CN109893533A - New application of the poly- acetylene compound in anti-trioxypurine - Google Patents
New application of the poly- acetylene compound in anti-trioxypurine Download PDFInfo
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- CN109893533A CN109893533A CN201711286456.9A CN201711286456A CN109893533A CN 109893533 A CN109893533 A CN 109893533A CN 201711286456 A CN201711286456 A CN 201711286456A CN 109893533 A CN109893533 A CN 109893533A
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- poly
- acetylene compound
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- ester
- solvate
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Abstract
The invention belongs to drug or field of health care products, and in particular to new application of the poly- acetylene compound in anti-trioxypurine.The poly- acetylene compound has structure shown in formula (I):R1、R2、R3And R4As shown in the definition of description of the invention.The research of the invention finds that the poly- acetylene compound separated from snow chrysanthemum and Radix Codonopsis has anti-trioxypurine activity, and without apparent toxic side effect, it can be used for treating gout caused by hyperuricemia and hyperuricemia or gout complication.
Description
Technical field
The invention belongs to drug or field of health care products, and in particular to new application of the poly- acetylene compound in anti-trioxypurine.
Background technique
Uric acid is the final metabolite of mankind's purine compound, and purine metabolic disturbance then leads to hyperuricemia.Just
Under normal purine diet state, non-empty stomach serum uric acid level male is higher than 416 μm of ol/L twice on the same day, and women is higher than 360 μm of ol/
L, i.e. referred to as hyperuricemia (hyperuricemia).Gout is the crystal correlation caused by monosodium urate salt (MSU) deposition
Arthropathy, clinical manifestation directly related with hyperuricemia caused by purine metabolic disturbance and (or) underexcretion
For hyperuricemia, gouty acute arthritis recurrent exerbation, gouty chornic arthritis and tophus, gouty nephropathy and
Kidney calculus urate etc., severe one may occur in which joint deformity and renal insufficiency.In addition, gout often with Central obesity, hyperlipidemia,
The diseases such as hypertension, type II diabetes and cardiovascular disease.Gout has become the second largest metabolism class disease after diabetes, seriously
Endanger the life and health of the mankind.According to " the Chinese gout status report white paper in 2017 " announced recently, China's height urine
For acidaemia patient numbers up to 1.7 hundred million, wherein patient with gout is more than 80,000,000 people, and just rapid with 9.7% annual growth
Increase；The year two thousand twenty is expected, the gout number in China is up to 100,000,000.
Currently, treatment hyperuricemia, gout and gout complication, mainly by being controlled to the uric acid in blood
System, mechanism of action mainly includes following two: (1) by inhibiting xanthine oxidase (xanthine oxidase, XO) living
Property effectively inhibits the formation of uric acid, and representative drugs have allopurinol, Febustat etc.；(2) excretion for promoting uric acid, represents
Property drug has probenecid, Benzbromarone etc..However, said medicine it is equal toxic side effect it is usually larger, such as: allopurinol can draw
Send out the serious toxic side effects such as allergy (disease incidence 10-15%), super quick syndrome, bone marrow suppression；Probenecid, Benzbromarone
Then there is stimulating gastrointestinal road, cause the side effects such as renal colic, excitation gout acute attack；Febustat will increase cardiovascular system
The risk of disease, serious person may occur in which Stevens-Johnson syndrome；Moreover, the tolerance of said medicine is generally lower.It is comprehensive
On, these problems limit the clinical application of these drugs to a certain extent.Therefore, the drug of novel treatment gout is studied
It is of great significance.
Radix Codonopsis Radix Codonopsis is Campanulaceae Radix Codonopsis Codonopsis pilosula (Franch.)
Or codonopsis pilosula var. modesta Codonopsis pilosula Nannf.var.modesta (Nannf.) L.T Shen or radix codonpsis tangshen Nannf.
The dry root of Codonopsis tangshen Oliv., autumn excavation, cleans, dries, nature and flavor are sweet, flat, returns spleen, lung channel, can mend
Middle QI invigorating, strengthening spleen and tonifying lung are coughed, the treatment of the diseases such as Heat Diabetes for spleen and lung abnormal heat, shortness of breath and palpitation, anorexia and loose stool, empty productive cough.So
And the compound not separated about Radix Codonopsis or from Radix Codonopsis still in the prior art has anti-trioxypurine effect or treats the phase of gout
Close report.
