CN104666319B - Rhodioside is preparing the application in treating gout medicine - Google Patents
Rhodioside is preparing the application in treating gout medicine Download PDFInfo
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- CN104666319B CN104666319B CN201510099303.8A CN201510099303A CN104666319B CN 104666319 B CN104666319 B CN 104666319B CN 201510099303 A CN201510099303 A CN 201510099303A CN 104666319 B CN104666319 B CN 104666319B
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Abstract
The present invention provides a kind of application of rhodioside in anti-gout drugs are prepared, the particularly preventive and therapeutic effect to experimental study.The invention has the advantages that finding that rhodioside has preventive and therapeutic effect to urarthritis, experimental study is particularly.Proved by zoopery, rhodioside can mitigate Monosodium urate inducing acute gouty arthritis really.Therefore rhodioside is used to prepare anti-gout drugs, is that treatment gout provides a kind of natural or imitative natural drug, so as to reduce using the drug induced adverse reaction of gout.
Description
Technical field
The present invention relates to pharmaceutical field, particularly a kind of rhodioside to prepare the application in treating gout medicine.
Background technology
Gout is because purine metabolic disturbance and internal uric acid is excessive causes.The incidence of gout rises year by year, it has also become
The second largest metabolic disease of the mankind after diabetes.12nd national rheumatology Annual Conference report display：One to 5
The investigation of a 40197 adults of provinces and cities shows that the illness rate of gout is 0.15% to 1.3%, is increased significantly in the past 20 years
Gesture.In 65320 Shanghai people of another studies have shown that Shanghai carries out, the incidence of hyperuricemia is 11.7%, male
17.2% is more up to, and morbidity tends to rejuvenation.
The clinical characters of gout are：Hyperuricemia, acute arthritis recurrent exerbation, gout calculus, chornic arthritis and
Joint distortion, gouty kidney essence lesion.
The pathological mechanisms that treatment gout medicine occurs according to gout, are broadly divided into：Suppress uric acid synthesis, promote uric acid row
Let out, suppress the types such as inflammatory reaction.The treatment of gout acute attack mainly uses colchicin, and chronic gout treatment is mainly used
Probenecid and Allopurinol reduce uric acid in blood content.The effect of these medicines, is limited, side effect is big.Do not have also clinically
Preferable gout treatment medicine.
Urarthritis（Gouty Arthritis, GA）It is to cause serum Uric Acid Concentration to raise by purine metabolic disturbance,
Joint deposits urate crystal, a kind of metabolic osteoarthropathy triggered.Sodium urate crystals are the non-of urarthritis
Microbes pathogen.
Experimental study breaking-out is mainly by synovial membrane inflammatory cell infiltration, uric acid deposition, tissue local necrosis.In early days
Urate crystal sheds into synovia from calm synovial membrane, and the protein in synovia is adsorbed in crystal surface, and thin by synovial membrane
Born of the same parents, multinuclear leucocyte, monocyte, macrophage are swallowed, synovial membrane surface hyperemia oedema, inflammatory cell infiltration.In treatment
Use colchicin, but its adverse reaction is heavier more.
Therefore the high-efficiency low-toxicity medicine for the treatment of experimental study is explored with significance pharmaceutically.
Rhodioside（Salidroside）For a kind of known compound, its structural formula is：
Rhodioside can be extracted from plant rhodiola root, be the main active of rhodiola root.Rhodiola root is in one kind
The valuable ingredient of traditional Chinese medicine of medicine, Tibetan medicine.Rhodioside can also be obtained by chemical synthesis at present.Pharmacological research shows that rhodioside has
There is good cardiovascular and cerebrovascular effect, it is a variety of such as to improve blood vessel function, ischemic myocardial protection, improvement heart function, anti-arrhythmia
Pharmacodynamic feature.
In addition patent research shows that rhodioside has the effect of soldier etc. is new in prevention muscular atrophy, brain.Patent
CN102727505A, which discloses rhodioside, can suppress the table of amyotrophia specific factor Atrogin-1 in amyotrophia generating process
Reach, myotube atrophy and the reduction of skeletal muscle fibre cross-sectional area, and with the content of slow switch fibers albumen in increase skeletal muscle, suppression
The effect of fast muscle fiber protein expression processed, so as to prevent and resist the generation of amyotrophia.Patent CN102846643A discloses red
Red-spotted stonecrop glycosides is preparing the application in treating c-type Fanconi anemia medicine, and rhodioside, which forms hematopoietic colonies, has stronger rush
Into effect, the exploitation for the treatment of Fanconi anemia medicine can be applied to.Patent CN103446167A discloses rhodioside and is preparing
Application in cerebral apoplexy medicine, shows good therapeutic effect in the experiment of animal correlation model, can effectively improve reduction
Nervous function damage scores, and reduces cerebral infarction volume, extends the therapeutic time window of cerebral apoplexy.
