CN109394753A - Application of the diosmetin in the drug of preparation prevention and/or treatment hyperuricemic nephropathy - Google Patents
Application of the diosmetin in the drug of preparation prevention and/or treatment hyperuricemic nephropathy Download PDFInfo
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- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
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Abstract
The invention belongs to biomedicine fields, and in particular to application of the diosmetin in the drug of preparation prevention and/or treatment hyperuricemic nephropathy.Diosmetin is applied alone or diosmetin is combined with two medicine of allopurinol; while reducing the serum uric acid of hyperuricemic nephropathy mouse; it also can significantly reduce its serum urea nitrogen and creatinine level; it can reduce the rising of the mouse renal index as caused by hyperuricemia simultaneously; spleen index is also significantly raised; illustrate that the combination of two medicines can reverse the damage that caused mouse kidney function is increased by serum uric acid while reducing hyperuricemic nephropathy mouse uric acid; and then the renal function of hyperuricemia mouse is protected, and there is protective effect to its immune system.
Description
Technical field
The invention belongs to biomedicine fields, treat hyperuricemic nephropathy in preparation more particularly, to diosmetin
Drug in application, active component is the pharmaceutical composition of the diosmetin being applied alone or diosmetin and allopurinol, with
And the application of diosmetin and allopurinol drug combination in the drug of preparation treatment hyperuricemic nephropathy.
Background technique
In recent years, with the improvement of people ' s living standards with the change of dietary structure, asymptomatic hyperuricemia and height
The disease incidence of uricacidemia nephrosis significantly increases.The uric acid that human body generates is discharged through kidney with urine there are about 2/3, therefore, height urine
Acidaemia can lead to the decline of renal function.Uric acid nephropathy refer to a large amount of urate crystal short time be deposited on kidney concetrated pipe,
Renal plevis and ureter simultaneously block renal tubule, cause renal tubule proximal stent, lead to that renal function is acute, serious damage, cause acute
Renal failure.The drug for the treatment of hyperuricemic nephropathy mainly has xanthine oxidase inhibition mainly based on Western medicine at present
Agent, such as: allopurinol, Febustat etc.；Or promote the drug of uric acid excretion, and such as: probenecid, Benzbromarone etc..But
It is that said medicine has serious side effect, such as: renal toxicity, allergic reaction, Cardiovascular Toxicity, liver renal toxicity etc., to lead
The use of these drugs clinically is caused to receive serious limitation.It is in recent years, curative for effect since Chinese medicine toxic side effect is small,
Show stronger advantage, therefore Chinese medicine treatment uric acid nephropathy earns widespread respect.
Summary of the invention
The present invention for existing treatment hyperuricemic nephropathy poisonous side effect of medicine it is big, patient is not easy-tolerated, clinical makes
With the defect being restricted, it is intended to the drug of efficient, less toxic inhibiting hyperuricemia nephrosis is developed, to solve at present clinically
Using the toxicity problem of drug, the tolerance and compliance of patient are improved.Present invention firstly provides chromocor compound diosmetins
Hyperuricemic nephropathy can be treated, and diosmetin has the anti-trioxypurine effect that cooperates with allopurinol, and has and restore kidney
The effect of function, curative effect is better than gastric infusion approach for drug administration by injection approach.
To achieve the goals above, the first aspect of the present invention provides diosmetin or its pharmaceutically acceptable salt, molten
Application of the object in the drug of preparation prevention and/or treatment hyperuricemic nephropathy is closed in agent.
Preferably, the dosage form of the drug is injection.
Preferably, the drug further includes one or more pharmaceutically acceptable carriers.
The second aspect of the present invention provides a kind of pharmaceutical composition, the active component of the pharmaceutical composition be diosmetin and
Allopurinol.
Preferably, described pharmaceutical composition further includes one or more pharmaceutically acceptable carriers.
Preferably, the dosage form of described pharmaceutical composition is injection.
In the present invention, " pharmaceutical composition " refers to its active component containing there are two types of, is not intended to limit two kinds of active components
Usage mode, can will two kinds of active components mix after be prepared as drug, two kinds of active components can also be prepared as respectively
Drug drug combination again.
