CN104666319A - Application of salidroside in preparation of medicine for treating gouty arthritis - Google Patents
Application of salidroside in preparation of medicine for treating gouty arthritis Download PDFInfo
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- CN104666319A CN104666319A CN201510099303.8A CN201510099303A CN104666319A CN 104666319 A CN104666319 A CN 104666319A CN 201510099303 A CN201510099303 A CN 201510099303A CN 104666319 A CN104666319 A CN 104666319A
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Abstract
The invention provides an application of salidroside in preparation of a medicine for resisting gouty arthritis, and particularly relates to prevention and curing functions of salidroside on acute gouty arthritis. The salidroside has the benefits as follows: the salidroside has prevention and curing functions on gouty arthritis, especially acute gouty arthritis. The animal experiment proves that sodium urate induced acute gouty arthritis can really be relieved by the salidroside. Therefore, when the salidroside is applied to preparation of the medicine for resisting gouty arthritis, one natural or natural-like medicine can be provided for treatment of gouty arthritis, and adverse effects caused by the medicine for treating gouty arthritis are reduced.
Description
Technical field
The present invention relates to pharmaceutical field, the particularly application of a kind of rhodioside in preparation treatment gout medicine.
Background technology
Gout causes because of in purine metabolic disturbance and body, uric acid is too high.The sickness rate of gout rises year by year, has become the second largest metabolic disease of the mankind after diabetes.12 national rheumatology Annual Conference report display: an investigation display to 5 provinces and cities 40197 adult, the prevalence of gout is 0.15% to 1.3%, is increased significantly trend over nearly 20 years.Another the research display carried out in Shanghai, in 65320 Shanghai people, the incidence rate of hyperuricemia is 11.7%, and male is especially up to 17.2%, and morbidity is tending towards rejuvenation.
The clinical characters of gout is: distort in hyperuricemia, acute arthritis recurrent exerbation, gout calculus, chronic arthritis and joint, gouty excess of the kidney matter pathological changes.
The pathological mechanisms that treatment gout medicine occurs according to gout, is mainly divided into: suppress uric acid synthesis, promote the type such as urate excretion, inflammation-inhibiting reaction.The treatment of gout acute attack mainly adopts colchicine, and chronic gout treatment mainly reduces uric acid in blood content with probenecid and allopurinol.The curative effect of these medicines is all limited, side effect is large.Also there is no desirable gout treatment medicine clinically.
Gouty arthritis (Gouty Arthritis, GA) has purine metabolic disturbance to cause serum Uric Acid Concentration to raise, at joint deposition urate crystal, and a kind of metabolic osteoarthritis caused.Sodium urate crystals is the non-microorganism pathogen of gouty arthritis.
Experimental study outbreak is mainly deposited by synovial membrane inflammatory cell infiltration, uric acid, tissue local is downright bad.Early stage urate crystal comes off from the synovial membrane of calmness and enters synovial fluid, the protein adsorption in synovial fluid in crystal surface, and by synovial cell, multinuclear leucocyte, monocyte, macrophage engulf, synovial membrane surface hyperemia edema, inflammatory cell infiltration.Treatment adopts colchicine more, but its untoward reaction is heavier.
Therefore the high-efficiency low-toxicity medicine of exploration treatment experimental study has significance pharmaceutically.
Rhodioside (Salidroside) is a kind of known compound, and its structural formula is:
Rhodioside can extract from plant Radix Rhodiolae, is the main active of Radix Rhodiolae.Radix Rhodiolae is the valuable ingredient of Chinese medicine of a kind of Chinese medicine, Tibetan medicine.Current rhodioside also can be obtained by chemosynthesis.Pharmacological research shows that rhodioside has good cardiovascular and cerebrovascular vessel effect, as improved blood vessel function, ischemic myocardial protection, improving the multiple pharmacodynamic feature such as cardiac function, arrhythmia.
Patent research shows effect that rhodioside has control amyotrophy, soldier etc. is new in brain in addition.Patent CN102727505A discloses the minimizing that rhodioside can suppress the expression of amyotrophy specific factor Atrogin-1 in amyotrophy generating process, myotube atrophy and skeletal muscle fiber cross-sectional area, and there is the content increasing slow switch fibers albumen in skeletal muscle, suppress the effect of fast muscle fiber protein expression, thus prevent and resist amyotrophic generation.Patent CN102846643A discloses the application of rhodioside in preparation treatment C type Fanconi anemia medicine, and rhodioside is formed hematopoietic colonies has stronger facilitation, can be applicable to the exploitation for the treatment of Fanconi anemia medicine.Patent CN103446167A discloses rhodioside and is preparing the application in apoplexy medicine, good therapeutic effect is shown in the experiment of animal correlation model, effectively can improve and reduce nervous function damage scoring, reduce cerebral infarction volume, extend the therapeutic time window of apoplexy.