So far, the present inventor is it is not yet found that the report of rhodioside antigout.
The content of the invention
The technical problems to be solved by the invention are：A kind of application of rhodioside in anti-gout drugs are prepared is provided,
Particularly to the preventive and therapeutic effect of experimental study.
Experimental study is treated, common drug is colchicin.But colchicin has a severe toxicity, common Nausea and vomiting,
Diarrhea, abdominal pain, gastrointestinal reaction are the premonitory symptoms being seriously poisoned, and are discontinued at once when symptom occurs, and the visible blood urine of kidney damage, lack
Urine, have marrow direct repression, cause agranulocytosis, alpastic anemia.The major side effects of colchicin：
(1) digestive tract reaction：It is most common side effect.Many gout patients occur after colchicin is taken nausea,
Anorexia, vomiting, belly discomfort and diarrhea.Some patients are because can not be hard nausea and vomiting or diarrhea are more serious
Hold medication.
(2) bone marrow toxicity reacts：Mainly there is inhibitory action to the hematopoiesis function of marrow, cause Neuroleptic Leukocytopenia, regeneration
Aplastic anemia etc..
(3) liver damage：Dysfunction of liver can be caused, jaundice can occur for severe patient.
(4) kidney damage：It may occur in which albuminuria phenomenon, will not generally cause renal failure.
(5) other side effects：Including alopecia, skin allergy, mental depression etc..
Rhodiola was announced in the Ministry of Public Health in 2002《Article list available for health food》.Rhodioside is red
The main active of red-spotted stonecrop, it is safe and non-toxic, and have passed through thousands of years of the traditional Chinese medical science and Tibetan medicine's verification.
In order to solve the above-mentioned technical problem, the technical solution adopted by the present invention is as follows：Rhodioside is preparing treatment gout
Application in medicine.
The gout is urarthritis.
The urarthritis is experimental study.
The medicine is the pharmaceutical composition containing rhodioside and using rhodioside as active ingredient.
The present invention observes rhodiola root by using joint cavity injection Monosodium urate induced rat experimental study model
Prevention effect of the glycosides to the model.
The present invention uses joint cavity injection Monosodium urate induced rat experimental study model, calculates rat articular swelling
Degree, has carried out rat behavior scoring, rat leukocyte detection, ankle-joint chamber hydrops smear, the section sight of ankle-joint pathological change
Examine.
The invention has the advantages that find that rhodioside has urarthritis preventive and therapeutic effect, it is particularly acute
Gouty arthritis.Proved by zoopery, rhodioside can mitigate Monosodium urate inducing acute gouty arthritis really.Therefore will
Rhodioside is used to prepare anti-gout drugs, is that treatment gout provides a kind of natural or imitative natural drug, so as to reduce use
The drug induced adverse reaction of gout.The mechanism of rhodioside treatment experimental study need to be studied further.The present invention is
The follow-up study that rhodioside is used for experimental study provides the foundation pharmacology foundation.
Brief description of the drawings
Fig. 1 is that the ankle-joint hydrops HE that rhodioside influences Monosodium urate inducing acute gouty arthritis dyes typical figure
Piece.Normal group（A）；Model control group（B）；Low dose group（C）；High dose group（D）；Positive controls（E）.
Fig. 2 is that the ankle-joint HE that rhodioside influences Monosodium urate inducing acute gouty arthritis dyes typical picture（×
40）.Normal group（A）；Model control group（B）；Low dose group（C）；High dose group（D）；Positive controls（E）.
Fig. 3 is that the ankle-joint HE that rhodioside influences Monosodium urate inducing acute gouty arthritis dyes typical picture（×
400）.Normal group（A）；Model control group（B）；Low dose group（C）；High dose group（D）；Positive controls（E）.
Embodiment
Illustrated with reference to specific embodiment.
Embodiment 1
1 material
1.1 animal
Male SD rat 40, weight 150-200g, is provided by Disease Prevention Control Center, Hubei Prov, animal licensing
Number：SCXK（Hubei Province）2008-0005.
1.2 instrument
Electronic analytical balance（FA1204B, Shanghai precision instrumentation Co., Ltd）；High speed freezing centrifuge（F45-30,
German Eppendorf companies）；Microscope（BM4000B, German Leica companies）；Paraffin slicing machine（Sandon companies of the U.S.）.