In the above drug or pharmaceutical composition, the pharmaceutically acceptable carrier includes the dilution of pharmaceutical field routine
Agent, excipient, filler, emulsifier, adhesive, lubricant, sorbefacient, surfactant, disintegrating agent or antioxidant.
The pharmaceutically acceptable carrier can also include flavouring agent, sweetener, preservative or colorant.
The pharmaceutically acceptable carrier can be selected from: mannitol, sorbierite, sodium pyrosulfite, sodium hydrogensulfite, sulphur
Sodium thiosulfate, cysteine hydrochloride, thioacetic acid, soybean lecithin, vitamin C, vitamin E, EDETATE SODIUM, Ethylenediaminetetraacetic Acid Calcium Salt, one
The carbonate of valence alkali metal, acetate, phosphate or its aqueous solution, hydrochloric acid, acetic acid, sulfuric acid, phosphoric acid, amino acid, sodium chloride, chlorine
Change potassium, sodium lactate, ethyl hydroxy benzoate, benzoic acid, potassium sorbate, chlorhexidine acetate, xylitol, maltose, glucose, fructose, the right side
Revolve glucosides, starch, sucrose, lactose, mannitol, silicon derivative, cellulose and its derivates, alginates, gelatin, polyethylene pyrrole
Pyrrolidone, glycerol, Tween 80, agar, calcium carbonate, calcium bicarbonate, surfactant, polyethylene glycol, cyclodextrin, phospholipid material
Material, kaolin, talcum powder, calcium stearate or magnesium stearate.
The third aspect of the present invention provides aforementioned pharmaceutical compositions in preparation prevention and/or treats hyperuricemic nephropathy
Application in drug.
Allopurinol is hypoxanthic isomers, is the Suicide substrate of XOD, can be in conjunction with XOD substrate competitive
The active site molybdenum pterin of XOD becomes the extensive line of clinical application and inhibits to prevent hypoxanthine from being metabolized as uric acid
Uric acid generates class drug.Result that diosmetin influences xanthine oxidase is measured it is found that diosmetin by experiment in vitro
The activity of agent xanthine oxidase can be significantly inhibited in vitro, and half-inhibitory concentration is less than positive drug allopurinol, i.e. body
Outer diosmetin inhibits xanthine oxidase activity effect stronger；The measurement of inhibited type experiment, shows diosmetin to Huang
The inhibition type of purine oxidase is Reverse transcriptase.Therefore, diosmetin is a kind of natural suppression of efficient xanthine oxidase
Preparation.The injury of kidney after renal ischaemia/Reperfu- sion can be improved by having document report diosmetin in recent years, but have no it to uric acid
Effect and the research of uric acid nephropathy report.Result of study of the present invention shows after intraperitoneal administration diosmetin, can be significant
The serum uric acid level of hyperuricemic nephropathy mouse is reduced, and can significantly reduce serum urea nitrogen, creatinine level, illustrates perfume (or spice)
Leaf lignin can reverse the damage of the mouse kidney function as caused by high lithemia, and then protect the kidney function of hyperuricemia mouse
Energy.And diosmetin intraperitoneal injection is low, middle dose group can reduce the rising of the mouse kidney index due to caused by hyperuricemia,
There is protective effect to mouse kidney, while spleen index increases, and illustrates diosmetin to the immune system of hyperuricemia mouse
With protective effect.
Diosmetin and two medicine of allopurinol are combined, while reducing the serum uric acid of hyperuricemic nephropathy mouse,
It also can significantly reduce its serum urea nitrogen and creatinine level, while can reduce the mouse renal index as caused by hyperuricemia
Rise, spleen index is also significantly raised, illustrates that the combination of two medicines can reverse while reducing hyperuricemic nephropathy mouse uric acid
The damage of mouse kidney function caused by being increased by serum uric acid, and then the renal function of hyperuricemia mouse is protected, and
There is protective effect to its immune system.Diosmetin administration is to the liver index of mouse, thymus index, weight without obvious shadow
It rings, shows that diosmetin is a kind of compound of hypotoxicity.
