug eruption to alleviate hyperuricemia.Because there is above untoward reaction in the Western medicine of treatment gout, if take in a large number or for a long time, very easily human body is caused comparatively serious toxic and side effects, and makes its clinical practice be subjected to bigger restriction.

The Chinese medicine catechu is the peeling branch of leguminous plant catechu Acacia catechu (L.f.) Willd., the dry soft extracts of bar.Gather winter branch, bar are removed crust, are chopped to bulk, decoct with water, and concentrate drying.Function with cure mainly: the removing dampness promoting tissue regeneration and ulcer healing.Be used for ulcer being unable to heal, eczema, aphtha, traumatic pain, traumatic hemorrhage.Still the relevant report of not having at present catechu treatment hyperuricemia and gout.

Summary of the invention

Technical scheme of the present invention has provided a kind of new purposes of medicine.The present invention also provides and has contained the medical composition and its use that catechu is an active component.

The invention provides the purposes of catechu in the medicine of preparation treatment hyperuricemia.

Wherein, described catechu derives from: the peeling branch of leguminous plant catechu Acacia catechu (L.f.) Willd., the dry soft extracts of bar.

Wherein, described catechu is catechu water extract, catechu alcohol extract.Wherein, described catechu alcohol extract is 95% catechu ethanol extraction.

The present invention also provides a kind of pharmaceutical composition for the treatment of hyperuricemia, and it is to be active component or raw material by the catechu that contains effective dose, adds the medicament that acceptable accessories or complementary composition are prepared from.

Wherein, also contain Cortex Phellodendri, Radix Gentianae Macrophyllae, Olibanum, Fructus Chebulae in the described raw material, its weight proportion is:

0.5～1.5 part in catechu, 2.0～3.0 parts of Radix Gentianae Macrophyllae, 0.5～1.5 part of Olibanum, 0.5～1.5 part of Fructus Chebulae, 0.5～1.5 part of Cortex Phellodendri.

Further, also contain Cortex Fraxini in the described raw material, its weight proportion is:

0.5～1.5 part in catechu, 2.0～3.0 parts of Radix Gentianae Macrophyllae, 0.5～1.5 part of Olibanum, 0.5～1.5 part of Fructus Chebulae, 0.5～1.5 part of Cortex Phellodendri, 2.5～3.5 parts of Cortex Fraxinis.

Pharmaceutical composition of the present invention, it is the medicament that is prepared from by the following weight proportion raw material:

0.5～1.5 part in catechu, 2.0～3.0 parts of Radix Gentianae Macrophyllae, 0.5～1.5 part of Olibanum, 0.5～1.5 part of Fructus Chebulae, 0.5～1.5 part of Cortex Phellodendri, 2.5～3.5 parts of Cortex Fraxinis.

Further, it is the medicament that is prepared from by the following weight proportion raw material:

1 part in catechu, 2.5 parts of Radix Gentianae Macrophyllae, 1 part of Olibanum, 3 parts of Cortex Fraxinis, 1 part of Fructus Chebulae, 1 part of Cortex Phellodendri.

Wherein, described medicament is oral formulations, injection.

The present invention also provides the purposes of this pharmaceutical composition in the medicine of preparation treatment gout.

The present invention contains in the feedstock composition of catechu, and the Six-element material combination under Chinese medical theory instructs, is selected scientific and reasonable.The catechu promoting blood circulation and stopping pain, and the good blood uric acid effect of falling is arranged, can suppress the activity of xanthine oxidase, thereby reduce the generation of uric acid.Sufficient knee joint red and swollen heat pain due to Cortex Phellodendri heat clearing and damp drying, the eliminating fire and detoxication in the side, outstanding Changzhi damp-heat in lower-JIAO is a little less than the lower limb flaccidity.Modern pharmacological research finds that Cortex Phellodendri has certain antiinflammatory action, and its antiinflammatory action can be alleviated the joint congestion and swelling pain of gout outbreak.Radix Gentianae Macrophyllae wind-damp dispelling, removing damp-heat, relaxing muscles and tendons and activating QI and blood in the collateral, removing obstruction in the collateral to relieve pain in the side also are the medicine commonly used of the damp and hot arthromyodynia of Chinese traditional treatment.Modern pharmacological research also finds that Radix Gentianae Macrophyllae has antiinflammatory, analgesia, diuresis.The contained gentianin of Radix Gentianae Macrophyllae can pass through nervous system, excited hypophysis-adrenal system and bring into play its antiinflammatory action; The alcohol leaching liquid of Radix Gentianae Macrophyllae swells to the rat foot also inhibitory action; Gentianin all has certain analgesic activity to rat and mice.The Radix Gentianae Macrophyllae water decoction has diuresis, can promote urate excretion, to alleviate hyperuricemia and to alleviate muscular soreness arthroncus due to the gout.Cortex Fraxini wind-damp dispelling, removing damp-heat, sharp joint in the side.Modern pharmacological research finds that Cortex Fraxini has the effect of good antiinflammatory, diuresis, reduction blood uric acid.Contained first element, second element all have tangible antiinflammatory action, aseculin can significantly suppress Pelvetia siliquosa Tseng et C. F. Chang colloidality, dextran, 5-HT and the histamine's property claw edema of rat, also can suppress the intoxicated property of first swelling of the feet, and can obviously suppress big pure and fresh granulation tissue hyperplasia due to the cotton balls; Aesculetin also has obvious inhibitory action to rat Ovum Gallus domesticus album and dextrorotation candy acid anhydride claw edema; Fraxin also can significantly suppress also can significantly suppress rat claw edema due to antler glue, dextran, histamine, the formaldehyde etc., and its antiinflammatory action may be can excited adrenal cortex function relevant with it.Contained fraxin can promote rabbit and rheumatisant's urate excretion; The multiple route of administration of aseculin also all can promote rat and rabbit urate excretion, and the mechanism that promotes urate excretion and exciting sympathetic nerves system, inhibition kidney are relevant to the heavily absorption of uric acid etc.Olibanum promoting blood circulation, removing blood stasis and relieving pain in the side, Compendium of Material Medica are called it can " muscle be stretched in the analgesic therapy of invigorating blood circulation ", and Olibanum is used it for the treatment of rheumatic arthritis in India's Ayurveda medical science.Modern pharmacological research finds that this medicine has antiinflammatory, analgesia, microcirculation improvement and hemorheology effect preferably.Experiment shows that the square medicine that with the Olibanum is the principal agent composition has the obvious suppression effect to the Ovum Gallus domesticus album rat paw edema; And can increase the phagocytic function of Turnover of Mouse Peritoneal Macrophages.Contained boswellic acid compounds has antiinflammatory, arthritis and anticomplementary activity.It stimulates production of antibodies similar with the steroidal anti-inflammatory drug effect.Olibanum analgesic effective ingredient is the acetic acid n-octyl; To mouse peritoneal injection glacial acetic acid, can obviously reduce the writhing response number of times of mice.Prescription so that Olibanum is formed can improve patient's nail fold microcirculation and erythrocyte aggregation shape clinically, can significantly reduce high blood viscosity and blood plasma viscosity; And can discharge β platelet microglobulin, regulate thromboxane β ₂With prostatitis element (TXB ₂And PGI) balance.The Fructus Chebulae is regarded as " the good merchantable brand king of medicine " in the side in Tibetan medicine and pharmacology, and is all effective in cure to all diseases.The treatment arthralgia has that multiselect uses as principal agent with the Fructus Chebulae in the efficacious prescriptions medicine in many Tibetan medicine and pharmacology, as the side's of Tibetan nine roc balls, ten distinguish the flavor of male roc ball, five roc balls, four colors, five roc balls etc.

At present Chinese medicine is to the treatment of gout, often the acute attack stage of gout is divided into damp-heat accumulation, heat in blood pyretic toxicity, stagnant heat retardance and cold-dampness numbness, strongly fragrant and heat-transformation type clinically.Six medicines share in the pharmaceutical composition of the present invention, can play removing damp-heat, eliminating fire and detoxication altogether, dampness removing is let out turbid, blood circulation promoting and blood stasis dispelling, the effect of removing obstruction in the collateral to relieve pain, thus anxious ashamed stage of attack, variously all there is a certain curative effect, to the catabasis at intermittence of hyperuricemia and gout, also can let out turbid detoxifcation, to alleviate the too much disease of its uric acid by dampness removing.

Catechu and the pharmaceutical composition that contains the raw material catechu reduce blood uric acid, one of mechanism of action that it falls blood uric acid is to reduce the activity of xanthine oxidase, gouty joint property to the gout acute attack has antiinflammatory, analgesic activity, has untoward reaction minimum, zoopery LD ₅₀Do not come out, provide a kind of safe, effective, stable, controlled medicine for clinical.

Obviously, according to foregoing of the present invention,,, can also make modification, replacement or the change of other various ways not breaking away under the above-mentioned basic fundamental thought of the present invention prerequisite according to the ordinary skill knowledge and the customary means of this area.

