CN103393761A - Application of nymphaea hybrid extract in preparing drugs for treatment of gout, hyperuricemia and uric acid nephropathy and preparation method of nymphaea hybrid extract - Google Patents

Application of nymphaea hybrid extract in preparing drugs for treatment of gout, hyperuricemia and uric acid nephropathy and preparation method of nymphaea hybrid extract Download PDF

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CN103393761A
CN103393761A CN2013103351556A CN201310335155A CN103393761A CN 103393761 A CN103393761 A CN 103393761A CN 2013103351556 A CN2013103351556 A CN 2013103351556A CN 201310335155 A CN201310335155 A CN 201310335155A CN 103393761 A CN103393761 A CN 103393761A
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flos nelumbinis
uric acid
extract
water extract
perfume flos
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张卫明
单承莺
姜洪芳
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NANJING INSTITUTE FOR COMPREHENSIVE UTILIZATION OF WILD PLANT CHINA CO-OP
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NANJING INSTITUTE FOR COMPREHENSIVE UTILIZATION OF WILD PLANT CHINA CO-OP
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Abstract

The invention relates to medical new application and a preparation method of a nymphaea hybrid extract. Studies of the invention show that: the nymphaea hybrid aqueous extract can effectively reduce the blood serum blood uric acid level in a mice hyperuricemia model, one of the mechanisms of the the nymphaea hybrid aqueous extract is that: through inhibition of in-vivo xanthine oxidase activity, the formation of uric acid is inhibited and uric acid excretion is promoted. Hyperuricemia damages physiological functions of the kidney with increasing of urea nitrogen concentration being shown, and the nymphaea hybrid aqueous extract can reduce the blood uric acid, reduce stimulation of the uric acid on the kidney, and has a therapeutic effect on uric acid nephropathy. Therefore, the nymphaea hybrid aqueous extract can be used for preparing drugs for the treatment of gout, the hyperuricemia and the uric acid nephropathy.

Description

Perfume Flos Nelumbinis extract application in preparation treatment gout, hyperuricemia and urate nephropathy medicine and preparation method thereof
Technical field
The present invention relates to the new purposes of perfume Flos Nelumbinis extract in medical science, especially relate to the new purposes of perfume Flos Nelumbinis water extract in preparation treatment gout, hyperuricemia and urate nephropathy medicine.
Background technology
Gout (gout) is the disease that chronic purine metabolism obstacle causes in body, be mainly due to uricopoiesis increase and (or) underexcretion, uric acid deposits in vivo, the pathophysiological change that causes.Gout shows as hyperuricemia, and the gouty of repeatedly showing effect acute arthritis, tophus, urate nephropathy, often accompany lithangiuria, and severe patient is joint deformity and dysfunction.Hyperuricemia is only arranged, or hyperuricemia merging uric acid nephrolithiasis, still be not defined as gout.At present, China's prevalence of gout was reaches 0.84% at population, and l200 ten thousand people are approximately arranged; Wherein 95% is the male patient; Men and women's ratio is about 20:1.China hyperuricemia person approximately has 1.2 hundred million (account for total population 10%); Age male occurred frequently is 50~59 years old, and the women is (estrogen has the uricosuric Excretion) after menopause.5~12% Patients with Hyperuricemia can develop into gout.
The most reason of gout is not bright, and 1% has found out congenital enzyme defects.Find that now birth defect has following two types: (1) polygenic inheritance defect, cause tubular secretion uric acid dysfunction, make underexcretion, cause hyperuricemia; (2) enzyme and metabolic deficiency,, for the X chromosome dominant inheritance, strengthen hypoxanthine-guanine phosphoribosyl transferase (HGPRT) Defect as 1-pyrophosphoric acid-5-ribose pyrophosphoric acid (PRPP) synthase activity, all can make the synthetic increase of purine, cause uricopoiesis to increase.
Along with the raising of China's living standards of the people, the sickness rate of gout has the trend that rises year by year.The conventional medicine of western medical treatment primary disease is the medicines such as colchicine, allopurinol and nonsteroidal antiinflammatory drug, certain curative effect is arranged, but side effect is comparatively remarkable, and digestive system and hepatic and renal function all have a certain impact.