Snow chrysanthemum, scientific name are Coreopsis tinctoria, double-colored golden wave (Coreopsis tinctoria), are composite family (Compositae)
Golden pheasant Chrysanthemum (Coreopsis) annual herb dichromatism golden wave (C.tinctoria) belongs to kindred plant coreopsis tinctoria
The capitulum of (Kunlun Chrysanthemum), originates in North America, introduces China afterwards.At present about snow chrysanthemum modern times drug effect,
Pharmaceutical research focuses primarily upon hypoglycemic, lowering blood pressure and blood fat, anti-inflammatory etc., such as: Chinese patent literature
CN105520984A is disclosed: coreopsis tinctoria extract has the function for the treatment of hyperuricemia, can effectively reduce in blood
Uric acid concentration, have certain therapeutic effect to metabolic relevant to hyperuricemia.However, not public in above-mentioned document
Open the concrete activity ingredient that anti-trioxypurine effect is played in coreopsis tinctoria extract.
Summary of the invention
For this purpose, the invention solves first technical problem be in the prior art still not about Radix Codonopsis or from Radix Codonopsis
Isolated compound has anti-trioxypurine effect or treats the relevant report of gout, to provide a kind of poly- acetylene compound anti-trioxypurine
New application.
The invention solves second technical problem be not disclose in coreopsis tinctoria extract to play in existing literature
The concrete activity ingredient of anti-trioxypurine effect, to provide a kind of new application of poly- acetylene compound anti-trioxypurine.
In order to solve the above technical problems, the present invention is achieved through the following technical solutions:
In a first aspect, the present invention provides poly- acetylene compound and its pharmaceutically acceptable salt shown in formula (I), ester, preceding
The application of medicine or solvate in the drug or health care product that preparation has anti-trioxypurine effect,
Wherein,Expression is selected fromOr
R1、R2、R3It is independently from each other H, OH, CH2CH2OH、COOCH3, by
At least one of be formed by glycosyl residue；R4Selected from unsubstituted or by 1 to 3 R4aSubstituted C1-C12Alkyl or alkenyl,
R4aSelected from OH, byAt least one of be formed by glycosyl residue.
Unless otherwise specified, the term of claims of the present invention and specification has following meanings.
Alkyl refers to: fully saturated straight chain or branch alkyl.Such as: alkyl include but is not limited to methyl, ethyl,
N-propyl, isopropyl, normal-butyl, sec-butyl, isobutyl group, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3- methyl
Hexyl, 2,2- dimethyl amyl group, 2,3- dimethyl amyl group, n-heptyl, n-octyl, n-nonyl, positive decyl etc..
Alkenyl refers to: the straight chain containing at least one ethylene linkage or branch alkyl.Such as: alkenyl includes but is not limited to second
Alkenyl, allyl etc..
Preferably, poly- acetylene compound and its pharmaceutically acceptable salt, ester, prodrug or solvent shown in above-mentioned formula (I)
Application of the object in the drug or health care product that preparation has anti-trioxypurine effect is closed,
R1、R2、R3It is independently from each other H, OH, CH2CH2OH、COOCH3, by
It is formed by monosaccharide groups residue or double glycosyl residues.
It is further preferred that poly- acetylene compound and its pharmaceutically acceptable salt, ester, prodrug shown in above-mentioned formula (I)
Or solvate is preparing the application in the drug or health care product with anti-trioxypurine effect, poly- acetylene compound shown in formula (I)
It is selected from:
It is further preferred that poly- acetylene compound and its pharmaceutically acceptable salt, ester, prodrug shown in above-mentioned formula (I)
Or solvate is preparing the application in the drug or health care product with anti-trioxypurine effect, poly- acetylene compound shown in formula (I)
And its pharmaceutically acceptable salt, ester, prodrug or solvate are added customary adjuvant, are made and clinically may be used according to common process
Tablet, capsule, powder, mixture, pill, granule, syrup, emplastrum, suppository, aerosol, ointment or the note of receiving
Penetrate agent.