Up to now, the present inventor not yet finds that there is the report of rhodioside gout.
Summary of the invention
Technical problem to be solved by this invention is: provide a kind of rhodioside preparing the application in anti-gout drugs, particularly to the preventive and therapeutic effect of experimental study.
Treatment experimental study, common drug is colchicine.But colchicine has severe toxicity, common nausea,vomiting,diarrhea, stomachache, gastrointestinal reaction are seriously poisoning prodromes, drug withdrawal at once when symptom occurs, the visible hematuria of kidney damage, oliguria, to have direct repression, causes agranulocytosis, aplastic anemia to bone marrow.The major side effects of colchicine:
(1) digestive tract reaction: be modal side effect.Feeling sick appears in many gout patients after taking colchicine, loss of appetite, vomiting, abdominal part discomfort and diarrhoea.Some patients cannot adhere to medication because nausea and vomiting or diarrhoea are comparatively serious.
(2) bone marrow toxicity reaction: mainly have inhibitory action to the hemopoietic function of bone marrow, cause leukopenia, aplastic anemia etc.
(3) liver injury: can cause abnormal liver function, can there is jaundice in severe patient.
(4) kidney damage: can occur albuminuria phenomenon, generally can not cause renal failure.
(5) other side effect: comprise alopecia, skin allergy, spirit depressing etc.
" can be used for the article list of health food " that rhodiola was announced in Ministry of Public Health in 2002.Rhodioside is the main active of Radix Rhodiolae, safety non-toxic, and the traditional Chinese medical science that have passed through thousands of years and Tibetan medicine's checking.
In order to solve the problems of the technologies described above, the technical solution used in the present invention is as follows: the application of rhodioside in preparation treatment gout medicine.
Described gout is gouty arthritis.
Described gouty arthritis is experimental study.
Described medicine is containing rhodioside and take rhodioside as the pharmaceutical composition of active component.
The present invention, by adopting joint cavity injection Monosodium urate induced rat experimental study model, observes the prevention effect of rhodioside to this model.
The present invention adopts joint cavity injection Monosodium urate induced rat experimental study model, calculates rat articular swelling, and carried out rat behavior scoring, rat leukocyte detects, ankle joint chamber hydrops smear, ankle joint pathological change sections observation.
The invention has the beneficial effects as follows, find that rhodioside has preventive and therapeutic effect to gouty arthritis, particularly experimental study.Proved by zoopery, rhodioside can alleviate Monosodium urate inducing acute gouty arthritis really.Therefore by rhodioside for the preparation of anti-gout drugs, be that treatment gout provides a kind of natural or imitative natural drug, thus reduce and use the drug induced untoward reaction of gout.The mechanism of rhodioside treatment experimental study needs research further.To be rhodioside to provide the foundation pharmacology's foundation for the follow-up study of experimental study in the present invention.
Accompanying drawing explanation
Fig. 1 is the ankle joint hydrops HE dyeing typical picture that rhodioside affects Monosodium urate inducing acute gouty arthritis.Normal group (A); Model control group (B); Low dose group (C); High dose group (D); Positive controls (E).
Fig. 2 is ankle joint HE dyeing typical picture (× 40) that rhodioside affects Monosodium urate inducing acute gouty arthritis.Normal group (A); Model control group (B); Low dose group (C); High dose group (D); Positive controls (E).
Fig. 3 is ankle joint HE dyeing typical picture (× 400) that rhodioside affects Monosodium urate inducing acute gouty arthritis.Normal group (A); Model control group (B); Low dose group (C); High dose group (D); Positive controls (E).
Detailed description of the invention
Be described below in conjunction with specific embodiment.
embodiment 1
1 material
1.1 animal
Male SD rat 40, body weight 150-200g, is provided by Disease Prevention Control Center, Hubei Prov, animal credit number: SCXK(Hubei Province) 2008-0005.
1.2 instrument
Electronic analytical balance (FA1204B, Shanghai precision instrumentation company limited); High speed refrigerated centrifuge (F45-30, German Eppendorf company); Microscope (BM4000B, German Leica company); Paraffin slicing machine (Sandon company of the U.S.).
