CN107998385A - Purposes of the hirudin as prevention antihyperuricemic disease drug - Google Patents
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Abstract
The present invention relates to a kind of purposes of hirudin as prevention antihyperuricemic disease drug, discloses the new application that hirudin is used to prepare the medicine of prevention hyperuricemia and its caused disease；Induce Kunming mouse to establish high lithemia model by hypoxanthine, Oteracil Potassium, and observe intervention effect of the hirudin to hyperuricemia.Result of study shows that Kunming mouse continuous 12d give hirudin, can substantially reduce hypoxanthine induction hyperuricemia mice serum uric acid level；It can also be used to prepare hyperuricemia and its caused disease：Obstructive sleep apnea and/or climacteric syndrome, or the disease such as caused hypertension, hyperlipidemia, atherosclerosis, obesity, insulin resistance, nephrosis, inflammation, infectious diseases, tumor lysis syndrome.The present invention has opened up new purposes for hirudin.
Description
Technical field
The present invention relates to a kind of technical field of hirudin application, more particularly to a kind of hirudin is as prevention antihyperuricemic
Disease and its purposes for causing disease medicament.
Background technology
Uric acid（uric acid）I.e. 2,6,8- tri- oxidation purine, are the end-product of purine metabolism.The mankind due to lacking in vivo
Uricolytic enzyme, it is impossible to purine metabolism end-product uric acid is sufficiently further decomposed into allantoin, makes hyperuricemia and pain
The eolian disease more special for the mankind.In recent years research shows that hyperuricemia is not only the most important biochemical basis of gout, and
And with hypertension, hyperlipidemia, atherosclerosis, obesity, insulin resistance, nephrosis, inflammation, the serious journey of infectious diseases
Degree, tumor lysis syndrome, menopausal syndrome, complication of transplanted organ and some difficult and complicated illness（Obstructive sleep respiratory is temporary
Stop, primary Sjogren's syndrome etc.）Generation it is closely related, so control hyperuricemia is to the treatment serious metabolic such as gout
Disease and associated disease are of great significance.
At present, the medicine clinically for inhibiting hyperuricemia relates generally to reduce uric acid generation and increase uric acid excretion two
Aspect.The medicine for reducing uric acid generation has xanthine oxidase（Xanthine oxidase, XOD）Inhibitor, it is main different fast
Purine alcohol, but allopurinol causes the adverse reactions such as allergy, lesions of liver and kidney and bone marrow suppression, and it is clinical to limit it to a certain extent
Using.FDA in 2009 have approved a kind of xanthine oxidase/dehydrogenase selective depressant medicine for treating hyperuricemia：fexbuxostat, which has more preferable security to appropriate impaired renal patient than allopurinol, but also has dysfunction of liver, stomach
The Reporting of harms such as enteron aisle reaction, arthralgia and eruption.Uricosureic agent has probenecid, sulfinpyrazone, Benzbromarone etc.,
The lithate transporter of kidney proximal tubule is acted on, so as to suppress the reabsorption of uric acid.Recently research finds that Benzbromarone, which has, to be drawn
The danger of fulminant hepatitis is played, is withdrawn from from part European market.So the anti-trioxypurine medicine listed at present is very limited, and
Toxic side effect is obvious, and the compliance of patient is poor.Therefore, the inhibiting hyperuricemia medicine for studying high-efficiency low-toxicity has been compeled in eyebrow
Eyelash.
Gout is by monosodium urate salt（MSU）Deposition caused by crystal correlation arthropathy, with purine metabolic disturbance and
（Or）Hyperuricemia caused by underexcretion is directly related, refers in particular to acute characteristic arthritis and chronic gout stone disease
Disease, mainly includes acute attack arthritis, tophus formation, tophaceous chornic arthritis, urate nephropathy and uric acid
Lithangiuria, severe one may occur in which joint deformity and renal insufficiency.Gout is often with Central obesity, hyperlipidemia, hypertension, 2 types
Diabetes and cardiovascular disease etc. show.