Other features and advantages of the present invention will then part of the detailed description can be specified.
Detailed description of the invention
Exemplary embodiment of the invention is described in more detail in conjunction with the accompanying drawings, it is of the invention above-mentioned and its
Its purpose, feature and advantage will be apparent.
Fig. 1 shows the bis- reciprocal equation figures of Lineweaver-Burk of diosmetin.
Specific embodiment
The preferred embodiment of the present invention is described in more detail below.Although the following describe preferred implementations of the invention
Mode, however, it is to be appreciated that may be realized in various forms the present invention without that should be limited by the embodiments set forth herein.
The present invention is studied using the method for in vitro and in vivo.
1, diosmetin is in vitro to the inhibiting effect of xanthine oxidase
1.1 material
1.1.1 drug and reagent
Diosmetin (purity >=97%), lot number D17081604 are purchased from Nanjing Di Erge Pharmaceutical Technology Co., Ltd；Phosphorus
Sour hydrogen dipotassium (analysis is pure), is purchased from Tianjin Tian Li chemical reagent Co., Ltd；Anhydrous potassium dihydrogenphosphate (analysis is pure), is purchased from Tianjin
Fine chemistry industry research institute is recovered in city；EDTA-2Na (analysis is pure), is purchased from Biosharp company；Xanthine (purity 98%, lot number:
D1606030), it is purchased from Aladdin reagent Co., Ltd；Xanthine oxidase (Xanthine Oxidase, XOD), lot number:
L04M8Y30480 is purchased from Shanghai Yuan Ye Biotechnology Co., Ltd；Dimethyl sulfoxide (analysis is pure), purchased from Chinese medicines group chemistry
Reagent Co., Ltd.
1.1.2 laboratory apparatus
AL204 electronic analytical balance (Mettler Toledo Inc.)；XH-C turbine mixer (Jintan City's Medical Instruments
Factory)；PHS-3C type acidometer (Ao Haosi Instrument Ltd.)；EnSpire microplate reader (PerkinElmer company).
1.2 method
1.2.1 the measurement of inhibiting rate
Using improvement ultraviolet spectrophotometer method measurement diosmetin in vitro to the inhibiting effect of xanthine oxidase activity
(Zhu Shenyin, Zhou Yuan great, Liu Qingshan etc..The foundation and application [J] of High-Throughput Screening Assay for Xanthine Oxidase Inhibitor in Vitro.China
Pharmaceutical journal, 2007,42 (3): 187-190).DMSO dissolution is respectively adopted in diosmetin and allopurinol, and uses phosphoric acid buffer
Liquid (pH=7.4) is diluted to 200 μm of ol/L, 100 μm of ol/L, 50 μm of ol/L, 25 μm of ol/L, 12.5 μm of ol/L, 6.25 μm of ol/L
Concentration it is spare.Substrates xanthine is first dissolved with the sodium hydroxide that concentration is 0.1mol/L, then with the left side dilute hydrochloric acid tune pH to 7.4
The right side, needed for being finally diluted to phosphate buffer (pH=7.4).Xanthine oxidase is prepared with the phosphate buffer of pH=7.4
At the solution for standby of required concentration.
100 μ L of sample and blank solution (blank PBS), 50 μ L of enzyme solutions (4U/mL) are sequentially added in 96 orifice plates,
It is anti-that substrates xanthine (0.12 μm of ol/L) 50 μ L starting enzymatic is added in 37 DEG C of hatching 3min of microplate reader in each 4 multiple holes of concentration
It answers, the final concentration of diosmetin and allopurinol is 100 μm of ol/L, 50 μm of ol/L, 25 μm of ol/L, 12.5 μm of ol/L, 6.25 μ
Mol/L, 3.625 μm of ol/L.It is primary every 20s reading at extinction wavelength 295nm, record absorbance A, total 10min.To inhale
Luminosity and time carry out linear regression, show that the slope of regression curve is that xanthine oxidase oxidation xanthine generates uric acid
Reaction rate.Drug calculates the inhibiting rate of XOD with following equation: inhibiting rate (%)=[1- (b/a)] × 100%, a is blank
The reaction rate of control group, b are the reaction rate of medicine group.Regression curve is done with inhibiting rate and concentration, finally uses software
GraphPad Prism 6 calculates IC50。
1.2.2 the measurement of inhibiting rate type
5 concentration gradients: 1.92 μm of ol/L, 0.96 μm of ol/L, 0.48 μ are arranged in the concentration (1U/mL) of immobilized enzyme, substrate
mol/L,0.24μmol/L,0.12μmol/L.The same 1.2.1 of method, respectively measure various concentration diosmetin (50 μm of ol/L,
3.625 μm of ol/L) reaction rate under different concentration of substrate.Lineweaver- is carried out with concentration of substrate and reaction rate
The bis- reciprocal equation mappings of Burk, judge the inhibition type of diosmetin.