Colchicine (colchicine) is the quick specific medicine for the treatment of at present gouty arthritis.The low dose of oral administration of general employing, but the oral diarrhoea that easily causes waits the intestines and stomach reaction; Also have and adopt low dose of intravenous administration, think side effect such as can avoiding diarrhoea, vomiting, but also have the scholar to dissent to this.Though colchicine is relief of symptoms rapidly, without the effect that reduces blood uric acid, and side effect is larger, and gastrointestinal reaction is strong, and liver, renal function and hemopoietic system are all had infringement, also has the scholar to think that it has carcinogenic risk.
Allopurinol is the medicine that suppresses uricopoiesis, and its mechanism of action is that the competitive inhibition xanthine oxidase reduces uricopoiesis, also can share and heighten the effect of a treatment with uricosuric.Its main side effects is liver, renal function injury (as interstitial nephritis) and bone marrow depression etc.Think in the past the patient who is applicable to renal hypofunction, but more deep to its serious toxic and side effects understanding in recent years, limited it in the paracmastic application of ventilating.
NSAID (non-steroidal anti-inflammatory drug),, as indomethacin, diclofenac, also can cause serious untoward reaction, and as digestive tract hemorrhage, aplastic anemia, hepatic and renal function injure etc., toxic and side effects is larger.
Adopt the Chinese medicine gout because curative effect is affirmed, untoward reaction is few, more and more is subject to the attention of medical circle.
Summary of the invention:
The objective of the invention is to overcome above-mentioned weak point, the application in preparation treatment gout, hyperuricemia and urate nephropathy medicine of a kind of perfume Flos Nelumbinis extract, particularly perfume Flos Nelumbinis water extract is provided.
Perfume Flos Nelumbinis (Nymphaea hybrid) is the large-scale Flos nymphaeae (Nymphaea teragona Georgi) in the Nymphaeceae Nymphaea torrid zone, is a kind of perennial root flowering marsh plants.20 century 70 China Taiwan gardens departments on the basis of introducing U.S.'s XIANGLIAN, cultivate and form through selection-breeding for many years, and the south China number is economized and started to introduce a fine variety in recent years, and has developed into certain scale.The perfume Flos Nelumbinis has certain cold tolerance, can bloom incessantly the whole year at suitable temperature, and the individual plant flower yield occupies the hat of the various Flos Nelumbinises in the world or Flos Nelumbinis.Perfume Flos Nelumbinis not only flower is very large, bright in luster, and more rare is that they also have elegant pleasant fragrance simultaneously, can be described as the advantage that integrates various places, world today lotus, lotus appreciable variety.
The present invention is achieved by the following technical solutions:
The perfume Flos Nelumbinis extract is applied in preparation treatment gout, hyperuricemia and urate nephropathy medicine as active component.
Above-mentioned perfume Flos Nelumbinis extract refers to perfume Flos Nelumbinis water extract, can prepare by the following method: get perfume Flos Nelumbinis dry product, add the decocting of 10~12 times of amounts to boil 1~3 time, and each 2~3 hours, filter, merging filtrate, concentrating under reduced pressure, obtain.
Described perfume Flos Nelumbinis extract, as active component, can be prepared into compositions with pharmaceutically acceptable carrier.
Above-mentioned pharmaceutically acceptable carrier comprises the adjuvant of oral formulations adjuvant or parenteral administration.Route of administration can be oral, injection, topical etc.According to technical scheme of the present invention, said composition can be oral formulations or injection preparation, and wherein oral formulations comprises capsule, soft capsule, granule, oral liquid, tablet, drop pill etc.Adjuvant used comprises: the conventional adjuvants such as sucrose, starch, lactose, glucose, mannose, xylitol, Polyethylene Glycol, isopropyl alcohol, tween 80, glycerol, propylene glycol, microcrystalline Cellulose sodium, dextrin, cyclodextrin, sodium chloride, vitamin C, cysteine, citric acid, sodium thiosulfate, sodium sulfite, stearate and gelatin, preparation later stage preparation technology and equipment all belong to the routine techniques of pharmaceutical field, the present invention is not construed as limiting this, therefore at this, will not describe in detail.