The customary adjuvant are as follows: filler, disintegrating agent, lubricant, suspending agent, adhesive, sweetener, corrigent, anti-corrosion
Agent, matrix etc..Filler includes: starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose, sucrose etc.；It collapses
Solving agent includes: starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, crosslinked polyvinylpyrrolidone, low substitution hydroxyl
Third cellulose, cross-linked carboxymethyl cellulose are received；Lubricant includes: magnesium stearate, lauryl sodium sulfate, talcum powder, dioxy
SiClx etc.；Suspending agent includes: polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methyl cellulose etc.；Bonding
Agent includes starch slurry, polyvinylpyrrolidone, hydroxypropyl methyl cellulose etc.；Sweetener includes: saccharin sodium, aspartame, sugarcane
Sugar, honey element, enoxolone etc.；Corrigent includes: sweetener and various essence；Preservative include: parabens, benzoic acid,
Sodium benzoate, sorbic acid and its esters, benzalkonium bromide, the fixed, eucalyptus oil of acetic acid chloroethene etc.；Matrix include: PEG6000,
PEG4000, insect wax etc..
Second aspect, the present invention also provides poly- acetylene compound shown in formula (I) and its pharmaceutically acceptable salt, ester,
The application of prodrug or solvate in the drug or health care product of preparation treatment gout,
Wherein,Expression is selected fromOr
R1、R2、R3It is independently from each other H, OH, CH2CH2OH、COOCH3, by
At least one of be formed by glycosyl residue；
R4Selected from unsubstituted or by 1 to 3 R4aSubstituted C1-C12Alkyl or alkenyl, R4aSelected from OH, byAt least one of be formed by glycosyl residue.
Preferably, poly- acetylene compound and its pharmaceutically acceptable salt, ester, prodrug or solvent shown in above-mentioned formula (I)
Application of the object in the drug or health care product of preparation treatment gout is closed,
R1、R2、R3It is independently from each other H, OH, CH2CH2OH、COOCH3, by
It is formed by monosaccharide groups residue or double glycosyl residues.
It is further preferred that poly- acetylene compound and its pharmaceutically acceptable salt, ester, prodrug shown in above-mentioned formula (I)
Or application of the solvate in the drug or health care product of preparation treatment gout, poly- acetylene compound shown in formula (I) are selected from:
It is further preferred that poly- acetylene compound and its pharmaceutically acceptable salt, ester, prodrug shown in above-mentioned formula (I)
Or solvate is preparing the application in the drug or health care product for the treatment of gout, poly- acetylene compound and its medicine shown in formula (I)
Acceptable salt, ester, prodrug or solvate on are added customary adjuvant, are made clinically acceptable according to common process
Tablet, capsule, powder, mixture, pill, granule, syrup, emplastrum, suppository, aerosol, ointment or injection.
Technical solution of the present invention has the advantages that
The research of the invention finds that the poly- acetylene compound separated from snow chrysanthemum and Radix Codonopsis has anti-trioxypurine activity, and without bright
Aobvious toxic side effect can be used for treating gout caused by hyperuricemia and hyperuricemia or gout complication.
Specific embodiment
In following embodiment of the present invention and experimental example, lobetyolin is commercially available, HPLC purity >=98%.
Xanthine, xanthine oxidase, allopurinol, dehydrated alcohol, chloroform, methanol, the ethyl acetate, steaming for analyzing pure grade
Distilled water, dimethyl sulfoxide, potassium dihydrogen phosphate, dipotassium hydrogen phosphate are commercial product.
Instrument of the present invention includes that standby liquid phase, Ika blender, Buchi vacuum rotary evaporator, whirlpool are suppressed in Buchi
Revolve oscillator, water-bath, Biofuge Primo R Multipurpose table type supercentrifuge, Mettlerae240 electronic balance,
Beckman Coulter AU480 Biochemical Analyzer.