1.3 result
1.3.1 inhibiting effect of the diosmetin to XOD
As shown in Table 1, with the increase of diosmetin and concentration of allopurinol, inhibiting rate is gradually increased, XOD activity
It gradually decreases.The IC of diosmetin and allopurinol50Respectively 5.83 μm of ol/L, 49.60 μm of ol/L, show diosmetin pair
The inhibiting effect of XOD is significantly stronger than allopurinol.
Inhibiting effect of 1 diosmetin of table to XOD
3.2 diosmetins inhibit type analysis to XOD
As shown in Figure 1, mapped according to the bis- reciprocal equation 1/V=Km/ of Lineweaver-Burk (Vmax* [S])+1/Vmax,
The diosmetin of various concentration and the Lineweaver-Burk double reciprocal curve of blank group almost intersect in Y-axis same point, show
Vmax is constant, i.e. the presence of the diosmetin change that does not cause xanthine oxidase maximum reaction rate Vmax；With spiceleaf
The increase of lignin concentration, the slope of curve increase, and show that Michaelis constant Km increases, and show suppression of the diosmetin to xanthine oxidase
Type processed is Reverse transcriptase.
2, protective effect of the diosmetin to Hyperuricemia injury of kidney mouse
2.1 experimental material
2.1.1 experimental animal
SPF grades of kunming mices, male, 20~22g of weight, Central China University of Science and Technology's Experimental Animal Center provide.Animal productiong
Credit number: SCXK (Hubei Province) 2016-0009.
2.1.2 drug and reagent
Allopurinol (lot number Y27O8C46913) is purchased from Shanghai Yuan Ye Biotechnology Co., Ltd；Diosmetin (purity
>=97%, lot number D17081604), it is purchased from Nanjing Di Erge Pharmaceutical Technology Co., Ltd；Oxonic Acid sylvite (lot number P137112),
Purchased from Shanghai Aladdin biochemical technology limited liability company；Yeast extract (lot number 20170802) is purchased from the extensive and profound in meaning star biology skill in Beijing
Art responsible company；Testing uric acid kit (lot number 20181017), xanthine oxidase testing cassete (lot number 20180920), urea
Nitrogen kit (lot number 20181024), creatinine reagent box (lot number 20181022), Coomassie brilliant blue kit (lot number
20180921) it is purchased from Nanjing and builds up Bioengineering Research Institute；DMSO (lot number 20161109), is purchased from Chinese medicines group chemical reagent
Co., Ltd.
2.1.3 laboratory apparatus
AL204 electronic analytical balance (Mettler Toledo Inc.)；SPS2001F electronic balance (Ao Haosi company)；
TGL-16C desk centrifuge (Anting Scientific Instrument Factory, Shanghai)；UV-2000 ultraviolet specrophotometer (You Nike)；FSH-2A can
Fast refiner (Medical Instruments factory, Jintan City) is turned up.