1.3 reagents and reagent
Rhodioside is provided by Wuhan Synchallenge Unipharm Inc., and HPLC identifies purity >99%; Colchicine is Banna Pharmacy Industry Co., Ltd., Xishuangbanna's product, 0.5 mg/ sheet, 20/box, the accurate word H53021369 of traditional Chinese medicines, lot number B1420211502; Monosodium urate purchased from American Sigma company.
2 methods
The configuration of 2.1 solution: added by 3.0 g Monosodium urate in 100 mL distilled water and boil and fully stir, after waiting Monosodium urate to dissolve completely, by ultrasonication process, is mixed with 3.0% Monosodium urate solution for standby.
The preparation of 2.2 experimental study models: give rats by intraperitoneal injection 0.6% pentobarbital sodium (10 ml/kg) anesthesia after gavage 5 d, lie on the back fixing, right hind ankle joint after iodophor disinfection, be inserted into inside tibia tendon from 45 degree of directions with No. 6 entry needles behind at rat right hind leg ankle joint, feel to have fall through sense after, injected slurry volume mark 3.0% Monosodium urate solution 50 μ L, heaves for injection standard with joint capsule offside, prepares experimental study model.Matched group right hind ankle joint injection equal-volume normal saline.
2.3 animal grouping and administrations: laboratory animal adaptability is divided into 5 groups after raising 7 d at random, often organizes 8.Specifically be grouped as follows: Normal group; Model control group; Low, high dose group; Positive controls.Low, high dose group distinguishes gavage to rhodioside 40 and 80 mg/kg, once a day, and successive administration 7 d.Positive controls gavage is to colchicine 0.15 mg/kg.The capacity distilled water gavages such as Normal group and model group give.Prepare experimental study model to after gavage 5 d rat right hind leg ankle joint injected slurry volume mark 3.0% Monosodium urate solution 50 μ L.Normal group right hind ankle joint injection equal-volume normal saline.
2.4 Testing index:
2.4.1 rat articular swelling: before modeling, after 1 h and modeling, 2,4,8,12,24 and 48 h thread methods measure the same position Zhou Jing of right hind ankle joint, according to following formulae discovery swelling rate.Swelling (%)=(right hind ankle joint Zhou Jing after causing inflammation-cause scorching forelimb ankle joint Zhou Jing)/cause scorching front right hind ankle joint Zhou Jing × 100%.
2.4.2 rat behavior scoring: after modeling, 9 h and 24 h observe rat gait.Concrete standards of grading are as follows: 0 is divided into normal gait, and biped evenly lands; 1 is divided into slight limping, and tested lower limb are slightly bending; 2 are divided into moderate to walk lamely, and tested lower limb just touch ground; 3 are divided into severe to walk lamely, and tested lower limb leave ground, and tripodia lands walking.
2.4.3 leukocyte counts: get and often organize the change that leukocyte count is surveyed in rat peripheral blood examination.
2.4.4 hydrops smear in ankle joint chamber detects: at rat right hind leg ankle joint with No. 5 syringe needles insert and extract hydrarthrosis behind, the hydrarthrosis extracted is coated on microscope slide uniformly, Hematoxylin-eosin (HE) dyes, light Microscopic observation ankle joint hydrops inflammatory cell infiltration situation.
2.4.5 the observation of rat ankle joint pathological change: put to death each group of rat after modeling 48 h, get its ankle joint to fix in 10% paraformaldehyde solution, 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 is used (
± s) represent, adopt medicostatistics software SPSS 11.5 to carry out variance analysis.Ranked data adopt Ridit to analyze.With P<0.05 for there being significant difference.
3 results
3.1 impacts of experimental study rat model ankle swelling rate on Monosodium urate induction
Result, there is obvious tumefaction at 2-48 h in each modeling group rat ankle joint, with Normal group ratio, model control group rat all significantly increases at the right ankle swelling degree of each time point, swelling rate reaches as high as more than 30%, shows successfully to establish experimental study rat model.Rhodioside all can reduce acute gouty arthritis rat articular swelling to some extent at 2-48 h, and in dose dependent, wherein high dose group effect is comparatively remarkable, with the curative effect substantially suitable (table 1) of colchicine.