Embodiment 1
Dry radix codonpsis tangshen root 30kg is crushed, is at room temperature 95% ethanol water with the volumetric concentration of 5 times of weight
It soak extraction 3 times, extracts one week every time, combined extract, vacuum distillation is concentrated into no alcohol taste, obtains medicinal extract.1 is dispersed by medicinal extract
In the distilled water of times volume, then Ethyl acetate fraction 212g is obtained, just with ethyl acetate and with extracting n-butyl alcohol respectively
Butanol, before immunoassay position 178g.
Ethyl acetate fraction is separated with silica gel column chromatography (100-200 mesh), using methylene chloride-methanol as eluant, eluent
(volume ratio 50:1-50:30) carries out gradient elution, is merged by TLC testing result, it is total to obtain Fr.1.1~Fr.1.5
Five eluates.Fr.1.2 eluate is separated with silica gel column chromatography again, is eluant, eluent (body with methylene chloride-methanol
Product than be 20:1-20:15) carry out gradient elution, merged according to HPLC testing result, respectively obtain Fr.1.2-1,
Tri- eluates of Fr.1.2-2, Fr.1.2-3.Wherein Fr.1.2-1 is through Agilent SD-1 preparative liquid chromatography, with reverse phase C18
The acetonitrile solution that filler chromatographic column is chromatographic column, is 12% using volumetric concentration is isolated and purified as mobile phase, obtains chemical combination
Object 19.Fr.1.2-2 is through Agilent SD-1 preparative liquid chromatography, using reverse phase C18 filler chromatographic column as chromatographic column, dense with volume
Degree is that mobile phase is isolated and purified for 15% acetonitrile solution, obtains 56mg compound 17 and 18mg compound 18.
Fr.1.3 is successively 25%, 40%, 60% and 80% with volumetric concentration through Sephadex LH-20 pillar layer separation
Methanol aqueous solution eluted, according to HPLC testing result merge same composition, through Agilent SD-1 prepare liquid phase, with anti-
Phase C18 filler chromatographic column is chromatographic column, the methanol aqueous solution that volumetric concentration is 45% is that mobile phase is purified, and obtains 38mgization
Close object 7 and 6mg compound 6.
Fr.1.5 use Sephadex LH-20 pillar layer separation, successively with volumetric concentration be 25%, 10%, 30%,
50% and 75% methanol aqueous solution elution, merges eluent according to HPLC testing result, prepares liquid phase through Agilent SD-1
Chromatography, the methanol aqueous solution for being 40% as chromatographic column, using volumetric concentration using reverse phase C18 filler chromatographic column are changed as mobile phase
Close object 43mg compound 8.
Extracting n-butyl alcohol position is separated using D101 macroreticular resin, carries out gradient elution according to the procedure below: successively
The methanol aqueous solution and methanol that methanol aqueous solution that taste water, volumetric concentration are 30%, volumetric concentration are 60%, collect each stream respectively
The eluent and reduced pressure, elution position 25g, the methanol for respectively obtaining the methanol aqueous solution that volumetric concentration is 60% of dynamic phase are washed
De- position 105g.The elution position for the methanol aqueous solution that volumetric concentration is 60% is by reversed C18 column chromatography separating purification, successively
It is successively eluted with the methanol aqueous solution that volumetric concentration is 30%, 40%, 50%, 60% and 70%, is by volumetric concentration
40% methanol aqueous solution eluent purifies after merging and being concentrated under reduced pressure through Agilent SD-1 preparative liquid chromatography, with reverse phase C8
The acetonitrile solution that chromatographic column is chromatographic column, is 25% with volumetric concentration carries out isocratic elution, detects spectrogram according to liquid phase and carries out
It collects, successively obtains 35mg compound 11 and 22mg compound 9.
Through Agilent SD-1 system after volumetric concentration is merged and is concentrated under reduced pressure for the eluent of 50% methanol aqueous solution
Standby liquid chromatogram carries out isocratic elution, root using the acetonitrile solution that reverse phase C8 chromatographic column is 30% as chromatographic column, with volumetric concentration
It is collected according to liquid phase detection spectrogram, obtains 28mg compound 10.