The specific embodiment of form is described in further detail foregoing of the present invention again by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following example.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.

Description of drawings

Respectively organize the influence of medicine behind the full side of Fig. 1 pharmaceutical composition of the present invention and the side of tearing open to antihyperuricemic disease mouse model serum uric acid level

The specific embodiment

The preparation of embodiment 1 Catechu extract of the present invention

The preparation of catechu water extract: get the 500g catechu, add ten times of water gagings and decoct 2 times, each 1 hour, merge behind twice medical filtration, be evaporated to every ml medicinal liquid with rotary evaporator and contain crude drug 1g.

The preparation of catechu ethanol extract: get the 500g catechu, add ten times of amount 95% ethanol, reflux, extract, 2 times, each 1 hour, merge behind twice medical filtration, be evaporated to every ml medicinal liquid with rotary evaporator and contain crude drug 1g.

The preparation of drug combination that contains catechu in embodiment 2 raw materials of the present invention

Water extract preparation: get catechu, Fructus Chebulae, Olibanum, each 80g of Cortex Phellodendri four medicines, Radix Gentianae Macrophyllae 200g, Cortex Fraxini 240g and add ten times of water gagings and decoct 2 times, each 1 hour, merge behind twice medical filtration, be evaporated to every ml medicinal liquid with rotary evaporator and contain crude drug 1g.

Ethanol extract preparation: get catechu, Fructus Chebulae, Olibanum, each 80g of Cortex Phellodendri four medicines, ten times of amounts of Radix Gentianae Macrophyllae 200g, Cortex Fraxini 240g adding, 95% ethanol, reflux, extract, 2 times, each 1 hour, merge behind twice medical filtration, be evaporated to every ml medicinal liquid with rotary evaporator and contain crude drug 1g.

The preparation of drug combination that contains catechu in embodiment 3 raw materials of the present invention

Get catechu 80g, Fructus Chebulae 27g, Olibanum 27g, Cortex Phellodendri 27g, Radix Gentianae Macrophyllae 107g, Cortex Fraxini 133g, press the preparation of embodiment 2 described water extractions or alcohol extracting method, add starch, dextrin, granulation, granulate, packing promptly gets granule.

The preparation of drug combination that contains catechu in embodiment 4 raw materials of the present invention

Catechu 80g, Fructus Chebulae 40g, Olibanum 40g, Cortex Phellodendri 40g, Radix Gentianae Macrophyllae 100g, Cortex Fraxini 120g press the preparation of embodiment 2 described water extractions or alcohol extracting method, add capsule adjuvant commonly used and are prepared into capsule.

Embodiment 5 raw materials of the present invention contain the preparation of drug combination of catechu

Catechu 40g, Fructus Chebulae 80g, Olibanum 80g, Cortex Phellodendri 80g, Radix Gentianae Macrophyllae 200g, Cortex Fraxini 240g press the preparation of embodiment 2 described water extractions or alcohol extracting method, add tablet adjuvant commonly used and are prepared into tablet.

Embodiment 6 preparation of drug combination of the present invention

Fructus Chebulae, Olibanum, each 80g of Cortex Phellodendri four medicines, Radix Gentianae Macrophyllae 200g press the preparation of embodiment 2 described water extractions or alcohol extracting method, add tablet adjuvant commonly used and are prepared into tablet.

Embodiment 7 preparation of drug combination of the present invention

Fructus Chebulae 27g, Olibanum 27g, Cortex Phellodendri 27g, Radix Gentianae Macrophyllae 107g press the preparation of embodiment 2 described water extractions or alcohol extracting method, add capsule adjuvant commonly used and are prepared into capsule.

Below prove beneficial effect of the present invention by pharmacodynamics test.

Test example 1 catechu is to the influence experiment of hyperuricemia animal model

1, experiment material:

1.1 animal: Kunming mouse, 22-25g,, provide the animal quality certification number by Chengdu University of Traditional Chinese Medicine Animal Experimental Study center: No. 6, the real moving Guan Zhidi in river.

1.2 experimental drug: experimental drug is the water extract (0.4g/ml) and the alcohol extract (0.4g/ml) of catechu.Treatment hyperuricemia positive drug allopurinol, excellent magnificent pharmaceutcal corporation, Ltd produces lot number U10166 by Beijing.

1.3 experiment reagent: hypoxanthine, SIGMA company produces, lot number 101K0022; Uricase inhibitor, Aldrich company produces, lot number 03510D0-483; The uric acid reagent box, Nanjing is built up bio-engineering research and is produced, lot number 20040923; Xanthine oxidase, Nanjing is built up bio-engineering research and is produced, lot number 20040923.

1.4 instrument: mice weighing balance DT5009 (0.1g/500g), weighing apparatus factory in Changshu City's produces.The 7560MC ultraviolet spectrophotometer, Shanghai Precision Scientific Apparatus Co., Ltd produces.80-2B low speed desk centrifuge, Anting Scientific Instrument Factory, Shanghai produces.

2. observation index:

2.1 influence to hyperuricemia mouse model (uricase inhibitor method)

Get Kunming mouse.Male and female half and half.Be divided into 9 groups at random.By group administration 5 days, once a day.After the last administration 1 hour, except that the blank group, all the other each treated animal lumbar injection oxonic acid potassium salt 300mg/kg cause the mice hyperuricemia.Behind the 1h of injection back, each treated animal is plucked eyeball and is got blood, and the centrifugal 5min of 2500r/min gets serum and surveys the hematuria acid number.Carry out group difference relatively.The result is as follows:

Table 1 catechu is to the influence of hyperuricemia mice (uricase inhibitor method) blood uric acid (X ± S)

Group	Dosage (g/kg)	The example number	Hematuria acid number (mg/L)
				It is low that the low alcohol of water extraction improves in the alcohol extracting alcohol extracting in the high water extraction of the positive water extraction of blank model	- - 0.02 1.2 0.6 0.3 1.2 0.6 0.3	12 12 12 12 12 12 12 12 12	14.86±3.43 27.32±8.53△ 14.70±6.54** 11.23±4.04** 10.38±6.86** 10.06±2.29** 15.55±4.90** 16.26±3.48** 13.00±3.25**

Notes: △ compares P＜0.01 * * with blank group and model group compares P＜0.01

2.2 influence to hyperuricemia mouse model (hypoxanthine method)

Get Kunming mouse, male and female half and half.Be divided into 9 groups at random.By group administration 5 days, once a day.After the last administration 1 hour, except that the blank group, all the other each treated animal Intraperitoneal injection of hypoxanthine 1g/kg cause the mice hyperuricemia.Behind the 1h of injection back, each treated animal is plucked eyeball and is got blood, and the centrifugal 15min of 2500r/min gets the activity that serum is surveyed hematuria acid number and xanthine oxidase.Carry out group difference relatively.The result is as follows:

Table 2 catechu is to the influence of hyperuricemia mice (hypoxanthine method) blood uric acid (X ± S)

Group	Dosage (g/kg)	The example number	Hematuria acid number (mg/L)
				Dosage group alcohol extracting low dose group in the alcohol extracting of dosage group water extraction low dose group alcohol extracting high dose group in the positive group of the blank group model group water extraction high dose group water extraction	- - 0.02 1.2 0.6 0.3 1.2 0.6 0.3	12 12 12 12 12 12 12 12 12	40.24±2.33 50.83±13.31△ 41.10±1.74* 41.87±1.53* 46.45±8.10 42.79±1.47* 41.58±2.18* 39.53±1.47* 41.79±3.21*

Notes: △ compares P＜0.01 * with blank group and model group compares P＜0.05

Table 3 catechu is to the influence of hyperuricemia mice (hypoxanthine method) xanthine oxidase (X ± S)

Group	Dosage (g/kg)	The example number	Xanthine oxidase activity (U/L)
				Dosage group alcohol extracting low dose group in the alcohol extracting of dosage group water extraction low dose group alcohol extracting high dose group in the positive group of the blank group model group water extraction high dose group water extraction	- - 0.02 1.2 0.6 0.3 1.2 0.6 0.3	12 12 12 12 12 12 12 12 12	72.72±4.10 77.72±5.57 63.90±3.97* 71.56±9.96 77.01±8.89 65.86±7.71* 77.37±4.86 71.44±15.55 77.15±6.04

Annotate: * and model group be P＜0.01 relatively

3, conclusion:

3.1 hyperuricemia belongs to metabolic disease and is difficult to radical cure, at present to the effective Western medicine of hyperuricemia if take for a long time, very easily human body is caused comparatively serious toxic and side effects, and makes its clinical practice be subjected to bigger restriction.We indicate that to finding in the screening of medicine and the experimentation that catechu has good reduction hyperuricemia effect this medicine has certain therapeutical effect to hyperuricemia early stage.This experimental result shows: the water extract of catechu and alcohol extract have good inhibition effect to the blood uric acid of hyperuricemia model mice due to two kinds of modeling methods.Water is put forward low dose group has the obvious suppression effect to xanthine oxidase activity.Above-mentioned result of study provides the pharmacodynamic experiment foundation for this medicine clinical treatment hyperuricemia.