1.3 reagents and reagent
Rhodioside is provided by Wuhan Synchallenge Unipharm Inc., HPLC identification purity>99%；Colchicin
For Banna Pharmacy Industry Co., Ltd., Xishuangbanna's product, 0.5 mg/ pieces, 20/box, Chinese medicines quasi-word H53021369, lot number
B1420211502；Monosodium urate is purchased from Sigma Co., USA.
2 methods
The configuration of 2.1 solution：3.0 g Monosodium urates are added in 100 mL distilled water and boils and is sufficiently stirred, wait Monosodium urate
After being completely dissolved, handled by ultrasonication, be configured to 3.0% Monosodium urate solution for standby.
The preparation of 2.2 experimental study models：0.6% yellow Jackets of rats by intraperitoneal injection are given after 5 d of gavage（10
ml/kg）Anaesthetize, fixation of lying on the back, right hind ankle-joint after iodophor disinfection, with No. 6 injection needles in rat right hind leg ankle-joint behind
It is inserted into from 45 degree of directions on the inside of shin bone tendon, feels to have and fall through after sense, 3.0% uric acid sodium solution of injected slurry volume fraction, 50 μ L, with
Capsular ligament offside is heaved for injection standard, prepares experimental study model.The injection of control group right hind ankle-joint is isometric
Physiological saline.
2.3 animal packets and administration：Experimental animal adaptability is randomly divided into 5 groups, every group 8 after raising 7 d.Specific packet
It is as follows：Normal group；Model control group；Low, high dose group；Positive controls.Low, high dose group distinguishes gavage to rhodiola root
40 and 80 mg/kg of glycosides, once a day, 7 d of successive administration.Positive controls gavage gives colchicin 0.15 mg/kg.It is normal right
The capacity distilled water gavage such as give according to group and model group.Rat right hind leg ankle-joint injected slurry volume fraction 3.0% is given after 5 d of gavage
50 μ L of uric acid sodium solution prepare experimental study model.Normal group right hind ankle-joint injects isometric physiology salt
Water.
2.4 Testing index：
2.4.1 rat articular swelling：2,4,8,12,24 and 48 h measure the right side with thread method after 1 h and modeling before modeling
The same position Zhou Jing of hind leg ankle-joint, swelling rate is calculated according to the following formula.Swelling（%）=（Right hind ankle-joint is all after causing inflammation
Footpath-cause inflammation forelimb ankle-joint Zhou Jing）/ cause right hind ankle-joint Zhou Jing × 100% before inflammation.
2.4.2 rat behavior scores：9 h and 24 h observations rat gait after modeling.Specific standards of grading are as follows：0 point
For normal gait, biped uniformly lands；1 point is walked lamely to be slight, and tested lower limb are slightly bent；2 points are walked lamely for moderate, tested lower limb
Just touch ground；3 points are walked lamely for severe, and tested lower limb leave ground, and tripodia lands walking.
2.4.3 leukocyte counts：Every group of rat peripheral blood examination is taken to survey the change of leukocyte count.
2.4.4 ankle-joint chamber hydrops smear detects：It is inserted into behind in rat right hind leg ankle-joint with No. 5 syringe needles and extracts pass
Hydrops is saved, the hydrops articuli extracted is uniformly coated on glass slide, Hematoxylin-eosin（HE）Dyeing, light Microscopic observation ankle
Hydrops articuli inflammatory cell infiltration situation.
2.4.5 the observation of rat ankle joint pathological change：Each group rat is put to death after 48 h of modeling, takes its ankle-joint in 10%
Paraformaldehyde solution is fixed, and EDTA-2Na solution carries out decalcification, conventional dehydration, transparent, embedding, section and Hematoxylin-eosin
（HE）Dyeing, light Microscopic observation ankle-joint Histopathologic changes.
2.5 statistical method：Measurement data result use (± s) represent, using Medical Statistics software SPSS 11.5 into
Row variance analysis.Ranked data are analyzed using Ridit.With P<0.05 is to have significant difference.
3 results
The influence of the experimental study rat model ankle swelling rate of 3.1 pairs of Monosodium urate inductions
As a result, there is obvious tumefaction in 2-48 h in each modeling group rat ankle joint, with Normal group ratio, model comparison
Right ankle swelling degree of the group rat at each time point dramatically increases, and swelling rate reaches as high as more than 30%, shows to be successfully established
Experimental study rat model.It is big that rhodioside in 2-48 h can reduce acute gouty arthritis to some extent
Mouse Articular swelling, and be in dose dependent, wherein high dose group effect is more notable, and substantially suitable the effect of colchicin
（Table 1）.