It is stream with the mixed solvent of methylene chloride-methanol by methanol elution position by silica gel column chromatography (100-200 mesh)
It is dynamic mutually to carry out gradient elution according to following procedure: the volume ratio of methylene chloride-methanol be followed successively by 10:1 → 8:1 → 5:1 → 3:1 →
1:1 respectively obtains five eluates, is concentrated under reduced pressure respectively, then the elution position of the volume ratio 8:1 of methylene chloride-methanol is led to
Silica gel column chromatography (200-300 mesh) is crossed, is carried out according to the procedure below using the mixed solvent of dichloromethane-ethyl acetate as mobile phase
Gradient elution: the volume ratio of methylene chloride-methanol is followed successively by 5:1 → 4:1 → 3:1 → 2:1, is analyzed and is tied according to thin-layer chromatography TLC
Fruit merges and is concentrated under reduced pressure, and respectively obtains the tri- elution positions Fr.2.1, Fr.2.2, Fr.2.3.By Fr.2.1 by warp
Agilent SD-1 preparative liquid chromatography is mobile phase using reverse phase C18 filler chromatographic column as chromatographic column, with 20% methanol aqueous solution
Isocratic elution is carried out, spectrogram is detected according to liquid phase and is collected eluent, obtains compound 152mg compound 2, HPLC purity >=
98%.
Fr.2.2 passes through through Agilent SD-1 preparative liquid chromatography, using reverse phase C18 chromatographic column as chromatographic column, dense with volume
The methanol aqueous solution of degree 25% carries out isocratic elution, detects spectrogram according to liquid phase and is collected eluent, obtains 112mg compound
3, HPLC purity >=98%.
The structure confirmation data of the above compound1H NMR and13C NMR refers to following document: Two new
polyacetylene glycosides from the roots of Codonopsis tangshen Oliv.《Natural
Product Research ", 2016,30 (20): 1-6.
C14-Polyacetylene glucosides from Codonopsis pilosula.《Journal of
Asian Natural Products Research ", 2015,17 (6): 601.
Embodiment 2
By dry lobus cardiacus Radix Codonopsis (Codonopsis cordifolioidea) 30kg, at room temperature with the volume of 5 times of weight
Concentration is ethanol water soak extraction 3 times of 95%, is extracted 1 week every time, combined extract, and vacuum distillation is concentrated into no alcohol
Taste obtains medicinal extract.It disperses medicinal extract in the distilled water of 1 times of volume, with extracting n-butyl alcohol, obtains extracting n-butyl alcohol position 151g.
Extracting n-butyl alcohol position is separated using AB-8 macroreticular resin, and carry out gradient elution according to the procedure below: water, volumetric concentration are
35% methanol aqueous solution, the methanol aqueous solution and methanol that volumetric concentration is 75%, collect the eluent of each mobile phase simultaneously respectively
It is concentrated under reduced pressure, obtains the elution position 36g for the methanol that mobile phase is.The elution position for the methanol that mobile phase is passes through silicagel column color
Spectrum (100-200 mesh) is separated, and carries out gradient elution: dichloro according to the procedure below with the mixed solvent of methylene chloride-methanol
The volume ratio of methane and methanol is 10:1 → 8:1 → 5:1 → 3:1 → 1:1, collects the eluent of each mobile phase respectively and depressurizes dense
Contracting, respectively obtains five eluates.The elution position that the volume ratio of methylene chloride and methanol is 10:1 is passed through into Sephadex again
LH-20 column chromatography is separated by eluting solvent of methanol, is analyzed result according to thin-layer chromatography TLC and is merged eluent, point
Fr.3.1 and Fr.3.2 are not obtained.By Fr.3.1 through Agilent SD-1 preparative liquid chromatography, using reverse phase C18 chromatographic column as chromatography
Column carries out isocratic elution with the methanol aqueous solution that volumetric concentration is 50%, detects spectrogram according to liquid phase and is collected, obtains
265mg compound 4, HPLC purity >=98%.Fr.3.2 is through Agilent SD-1 preparative liquid chromatography, with reverse phase C18 chromatographic column
Isocratic elution is carried out for chromatographic column, with the methanol aqueous solution of volumetric concentration 65%, spectrogram is detected according to liquid phase and is collected, is obtained
121mg compound 5, HPLC purity >=98%.