The most important biochemical basis of gout are hyperuricemias.Normal adult about produces uric acid 750mg daily, wherein 80%
It is exogenous uric acid for endogenous, 20%, these uric acid enter uric acid metabolism pond（About 1200mg）, the urine in daily metabolic pool
Acid about 60% is metabolized, wherein 1/3 about 200mg, through enteron aisle catabolism, 2/3 about 400mg is through kidney excretion, so as to maintain
The stabilization of internal uric acid level, any of which link, which goes wrong, can cause hyperuricemia.
Hirudin (Hirudin) it is leech section animal, it is particularly hirutoPoecilobdella manillensis LessonDeng extracted that activity is most notable and most studied in a variety of active ingredients in dry all and its saliva one
Kind component, the small protein being made of 65-66 amino acid (polypeptide), has fibrin ferment extremely strong inhibitory action, is so far
The natural specific inhibitor of most strong fibrin ferment is found untill the present.Modern scientific research shows, all hirudinaria manillensis（Include
Annelida, Hirudinea, Arhynchobdellae, the hirudinaria manillensis of Yi Zhi sections, such as hiruto, Hirudo japonica, Haemadipsa hainana）Saliva
It is all a variety of containing hirudin, hyaluronidase, prostaglandin, vasodilator and fibrinolytic enzyme etc. in gland and its secreted saliva
Bioactive ingredients, wherein hirudin are that at most and the most significant one kind of activity, it is by 65~66 to content in these components
The low molecular polypeptide of amino acid composition, molecular weight only 7000 dalton, are highly soluble in water, insoluble in organic formulations such as ethanol, often
Temperature rise sufficiently stable under temperature, simple（100 DEG C water-soluble）Change with pH value does not influence its activity, only when temperature and
Its activity is just begun to decline when pH value raises simultaneously.Also substantial amounts of research data proves that hirudin is so far in the world
It was found that material in most strong thrombin inhibitor, it has extremely strong anticoagulation, while also has good
Anti- bolt, thrombolysis, lipid-loweringing, anti-inflammatory and antitumor and other effects.Modern pharmacology research shows that hirudin is lived with extensive pharmacology
Property, all there is good pharmacological activity in antitumor, cardiovascular and cerebrovascular disease, kidney etc..But the anti-antihyperuricemic of hirudin
The pharmacological activity of disease, yet there are no report.
Through retrieving the Chinese patent literature in relation to hirudin, it is as follows now to enumerate some：
1st, Chinese patent<Application number>200610018321. X<Denomination of invention>Sublingual tablet of natural hirudin<Summary>A kind of day
Right hirudin sublingual lozenge, it is characterised in that contain natural hirudin and water-soluble filler in the lozenge, contain in every tablet of lozenge
5~6000 international unit of natural hirudin.Have the advantages that easily absorption, it is eutherapeutic, to prevention cardiovascular and cerebrovascular disease such as hypertension,
Hyperlipidemia, apoplexy and its sequelae etc. have good effect.
2nd, Chinese patent<Application number> 200910180216.X<Denomination of invention>Treat the hirudin of cardiovascular and cerebrovascular disease
Composition of medicine<Summary>The present invention relates to the hirudin combination medicament for the treatment of cardiovascular and cerebrovascular disease, the composition of medicine is with natural water
The plain and other Chinese medical extract of leech is active ingredient, adds the auxiliary materials such as associated dispersion agent, preservative, other mutually auxiliary Chinese medicines such as pellet
Ginseng, pseudo-ginseng, Snakegourd Fruit, earthworm, radix astragali, the extract of ginseng.Hirudin combination medicament promoting blood circulation to remove blood stasis, coronary circulation-promoting pain-relieving, suitable for controlling
Treat cerebral infarction disease, coronary heart diseases and angina pectoris, acute myocardial infarction, ischemia apoplexy.Vertebral artery resistance can be significantly reduced, is improved
Cerebral ischemia and brain blood circulation, it can also be used to the suction of the intracerebral hematoma of disseminated intravascular coagulation, cerebral hemorrhage convalescence and sequelae
Receive.
3rd, Chinese patent<Application number> 200310107682.8<Denomination of invention>A kind of medicine for being used to treat apoplexy<Pluck
Will>A kind of to be used to treat the medicine of apoplexy, it is related to a kind of for the mixed of stroke in convalescent stage and sequela stage adjuvant therapy medicaments
Compound.More particularly to a kind of medicine mixed using Chinese herbal medicine as raw material.Mixed by weight by following raw materials according：Leech
850g -12009, Radix Salviae Miltiorrhizae 140g -320g.