3.2 hyperuricemia belongs to the purine metabolism obstacle, due to uricopoiesis too much and/or urate excretion reduces.The intravital purine of people mainly comprises adenine, guanine, hypoxanthine and xanthine etc., wherein based on adenine, guanine.Purine mainly exists with the form of purine nucleotides, and uric acid then is the catastate of purine nucleotides.Adenylic acid (AMP) and guanylic acid (GMP) generate hypoxanthine and guanine respectively by the effect of purine nucleoside phosphatase.Guanine is transformed into xanthine by guanine deaminase catalysis; And hypoxanthine also is transformed into xanthine under the catalysis of xanthine oxidase.At last, under the further effect of xanthine oxidase, generate uric acid.This shows that in the production process of uric acid, xanthine oxidase plays important effect.The activity of xanthine oxidase increases, and the intravital uric acid of people is produced to be increased; Otherwise the activity of xanthine oxidase is suppressed, and then intravital uric acid produces and just can significantly reduce, thereby to alleviate hyperuricemia.Therefore we have observed the activity of catechu to xanthine oxidase in the experiment with the hypoxanthine modeling method, in experimenting, we find out that this medicine has the obvious suppression effect to the xanthine oxidase activity of hyperuricemia mice due to the hypoxanthine, is one of this medicine mechanism of action of reducing hyperuricemia mice uric acid level.

Test example 2 catechu are to the influence experiment of gouty arthritis animal model

1, experiment material:

1.1 animal: SD rat, 180-220g; Provide the animal quality certification number by Chengdu University of Traditional Chinese Medicine Animal Experimental Study center: No. 6, the real moving Guan Zhidi in river.

1.2 experimental drug: experimental drug is the water extract (0.4g/ml) and the alcohol extract (0.4g/ml) of catechu.Treatment gouty arthritis positive drug indometacin tablets, the limited manufacturing of inferior nation's Pharmaceutical group share branch company produces lot number 0404111 by Jiangsu.

1.3 experiment reagent: uric acid, SIGMA company produces, lot number 050K08822

2. method and result:

2.1 the preparation of crystallization of uric acid sodium and uric acid sodium solution: with reference to McCarty, methods such as D.J slightly make improvements.Get the 194ml distilled water and add 6mlNaOH (1M), add the 1g uric acid after boiling, use 1NHCL, transfer pH to 7.2, stir cooling, be stored in 24h in 4 ℃ of refrigerators, remove supernatant, precipitate moisture content is blotted with filter paper, in dry get final product the crystallization of uric acid sodium.Get the crystallization of 1250mg uric acid sodium, add the 45ml normal saline.Add the 5ml Tween 80 simultaneously, heated and stirred, it is standby to be made into 50ml uric acid sodium solution.

2.2 modelling and medication slightly make improvements by the classical way of Codene etc.: getting 60 rats is divided into 5 groups at random, modeling beginning in preceding 2 days gastric infusion, and experimental drug is the mixed solution of Lignum Rhamnellae franguloidis gout soup extract and alcohol extract, once a day.Blank group is to irritate stomach with the volume normal saline.Being tried rat right side ankle joint dorsal part,, cause acute gouty arthritis pathological changes model with No. 6 entry needles with 0.2ml uric acid sodium solution (2.5mg/100ml) injection model group and medication group rat ankle joint chamber from 45 ℃ of directions insertion tibia tendon inboards.Each organizes rat before modeling, 3h after the modeling, and 72h after the modeling is tried the volume of ankle joint respectively.

2.3 collection of specimens

8h after the last administration, the sacrificed by decapitation rat is got rat left side ankle joint tissue, and is fixing with FAA liquid (5% ethanol, 10% formalin, 5% acetic acid) perfusion, send Chengdu University of Traditional Chinese Medicine's Pathological Staff Room to be equipped with inspection immediately.

2.4 observation index

(1) rat paw swollen joint expansibility;

(2) HE dyeing is observed.

2.5 interpretation of result

(1) rat paw swollen joint expansibility

Each organizes rat before modeling, 3h after the modeling, and 72h after the modeling is tried the volume of ankle joint respectively.The model group rat after causing scorching back 30min red and swollen beginning obviously, its sufficient sole of the foot arthroncus of catechu group and indometacin tablets group has in various degree and alleviates, and respectively organizes the variation of arthroncus according to the observation before and after the treatment of modeling rat, carries out group difference and compares.Experimental result is as follows:

Table 4 catechu is to the influence of gouty arthritis rat model (X ± S)

Group	Dosage (g/kg)	The example number	Modeling front volume (ml)	Volume after the modeling (ml)	Treatment back volume (ml)
						It is low that the low alcohol of water extraction improves in the alcohol extracting alcohol extracting in the high water extraction of the positive water extraction of blank model	- - 0.038 1.2 0.6 0.3 1.2 0.6 0.3	11 11 11 11 11 10 11 11 11	1.14±0.16 1.02±0.23 0.94±0.17 0.85±0.18 0.88±0.08 0.97±0.13 1.00±0.15 1.09±0.14 0.91±0.11	0.94±0.14 1.44±0.17 1.00±0.11 1.16±0.19 1.09±0.13 1.07±0.13 1.18±0.19 1.33±0.09 1.25±0.19	1.00±0.14 1.08±0.12 0.88±0.09* 1.09±0.14 1.03±0.15* 0.99±0.18* 0.90±0.14* 0.94±0.13 1.00±0.09

Annotate: * compares P＜0.05 with blank group

(2) HE dyeing is observed: this is tested blank group, model group, positive group, water improve the left ankle joint tissue of respectively organizing 11 rats in the dosage group, amount to 44 samples and adopt in 10% formalin and fix.The formic acid decalcification, conventional dehydration, paraffin embedding, section, HE dyeing, optical microscope is observed down, and its observed result is a normal group: articular cartilage face is complete.Synovial membrane is made of layer 2-4 epithelium sample connective tissue cell in the joint capsule, and no basement membrane, iuntercellular have a small amount of substrate or fiber.Synovial membrane is outward loose connective tissue and muscular tissue.Model group: articular cartilage face is complete, does not see damaging variation.This is organized and occurs significantly congested, downright bad, cell infiltration in all sample synovial membrane surrounding tissues.The necrosis of part sample involves synovial membrane.Positive group: articular cartilage face is complete, does not see damaging variation.In 11 samples, have and occur downright bad, cell infiltration in 4 sample synovial membrane surrounding tissues.Water improves the dosage group: articular cartilage face is complete, does not see damaging variation.In 11 samples, have and occur downright bad, cell infiltration in 4 sample synovial membrane surrounding tissues.From above-mentioned observed result as seen: downright bad, cell infiltration appear in rat ankle joint after the modeling, and partly sample is significantly congested; And medication therapy groups, partly sample is not seen remarkable pathological changes.

3, discuss:

3.1 gout belongs to metabolic disease and is difficult to radical cure, gout can produce tophus (urate) and deposits, causes joint deformity and renal calculus because of it shows effect repeatedly, produces higher hazardness.At present to the effective Western medicine of gout if take for a long time, very easily human body is caused comparatively serious toxic and side effects, and makes its clinical practice be subjected to bigger restriction.We indicate that to finding in the screening of medicine and the experimentation that catechu has the effect of the rat of improvement gout model this medicine has certain therapeutical effect to gouty arthritis early stage.

3.2 this experimental result shows: low dose group had the obvious suppression effect to the gouty arthritis rat during catechu alcohol extraction high dose group and water were carried.From the result of pathological section, HE dyeing, observation by light microscope as can be known, downright bad, cell infiltration appear in rat ankle joint after the modeling, and partly sample is significantly congested; And medication therapy groups, partly sample is not seen remarkable pathological changes.Above-mentioned result of study provides the pharmacodynamic experiment foundation for this medicine clinical treatment gout.

The antiinflammatory test of test example 3 catechu

1, experiment material:

1.1 animal: SD rat, 180-220g; Kunming mouse, 22-25g,, provide the animal quality certification number by Chengdu University of Traditional Chinese Medicine Animal Experimental Study center: No. 6, the real moving Guan Zhidi in river.

1.2 experimental drug: experimental drug is the water extract (0.4g/ml) and the alcohol extract (0.4g/ml) of catechu.Antiinflammatory positive drug prednisone acetate tablets is produced lot number 030715 by factory of the celestial jade pendant in Zhejiang pharmaceutical Co. Ltd.Analgesia positive drug aspirin tablet is produced lot number 021009 by Ouyi Pharmaceutical Industry Co., Ltd., Shijiazhuang Pharmaceutical Group.

1.3 instrument YLS-6A intelligence hot-plate instrument, Shandong Academy of Medical Sciences equipment station produces.