The structure confirmation data of the above compound1H NMR and13C NMR refers to following document: Three New Polyyne
(=Polyacetylene) Glucosides from the Edible Roots of Codonopsis
Cordifolioidea. " Helvetica Chimica Acta ", 2008,91 (1): 90-96.
Embodiment 3
Snow chrysanthemum medicinal material 100kg is taken, with the ethanol water soak extraction of the volumetric concentration 70% of 15 times of volumes after crushing, is subtracted
Pressure concentration removes organic solvent, and concentrate is extracted 3 times with 1 times of amount ethyl acetate, combined ethyl acetate layer, and being concentrated under reduced pressure to remove has
Solvent obtains Ethyl acetate fraction.Ethyl acetate fraction is separated through ODS reversed-phase silica gel column chromatography, with methanol-water
Mixed solvent gradient elution is carried out with 1mL/min according to the procedure below: the volume fraction of methanol is followed successively by 10%, 30%,
45%, 60%, 80%, 90%, 100%, respectively obtain 6 eluate Fr.A-G.
Wherein, Fr.B is separated through silica gel column chromatography, is mobile phase according to the two body using the mixed solvent of ethyl acetate-ethanol
Product carries out gradient elution than 30:1 → 7:3, obtains 5 eluate Fr.B-1-5.Fr.B2 is with volumetric concentration through gel column chromatography
20% methanol aqueous solution is that mobile phase is eluted, and obtains compound 12 and 13.Fr.B3 is through gel column chromatography with volumetric concentration
Methanol aqueous solution for 20% is mobile phase elution, obtains compound 14.Fr.B4 is through gel column chromatography with volumetric concentration for 30%
Methanol aqueous solution be mobile phase elution, respectively obtain compound 15 and 16.
The structure confirmation data of the above compound1H NMR and13C NMR refers to following document: C14-polyacetylene
glycosides from the capitula of Coreopsis tinctoria and its anti-inflammatory
Activity against COX-2. " Fitoterapia ", 2013,87 (1): 93-97.
The research " Chinese herbal medicine " of carbene class chemical component, 2016,47 (11): 1834- in dichromatism golden wave capitulum
1837.
Experimental example 1The research of the compounds of this invention anti-trioxypurine effect
1, experimental material
It healthy male KM mouse 240, weight 15-18g, is provided by Shanghai Ling Chang Biotechnology Co., Ltd；By every
After cage 5 only carries out point cage processing, adaptive feeding 4 days in barrier system.
2, experimental method
2.1 experimental group
220 mouse that weight is concentrated are chosen from 240 mouse is divided into 22 groups by weight stochastic averagina, every group 10,
Respectively blank control group, model control group, positive controls, experimental group 1-19 group.
2.2 medication
Laundering period carries out gastric infusion to mouse immediately later, and every morning stomach-filling 1 time, continuous gavage is administered 7 days.
The compound 1-19 30mg/kg that experimental group 1-19 group gives embodiment 1-3 preparation respectively uses 0.5% carboxylic first respectively
Base sodium cellulosate (CMC-Na) solution is suspended；Positive controls give Febustat 2.5mg/kg, with 0.5% carboxymethyl fibre
Plain sodium (CMC-Na) solution is tieed up to be suspended；Blank control group and model control group use 0.5% sodium carboxymethylcellulose (CMC-
Na) solution stomach-filling；The equal continuous gavage of each group is administered 7 days.
After morning gastric infusion 0.5 hour the 7th day, intraperitoneal injection progress hyperuricemia is carried out to each group mouse and is made
Mould.Wherein, 0.5% sodium carboxymethylcellulose (CMC-Na) solution is injected intraperitoneally in blank control group；Model control group, positive control
Group, experimental group 1-19 group inject 300mg/kg Oteracil Potassium (OA), are dissolved with CMC-Na solution.