Note：Compared with Normal group,** P＜ 0.01；Compared with model control group,# P＜ 0.05,## P＜ 0.01
The influence of the acute gouty arthritis rat behavior scoring of 3.2 pairs of uric acid sodium solution inductions
As a result, after 9 h of modeling, model control group activities in rats starts to reduce, and right hind bending is obvious, and shows different journeys
The limping of degree, 24 h performances are the most obvious, can continue until 36 h.Ridit analysis results show that five groups of rat behavior scorings have
Marked difference.Compared with Normal group, model control rats neurological deficit score dramatically increases after 24 h of modeling, illustrates successfully
It is prepared for acute gouty arthritis model.Compared with model control group, low, high dose group rat behavior scoring has difference
Degree reduces（Table 2）.
The influence for the acute gouty arthritis rat behavior scoring that 2 rhodioside of table induces Monosodium urate
Note：Compared with Normal group,** P＜ 0.01
The influence of the acute gouty arthritis rat peripheral Leukocyte Counts of 3.3 pairs of Monosodium urate inductions
As a result, with Normal group ratio, model control group peripheral white blood cell amount dramatically increases.Rhodioside can dosage
Dependence reduces acute gouty arthritis rat peripheral blood leukocytes quantity, and wherein high dose rhodioside effect is more aobvious
Write, the effect with colchicin is substantially suitable（Table 3）.
The influence for the acute gouty arthritis rat peripheral Leukocyte Counts that 3 rhodioside of table induces Monosodium urate
Note：Compared with Normal group,** P＜ 0.01；Compared with model control group,# P＜ 0.05
The influence of the acute gouty arthritis rat ankle joint pathological change of 3.4 pairs of Monosodium urate inductions
Ankle-joint hydrops pathological observation is the results show that visible a large amount of inflammation are thin in model control group rat ankle joint hydrops
Born of the same parents.Rhodioside is low, inflammatory cell has different degrees of reduction, wherein high dose group in high dose group rat ankle joint hydrops
Effect is more notable, and the effect with colchicin is substantially suitable, as shown in Figure 1.
Synovial membrane pathological observation is the results show that blank control group rat ankle joint synovial membrane and surrounding tissue are normal, no inflammatory
Cellular infiltration；Model group rats Ankle Joint Inflammation is more significant, and synovial membrane rough surface is uneven, congestion and edema, it is seen that substantial amounts of inflammatory
Cellular infiltration, synovial membrane are presented hyperplasia sample and change；Each dosage group of rhodioside and positive drug（Colchicin）Group Ankle Joint Inflammation
Different degrees of mitigation, surrounding soft tissue's hyperemia is not notable, and inflammatory cell infiltration significantly reduces, as shown in Figures 2 and 3.
Embodiment 2
Rhodioside 50g, medical starch 72g, microcrystalline cellulose 20g are taken, medical starch is dried, excessively 80 mesh sieves, then with
Rhodioside, microcrystalline cellulose mixing, cross 80 mesh sieves, insert in hard shell capsules, 1000 capsules are made.Every hard shell capsules contain red scape
Its glycosides 50mg.
Embodiment 3
Acute toxicity test
Rhodioside 1g/kg prepared by 20 tested SD Oral Administration in Rats embodiments 2, is observed 14 days.During the experiment is tested big
None is dead for mouse, slightly dry dynamic outer during tested rat is administered, not it was observed that other acute toxic reactions.The result shows that SD is big
Mouse rhodioside LD50 ＞ 1g/kg.
It is by oral administration 5mg/kg with the SD rats LD50 of colchicin.Rat oral LD50≤50mg/kg is severe toxicityization
Product, illustrate that colchicin belongs to toxic articles.The security of rhodioside is very high, this experiment does not find acute toxicity.
Claims (3)
1. rhodioside is preparing the application in treating gout medicine, it is characterised in that：The rhodioside purity>99%；It is described
Gout is urarthritis.
2. application according to claim 1, it is characterised in that：The urarthritis is experimental study.
3. application according to claim 1 or 2, it is characterised in that：The medicine is containing rhodioside and with rhodioside
For the pharmaceutical composition of active ingredient.
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Non-Patent Citations (3)
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| 痛风性关节炎动物模型的改良;姚丽;《中国实验动物学报》;20060630;第17卷(第3期);第1页第3段 * |
| 糖苷化在糖类药物中的作用和应用;李英霞;《山东省药学会药物化学与抗生素专业委员会会议资料》;20071231;第3页第2段 * |
| 红景天甙元的药理研究;袁文学;《沈阳药学院学报》;19870531;第4卷(第2期);第3页倒数第2段,第2页倒数第1段 * |
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