2. method and result:

2.1 observe catechu causes rat paw edema to Ovum Gallus domesticus album influence

Get 80 of male SD rats, be divided into 8 groups at random.Every treated animal is tested preceding 5 days gastric infusions respectively, before the last administration, makes a labelling with marking pen around the rat right hind leg ankle joint, presses amplifying method (device self-control) and measures every right back sufficient volume twice of rat, and averaging is normal volume before each Mus administration.Be administered once again to each group rat, after causing inflammation for after 30 minutes every right back whole plantar subcutaneous injection 10% Ovum Gallus domesticus album of rat (0.1ml/ only), 30min, 1h, 2h, 3h, 4min measure right back sufficient volume after causing inflammation respectively, and the difference of sufficient sole of the foot volume is the swelling degree before and after the administration.Carry out the group difference significance relatively.Experimental result shows, catechu water mentions that each dosage group of alcohol extract can suppress rat paw edema due to the Ovum Gallus domesticus album in one hour after administration, and relatively there were significant differences (seeing Table 5) with the blank group:

Table 5 catechu causes the influence (X ± S) of rat paw edema to Ovum Gallus domesticus album

Group	Dosage g/kg	Example number n	Administration front volume ml	Swelling degree ml
									30min	1h	2h	3h	4h
				It is low that the low alcohol of water extraction improves in the alcohol extracting alcohol extracting in the high water extraction of blank group positive group water extraction	- 0.01 1.2 0.6 0.3 1.2 0.6 0.3	10 10 10 10 10 10 10 10	1.08±0.09 1.10±0.09 1.13±0.14 1.04±0.17 0.97±0.19 1.18±0.09 1.15±0.12 1.09±0.09	0.50±0.29 0.41±0.20 0.47±0.23 0.72±0.27 0.67±0.33 0.49±0.24 0.45±0.25 0.47±0.25						0.67±0.19 0.19±0.24** 0.34±0.14** 0.44±0.28* 0.39±0.25** 0.42±0.22** 0.39±0.25** 0.32±0.23**	0.21±0.21 0.08±0.14 0.13±0.23 0.19±0.13 0.21±0.22 0.10±0.11 0.09±0.11 0.22±0.19	0.03±0.07 0.01±0.02 0.02±0.04 0.04±0.07 0.09±0.11 0.02±0.04 0.09±0.10 0.05±0.12	0.02±0.02 0±0 0.01±0.03 0.02±0.06 0.02±0.08 0.004±0.01 0±0 0±0

Annotate: compare * P＜0.05, * * P＜0.01 with the blank group

2.2 implantation causes the granulomatous influence of mice to cotton balls to observe catechu

Get 96 of Male Kunming strain mice, be divided into 8 groups.Every mice, sterilization are cut off left side groin cortex, will weigh in advance and the disinfectant cotton balls (the external gentamycin is to protect from infection for 10mg ± 0.5mg), imbed homonymy oxter Intradermal, sew up wound.Matched group was given the equal-volume normal saline to postoperative by listed dosage (administration volume 0.2ml/10g) in 24 hours.Be administered once every day, and successive administration 7d took off cervical vertebra on the 8th day and puts to death animal and weigh, and took out cotton balls, carefully peeled off, and blotted blood and tissue fluid with filter paper, placed 60 ℃ of 4h of baking oven, scales/electronic balance weighing, and gained weight deducts the cotton balls known weight, and to be granuloma heavy.Carry out the group difference significance relatively with granuloma/100g.Experimental result shows: the water of catechu puies forward low dose group and the alcohol extraction low dose group can both significantly suppress the granulomatous formation of cotton balls induced mice (seeing Table 6).

Table 6 catechu causes the granulomatous influence of mice (X ± S) to cotton balls

Group	Dosage (g/kg)	The example number	Granuloma weight (mg/100g)
				Blank group positive controls water extraction get the high dose group water extraction get in dosage group water extraction get dosage group alcohol extracting low dose group in the alcohol extracting of low dose group alcohol extracting high dose group	- 0.01 1.2 0.6 0.3 1.2 0.6 0.3	12 12 12 12 12 12 12 12	63.34±13.77 36.63±9.16** 50.68±16.28 57.63±25.20 44.18±25.69* 66.88±30.63 48.76±21.92 40.27±13.13**

Annotate: compare * P＜0.05 * * P＜0.01 with the blank group

2.3 observe the effect of catechu to mice caused by dimethylbenzene xylene ear swelling

Get 80 of Male Kunming strain mice, be divided into 8 groups at random, difference administration 3d (administration volume 0.2ml/10g), once a day, after three days, 1h after the last administration, every Mus left side ear melted paraxylene 0.2ml puts to death mice behind the 1h, cut left and right sides ear, along left and right sides ear same area punching, the both sides auricle is weighed respectively with the 7mm card punch, with two auricle weight differences as the swelling degree.Carry out group difference relatively.Experimental result shows that the water raising of catechu, middle dosage group and the height of alcohol extraction, middle dosage group can significantly suppress the ear swelling (seeing Table 7) that mice causes because of dimethylbenzene.

Table 7 catechu xylol causes the influence (X ± S) of mice ear

Group	Dosage (g/kg)	The example number	Auricle swelling degree (mg)
				Blank group positive controls water extraction get the high dose group water extraction get in dosage group water extraction get dosage group alcohol extracting low dose group in the alcohol extracting of low dose group alcohol extracting high dose group	- 0.01 1.2 0.6 0.3 1.2 0.6 0.3	10 10 10 10 10 10 10 10	5.17±1.49 2.44±0.86** 3.02±1.67** 3.54±2.37* 3.77±1.49 3.01±1.53** 2.51±1.30** 4.40±1.08

Annotate: compare * P＜0.05 * * P＜0.01 with the blank group

2.4 observe catechu causes mice pain to hot-plate instrument effect

Get 96 of Kunming kind female mices, be divided into 8 groups at random.The grouping row filter that advances is regulated mice hot plate dolorimeter, makes temperature remain on 55 ± 0.2 ℃. and get a mice at every turn, put into dolorimeter, record the pain threshold of required time of metapedes (s) as this Mus occur licking from putting into.All less than 5s or greater than the 30s person that occurs licking the metapedes, and the happiness leaper, discarding without exception need not.Get eligible and divide into groups, labelling remeasures twice, averages as the pain threshold before this Mus administration.Gavage other medicine of respective sets then, measure each Mus pain threshold at mensuration 15min, 30min, 60min, 90min, 120min respectively after the administration.If mice is still analgesia reaction of 60S in dolorimeter, should take out, by 60S.Experimental result show catechu water carry in, low dose group and pure high dose group can improve the threshold of pain (seeing Table 8) that hot-plate instrument causes the pain mice.

Table 8 catechu causes the influence (X ± S) of mice pain to hot plate

Group g/kg	The example number	Dosage	The preceding threshold of pain of administration (s)	The threshold of pain after the administration
									15min	30min	60min	90min	120min
				It is low that the low alcohol of water extraction improves in the alcohol extracting alcohol extracting in the high water extraction of blank group positive group water extraction	12 12 12 12 12 12 12 12	- 0.25 1.2 0.6 0.3 1.2 0.6 0.3	10.82±2.89 12.58±5.43 13.01±7.23 12.29±3.62 8.56±2.49 6.56±1.28 12.06±4.07 9.24±3.17	10.50±3.72 11.72±5.61 12.46±3.73 16.11±9.88 13.61±5.27** 8.94±3.12* 12.37±4.25 10.09±3.21						10.11±4.69 10.79±3.55 13.51±5.75 11.73±4.16 12.42±6.17 10.72±3.44** 10.04±4.18 12.27±5.05	11.96±7.63 17.31±7.29 12.21±6.25 14.59±6.01 13.60±6.27* 7.25±2.13 11.07±5.18 11.64±4.91	15.14±10.46 14.67±8.95 13.61±6.58 18.55±14.02 18.78±7.61** 9.36±3.16 14.88±8.33 14.74±10.17	15.75±7.98 27.37±12.84* 20.02±13.83 20.57±13.45* 22.02±9.87** 9.61±5.06 20.68±11.17 15.45±11.00

Annotate: compare * P＜0.05 * * P＜0.01 with each preceding threshold of pain of group administration respectively

2.5 observe the effect of catechu Dichlorodiphenyl Acetate induced mice writhing response

Get 96 of Kunming mouses, be divided into 8 groups at random by body weight.Every group gavages respectively and gives relative medicine.The administration volume is 0.2ml/10g.30min after the administration, each Mus lumbar injection 0.6% acetum (0.2ml/ is only).Observe and record injection acetic acid after the number of times of writhing response occurs in the 15min and occur time (latent time) of writhing response for the first time.Carry out group difference relatively.Experimental result shows that catechu water improves low dose group and can significantly suppress writhing response (seeing Table 9) due to the acetic acid.