3, experimental data detection and processing
3.1 Testing index
After intraperitoneal injection 1.5 hours, each group mouse extracts eyeball, and blood was collected, and blood sampling capacity is not less than 0.5mL, and blood sample is adopted
In being placed at room temperature for about 1 hour after collecting, it is centrifuged 10 minutes under the conditions of 3500rpm/4 DEG C after blood solidifies completely, serum is taken to exist
It is multiple from 5 minutes under equal conditions, then take 0.2mL serum to detect UA value by Biochemical Analyzer.
3.2 statistical analysis
It is for statistical analysis to data with Excel and SPSS, average and SD are calculated, is compared after one-way analysis of variance
The group difference of each experimental group.
4, experimental result
Influence to the serum uric acid level of hyperuricemia mouse is as shown in table 1.
Influence (mean value, μm ol/L) of the table 1 to hyperuricemia mice serum uric acid level
| Sample | Uric acid (μm ol/L) | Sample | Uric acid (μm ol/L) |
| Blank control group | 52.36 | 10 groups of experimental group | 72.37** |
| Model control group | 149.73## | 11 groups of experimental group | 85.53* |
| Positive controls | 38.49** | 12 groups of experimental group | 75.68** |
| 1 group of experimental group | 65.62** | 13 groups of experimental group | 74.48** |
| 2 groups of experimental group | 72.33** | 14 groups of experimental group | 73.17** |
| 3 groups of experimental group | 69.91** | 15 groups of experimental group | 70.26** |
| 4 groups of experimental group | 70.28** | 16 groups of experimental group | 69.42** |
| 5 groups of experimental group | 77.39** | 17 groups of experimental group | 71.53** |
| 6 groups of experimental group | 89.74* | 18 groups of experimental group | 88.76* |
| 7 groups of experimental group | 63.39** | 19 groups of experimental group | 73.79** |
| 8 groups of experimental group | 90.29* | ||
| 9 groups of experimental group | 73.36** |
Note:**Indicate P < 0.01 (the t-test inspection) compared with hyperuricemia model group；*It indicates and hyperuricemia mould
Type group compares P < 0.05；##Indicate P < 0.01 compared with blank control group.
As shown in Table 1: (1) with blank control group compared with, the uric acid in serum of model control group mouse significantly increase (P <
0.01), there is significant difference, this shows hyperuricemia model modeling success；
(2) compared with model control group, the reduction of the uric acid in serum level of experimental group 1-19 group mouse has conspicuousness
Difference (P < 0.01 or P < 0.05).
5, experiment conclusion
The poly- acetylene compound that the present invention is separated from snow chrysanthemum and Radix Codonopsis can be substantially reduced small with hyperuricemia
The serum uric acid level of mouse has statistical significance compared with hyperuricemia model group, can be used as potential anti-trioxypurine drug and uses
In the treatment of hyperuricemia.
Obviously, the above embodiments are merely examples for clarifying the description, and does not limit the embodiments.It is right
For those of ordinary skill in the art, can also make on the basis of the above description it is other it is various forms of variation or
It changes.There is no necessity and possibility to exhaust all the enbodiments.And it is extended from this it is obvious variation or
It changes still within the protection scope of the invention.
Claims (8)
1. poly- acetylene compound shown in formula (I) and its pharmaceutically acceptable salt, ester, prodrug or solvate have in preparation
Application in the drug or health care product of anti-trioxypurine effect,
Wherein,Expression be selected from or
R1、R2、R3It is independently from each other H, OH, CH2CH2OH、COOCH3, by
At least one of be formed by glycosyl residue；
R4Selected from unsubstituted or by 1 to 3 R4aSubstituted C1-C12Alkyl or alkenyl, R4aSelected from OH, byAt least one of be formed by glycosyl residue.
2. poly- acetylene compound and its pharmaceutically acceptable salt, ester, prodrug shown in formula (I) according to claim 1
Or application of the solvate in the drug or health care product that preparation has anti-trioxypurine effect, which is characterized in that
R1、R2、R3It is independently from each other H, OH, CH2CH2OH、COOCH3, by
It is formed by monosaccharide groups residue or double glycosyl residues.