2.2 method
2.2.1 animal packet and administration
Male mouse of kunming 80, after adaptable fed 2d, 8 groups, every group 10 are randomly divided by weight.It is divided into normal
Low dose group, middle dose group, high dose group (10mg/ is injected intraperitoneally in group, model group, allopurinol group (5mg/kg), diosmetin
Kg, 20mg/kg, 40mg/kg), diosmetin stomach-filling group (20mg/kg), diosmetin (20mg/kg)+allopurinol (5mg/
Kg) group.1d starts morning timing intraperitoneal injection, normal group and model group injecting normal saline, and diosmetin is low, high agent
Relative medicine is injected intraperitoneally in amount group, and diosmetin middle dosage is divided into intraperitoneal injection group and gastric infusion group, gives corresponding agent respectively
Measure drug, continuous 15d, 6d stomach-filling 0.5%CMC-Na before allopurinol group, last 9d stomach-filling corresponding dosage allopurinol.Abdominal cavity
Drug administration by injection volume is 0.15ml/10g, and gastric infusion volume is 0.2ml/10g.
2.2.2 the foundation of hyperuricemia renal damage animal model
Mouse hyperuricemia renal damage model is established using yeast extract stomach-filling joint Oteracil Potassium intraperitoneal injection.Except normal
Group is outer, the daily stomach-filling 30g/kg yeast extract of remaining each group mouse, continuous 15d, and 300mg/kg Oteracil Potassium is injected intraperitoneally in last 1d,
In addition to allopurinol group, remaining each group stomach-filling volume is 0.2ml/10g, and intraperitoneal injection volume is 0.15ml/10g, allopurinol
Group stomach-filling volume is 0.1ml/10g.1h after intraperitoneal injection diosmetin, except for the normal group, remaining each group stomach-filling yeast soln, most
Oteracil Potassium solution is injected intraperitoneally after the stomach-filling of 1d yeast extract afterwards.
2.2.3 the preparation of drug solution
Diosmetin is dissolved in DMSO, with normal saline dilution be configured to 0.67mg/mL, 1.33mg/mL,
2.67mg/mL diosmetin suspension (contains 5%DMSO).
Do solvent with 0.5%CMC-Na, respectively prepare 0.5mg/mL allopurinol suspension, 3g/mL yeast extract suspension,
1.5g/mL yeast suspension, 20mg/mL Oteracil Potassium suspension.
2.2.4 Biochemical Indexes
Daily observation mouse ordinary circumstance and weighing, calculate every mouse weight relative change rate (%)=(every time
Weigh in/test beginning when weight) × 100.15d, 1h after modeling in afternoon, normal group, model group, allopurinol is administered
Each dosage group eyeball of mouse of group, diosmetin takes blood, and 3500r/min is centrifuged 10min, takes supernatant, freeze in -20 DEG C, be used for
Serum uric acid, BUN, Cr level are measured, cervical dislocation puts to death mouse, weighs holonephros, liver, thymus gland, spleen weight, calculates internal organs
Index.
2.3 result
2.3.1 influence of the diosmetin to hyperuricemia mouse renal function
Experimental result is shown in Table 2.As shown in Table 2, compared with normal group, model group mice serum uric acid, urea nitrogen, creatinine water
Average extremely significant raising (P < 0.01), explanation, which combines Oteracil Potassium with yeast extract, can result in mouse hyperuricemia, and to kidney
It is dirty to have damage；Compared with model group, the extremely significant reduction (P < 0.01) of positive drug group mice serum uric acid level illustrates allopurinol
It can reduce mice serum uric acid, but mice serum urea nitrogen and creatinine level are not statistically significant (P > 0.05), illustrate not fast
Purine alcohol acts on kidney unprotect；Be injected intraperitoneally diosmetin low dosage can extremely significant reduction mice serum uric acid (P <
0.01) diosmetin middle dosage and high dose, which is injected intraperitoneally, can be substantially reduced mice serum uric acid level (P < 0.05), simultaneously
The basic, normal, high dosage mice serum urea nitrogen of diosmetin, the extremely significant reduction (P < 0.01) of creatinine level, explanation is injected intraperitoneally
By the way that diosmetin is injected intraperitoneally, can also there be certain protection to its kidney while reducing hyperuricemia mouse uric acid
Effect；Stomach-filling give diosmetin can extremely significant reduction mice serum uric acid (P < 0.01), but mice serum urea nitrogen, creatinine
Horizontal not statistically significant (P > 0.05) illustrates to can reduce hyperuricemia mice serum uric acid but right by gastric infusion
The effect of kidney unprotect；Diosmetin and two medicine of allopurinol are combined, the extremely significant reduction (P of serum uric acid, urea nitrogen levels
< 0.01), serum creatinine level is substantially reduced (P < 0.05), illustrates that the combination of two medicines can be while reducing mouse uric acid to it
Kidney also has certain protective effect.