Table 9 catechu Dichlorodiphenyl Acetate causes the influence (X ± S) of mouse writhing

Group	The example number	Dosage (g/kg)	Latent time s	Turn round the body number of times in the 15min
					The positive group of blank group water extraction get the high dose group water extraction get in dosage group water extraction get dosage group alcohol extracting low dose group in the alcohol extracting of low dose group alcohol extracting high dose group	12 12 12 12 12 12 12 12	- 0.25 1.2 0.6 0.3 1.2 0.6 0.3	3.41±1.77 7.76±3.52** 4.66±1.95 4.13±1.14 3.76±1.11 3.87±0.92 4.58±1.61 4.65±1.44	18.3±11.52 8.50±9.38* 9.40±5.98* 10.80±7.02 10.20±7.61** 24.30±11.22 14.10±9.32 10.60±6.78

Annotate: compare * P＜0.05 * * P＜0.01 with the blank group

3. conclusion

3.1 being long-term purine metabolism obstacle, blood uric acid, gout increases a kind of disease that causes tissue injury.Clinical characters is that hyperuricemia, acute gouty arthritis show effect repeatedly, seriously can cause joint movement disorder and deformity ⁽¹⁾In Tibetan medicine and pharmacology, Mongolian medicine's medicine, often catechu is used for the treatment of the joint yellow fluid and increases the joint congestion and swelling pain that Sheng causes.

3.2 the antiinflammatory pharmacodynamic experiment to catechu shows, this medicine can significantly suppress rat paw edema and dimethylbenzene induced mice auricle edema due to the Ovum Gallus domesticus album, significantly suppress cotton balls and cause the granulomatous formation of mice, can significantly reduce the threshold of pain of turning round body number of times and rising thermic pain mice that acetic acid causes the pain mice.Pain and inflammation that physics and chemical factor are caused have tangible antagonism, and these may be exactly the pharmacodynamics basis of catechu treatment gouty arthritis.

Test example 4 pharmaceutical compositions of the present invention are to the influence experiment of hyperuricemia animal model

1. experiment material:

1.1 the animal Kunming mouse, 22-25g is provided by Chengdu University of Traditional Chinese Medicine Animal Experimental Study center, the animal quality certification number: No. 6, the real moving Guan Zhidi in river.

1.2 experimental drug: pharmaceutical composition full presciption medicine thing of the present invention is available from five stone medical materials market, Chengdu, through associate professor's Lu Xianming of Chengdu University of Traditional Chinese Medicine evaluation, by the method preparation of embodiment 2.Experimental drug is the water extract and the alcohol extract of pharmaceutical composition of the present invention.Treatment hyperuricemia positive drug allopurinol sheet, excellent magnificent pharmaceutcal corporation, Ltd produces lot number U10166 by Beijing.

1.3 experiment reagent: hypoxanthine, SIGMA company produces, lot number 101K0022; Uricase inhibitor, Aldrich company produces, lot number 03510DO-483; The uric acid reagent box, Nanjing is built up bio-engineering research and is produced, lot number 20040923; The xanthine oxidase test kit, Nanjing is built up bio-engineering research and is produced, lot number 20040923.

1.4 instrument: mice weighing balance DT5009 (0.1g/500g), weighing apparatus factory in Changshu City's produces.The 7560MC ultraviolet spectrophotometer, Shanghai Precision Scientific Apparatus Co., Ltd produces.80-2B low speed desk centrifuge, Anting Scientific Instrument Factory, Shanghai produces.

2. method and result:

2.1 influence to hyperuricemia mouse model (uricase inhibitor method)

Get Kunming mouse.Male and female half and half.Be divided into 9 groups at random.By group administration 5 days, once a day.Behind the last administration 1h, except that the blank group, all the other each treated animal lumbar injection oxonic acid potassium salt 300mg/kg cause the mice hyperuricemia.Behind the 1h of injection back, each treated animal is plucked eyeball and is got blood, and the centrifugal 5min of 2500r/min gets serum and surveys the hematuria acid number.Carry out group difference relatively.Experimental result shows that high, medium and low dosage group of pharmaceutical composition water extraction of the present invention and alcohol improve, the remarkable uric acid level of hyperuricemia mice due to the uric acid reducing enzyme inhibitor of middle dosage group.See Table 10:

Table 10 pharmaceutical composition of the present invention is to hyperuricemia mice (uricase inhibitor method)

The influence of serum uric acid level (X ± S)

Group	Dosage (g/kg)	The example number	Hematuria acid number (mg/L)
				It is low that the low alcohol of water extraction improves in the alcohol extracting alcohol extracting in the high water extraction of the positive water extraction of blank model	- - 0.02 20 10 5 20 10 5	11 11 12 11 11 11 11 11 11	18.48±6.86 29.90±12.09△ 10.96±4.59** 14.89±6.32** 13.18±4.41** 21.55±10.63* 17.82±9.83** 16.11±8.62** 27.59±10.22

Notes: △ and blank group compare P＜0.01 * and model group compares P＜0.05 * * and model group compares P＜0.01

2.2 influence to hyperuricemia mouse model (hypoxanthine method)

Get Kunming mouse, male and female half and half.Be divided into 9 groups at random.By group administration 5 days, once a day.After the last administration 1 hour, except that the blank group, all the other each treated animal Intraperitoneal injection of hypoxanthine 1g/kg cause the mice hyperuricemia.Behind the 1h of injection back, each treated animal is plucked eyeball and is got blood, and the centrifugal 15min of 2500r/min gets the activity that serum is surveyed hematuria acid number and xanthine oxidase.Carry out group difference relatively.Experimental result shows in the pharmaceutical composition water extraction of the present invention, in low dose group and the alcohol extraction, low dose group can significantly reduce the uric acid level of hyperuricemia mice due to the hypoxanthine; The dosage group can significantly suppress the activity of the xanthine oxidase of hyperuricemia mice due to the hypoxanthine in the pharmaceutical composition water extraction of the present invention.See Table 11 and table 12:

Table 11 pharmaceutical composition of the present invention is to hyperuricemia mice (hypoxanthine method)

The influence of serum uric acid level (X ± S)

Group	Dosage (g/kg)	The example number	Hematuria acid number (mg/L)
				Dosage group alcohol extracting low dose group in the alcohol extracting of dosage group water extraction low dose group alcohol extracting high dose group in the positive group of the blank group model group water extraction high dose group water extraction	- - 0.02 20 10 5 20 10 5	11 11 12 11 11 11 11 11 11	40.24±2.33 50.83±13.31△ 41.10±1.74** 46.72±5.12 42.09±1.32** 43.73±4.63** 50.06±11.33 43.07±3.63** 43.19±3.35**

Notes: △ compares P＜0.01 * with blank group and model group compares P＜0.05

Table 12 pharmaceutical composition of the present invention is to hyperuricemia mice (hypoxanthine method)

The influence of xanthine oxidase (X ± S)

Group	Dosage (g/kg)	The example number	Xanthine oxidase activity (U/L)
				Dosage group alcohol extracting low dose group in the alcohol extracting of dosage group water extraction low dose group alcohol extracting high dose group in the positive group of the blank group model group water extraction high dose group water extraction	- - 0.02 20 10 5 20 10 5	12 12 12 12 12 12 12 12 12	72.72±4.10 77.72±5.57 63.90±3.97** 82.97±10.65 59.73±6.97** 76.78±9.89 72.61±16.71 79.35±13.47 74.29±5.53

Annotate: * * and model group be P＜0.01 relatively

3 discuss:

Hyperuricemia belongs to metabolic disease and is difficult to radical cure, at present to the effective Western medicine of hyperuricemia if take for a long time, very easily human body is caused comparatively serious toxic and side effects, and makes its clinical practice be subjected to bigger restriction.This experimental result shows: pharmaceutical composition water extraction object height of the present invention, middle low dose group and alcohol extraction object height, middle dosage group be the remarkable uric acid level of hyperuricemia mice due to the uric acid reducing enzyme inhibitor all; In the water extract, in low dose group and the alcohol extract, low dose group all can significantly reduce the uric acid level of hyperuricemia mice due to the hypoxanthine; The dosage group can significantly suppress the activity of the xanthine oxidase of hyperuricemia mice due to the hypoxanthine in the water extract.Above experimental result may be exactly the pharmacodynamics basis of medicine composite for curing hyperuricemia of the present invention.