4th, Chinese patent<Application number> 201110007658.1<Denomination of invention>Raw material is hirudin, fibrinolytic is plain and hyaluronic acid
The purposes of the medicine of enzyme<Summary>The invention belongs to technical field of traditional Chinese medicines, is hirudin, hyaluronic acid the invention discloses raw material
Application of the medicine of enzyme and fibrinolytic element in the medicine for preparing treatment nephrosis.By " influence to Acute Experimantal Serum Sickness Glomerulonephritis Rats ",
The pharmacological testing of " protective effect to adriamycin-induced nephropathy in rats ", it was demonstrated that prepared by hirudin, fibrinolytic element and hyaluronidase
Medicine has extraordinary pharmacological action to nephrosis, particularly ephritis.
5th, Chinese patent<Application number> 201710464335.2<Denomination of invention>A kind of prevention diabetes and its complication
Pharmaceutical composition<Summary>The invention discloses a kind of pharmaceutical composition for preventing diabetes and its complication, its drug regimen into
Part composition：Sea cucumber polypeptide, brown alga oligose, kudzu root extract, water Herba Spirodelae extract, Radix Trichosanthis extract, pink extract, ginkgo
Leaf extract, hirudin and Nattokinase.The present invention can treat the diabetes of insulin-resistant, and active ingredient compounding is than single
One component is more preferable to prevention and treatment diabetes effect, but also can prevent and treat some extremely adjoint with blood glucose rise
Chronic complicating diseases.
6th, Chinese patent<Application number> 200710111590.5<Denomination of invention>A kind of medicine for cardiovascular and cerebrovascular disease
Composition<Summary>The present invention relates to a kind of pharmaceutical composition, more particularly to it is a kind of be used for the apoplexy sign phase, stroke in convalescent stage and
Sequela stage, symptoms include language owe profit, and hemianesthesia is dizzy, and the treatment of all diseases of fatigue, miocardial infarction, anginal treatment, also may be used
Pharmaceutical composition for the treatment of the diseases such as diabetes, hyperlipemia, hypertension.
From the document retrieved we it can be appreciated that also hirudin is not used to treat the medicine of gout in the prior art
Thing, and only carried out in the prior art using hirudin as the medicine for the treatment of cardiovascular and cerebrovascular, headstroke, the diabetes of insulin resistance
Open, these medicines perhaps can obtain some curative effects, and still, effect is not optimal；So how making of more magnifying of hirudin
With the effect of being allowed to produce maximum, having given play to due efficiency, be still the main direction of medical research so far.
The content of the invention
The defects of the purpose of the present invention is for the prior art, and provide a kind of hirudin as prevention hyperuricemia and
It causes the purposes of disease medicament；The present invention can effectively prevent hyperuricemia and its caused gout, hypertension, hyperlipemia
Disease, atherosclerosis, obesity, insulin resistance, nephrosis, inflammation, the order of severity of infectious diseases, tumor lysis synthesis
The diseases such as disease, menopausal syndrome, complication of transplanted organ, obstructive sleep apnea and primary dry syndrome.
Content provided by the invention is：Hirudin is as preparing prevention hyperuricemia and its cause use in disease medicament
On the way.
The hyperuricemia causes disease to cause gout, obstructive sleep apnea and/or more for uric acid rise
Term syndrome.
The hyperuricemia cause disease further include hyperuricemia caused by hypertension, hyperlipidemia, artery congee
Sample hardening, obesity, insulin resistance, nephrosis, inflammation, infectious diseases, tumor lysis syndrome, complication of transplanted organ and/
Or primary Sjogren's syndrome disease.