The dosage of above-mentioned composition oral administration is 2~3 times/days, amounts to the raw-material dosage of perfume Flos Nelumbinis at every turn and is respectively 3g/ time.The perfume Flos Nelumbinis is safe to use, without overt toxicity (done acute toxicity test, for reality nontoxic).Perfume Flos Nelumbinis extract of the present invention extracts and obtains from natural plants perfume Flos Nelumbinis, the test of pesticide effectiveness shows, the perfume Flos Nelumbinis extract, especially perfume Flos Nelumbinis water extract, has xanthine oxidase activity in the hyperuricemia model of inhibition animal body, can reduce the utmost point remarkable effect of animal pattern serum uric acid, also have simultaneously the utmost point remarkable effect of repairing the injury of kidney that hyperuricemia causes.
Beneficial effect of the present invention compared with the prior art: present anti-gout drugs is mainly the purine oxidase inhibitor, this research shows the perfume Flos Nelumbinis extract first, and particularly perfume Flos Nelumbinis water extract has the pharmacologically active of uric acid resisting gout and the activity of the courageous and upright injury of kidney of reparation metabolic arthritis.Research shows that the uric acid resisting effect of perfume Flos Nelumbinis extract is mainly to realize by the kidney discharge capacity of repairing the courageous and upright injury of kidney of metabolic arthritis, increase uric acid.Therefore, the perfume Flos Nelumbinis extract has the prospect that is developed to anti-hyperuricemia, gout and repairs the medicine of the courageous and upright injury of kidney of metabolic arthritis.
The specific embodiment:
Embodiment 1 perfume Flos Nelumbinis (Nymphaea hybrid) is with the preparation of the ovary water extract of pistil
Get the ovary dry product 500g of perfume Flos Nelumbinis (Nymphaea hybrid) with pistil, add in the 10000mL round-bottomed flask, add the 6000mL distilled water, heating and refluxing extraction 3 hours, filtered while hot obtains filtrate; Medicinal residues add 4000mL distilled water heating and refluxing extraction 2 hours again, and filtered while hot obtains filtrate; Merging filtrate, concentrating under reduced pressure is removed moisture, obtains the ovary water extract 248g of perfume Flos Nelumbinis band pistil.
Embodiment 2 perfume Flos Nelumbinis (Nymphaea hybrid) are with the preparation of the ovary water extract of pistil
Get the ovary dry product 500g of perfume Flos Nelumbinis (Nymphaea hybrid) with pistil, add in the 10000mL round-bottomed flask, add the 6000mL distilled water, heating and refluxing extraction 3 hours, filtered while hot obtains filtrate; Filtrate is carried out concentrating under reduced pressure remove moisture, obtain the ovary water extract 179g of perfume Flos Nelumbinis band pistil.
Embodiment 3 perfume Flos Nelumbinis (Nymphaea hybrid) are with the preparation of the ovary water extract of pistil
Get the ovary dry product 500g of perfume Flos Nelumbinis (Nymphaea hybrid) with pistil, add in the 10000mL round-bottomed flask, add the 6000mL distilled water, heating and refluxing extraction 2 hours, filtered while hot obtains filtrate; Medicinal residues add 4000mL distilled water heating and refluxing extraction 2 hours again, and filtered while hot obtains filtrate; Medicinal residues add 4000mL distilled water heating and refluxing extraction 2 hours again, and filtered while hot obtains filtrate; Merging filtrate, concentrating under reduced pressure is removed moisture, obtains the ovary water extract 295g of perfume Flos Nelumbinis band pistil.
The preparation of embodiment 4 perfume Flos Nelumbinis (Nymphaea hybrid) holder water extract
Get perfume Flos Nelumbinis (Nymphaea hybrid) holder dry product 500g, add in the 10000mL round-bottomed flask, add the 6000mL distilled water, heating and refluxing extraction 3 hours, filtered while hot obtains filtrate; Medicinal residues add 4000mL distilled water heating and refluxing extraction 2 hours again, and filtered while hot obtains filtrate; Merging filtrate, concentrating under reduced pressure is removed moisture, obtains perfume Flos Nelumbinis holder water extract 265g.
The preparation of embodiment 5 perfume Flos Nelumbinis (Nymphaea hybrid) holder water extract
Get perfume Flos Nelumbinis (Nymphaea hybrid) holder dry product 500g, add in the 10000mL round-bottomed flask, add the 6000mL distilled water, heating and refluxing extraction 2 hours, filtered while hot obtains filtrate; Filtrate is carried out concentrating under reduced pressure remove moisture, obtain perfume Flos Nelumbinis holder water extract 189g.