Hyperuricemia belongs to the purine metabolism obstacle, due to uricopoiesis too much and/or urate excretion reduces.The intravital purine of people mainly comprises adenine, guanine, hypoxanthine and xanthine etc., wherein based on adenine, guanine.Purine mainly exists with the form of purine nucleotides, and uric acid then is the catastate of purine nucleotides.Adenylic acid (AMP) and guanylic acid (GMP) generate hypoxanthine and guanine respectively by the effect of purine nucleoside phosphatase.Guanine is transformed into xanthine by guanine deaminase catalysis; And hypoxanthine also is transformed into xanthine under the catalysis of xanthine oxidase.At last, under the further effect of xanthine oxidase, generate uric acid.This shows that in the production process of uric acid, xanthine oxidase plays important effect.The activity of xanthine oxidase increases, and the intravital uric acid of people is produced to be increased; Otherwise the activity of xanthine oxidase is suppressed, and then intravital uric acid produces and just can significantly reduce, thereby to alleviate hyperuricemia.Therefore we have observed the activity of pharmaceutical composition of the present invention to xanthine oxidase in the experiment with the hypoxanthine modeling method, in experimenting, we find out that this side has the obvious suppression effect to the xanthine oxidase activity of hyperuricemia mice due to the hypoxanthine, and we infer that it may reduce one of mechanism of action of hyperuricemia mice uric acid level for this medicine.But the action pathway that also may have other, we will continue research in the experiment afterwards.The uric acid level that we also observe model mice in experiment significantly raises and the activity of xanthine oxidase there is no remarkable rising in addition, cause the reason of this phenomenon to suppress relevant with feedback, but also might be relevant with other factors, also need in research from now on, in depth to explore.

Test example 5 pharmaceutical compositions of the present invention are to the influence experiment of gouty arthritis rat model

1. experiment material:

1.1 animal SD rat, 180-220g is provided by Chengdu University of Traditional Chinese Medicine Animal Experimental Study center, the animal quality certification number: No. 6, the real moving Guan Zhidi in river.

1.2 experimental drug: pharmaceutical composition full presciption medicine thing of the present invention is available from five stone medical materials market, Chengdu, through associate professor's Lu Xianming of Chengdu University of Traditional Chinese Medicine evaluation.Prepare by embodiment 2 methods.Experimental drug is the water extract and the alcohol extract of pharmaceutical composition of the present invention.Treatment gouty arthritis positive drug indometacin tablets, the limited manufacturing of inferior nation's Pharmaceutical group share branch company produces lot number 0404111 by Jiangsu.

1.3 experiment reagent: uric acid, SIGMA company produces, lot number 050K08822.

2. method and result:

2.1 the preparation of crystallization of uric acid sodium and uric acid sodium solution: with reference to McCarty, methods such as D.J slightly make improvements.Get the 194ml distilled water and add 6mlNaOH (1M), add the 1g uric acid after boiling, use 1NHCL, transfer pH to 7.2, stir cooling, be stored in 24h in 4 ℃ of refrigerators, remove supernatant, precipitate moisture content is blotted with filter paper, in dry get final product the crystallization of uric acid sodium.Get the crystallization of 1250mg uric acid sodium, add the 45ml normal saline. add the 5ml Tween 80 simultaneously, heated and stirred, it is standby to be made into 50ml uric acid sodium solution.

2.2 modelling and medication slightly make improvements by the classical way of Codene etc.: getting 60 rats is divided into 5 groups at random, modeling beginning in preceding 2 days gastric infusion, and experimental drug is the mixed solution of Lignum Rhamnellae franguloidis gout soup extract and alcohol extract, once a day.Blank group is to irritate stomach with the volume normal saline.Being tried rat right side ankle joint dorsal part,, cause acute gouty arthritis pathological changes model with No. 6 entry needles with 0.2ml uric acid sodium solution (2.5mg/100ml) injection model group and medication group rat ankle joint chamber from 45 ℃ of directions insertion tibia tendon inboards.Each organizes rat before modeling, 3h after the modeling, and 72h after the modeling is tried the volume of ankle joint respectively.

2.3 collection of specimens

8h after the last administration, the sacrificed by decapitation rat is got rat left side ankle joint tissue, and is fixing with FAA liquid (5% ethanol, 10% formalin, 5% acetic acid) perfusion, send Chengdu University of Traditional Chinese Medicine's Pathological Staff Room to be equipped with inspection immediately.

2.4 observation index

(1) rat paw swollen joint expansibility;

(2) HE dyeing is observed.

2.5 interpretation of result

(1) rat paw swollen joint expansibility

Each organizes rat before modeling, 3h after the modeling, and 72h after the modeling is tried the volume of ankle joint respectively.The red and swollen beginning after causing scorching back 30min of model group rat is obvious, its the sufficient sole of the foot arthroncus of pharmaceutical composition group of the present invention and indometacin tablets group has in various degree and alleviates, respectively organize the variation of arthroncus according to the observation before and after the treatment of modeling rat, carry out group difference relatively.Experimental result shows: the high dose group of the water extract of pharmaceutical composition of the present invention and the mixture of alcohol extract and low dose group all can significantly suppress the foot swelling of gouty arthritis rat.Experimental result sees Table 13.

Table 13 pharmaceutical composition of the present invention is to the influence of gouty arthritis rat model (X ± S)

Group	Dosage (g/kg)	The example number	Modeling front volume (ml)	Volume after the modeling (ml)	Treatment back volume (ml)
						The positive high dose low dosage of blank model	- - 0.038 20 5	11 11 12 11 12	0.98±0.14 0.93±0.08 0.91±0.09 0.96±0.08 0.96±0.08	0.96±0.14 1.37±0.17** 1.45±0.12** 1.48±0.12** 1.63±0.24**	0.91±0.12 1.21±0.09 0.97±0.11** 1.05±0.14** 1.12±0.15**

Annotate: * * compares P＜0.01 with blank group

(2) HE dyeing is observed: the left ankle joint tissues of 11 rats is respectively organized in this experiment, and 55 samples adopt in 10% formalin and fix altogether.The formic acid decalcification, conventional dehydration, paraffin embedding, section, HE dyeing, optical microscope is observed down, and its observed result is a normal group: articular cartilage face is complete.Synovial membrane is made of layer 2-4 epithelium sample connective tissue cell in the joint capsule, and no basement membrane, iuntercellular have a small amount of substrate or fiber.Synovial membrane is outward loose connective tissue and muscular tissue.Model group: articular cartilage face is complete, does not see damaging variation.This is organized and occurs significantly congested, downright bad, cell infiltration in all sample synovial membrane surrounding tissues.The necrosis of part sample involves synovial membrane.Positive group: articular cartilage face is complete, does not see damaging variation.In 11 samples, have and occur downright bad, cell infiltration in 4 sample synovial membrane surrounding tissues.High dose group: articular cartilage face is complete, does not see damaging variation.In 11 samples, have and occur downright bad, cell infiltration, accidental hyperemia in 5 sample synovial membrane surrounding tissues.Low dose group: articular cartilage face is complete, does not see damaging variation.Have to occur downright bad, cell infiltration in 7 sample synovial membrane surrounding tissues in 11 samples, the necrosis of part sample involves synovial membrane.From above-mentioned observed result as seen: downright bad, cell infiltration appear in rat ankle joint after the modeling, and partly sample is significantly congested; And medication therapy groups, partly sample is not seen remarkable pathological changes.

3. discuss:

Gout belongs to metabolic disease and is difficult to radical cure, and gout can produce tophus (urate) and deposits, causes joint deformity and renal calculus because of it shows effect repeatedly, produces higher hazardness.At present to the effective Western medicine of gout if take for a long time, very easily human body is caused comparatively serious toxic and side effects, and makes its clinical practice be subjected to bigger restriction.This experimental result shows: the high and low dose group of the mixture of pharmaceutical composition water of the present invention, alcohol extract all can significantly suppress the foot swelling of gouty arthritis rat.From the result of pathological section, HE dyeing, observation by light microscope as can be known, downright bad, cell infiltration appear in rat ankle joint after the modeling, and partly sample is significantly congested; And medication therapy groups, partly sample is not seen remarkable pathological changes.Above experimental result may be exactly the pharmacodynamics basis of medicine composite for curing gouty arthritis of the present invention.

The anti-inflammatory and antalgic experiment of test example 6 pharmaceutical compositions of the present invention

1, experiment material:

1.1 animal: SD rat, 180-220g; Kunming mouse, 22-25g,, provide the animal quality certification number by Chengdu University of Traditional Chinese Medicine Animal Experimental Study center: No. 6, the real moving Guan Zhidi in river.

1.2 experimental drug: pharmaceutical composition full presciption medicine thing of the present invention is available from five stone medical materials market, Chengdu, through associate professor's Lu Xianming of Chengdu University of Traditional Chinese Medicine evaluation.By embodiment 2 preparations.Water extract (1g/ml) that experimental drug looses for Tibetan side's Lignum Rhamnellae franguloidis and alcohol extract (1g/ml).High, normal, basic dosage be equivalent to approximately to be grown up 20,10,5 times of amounts of clinical consumption.Antiinflammatory positive drug prednisone acetate tablets, pharmaceutical Co. Ltd produces lot number 030715 by the celestial jade pendant in Zhejiang.Analgesia positive drug aspirin tablet is produced lot number 021009 by Ouyi Pharmaceutical Industry Co., Ltd., Shijiazhuang Pharmaceutical Group.

1.3 instrument YLS-6A intelligence hot-plate instrument, Shandong Academy of Medical Sciences equipment station produces.