The preparation method of hirudin described above is：
（1）Take hirudinaria manillensis live body or freezing freeze preserve hirudinaria manillensis corpse, by its weight calculate, add physiological saline or
1~10 times of drinking water, is homogenized 2~6 times repeatedly in colloid mill, and hirudinaria manillensis slurries are made；
（2）Hirudinaria manillensis slurries are filtered with 60~150 mesh sieve nets, hirudinaria manillensis filtrate is obtained after removing filter residue；
（3）Auxiliary material is added in hirudinaria manillensis filtrate, its dosage：It is by weight：50~90 parts of hirudinaria manillensis filtrate, forms sediment
10~50 parts of powder, such as tapioca, cornstarch, water-soluble filler, such as lactose, sucrose, mannitol, maltodextrin 0
~5 parts；
（4）By said ratio, starch and/or water-soluble filler are put into hirudinaria manillensis filtrate, obtained after stirring evenly
Suspension；
（5）Above-mentioned hirudinaria manillensis suspension is placed in spray dryer and is spray-dried, its condition be inlet temperature 165~
195 DEG C, 68~85 DEG C of outlet temperature, is made dried powder；
（6）Powder obtained above, its main active are hirudins, can use Markwardt fibrin ferment direct titrimetric methods
The content of its natural hirudin is detected, is usually every gram of dry powder 60~4000ATU containing natural hirudin.
Hirudin described above can be the clinical preparation received of pharmaceutically acceptable carrier composition.
Carrier described above is the diluent of pharmaceutical field, excipient, filler, adhesive, wetting agent, disintegrant, suction
Receive accelerating agent, surfactant, absorption carrier or lubricant etc..
Hirudin described above as prevention antihyperuricemic disease drug be made tablet, pulvis, granula, capsule, oral liquid or
The diversified forms such as injecting drug use, the medicine of above-mentioned each formulation can be prepared according to the conventional method of pharmaceutical field.
The hirudin has fibrin ferment extremely strong inhibitory action, is to find that most strong fibrin ferment is naturally special so far
Different inhibitor；With anti-freezing, antithrombotic, suppress a variety of medicines such as platelet aggregation, reducing blood lipid, improvement hemorheology, antitumor
Reason acts on；Animal experiment shows that hirudin can efficiently anticoagulation, antithrombus formation, and prevent fibrin ferment from urging with clinical research
The further blood stasis phenomenon such as the clotting factor activation of change and platelet response.In addition, it can also suppress thrombin induction into fibre
Tie up the propagation of cell and the stimulation of fibrin ferment Human Umbilical Vein Endothelial Cells.Compared with heparin, not only dosage is few for it, will not cause bleeding,
Independent of endogenous co-factor；And heparin then has the danger to cause bleeding, in the pathogenic process of disseminated intravascular coagulation
The effect of middle Antithrombin III is often reduced, this will limit heparin, preferable effect is had using leech.
At present, the pathological basis of high lithemia is caused not yet to illustrate completely, the research to high lithemia is primarily upon uric acid
Synthesis and the excretion of uric acid thank to two aspects, and the target spot for influencing uric acid synthesis is mainly key enzyme --- the xanthine of uric acid synthesis
Oxidizing ferment, influences uric acid excretion and is primarily upon uric acid transfer factor Glut, OAT of kidney tubule etc..
And the xanthine oxidase, as internal the most common type nucleic acid metabolism correlation rate-limiting enzyme, it is distributed mainly on
In the cytoplasms of vital tissue such as internal heart, lungs, liver.Xanthine oxidase can effectively be catalyzed xanthine and time Huang is fast
Purine oxidation generation uric acid, causes internal peroxide radical generation increase.Internal peroxide radical, which increases, to be caused
The appearance of body inflammatory reaction, the damage and hardening of vascular endothelial cell, the aging for causing body, even result in the canceration of cell
And cause the generation of tumour.Uric acid is a kind of faintly acid metabolite, its water solubility is low, when body produces excessive or is metabolized
It will cause the generation of hyperuricemia during obstacle, the breaking-out of body gout will be caused with the extension of the course of disease, finally because of gout phase
Close the recurrent exerbation of clinical manifestation and cause urarthritis and gout correlation renal lesions.
A kind of disease caused by gout belongs to purine substance dysbolism, is mainly raised with serum uric acid level, urinated
Acid crystal and in soft tissue deposit caused by.Clinically mainly deposited with hyperuricemia, urarthritis and gout knot
For a kind of chornic arthritis of main clinical characteristics, serious arthritis deformans will be caused when the course of disease is longer, this disease is involved small more
Joint and kidney, cause arteriosclerotic kidney and kidney uric acid calculus.Research thought that gout mainly resulted in internal height in the past
Uricacidemia, it is deposited with occurrence and development such as hypertension, hyperlipidemia, coronary atherosclerosis and diabetes insulin resistances
It is wide concerned as a kind of metabolic disease of serious threat human health in close correlation.With people's life water
The significantly developed regions such as rise trend, especially southeastern coast, and be considered as after glycosuria are presented in flat improvement, gout incidence
Another kind " rich people's disease " after disease, hyperlipidemia, hypertension.