The preparation of embodiment 6 perfume Flos Nelumbinis (Nymphaea hybrid) holder water extract
Get perfume Flos Nelumbinis (Nymphaea hybrid) holder dry product 500g, add in the 10000mL round-bottomed flask, add the 6000mL distilled water, heating and refluxing extraction 3 hours, filtered while hot obtains filtrate; Medicinal residues add 6000mL distilled water heating and refluxing extraction 3 hours again, and filtered while hot obtains filtrate; Medicinal residues add 6000mL distilled water heating and refluxing extraction 3 hours again, and filtered while hot obtains filtrate; Merging filtrate, concentrating under reduced pressure is removed moisture, obtains perfume Flos Nelumbinis holder water extract 321g.
The preparation of embodiment 7 perfume Flos Nelumbinis (Nymphaea hybrid) plant root water extract
Get perfume Flos Nelumbinis (Nymphaea hybrid) plant root dry product 500g, add in the 10000mL round-bottomed flask, add the 6000mL distilled water, heating and refluxing extraction 3 hours, filtered while hot obtains filtrate; Medicinal residues add 4000mL distilled water heating and refluxing extraction 2 hours again, and filtered while hot obtains filtrate; Merging filtrate, concentrating under reduced pressure is removed moisture, obtains perfume Flos Nelumbinis plant root water extract 260g.
The preparation of embodiment 8 perfume Flos Nelumbinis (Nymphaea hybrid) plant root water extract
Get perfume Flos Nelumbinis (Nymphaea hybrid) plant root dry product 500g, add in the 10000mL round-bottomed flask, add the 4000mL distilled water, heating and refluxing extraction 2 hours, filtered while hot obtains filtrate; Filtrate is carried out concentrating under reduced pressure remove moisture, obtain perfume Flos Nelumbinis plant root water extract 174g.
The preparation of embodiment 9 perfume Flos Nelumbinis (Nymphaea hybrid) plant root water extract
Get perfume Flos Nelumbinis (Nymphaea hybrid) plant root dry product 500g, add in the 10000mL round-bottomed flask, add the 6000mL distilled water, heating and refluxing extraction 2 hours, filtered while hot obtains filtrate; Medicinal residues add 6000mL distilled water heating and refluxing extraction 2 hours again, and filtered while hot obtains filtrate; Medicinal residues add 6000mL distilled water heating and refluxing extraction 2 hours again, and filtered while hot obtains filtrate; Merging filtrate, concentrating under reduced pressure is removed moisture, obtains perfume Flos Nelumbinis plant root water extract 302g.
The acute toxicity testing of embodiment 10 perfume Flos Nelumbinis water extract dry powder to mice
Tested material is the perfume Flos Nelumbinis water extract dry powder of ovary water extract crushed after being dried (the crossing 40 mesh sieves) gained of perfume Flos Nelumbinis band pistil.
Laboratory animal is selected 60 of ICR mices, the cleaning level, and male and female half and half, body weight 22-25g left and right, provided by Yangzhou University's comparative medicine center, the Quality of Experimental Animals quality certification number: SCXK(Soviet Union) 2007-0001.Laboratory animal occupancy permit number: SYXK(Soviet Union) 2008-0003.
Experiment equipment is Feedstuff mould, electric drying oven with forced convection, electronic balance, beaker, mortar etc.
SPF Animal House experimental situation is room temperature 20-25 ℃, relative humidity 50-70%.
Experimental procedure is: mice is divided into high, medium and low dosage group at random by body weight after all adaptability is fed, each 10 of every group of male and female.Because the perfume Flos Nelumbinis water extract dry powder utmost point is insoluble in water, be difficult to take the mode administration of gavage, therefore adopt, the ovary water extract dry powder of the perfume Flos Nelumbinis band pistil mode in feedstuff that adds is carried out administration.Concrete grammar is:
SPF level experimental mouse pellet is ground and makes powder, the ovary dry powder that takes perfume Flos Nelumbinis band pistil according to the dosage of 21.5g/kg body weight, 10g/kg body weight and 5g/kg body weight adds in ground feedstuff powder (amount of taking of feedstuff powder is taken in body weight 8% forage volume according to every every 24h of mouse and calculated), mix, stir after adding appropriate hot distilled water, utilize mould to make the Mus pellet, 80 ℃ of drying formings in drying baker; After all experimental animal fasting 24h, freely ingest, feedstuff is the above-mentioned feedstuff that adds perfume Flos Nelumbinis water extract dry powder.Give normal diet after 24h, freely drink water, observe a week.