Influence (n=10) of 2 diosmetin of table to hyperuricemia mice serum uric acid, urea nitrogen, creatinine level
Compared with normal group,#P < 0.05,##P<0.01；Compared with model group,*P < 0.05,**P<0.01.Ig: stomach-filling；Ip:
Intraperitoneal injection.
2.3.2 influence of the diosmetin to hyperuricemia renal damage mice organs index
Experimental result is shown in Table 3.As shown in Table 3, compared with normal group, the renal index of model group significantly increases (P < 0.05),
Illustrate that hyperuricemia mouse kidney increases, this modeling mode has certain damage to kidney.Compared with model group, positive drug group is small
Mouse renal index no difference of science of statistics (P > 0.05) illustrates that allopurinol acts on hyperuricemia mouse injury of kidney unprotect；It is fragrant
Leaf lignin low dose group mouse renal index is substantially reduced (P < 0.05), the extremely significant reduction of diosmetin middle dose group mouse renal index
(P < 0.01) illustrates that diosmetin has certain protective role to hyperuricemia mouse renal damage.Diosmetin and allopurinol
The combination of two medicines, the extremely significant reduction (P < 0.01) of mouse renal index illustrate that the combination of two medicines can play hyperuricemia mouse kidney
Protective effect.Compared with normal group, kidney associated with diosmetin low dosage, middle dosage and diosmetin and two medicine of allopurinol
Index no difference of science of statistics (P > 0.05) illustrates that diosmetin low dosage, middle dosage and the combination of two medicines can be such that uric acid induces
Mouse renal index, which increases, to be restored to normal mouse level.Compared with normal group, the spleen index of model group is substantially reduced (P < 0.05),
Illustrate that this modeling mode has damage mouse immune system.Compared with model group, the spleen of diosmetin low dosage and high dose refers to
The extremely significant raising (P < 0.01) of number, middle dosage apparent increase (P < 0.05) illustrate diosmetin to hyperuricemia mouse immune
System shields；Diosmetin and two medicine of allopurinol are combined, and the extremely significant raising (P < 0.01) of mouse spleen index illustrates two
Medicine combination shields to hyperuricemia mouse immune system；Compared with normal group, diosmetin low, middle and high dose groups
And diosmetin and the two medicine equal no difference of science of statistics of combination group spleen index (P > 0.05) of allopurinol, illustrate that diosmetin can
Restore the spleen index of hyperuricemia renal damage mouse to normal mouse level.Diosmetin stomach-filling its renal index, spleen index
The equal no difference of science of statistics (P > 0.05) compared with model group illustrates that gastric infusion makees hyperuricemia mouse renal damage unprotect
With, while to its immune system also without effect.
Influence (n=10) of 3 diosmetin of table to mice organs index
Compared with normal group,#P < 0.05,##P<0.01；Compared with model group,*P < 0.05,**P<0.01.Ig: stomach-filling；Ip:
Intraperitoneal injection.
2.3.3 diosmetin is on the active influence of hyperuricemia renal damage mouse XOD
Experimental result is shown in Table 4.As shown in Table 4, compared with normal group, model group XOD activity is significantly raised (P < 0.05), says
Bright hyperuricemia mouse can increase the activity of XOD.Compared with model group, positive drug group, intraperitoneal injection diosmetin it is low,
Middle and high dosage group, stomach-filling diosmetin group, diosmetin and allopurinol combination group, XOD activity have decreasing trend, but
No difference of science of statistics (P > 0.05).
Influence (n=10) of 4 diosmetin of table to mouse liver xanthine oxidase activity
Compared with normal group,#P<0.05.Ig: stomach-filling；Ip: intraperitoneal injection.