2. method and result

Observe the influence of pharmaceutical composition of the present invention 2.1 adopt Ovum Gallus domesticus album to cause scorching method to rat paw edema

Get 80 of healthy male SD rats, be divided into 8 groups at random.Every treated animal is tested preceding 5 days gastric infusions respectively.During formal the experiment, make a labelling with marking pen around the rat right hind leg ankle joint, press capillary tube amplifying method (device self-control) and measure every right back sufficient volume twice of rat, averaging is normal volume before each Mus administration.Be administered once again to each group rat, after causing inflammation for after 30 minutes every right back whole plantar subcutaneous injection 0.1% Ovum Gallus domesticus album of rat (0.1ml/ only), 30min, 60min, 120min, 240min measure right back sufficient volume after causing inflammation respectively, and the difference of sufficient sole of the foot volume is the swelling degree before and after the administration.Carry out the group difference significance relatively.The result shows: 30min after the administration, water put forward low dose group and blank group relatively there were significant differences P＜0.05; 60min after the administration, water improve, low dose group, and the alcohol extraction low dose group relatively has utmost point significant difference P＜0.01 with blank group, alcohol extraction high dose group and blank group relatively there were significant differences P＜0.05; 120min after the administration, each group more all has utmost point significant difference P＜0.01 with blank group; 240min after the administration, water improves, low dose group, and alcohol extraction high and low dose group relatively has utmost point significant difference, P＜0.01 with blank group.See Table 14:

Table 14 pharmaceutical composition of the present invention causes the influence (X ± SD) of rat paw edema to Ovum Gallus domesticus album

Group	Dosage g/kg	Example number n	Swelling degree after the administration
							30min	60min	120min	240min
			It is low that the low alcohol of water extraction improves in the alcohol extracting alcohol extracting in the high water extraction of blank positive water extraction	- 0.01 20 10 5 20 10 5	10 10 10 10 10 10 10 10	0.544±0.260 0.206±0.139* 0.372±0.298 0.631±0.209 0.236±0.253* 0.650±0.300 0.693±0.297 0.421±0.346					1.093±0.304 0.350±0.207** 0.506±0.434** 0.781±0.419 0.407±0.169** 0.762±0.290* 0.831±0.210 0.594±0.382**	1.119±0.365 0.469±0.248** 0.344±0.207** 0.606±0.283** 0.307±0.221** 0.575±0.367** 0.568±0.296** 0.225±0.205**	0.819±0.468 0.400±0.277** 0.389±0.196** 0.562±0.231 0.193±0.216** 0.781±0.374 0.581±0.319 0.244±0.163**

Annotate: compare * P＜0.05, * * P, 0.01 with the blank group

Observe pharmaceutical composition of the present invention to the granulomatous influence of mice 2.2 adopt the cotton balls implantation

Get 96 of Male Kunming strain mice, be divided into 8 groups.Every mice, sterilization are cut off left side groin cortex, will weigh in advance and the disinfectant cotton balls (the external gentamycin is to protect from infection for 10mg ± 0.5mg), imbed homonymy oxter Intradermal, sew up wound.Matched group was given the equal-volume normal saline to postoperative by listed dosage (administration volume 0.2ml/10g) in 24 hours.Be administered once every day, and successive administration 7 days took off cervical vertebra on the 8th day and puts to death animal and weigh, and took out cotton balls, carefully peel off, and 60 ℃ of baking 12h, scales/electronic balance weighing, gained weight deducts the cotton balls known weight and is granuloma weight.Carry out the group difference significance relatively.The result shows: positive group relatively has utmost point significant difference with blank the group, all the other each groups and the blank relatively no significant difference of organizing.See Table 15:

Table 15 pharmaceutical composition of the present invention is to the influence of granuloma induced by implantation of cotton pellets mice (X ± SD)

Group	Dosage (g/kg)	The example number	Granuloma weight (mg/100g)
				It is low that the low alcohol of water extraction improves in the alcohol extracting alcohol extracting in the high water extraction of blank positive water extraction	- 0.01 20 10 5 20 10 5	12 12 12 12 12 12 12 12	63.34±13.77 36.62±9.16** 50.46±15.63 51.16±14.58 50.85±15.42 54.78±13.77 52.87±12.82 55.21±19.46

Annotate: compare P＜0.01 with the blank group

Observe the effect of pharmaceutical composition of the present invention 2.3 adopt the dimethylbenzene molding method to mice ear

Get 96 of Male Kunming strain mice, be divided into 8 groups at random, administration three days (administration volume 0.2ml/10g) respectively, once a day, after three days, after the last administration one hour, every Mus left side ear melted paraxylene 0.05ml put to death mice after 1 hour, cut left and right sides ear, along left and right sides ear same area punching, the both sides auricle is weighed respectively with the 7mm card punch, with two auricle weight differences as the swelling degree.The result shows: water is put forward low dose group relatively has utmost point significant difference P＜0.01 with blank group, and water improves dosage group and alcohol extraction low dose group and blank group relatively there were significant differences P＜0.05.See Table 16:

Table 16 pharmaceutical composition xylol of the present invention causes the influence (X ± SD) of mice ear

Group	Dosage (g/kg)	The example number	Swelling degree (mg)	Inflammation suppression ratio %
					It is low that the low alcohol of water extraction improves in the alcohol extracting alcohol extracting in the high water extraction of blank positive water extraction	- 0.01 20 10 5 20 10 5	12 12 12 12 12 12 12 12	5.18±1.49 2.44±0.86** 3.53±1.51* 4.33±2.44 2.72±2.04** 3.84±1.71 4.19±1.79 3.51±2.13*	52.90 31.85 16.40 47.49 25.87 19.11 32.24

Annotate: compare * P＜0.05, * * P＜0.01 with the blank group

2.4 observe pharmaceutical composition of the present invention causes mice pain to hot-plate instrument effect

Get 96 of Kunming kind female mices, be divided into 8 groups at random.The grouping row filter that advances is regulated mice hot plate dolorimeter, makes temperature remain on 55 ± 0.2 ℃. and get a mice, record the pain threshold of required time of metapedes (s) as this Mus occur licking from putting at every turn.All less than 5s or greater than 30s person, and the happiness leaper discard need not.Get eligible and divide into groups, measure the preceding pain threshold of each Mus administration.Measure each Mus pain threshold at mensuration 15min, 30min, 60min, 90min, 120min respectively after the administration.Exceed 60S by 60S.The result shows: pharmaceutical composition water of the present invention improves the dosage group and the alcohol extraction low dose group can improve the threshold of pain that hot-plate instrument causes the pain mice.See Table 17:

Table 17 pharmaceutical composition of the present invention causes the influence (X ± S) of mice pain to hot plate

Group	The example number	Dosage g/kg	The preceding threshold of pain of administration (s)	The threshold of pain after the administration
									15min	30min	60min	90min	120min
				It is low that the low alcohol of water extraction improves in the alcohol extracting alcohol extracting in the high water extraction of blank group positive group water extraction	12 12 12 12 12 12 12 12	- 0.25 20 10 5 20 10 5	13.75±2.54 11.05±3.73 14.55±3.46 14.70±4.48 10.25±3.01 14.34±4.04 13.68±5.30 13.03±3.08	9.89±3.30 8.80±2.48 12.08±4.08 12.39±6.13 7.08±2.18 16.57±11.17 7.96±3.80 17.39±16.47						9.56±4.42 9.02±4.05 13.16±6.40 12.11±5.41 14.55±7.50 10.65±3.98 10.48±4.79 14.54±9.63	12.27±4.24 10.95±4.46 16.37±7.80 14.79±6.82 15.93±6.99 16.07±8.30 13.64±10.23 19.77±13.95	14.13±7.86 12.62±6.45 22.88±7.87** 22.55±17.93 16.57±6.72 23.96±16.47 16.63±8.63 25.53±16.01*	14.86±8.48 15.61±5.70* 21.99±12.39 23.93±16.02 19.97±15.97 18.60±10.19 17.97±16.65 30.91±19.55*

Annotate: compare * P＜0.05 with each preceding threshold of pain of group administration respectively

2.5 observe the effect of pharmaceutical composition Dichlorodiphenyl Acetate induced mice writhing response of the present invention

Get 96 of Kunming mouses, be divided into 8 groups at random by body weight.Every group gavages respectively and gives relative medicine.The administration volume is 0.2ml/10g.30min after the administration, each Mus lumbar injection 0.6% acetum (0.2ml/ is only).Observe and record injection acetic acid after the number of times of writhing response occurs in the 15min and occur time (latent time) of writhing response for the first time.Carry out group difference relatively.The result show pharmaceutical composition water of the present invention improve in dosage group and alcohol extraction low dose group can significantly suppress writhing response due to the acetic acid.See Table 18:

Table 18 pharmaceutical composition Dichlorodiphenyl Acetate of the present invention causes the influence (X ± S) of mouse writhing

Group	The example number	Dosage (g/kg)	Latent time s	Turn round the body number of times in the 15min
					Dosage group alcohol extracting low dose group in the alcohol extracting of dosage group water extraction low dose group alcohol extracting high dose group in the positive group of the blank group water extraction high dose group water extraction	12 12 12 12 12 12 12 12	- 0.25 20 10 5 20 10 5	3.43±1.63 7.89±3.28** 4.84±2.16 4.13±1.14 4.22±1.18 4.08±0.93 3.94±1.13 4.86±1.49	17.00±7.10 8.30±6.52* 8.50±5.95* 10.10±6.72* 10.20±7.61 10.80±7.66 12.20±8.31 9.80±6.33*

Annotate: compare * P＜0.05 * * P＜0.01 with the blank group

3. discuss

By experiment shows to the anti-inflammatory and antalgic drug effect of pharmaceutical composition of the present invention, this can reach and significantly suppress rat paw edema and dimethylbenzene induced mice auricle edema due to the Ovum Gallus domesticus album, but chronic proliferous type inflammation granuloma induced by implantation of cotton pellets is not had obvious curative effects.Can significantly reduce acetic acid and cause the threshold of pain of turning round body number of times and rising thermic pain mice of mice bitterly.Pain and inflammation that physics and chemical factor are caused have tangible antagonism, and these may be exactly the pharmacodynamics basis of medicine composite for curing gouty arthritis of the present invention.