Observe and find after 24h, feedstuff is eaten up substantially.High, in and low dosage all find dead.After one week, have not yet to see experiment mice death.
Experiment conclusion is: in reference " health food check and assessment technique standard " (version in 2003) " acute toxicity test ", about acute toxicity (LD50) dosage classification relevant regulations, the oral LD50 of mice surpasses 21.5g/kg and namely thinks nontoxic.The concentration that the ovary water extract dry powder of perfume Flos Nelumbinis band pistil is made experiment material in oral feedstuff is 21.5g/kg, has no dead mouse and poisoning symptom, and its LD50 should surpass this value, therefore think nontoxic grade of this material.
The experimentation of embodiment 11 perfume Flos Nelumbinis water extract gouts, hyperuricemia and urate nephropathy
1 materials and methods
1.1 sample
Tested material is perfume Flos Nelumbinis holder water extract, with ovary water extract and the plant root water extract of pistil, the every 1g of water extract extractum is equivalent to the 2g crude drug.It is 12g/60kg that the adult takes crude drug recommended dose every day.Water extract extractum carries out the gavage intervention with the gavage liquid that deionized water is mixed with variable concentrations to laboratory animal after converting.
1.2 laboratory animal
Select 72 of the female ICR mices of cleaning level, body weight 18~22g left and right, provided by Nantong University's Experimental Animal Center, the Quality of Experimental Animals quality certification number: SCXK(Soviet Union) 2008-0010.Laboratory animal occupancy permit number: SYXK(Soviet Union) 2008-0003.
1.3 key instrument and reagent
1.3.1 instrument: visible spectrophotometer (722N, Shanghai Precision Scientific Apparatus Co., Ltd), desk centrifuge (TGL-16G, Town in Shanghai booth scientific instrument maker).
1.3.2 reagent: hypoxanthine: available from Aladdin, the 5g/ bottle; Allopurinol: available from Aladdin, the 25g/ bottle; Oteracil Potassium: available from Tokyo HuaCheng Industry Co., Ltd, the 5g/ bottle; Xanthine oxidase is measured test kit: bio-engineering research institute, lot number: 20120420 are built up in Nanjing; The testing uric acid test kit: bio-engineering research institute, lot number: 20120411 are built up in Nanjing; The blood urea nitrogen testing cassete: bio-engineering research institute, lot number: 20120326 are built up in Nanjing.
Except above instrument and reagent, also use syringe, gavage pin, pallet, small animal surgical apparatus, beaker etc. in experiment.
1.4 experimental procedure
Mice is divided into ovary water extract group, holder water extract group and the plant root water extract group of positive controls, model control group, negative control group, perfume Flos Nelumbinis band pistil at random by body weight after all adaptabilities are fed.Each treated animal uses the mode of gastric infusion to intervene, wherein model group and negative control group give normal saline, front 2 weeks of positive controls give normal saline, give allopurinol solution (concentration is equivalent to the 20mg/kg body weight) rear two weeks, the holder water extract, give dosage with the ovary water extract of pistil and plant root water extract group and be the 0.75g/kg body weight.Successive administration 30d.All experimental animals are all freely ingested.SPF Animal House experimental situation is room temperature 20-25 ℃, relative humidity 50-70%.
After the last gavage is intervened 30min, all the other each group employing Intraperitoneal injection of hypoxanthine (500mg/kg) and subcutaneous injection Oteracil Potassium (are uricase inhibitor except negative control group, 80mg/kg) Studies on Animal Models of Hyperuricemic Mice is set up in the associating modeling, negative control group injection equal-volume blank liquid.After injection 30min, each treated animal eyeball blood sampling, the centrifugal 15min of 2500r/min, get serum and survey blood uric acid, xanthine oxidase activity, urea nitrogen concentration with test kit.
Check 1.6 nephropathy is of science
Get mouse kidney after experiment finishes and fix with 10% formalin, routine is drawn materials, dehydration, paraffin embedding.Section is dyeed through HE, observation by light microscope: glomerule, the pathological changes of matter between renal tubules reaches.Observation index comprises that (1) renal tubules has or not expansion, and epithelial cell has or not degeneration, necrosis, cast, uric acid deposition; (2) between, matter has or not cell infiltration, proliferation of fibrous tissue; (3) glomerule has or not obvious atrophy, and extracellular matrix has or not hypertrophy etc.