2.3.4 influence of the diosmetin to hyperuricemia renal damage mouse weight
As shown in Table 5, compared with normally group mouse, model group mouse relative body weight is on a declining curve, but difference is without statistics
It learns meaning (P > 0.05).Diosmetin low, middle and high dose groups, diosmetin stomach-filling group, diosmetin+allopurinol combination group
Mouse relative body weight is compared with model group, no significant difference (P > 0.05).
Influence (n=10) of 5 diosmetin of table to hyperuricemia mouse weight
Ig: stomach-filling；Ip: intraperitoneal injection.
Various embodiments of the present invention are described above, above description is exemplary, and non-exclusive, and
It is not limited to disclosed each embodiment.Without departing from the scope and spirit of illustrated each embodiment, for this skill
Many modifications and changes are obvious for the those of ordinary skill in art field.
Claims (9)
1. diosmetin or its pharmaceutically acceptable salt, solvate are in preparation prevention and/or treatment hyperuricemic nephropathy
Drug in application.
2. application according to claim 1, which is characterized in that the dosage form of the drug is injection.
3. application according to claim 1, which is characterized in that the drug further includes one or more pharmaceutically acceptable
Carrier.
4. application according to claim 3, which is characterized in that the pharmaceutically acceptable carrier includes diluent, assigns
Shape agent, filler, emulsifier, adhesive, lubricant, sorbefacient, surfactant, disintegrating agent or antioxidant.
5. a kind of pharmaceutical composition, the active component of the pharmaceutical composition is diosmetin and allopurinol.
6. pharmaceutical composition according to claim 5, which is characterized in that the dosage form of described pharmaceutical composition is injection.
7. pharmaceutical composition according to claim 5, which is characterized in that described pharmaceutical composition further includes one or more
Pharmaceutically acceptable carrier.
8. pharmaceutical composition according to claim 7, which is characterized in that the pharmaceutically acceptable carrier includes dilution
Agent, excipient, filler, emulsifier, adhesive, lubricant, sorbefacient, surfactant, disintegrating agent or antioxidant.
9. pharmaceutical composition described in any one of claim 5-8 is in preparation prevention and/or treatment hyperuricemic nephropathy
Drug in application.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201811582331.5A CN109394753B (en) | 2018-12-24 | 2018-12-24 | Application of diosmetin in preparation of medicine for preventing and/or treating hyperuricemia nephropathy |
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|---|---|---|---|
| CN201811582331.5A CN109394753B (en) | 2018-12-24 | 2018-12-24 | Application of diosmetin in preparation of medicine for preventing and/or treating hyperuricemia nephropathy |
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| CN109394753A true CN109394753A (en) | 2019-03-01 |
| CN109394753B CN109394753B (en) | 2020-10-02 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0505937A1 (en) * | 1991-03-28 | 1992-09-30 | GEYMONAT S.p.A. | Flavone derivatives, a process for the preparation thereof and pharmaceutical compositions containing them |
| CN101550124A (en) * | 2008-04-01 | 2009-10-07 | 瑟维尔实验室 | Diosmetin compounds, a process for their preparation and pharmaceutical composition containing them |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0505937A1 (en) * | 1991-03-28 | 1992-09-30 | GEYMONAT S.p.A. | Flavone derivatives, a process for the preparation thereof and pharmaceutical compositions containing them |
| CN101550124A (en) * | 2008-04-01 | 2009-10-07 | 瑟维尔实验室 | Diosmetin compounds, a process for their preparation and pharmaceutical composition containing them |
Non-Patent Citations (4)
| Title |
|---|
| SHIVRAJ HARIRAM NILE ET AL: ""Antioxidant,anti-inflammatory,and enzyme inhibitory activity of natural plant flavonoids and their synthesized derivatives"", 《J BIOCHEM MOL TOXICOL》 * |
| 吴开春主编: "《内科学》", 30 June 2017, 中国医药科技出版社 * |
| 杨玺主编: "《专家谈痛风用药技巧》", 30 June 2012, 人民军医出版社 * |
| 齐万虎等: ""黄瑞香中化学成分抑制黄嘌呤氧化酶的活性及其机制研究"", 《中国实验方剂学杂志》 * |
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