The present invention can be to gout, hypertension, hyperlipidemia, atherosclerosis, obesity, pancreas islet caused by hyperuricemia
Plain resistance, nephrosis, inflammation, the order of severity of infectious diseases, tumor lysis syndrome, menopausal syndrome, organ transplant are simultaneously
The diseases such as hair disease, obstructive sleep apnea and primary Sjogren's syndrome have obvious therapeutic effect；Particularly with high lithemia
The treatment of gout caused by mass formed by blood stasis, this is the quantum jump on medical domain；Hirudin can be used to treat in traditional medicine
Apoplexia disease, but for gout also without progress system research.
Embodiment
It is that the present invention is described in further detail with reference to the embodiment of the present invention below：
Embodiment 1：The influence for the hyperuricemia mice serum uric acid that hirudin induces hypoxanthine
Material：Hirudin, allopurinol tablet, hypoxanthine, uric acid reagent box.
Experimental animal：Kunming mouse.
1st, experimental method
Choose weight 18~22 g Kunming mouses 70, male is randomly divided into 10 groups, every group of l0 only, i.e. control group, model
Group, positive drug Allopurinol (0.01 g.kg-1) group, golden-rimmed leech dry powder（2.0 g medicinal materials .kg-1）Group, high, medium and low dose of hirudin
Measure (0.8,0.4,0.2 g medicinal materials .kg-1) group.Each group ig is administered, and 1 time a day, control group and model group ig give isometric distillation
Water, continuous 12 d.In addition to control group, 600 mg.kg of ip hypoxanthine after 1 h of each group last dose-1, eyeball takes blood after 1 h, and 3
000 r/min centrifuges 10 min, takes supernatant to measure serum uric acid level (phosphotungstic acid colorimetric method).
Data are represented with (average value ± standard error), are carried out one-way analysis of variance using SPSS22.0 softwares, are compared between group
Analyzed compared with using L-S-D.
2nd, experimental result
The results show that comparing with Normal group, model group mice serum uric acid level significantly raises table 1（P ＜ 0.01）;With
Model group compares, 0.01 g.kg of Allopurinol-1, hirudin 0.8,0.4 and 0.2 g.kg-1, can obviously reduce serum uric acid level
（P ＜ 0.01, P ＜ 0.05）.
1 hirudin of table causes hypoxanthine the influence of hyperuricemia mice serum uric acid（, n=10）
Compared with model group：* P ＜ 0.05, * * P ＜ 0.01.
Embodiment 2：The influence for the hyperuricemia mice serum uric acid that hirudin induces Oteracil Potassium
Material：Hirudin, allopurinol tablet, Oteracil Potassium, uric acid reagent box.
Experimental animal：Kunming mouse.
1st, experimental method
Choose weight 18~22 g Kunming mouses 70, male is randomly divided into 10 groups, every group of l0 only, i.e. control group, model
Group, positive drug Allopurinol (0.005 g.kg-1) group, golden-rimmed leech dry powder（2.0 g medicinal materials .kg-1）Group, hirudin are high, medium and low
Dosage (0.8,0.4,0.2 g medicinal materials .kg-1) group.Each group ig is administered, and 1 time a day, control group and model group ig give isometric steaming
Distilled water, continuous 45 d.In addition to control group, the daily gavage of each group mouse gives 2.5 g.kg-1The Oteracil Potassium of weight, replicates high urine
Acidaemia model.After 1 h of last dose, in addition to control group, the daily gavage of each group mouse gives Oteracil Potassium, and eyeball takes after 3 h
Blood, 3 000 r/min centrifuge 10 min, take supernatant to measure serum uric acid level (phosphotungstic acid colorimetric method).