Be 0.5 minute (slightly) according to pathological changes by gently to heavy degree, scoring respectively, 1 minute (slightly), 2 minutes (moderate), and 3 minutes (severe), be 0 minute without obvious pathological changes, cumulative obatained score, and calculate dividing equally of every group every animal.
1.5 data statistics
Use Excel2003 and SPSS13.0 statistical software to carry out data statistic analysis.Data are expressed as meansigma methods (mean) ± standard error (S.E.M.).Pathological uses the nonparametric rank test to carry out statistical analysis.
2 results
2.1 the impact of perfume Flos Nelumbinis extract on the weight of animals
Each is organized Mouse Weight and changes in Table 1.
Table 1 is respectively organized the Mouse Weight change records
Known by table 1, the experiment initial stage is respectively organized the Mouse Weight zero difference, and grouping evenly.When the 4th week experiment finishes, plant root water extract group, holder water extract group, with the ovary water extract group Mice Body weight average of pistil, there is no significant difference.Therefore, each water extract under low dosage concentration on Mouse Weight without impact.
2.2 the impact of perfume Flos Nelumbinis extract on serum uric acid and index of correlation
Respectively organize mice detection index after gavage 30d and the results are shown in lower page table 2.
Table 2 is respectively organized the mice indices relatively
Figure BDA00003613713000072
A has compared significant difference with the model matched group, P<0.05
B has compared significant difference with negative control group, P<0.05
There were significant differences with plant root water extract group ratio for c, P<0.05
There were significant differences with holder water extract group ratio for d, P<0.05
Can find out from the xanthine oxidase activity of table 2 secondary series, with model control group, compare, 3 administration group xanthine oxidase activities all have significance to reduce (P<0.05).With negative control group relatively, without significant difference (P〉0.05), and plant root water extract group slightly raises, and has significant difference (P<0.05) with the ovary water extract group of pistil, holder water extract group xanthine oxidase activity.Relatively draw between three administration groups, have significant difference (P<0.05) between plant root water extract group and holder water extract group.Therefore, with regard to this index of xanthine oxidase activity, holder water extract group effect is the most remarkable.
The tertial urea nitrogen concentration result of table 2 shows, the difference of positive controls, negative control group, 3 administration groups and model control group urea nitrogen concentration all has utmost point significant difference (P<0.01), and holder water extract group is compared with negative control group, positive controls and no significant difference (P〉0.05).Therefore, with regard to this index of urea nitrogen concentration, the water extract at each position of perfume Flos Nelumbinis all produces effect.
And 3 administration group serum uric acid levels of table 2 the 4th row and model group more all have significant difference (P<0.01).Compare the administration group with positive controls with negative control group and still have significant difference (P<0.01).Relatively can draw between three administration groups, holder water extract group and plant root water extract group, with between these two groups of the ovary water extract groups of pistil, have significant difference (P<0.05).Therefore, just fall serum uric acid level, the effect of holder water extract group is even better.
In sum, perfume Flos Nelumbinis water extract and allopurinol all can suppress xanthine oxidase activity in body, reduce urea nitrogen concentration and Uric Acid Content is reduced, therefore infer that both mechanism of action is similar, thereby be all to reduce uricopoiesis by suppressing xanthine oxidase activity, reduced uric acid level in body.It is more obvious that wherein the holder water extract suppresses the xanthine oxidase activity effect, thereby also corresponding raising of uric acid resisting effect reduces urea nitrogen concentration, and the protection kidney is more remarkable.Therefore, in the water extract at three positions of perfume Flos Nelumbinis, the water extract effect of perfume Flos Nelumbinis holder is the most remarkable.
As can be seen from Table 2, after model group mouse peritoneal injection hypoxanthine, subcutaneous injection Oteracil Potassium, in body, the activity of xanthine oxidase significantly improves, and be subject to the effect of urease inhibitor, and increase suddenly hypoxanthic content in body, cause irritability in body to strengthen, rapidly hypoxanthine is converted into xanthine, and then the generation uric acid, cause uric acid level significantly to increase., because uric acid raises suddenly, cause renal function to be subject to certain infringement, and urea nitrogen concentration has reflected whether renal function is affected, so urea nitrogen concentration also have increase to a certain degree again.Compare with negative control, all there were significant differences for the xanthine oxidase activity of model control group, urea nitrogen concentration and serum uric acid value (P<0.05), and the modeling success is described.And positive controls shows that with there not being significant difference (P〉0.05) between negative control group the positive material allopurinol can make mice xanthine oxidase activity, urea nitrogen concentration and the Level of Serum Uric Acid of metabolic arthritis drop to the level of common not modeling mice.