The gout acute attack is the acute inflammatory reaction that uric acid sodium crystallization (MSUC) causes in joint surrounding tissue deposition.MSUC combines with IgG in the synovial membrane liquid, is engulfed by leukocyte and synovial cell.Impel these cells to discharge histamine, thrombin, complement and arachidonic acid materials such as (AA) immediately, from generating PGE respectively by Cycloxygenase and two approach of lipoxidase ₂And leukotriene, the latter stimulates IL-1, IL-6 to produce.All these material short-terms can cause inflammatory reactions such as local vascular dilation, permeability increase, ooze out, edema, leukocyte recruitment, heating.And develop into the peak: add H along with intra-articular pressure increases ⁺, K ⁺, 5-HT, Kallidin I, P material, acetylcholine and gland former times class material (ADP:ATP) etc. stimulate periphery affective neuron tip, cause to have an intense pain.

Experimental example 7 pharmaceutical compositions of the present invention are to the side's of tearing open research of antihyperuricemic disease mouse model

1. experiment material and reagent:

1.1 animal: Kunming mouse, male and female half and half, body weight 22-25g is provided by Chengdu University of Traditional Chinese Medicine Animal Experimental Study center, the animal quality certification number: No. 11

1.2 experiment material: medical material is available from five stone medical materials market, Chengdu.Award evaluation by Lu of Chengdu University of Traditional Chinese Medicine elder generation penetrating judgment.Used dosage all calculates with the crude drug amount, is equivalent to 10 times of clinical consumption, and water extract mixes mutually with 95% ethanol extract, and promptly 1g water is carried+1g alcohol extraction=2g crude drug.The positive drug allopurinol is by the excellent magnificent pharmaceutcal corporation, Ltd in Beijing, and lot number U10166 faces with preceding and is made into desired concn with distilled water.Oxonic acid potassium salt (K-oxonate), Aldrich company produces Lot:03510DO-483.Uric acid detection kit (URO-PAP method) Maike Tech Co., Ltd., Sichuan Prov., lot number 1104121;

1.3 instrument: mice weighing balance DT5009 (0.1g/500g), weighing apparatus factory in Changshu City's produces; The 7560MC ultraviolet spectrophotometer, Shanghai Precision Scientific Apparatus Co., Ltd produces.80-2B low speed desk centrifuge, Anting Scientific Instrument Factory, Shanghai produces.

2. method and result:

Get 90 of Kunming mouses, be divided into 7 groups at random.By group administration 7 days, once a day.After the last administration 1 hour, except that the blank group, all the other each treated animal lumbar injection oxonic acid potassium salt 300mg/kg cause the mice hyperuricemia, blank group injection equivalent normal saline.Behind the 1h of injection back, each treated animal is plucked eyeball and is got blood, and the centrifugal 5min of 3000r/min gets serum and surveys the hematuria acid number with test kit, the results are shown in Figure 1: table 19

Respectively organize medicine to the antihyperuricemic disease mouse model behind the full side of table 19 pharmaceutical composition of the present invention and the side of tearing open

The influence of serum uric acid level

Group	The example number	Hematuria acid number (μ mol/l)
			1. blank group 2. model group 3. positive group 4. complete square groups 5. full sides subtract the catechu 6. complete square bark of ash 7. full sides that subtract and subtract catechu, the barks of ash	10 10 10 10 10 10 10	140.93±45.54 346.12±163.31☆ 72.14±51.33** 37.74±33.57** 109.16±118.58** 113.94±64.37** 48.49±35.07**

Annotate: ☆ compares p＜0.05 with blank group

* and model group be p＜0.05 relatively

By this side's of tearing open test, catechu is a monarch drug in the raw material prescription, has brought into play main therapeutic efficiency.Simultaneously, also prove the scientific and reasonable of raw material prescription of the present invention.

By above-mentioned pharmacodynamics test, proof catechu and the pharmaceutical composition that contains the raw material catechu reduce blood uric acid, one of mechanism of action that it falls blood uric acid is to reduce the activity of xanthine oxidase, gouty joint property to the gout acute attack has antiinflammatory, analgesic activity, untoward reaction is minimum, zoopery LD ₅₀Do not come out, provide a kind of safe, effective, stable, controlled medicine for clinical.

Claims (13)

1, the purposes of catechu in the medicine of preparation treatment hyperuricemia.

2, purposes according to claim 1, its thing is levied and is: described catechu derives from: the peeling branch of leguminous plant catechu Acacia catechu (L.f.) Willd., the dry soft extracts of bar.

3, purposes according to claim 1 and 2 is characterized in that: described catechu is catechu water extract, catechu alcohol extract.

4, a kind of pharmaceutical composition for the treatment of hyperuricemia, it is to be active component or raw material by the described catechu of the claim 1 that contains effective dose, adds the medicament that acceptable accessories or complementary composition are prepared from.

5, the pharmaceutical composition of treatment hyperuricemia according to claim 4 is characterized in that: also contain Cortex Phellodendri, Radix Gentianae Macrophyllae, Olibanum, Fructus Chebulae in the described raw material, its weight proportion is:

0.5～1.5 part in catechu, 2.0～3.0 parts of Radix Gentianae Macrophyllae, 0.5～1.5 part of Olibanum, 0.5～1.5 part of Fructus Chebulae, 0.5～1.5 part of Cortex Phellodendri.

6, the pharmaceutical composition of treatment hyperuricemia according to claim 5 is characterized in that: also contain Cortex Fraxini in the described raw material, its weight proportion is:

0.5～1.5 part in catechu, 2.0～3.0 parts of Radix Gentianae Macrophyllae, 0.5～1.5 part of Olibanum, 0.5～1.5 part of Fructus Chebulae, 0.5～1.5 part of Cortex Phellodendri, 2.5～3.5 parts of Cortex Fraxinis.

7, the pharmaceutical composition of treatment hyperuricemia according to claim 6 is characterized in that: it is the medicament that is prepared from by the following weight proportion raw material:

0.5～1.5 part in catechu, 2.0～3.0 parts of Radix Gentianae Macrophyllae, 0.5～1.5 part of Olibanum, 0.5～1.5 part of Fructus Chebulae, 0.5～1.5 part of Cortex Phellodendri, 2.5～3.5 parts of Cortex Fraxinis.

8, the pharmaceutical composition of treatment hyperuricemia according to claim 7 is characterized in that: it is the medicament that is prepared from by the following weight proportion raw material:

1 part in catechu, 2.5 parts of Radix Gentianae Macrophyllae, 1 part of Olibanum, 3 parts of Cortex Fraxinis, 1 part of Fructus Chebulae, 1 part of Cortex Phellodendri.

9, according to the pharmaceutical composition of each described treatment hyperuricemia of claim 4-8, it is characterized in that: described medicament is oral formulations, injection.

10, the purposes of the described pharmaceutical composition of claim 9 in the medicine of preparation treatment gout.

11, a kind of pharmaceutical composition for the treatment of hyperuricemia, it is to be the medicament that feedstock production forms by each described raw material of claim 5-8, Radix Gentianae Macrophyllae, Olibanum, Fructus Chebulae, Cortex Phellodendri, and it is characterized in that: the weight proportion of described raw material is: 2.0～3.0 parts of Radix Gentianae Macrophyllae, 0.5～1.5 part of Olibanum, 0.5～1.5 part of Fructus Chebulae, 0.5～1.5 part of Cortex Phellodendri.

12, the pharmaceutical composition of treatment hyperuricemia according to claim 11 is characterized in that: it is to be prepared from medicament by the following weight proportion raw material:

2.5 parts of Radix Gentianae Macrophyllae, 1 part of Olibanum, 1 part of Fructus Chebulae, 1 part of Cortex Phellodendri.

13, claim 11 or the 12 described pharmaceutical compositions purposes in the medicine of preparation treatment gout.

Images