Data are represented with (average value ± standard error), are carried out one-way analysis of variance using SPSS22.0 softwares, are compared between group
Analyzed compared with using L-S-D.
2nd, experimental result
The results show that comparing with Normal group, model group mice serum uric acid level significantly raises table 2（P ＜ 0.01）；With mould
Type group compares, 0.005 g.kg of Allopurinol-1, hirudin 0.8,0.4 and 0.2 g.kg-1, can obviously reduce serum uric acid level（P
＜ 0.01, P ＜ 0.05）.
2 hirudin of table causes Oteracil Potassium the influence of hyperuricemia mice serum uric acid（, n=10）
Compared with model group：* P ＜ 0.05, * * P ＜ 0.01.
Embodiment 3：Hirudin crystallizes micro-crystal type Monosodium urate（MSU）Cause the influence of rat paw edema
Material：Hirudin, allopurinol tablet, the crystallization of micro-crystal type Monosodium urate.
Experimental animal：Wistar male rats.
1st, experimental method
The preparation of MSU：5g uric acid is put in 1000mL boiling water, with NaOH tune pH to 7.4, is heated to 95 DEG C.It is cold to put room temperature condition
But and it is gently mixed, filters up to MSU, MSU is placed in 200 DEG C of high-temperature sterilizations, face the used time is made into 100 with sterile saline
The suspension of mg/mL is spare.
Weight 180~220g Wistar male rats 50 are chosen, are randomly divided into 5 groups, every group 10, i.e. normal control
High and low (800,200 mg.kg of group, model group, positive drug allopurinol tablet group (10mg/kg), hirudin-1) dosage group.Gavage is given
Medicine, 1 time/d, Normal group and model group gavage such as give at capacity distilled water, continuous 12 d.After last dose 1h, in rat
Right 0.15 mL MSU of metapedes plantar subcutaneous injection (100 mg/mL) cause scorching, the vola pedis Zhou Jing after causing scorching front and rear measure right.See
1h, 3h, 5h, 7h, 8h pedal swelling situation and its Zhou Jing after Rat Right at different moments are examined and measured after injection, calculates its swelling
Degree.Swelling degree of the paw=(t times Zhou Jing-t0Time Zhou Jing)/t0Time Zhou Jing × 100%.
Data are represented with (average value ± standard error), are carried out one-way analysis of variance using SPSS22.0 softwares, are compared between group
Analyzed compared with using L-S-D.
2nd, experimental result
For table 3 the results show that compared with Normal group, model group rats swelling degree of the paw is significantly raised, there is significant difference (P<
0.01) modeling success, is prompted.Compared with model group, high and low (800,200 mg.kg of hirudin-1) dosage group can significantly inhibit
Rat paw edema, difference have conspicuousness (P<0.05).Prompting, hirudin have the degree of rat paw edema caused by MSU
Obvious inhibitory action.It the results are shown in Table 3.
3 hirudin of table causes MSU the influence of rat paw edema
Compared with model group：* P ＜ 0.05, * * P ＜ 0.01.
Embodiment 4：Influence of the hirudin to Patients with Hyperuricemia serum uric acid level
200 grams of hirudin (its natural hirudin content for 200 ATU/ grams) is taken, capsule, 0.2 gram/are made according to a conventional method
(leech cellulose content is 40 ATU/).Day takes 2~3 times, 2~4 every time, can prevent the diseases such as hyperuricemia, gout.
Clinical test results：Treatment high lithemia disease 102, effective 70, effective 25, invalid 7, total effective rate
93.14%, serum uric acid level is by 712 ± 97 μm of olL-1Drop to 501 ± 76 μm of olL-1。
1st, data and method
1.1 general information
All 108 are that the outpatient service of division of endocrinology of hospital meets high blood uric acid patient, are randomly divided into treatment group and control group, and each 54
Example.Include and exclusion standard hyperuricemia diagnostic criteria reference《The Chinese Consensus of experts of hyperuricemia and gout treatment》,
Sign informed consent form.Exclusion standard：1. acute gout arthritis；2. the trouble of serious kidney stone and serious kidney function damage
Person；3. Chinese medical discrimination is fire excess from yin deficiency patient.Treatment group, man 30, female 24 are average（50.6±10.1）Year, the course of disease 5
It is~24 months, average（17.6±5.8）A month.Control group, man 29, female 25 are average（49.5±11.0）Year, the course of disease 6~
It is 25 months, average（17.2±7.7）A month.Two groups of general information comparing differences are not statistically significant (P ＞ 0.05), have comparable
Property.