2.3 the impact of perfume Flos Nelumbinis extract on Pathological
Negative control group animal cortex section's glomerular volume and cell number are without obvious change, and glomerule is without fibrosis, and extracellular matrix is without hypertrophy, and balloon cavity is without expansion; Cortex section, the pathological changes such as medullary substance section and renal papillae section renal tubules non-blocking, expansion, atrophy, necrosis, fibrosis; 4 slight degeneration of renal cells, fixing relevant with tissue, all Mouse Kidney tubule intracavity are without cast, without abnormal electrodeposition substance; Between matter without cell infiltration, without proliferation of fibrous tissue.Model control group (12) major lesions is tubular ectasia, and epithelial cell has degeneration in various degree; Look in most Mouse Kidney tubules see Yihong dye, without the uric acid deposit of definite shape, how many amounts differs; Between matter have no obvious cell infiltration or proliferation of fibrous tissue; Tubular ectasia is obviously located the glomerular volume compared with normal and is dwindled.Tested material group (plant root water extract group, holder water extract group and with the ovary water extract group of pistil) pathological changes has alleviating in various degree.Each treated animal pathological changes scoring situation is in Table 3.
Table 3 nephropathy degree appraisal result and mean rank order
Figure BDA00003613713000091
A has compared significant difference with the model matched group, P<0.05
Three kinds of extracts have the effect of significant anti-metabolic arthritis nephropathy, wherein with the effect of the ovary with pistil and holder extract for well.The mouse kidney pathologic condition of extract group is compared and is still had certain gap with the allopurinol group, and lesion degree slightly overweights the allopurinol group.
3 conclusions
3.1 adopt Oteracil Potassium and hypoxanthine associating modeling can successfully copy Studies on Animal Models of Hyperuricemic Mice, and the persistent period is long, good stability.
3.2 perfume Flos Nelumbinis water extract (plant root water extract, holder water extract and with the ovary water extract of pistil) all can effectively reduce Studies on Animal Models of Hyperuricemic Mice serum serum uric acid level, and the effect of inhibition injury of kidney is arranged.Its effect may suppress uricopoiesis by suppressing xanthine oxidase activity in body, promotes urate excretion to realize.It is more obvious that wherein the holder water extract suppresses the xanthine oxidase activity effect, thereby the also corresponding raising of uric acid resisting level reduces urea nitrogen concentration, and the protection kidney is more remarkable.And nephropathy testing result of science shows that three kinds of extracts (plant root water extract, holder water extract and with the ovary water extract of pistil) have the effect of significant anti-metabolic arthritis, wherein with the effect of the ovary with pistil and holder extract for well.
3.3 perfume Flos Nelumbinis water extract (plant root water extract, holder water extract and with the ovary water extract of pistil) reduces blood uric acid, reduces the stimulation of uric acid to kidney.Hyperuricemia infringement kidney physiological function, show as urea nitrogen concentration and raise, and above-mentioned situation can effectively be reversed by perfume Flos Nelumbinis water extract (plant root water extract, holder water extract and with the ovary water extract of pistil).

Claims (3)

1. the application of perfume Flos Nelumbinis extract in preparation treatment gout, hyperuricemia and urate nephropathy medicine, described perfume Flos Nelumbinis extract is the water extract of perfume Flos Nelumbinis.
2. the preparation method of perfume Flos Nelumbinis extract as claimed in claim 1, it is characterized by and pass through following steps: the holder of dry perfume Flos Nelumbinis, join 8-12 times of quality with ovary or the plant root of pistil distilled water in the middle of decoct 1-3 time, each 2-3 hour, filtered while hot obtains filtrate, merging filtrate, concentrating under reduced pressure, obtain the perfume Flos Nelumbinis extract.
3. the application of perfume Flos Nelumbinis extract as claimed in claim 1 in preparation treatment gout, hyperuricemia and urate nephropathy medicine, is characterized by the perfume Flos Nelumbinis extract and can reduce the xanthine oxidase activity that causes hyperuricemia.
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