Note: compare with Normal group,
* p< 0.01; Compare with model control group,
# p< 0.05,
## p< 0.01
3.2 impacts that the acute gouty arthritis rat behavior of Monosodium urate solution induction is marked
As a result, after modeling 9 h, model control group activities in rats starts to reduce, and right hind is obviously bending, and performance limping in various degree, 24 h performances are the most obvious, can continue until 36 h.Ridit analysis result shows, five groups of rat behavior scorings have marked difference.Compared with Normal group, after modeling 24 h, model control rats neurological deficit score significantly increases, and illustrates and has successfully prepared acute gouty arthritis model.Compared with model control group, low, high dose group rat behavior scoring all has reduction (table 2) in various degree.
Table 2 rhodioside is on the impact of the acute gouty arthritis rat behavior scoring that Monosodium urate is induced
Note: compare with Normal group,
* p< 0.01
3.3 impacts of acute gouty arthritis rat peripheral Leukocyte Counts on Monosodium urate induction
As a result, with Normal group ratio, model control group peripheral white blood cell amount significantly increases.Rhodioside can reduce acute gouty arthritis rat peripheral blood leukocytes quantity by dose dependent, and wherein high dose rhodioside effect is comparatively remarkable, with the effect substantially suitable (table 3) of colchicine.
Table 3 rhodioside is on the impact of the acute gouty arthritis rat peripheral Leukocyte Counts that Monosodium urate is induced
Note: compare with Normal group,
* p< 0.01; Compare with model control group,
# p< 0.05
3.4 impacts of acute gouty arthritis rat ankle joint pathological change on Monosodium urate induction
Ankle joint hydrops pathological observation result shows, visible a large amount of inflammatory cell in model control group rat ankle joint hydrops.Rhodioside is low, inflammatory cell all has minimizing in various degree in high dose group rat ankle joint hydrops, and wherein high dose group effect is comparatively remarkable, substantially suitable with the effect of colchicine, as shown in Figure 1.
Synovial membrane pathological observation result shows, and blank group rat ankle joint synovial membrane and surrounding tissue are normal, without inflammatory cell infiltration; Model group rats Ankle Joint Inflammation is comparatively remarkable, and synovial membrane rough surface is uneven, congestion and edema, inflammatory cell infiltrations a large amount of as seen, and synovial membrane presents hypertrophy sample and changes; The each dosage group of rhodioside and positive drug (colchicine) organize Ankle Joint Inflammation alleviating all in various degree, and surrounding soft tissue's hyperemia is remarkable, and inflammatory cell infiltration obviously reduces, as shown in Figures 2 and 3.
embodiment 2
Get rhodioside 50g, medical starch 72g, microcrystalline Cellulose 20g, medical starch is dry, cross 80 mesh sieves, then mix with rhodioside, microcrystalline Cellulose, cross 80 mesh sieves, insert in hard capsule, make 1000 capsules.Every hard capsule is containing rhodioside 50mg.
embodiment 3
Acute toxicity test
The rhodioside 1g/kg of 20 tested SD Oral Administration in Rats embodiment 2 preparations, observes 14 days.None is dead for the tested rat of experimental session, except during tested rat administration slightly dry dynamic except, do not observe other acute toxic reaction.Result shows SD rat rhodioside LD50 > 1g/kg.
The SD rat LD50 of oral administration colchicine is 5mg/kg.Rat oral LD50≤50mg/kg is severe poisonous chemicals, illustrates that colchicine belongs to toxic articles.The safety of rhodioside is very high, and this test does not find acute toxicity.
Claims (4)
1. the application of rhodioside in preparation treatment gout medicine.
2. application according to claim 1, is characterized in that: described gout is gouty arthritis.
3. application according to claim 2, is characterized in that: described gouty arthritis is experimental study.
4. the application according to claim 1 or 2 or 3, is characterized in that: described medicine is containing rhodioside and take rhodioside as the pharmaceutical composition of active component.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017125076A1 (en) * | 2016-01-21 | 2017-07-27 | 重庆大学 | Application of rhodioloside for preparing pharmaceutical product for treating ischemic disease |
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Non-Patent Citations (3)
| Title |
|---|
| 姚丽: "痛风性关节炎动物模型的改良", 《中国实验动物学报》 * |
| 李英霞: "糖苷化在糖类药物中的作用和应用", 《山东省药学会药物化学与抗生素专业委员会会议资料》 * |
| 袁文学: "红景天甙元的药理研究", 《沈阳药学院学报》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017125076A1 (en) * | 2016-01-21 | 2017-07-27 | 重庆大学 | Application of rhodioloside for preparing pharmaceutical product for treating ischemic disease |
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