1.2 treatment method
1.2.1 control group mainly carries out life style guidance, including avoids the high purine food such as pluck, smoking cessation from prohibiting
Wine, daily urine volume ensure in 2 000 more than mL；Adhere to moving, control weight；Ensure sufficient sleep etc..
1.2.2 treatment group gives hirudin on the basis of the general treatment instructed using life style.Daily morning and evening before the meal
Take.
1.3 two groups of the courses for the treatment of treat observation 1 month.
1.4 two groups of observation index are before and after treatment using 3960 type iMark microplate reader detection patient's serum uric acid level.
1.5 statistical methods carry out statistical analysis using 16.0 statistical softwares of SPSS, and measurement data uses mean
± standard deviation（）Represent, examined using t.
As a result two groups of pretherapy and post-treatment uric acid by table 4 as it can be seen that treatment group treatment after uric acid decline, with this group before treatment
Difference is statistically significant（P ＜ 0.05）；Treatment group, control group comparing difference are statistically significant（P ＜ 0.05）：
The influence of table 4, hirudin to hyperuricemia patients serum levels
With this group before treatment, * P ＜ 0.05；Compared with after control group treatment, △ P ＜ 0.05.
Above-mentioned to point out, hirudin of the present invention is as preparing prevention hyperuricemia and its cause purposes in disease medicament
In, the hyperuricemia causes the case that disease is gout, obstructive sleep apnea and/or menopausal syndrome.
Claims (7)
1. hirudin is as preparing prevention hyperuricemia and its cause purposes in disease medicament.
2. purposes of the hirudin according to claim 1 as prevention antihyperuricemic disease drug, it is characterised in that：Described
Hyperuricemia causes disease to cause gout for uric acid rise.
3. purposes of the hirudin according to claim 1 as prevention antihyperuricemic disease drug, it is characterised in that：Described
Hyperuricemia causes disease to be obstructive sleep apnea and/or climacteric syndrome.
4. purposes of the hirudin according to claim 1 as prevention antihyperuricemic disease drug, it is characterised in that：Described
Hyperuricemia cause disease further include hyperuricemia caused by hypertension, hyperlipidemia, atherosclerosis, obesity, pancreas
Insulin resistance, nephrosis, inflammation, infectious diseases, tumor lysis syndrome, complication of transplanted organ and/or primary drying are comprehensive
Close disease.
5. purposes of the hirudin according to claim 1 as prevention antihyperuricemic disease drug, it is characterised in that：The water
Leech element is the clinical preparation received of pharmaceutically acceptable carrier composition.
6. purposes of the hirudin as prevention antihyperuricemic disease drug according to claim 1 or 5, it is characterised in that：Institute
Carrier is stated as diluent, excipient, filler, adhesive, wetting agent, disintegrant, sorbefacient, surfactant, absorption
Carrier or lubricant.
7. purposes of the hirudin according to claim 1 as prevention antihyperuricemic disease drug, it is characterised in that：The water
Leech element is tablet, pulvis, granula, capsule, oral liquid or injecting drug use as the medicine described in prevention hyperuricemia.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711293701.9A CN107998385A (en) | 2017-12-08 | 2017-12-08 | Purposes of the hirudin as prevention antihyperuricemic disease drug |
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| CN109999076A (en) * | 2019-05-14 | 2019-07-12 | 上海中医药大学附属曙光医院 | It is a kind of adjust reverse cholesterol transport Chinese medicine composition and its application |
| CN115429874A (en) * | 2022-09-20 | 2022-12-06 | 暨南大学 | Hirudin targeting and DPP4 inhibition for treating diabetes |
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| CN109999076A (en) * | 2019-05-14 | 2019-07-12 | 上海中医药大学附属曙光医院 | It is a kind of adjust reverse cholesterol transport Chinese medicine composition and its application |
| CN115429874A (en) * | 2022-09-20 | 2022-12-06 | 暨南大学 | Hirudin targeting and DPP4 inhibition for treating diabetes |
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