3. poly- acetylene compound shown in formula (I) according to claim 1 or 2 and its pharmaceutically acceptable salt, ester, preceding
The application of medicine or solvate in the drug or health care product that preparation has anti-trioxypurine effect, which is characterized in that shown in formula (I)
Poly- acetylene compound is selected from:
4. poly- acetylene compound shown in formula (I) according to claim 1-3 and its pharmaceutically acceptable salt,
The application of ester, prodrug or solvate in the drug or health care product that preparation has anti-trioxypurine effect, which is characterized in that formula (I)
Shown in poly- acetylene compound and its pharmaceutically acceptable salt, ester, prodrug or solvate be added normal according to common process
Auxiliary material is advised, clinically acceptable tablet, capsule, powder, mixture, pill, granule, syrup, emplastrum, bolt is made
Agent, aerosol, ointment or injection.
5. poly- acetylene compound shown in formula (I) and its pharmaceutically acceptable salt, ester, prodrug or solvate are treated in preparation
The drug of gout or the application in health care product,
Wherein,Expression be selected from or
R1、R2、R3It is independently from each other H, OH, CH2CH2OH、COOCH3, by
At least one of be formed by glycosyl residue；
R4Selected from unsubstituted or by 1 to 3 R4aSubstituted C1-C12Alkyl or alkenyl, R4aSelected from OH, byAt least one of be formed by glycosyl residue.
6. poly- acetylene compound and its pharmaceutically acceptable salt, ester, prodrug shown in formula (I) according to claim 5
Or application of the solvate in the drug or health care product of preparation treatment gout, which is characterized in that
R1、R2、R3It is independently from each other H, OH, CH2CH2OH、COOCH3, by
It is formed by monosaccharide groups residue or double glycosyl residues.
7. poly- acetylene compound shown in formula (I) according to claim 5 or 6 and its pharmaceutically acceptable salt, ester, preceding
The application of medicine or solvate in the drug or health care product of preparation treatment gout, which is characterized in that carbene class shown in formula (I)
Compound is selected from:
8. according to poly- acetylene compound shown in the described in any item formulas of claim 5-7 (I) and its pharmaceutically acceptable salt,
The application of ester, prodrug or solvate in the drug or health care product of preparation treatment gout, which is characterized in that shown in formula (I)
Customary adjuvant is added according to common process in poly- acetylene compound and its pharmaceutically acceptable salt, ester, prodrug or solvate,
Clinically acceptable tablet, capsule, powder, mixture, pill, granule, syrup, emplastrum, suppository, aerosol is made
Agent, ointment or injection.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111714486A (en) * | 2019-03-20 | 2020-09-29 | 苏州凯祥生物科技有限公司 | New application of polyacetylene compound |
| CN111714485A (en) * | 2019-03-20 | 2020-09-29 | 苏州凯祥生物科技有限公司 | Hyperuricemia pharmaceutical composition and application thereof |
| CN113491689A (en) * | 2020-04-08 | 2021-10-12 | 苏州凯祥生物科技有限公司 | Use of compounds as Sirt1 receptor agonists |
| WO2021204193A1 (en) * | 2020-04-08 | 2021-10-14 | 苏州凯祥生物科技有限公司 | Sirt1 receptor agonist and medicament comprising same |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111714486A (en) * | 2019-03-20 | 2020-09-29 | 苏州凯祥生物科技有限公司 | New application of polyacetylene compound |
| CN111714485A (en) * | 2019-03-20 | 2020-09-29 | 苏州凯祥生物科技有限公司 | Hyperuricemia pharmaceutical composition and application thereof |
| CN111714486B (en) * | 2019-03-20 | 2023-06-20 | 苏州凯祥生物科技有限公司 | Application of polyacetylene compound |
| CN113491689A (en) * | 2020-04-08 | 2021-10-12 | 苏州凯祥生物科技有限公司 | Use of compounds as Sirt1 receptor agonists |
| WO2021204193A1 (en) * | 2020-04-08 | 2021-10-14 | 苏州凯祥生物科技有限公司 | Sirt1 receptor agonist and medicament comprising same |
| WO2021204192A1 (en) * | 2020-04-08 | 2021-10-14 | 苏州凯祥生物科技有限公司 | Use of compound as sirt1 receptor agonist |
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