CN101049301A - Pharmaceutical preparation of biflavone compound for anti gout - Google Patents
Pharmaceutical preparation of biflavone compound for anti gout Download PDFInfo
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Abstract
A bisflavone medicine for preventing and treating gout, preventing the xanthine and hypoxanthine from being oxidized to become uric acid, and relaxing the hyperuricemia and its secondary diseases is prepared from one or more of bisflavone compounds and the auxiliaries.
Description
Affiliated technical field
The present invention relates to contain the plant extract of bisflavones composition or the derivant or the salt of bisflavones composition, be prepared into the medicine of prevention or treatment hyperuricemia and gout.
Background technology
Gout is the disease that a kind of purine metabolic disturbance causes.Clinical characters is hyperuricemia, gouty arthritis, joint deformity, nephropathy and urate calculus, the formation of gout calculus etc.Wherein hyperuricemia is the paranormal a kind of state of uric acid in the blood, is a stage in the gout evolution; Gouty arthritis is that uric acid was deposited on joint tissue after serum uric acid level increased, and stimulates the joint and causes a series of inflammatory reaction.
Existing medicine is treated at the symptom selectivity that different times showed at patient with gout.Be used for gout acute attack treatment as anti-inflammation analgesis medicament colchicine and indometacin; Uricotelic drugs such as probenecid, benzbromarone are used for gap phase and chronic phase treatment; It is synthetic that xanthine oxidase inhibitor medicine allopurinol suppresses uric acid.But the said medicine toxic and side effects is big, and the patient often can not adhere to taking for a long time, so that the wayward state of an illness.Colchicine and indometacin have the GI irritation effect, and the former also causes leucocytes reduction and alopecia etc.; Probenecid, benzbromarone have gastrointestinal reaction, renal colic and excite side effect such as gout acute attack; Allopurinol high-quality allergy incidence rate up to 10~15%, super quick syndrome can cause 27.5% the disease death of speckle mound occurring, though bone marrow depression is rare, consequence is serious.
Hypoxanthine in the blood is oxidized to xanthine under the catalytic action of xanthine oxidase, xanthine generates uric acid and water under the catalytic action of xanthine oxidase, and the uric acid of high concentration has just formed hyperuricemia in blood.Allopurinol is owing to energy competitive inhibition xanthine oxidase, so can effectively block the formation of uric acid, relief of symptoms.But this only is a kind of symptomatic treatment, and prolonged application has side effect.
Naturally occurring flavones ingredient is that xanthine oxidase inhibitor is originated the most widely, and wherein Quercetin has the activity of stronger inhibition xanthine oxidase, with the pure product of Quercetin curative effect is not preferably arranged merely but also there is clear evidence to show.Find at present and report that naturally occurring Selaginella various plants and extract thereof have various active such as suppressing xanthine oxidase and lipoxidase, but do not disclose its main active group of working and combination matching thereof.
This patent is discovered, naturally occurring bisflavone chemical compound has the curative effect of xanthine oxidase inhibitory activity preferably and treatment gout, wherein especially to include sieve S bisflavone (robustaflavone), sieve S bisflavone-4 '--and it is higher that methyl ether, amentoflavone (amentoflavone) biflavone ingredient of etc.ing carry out the inhibition potency ratio of the plant extract that proportioning makes up.We observe like this some facts: the molecular weight of these bisflavone chemical compounds is generally greater than 500, has bigger sterically hindered.Therefore; we can not free in and out cell by these bisflavone chemical compounds of inference; the general redox reaction that can not enter in cell, the interference cell; and the main effect of in extracellular fluid, bringing into play antioxidation and suppressing xanthine oxidase; protect cell membrane to make it not oxidized simultaneously; though so they are to the compositions such as the too late Quercetin of activity of xanthine oxidase, its curative effect is higher, side effect is less.Though the monomer that second fact is some composition in these bisflavone chemical compounds is tired higher to the inhibition of xanthine oxidase, but their pure product are water solublity or fat-soluble all bad, so dispersion is not high, curative effect still is limited, must improve solubility property by derivatization.The 3rd, the solubility property that contains the medicinal plant extract of a certain proportion of multiple bisflavones constituents mixt can improve greatly, contains a certain proportion of sieve S bisflavone, sieve S bisflavone-4 '--methyl ether and amentoflavone in these mixture usually.Under same ratio, the crude extract that contains these bisflavone chemical compounds its inhibition of comparing with purer total bisflavone extract is tired and is not reduced, and perhaps inhibition is tired higher; And in fact their dissolubility and therapeutic effect is also better.
Summary of the invention
Separation obtains from medicinal plants amentoflavone, sieve S bisflavone, sieve S bisflavone-4 '--bisflavone chemical compounds such as methyl ether have the activity that suppresses xanthine oxidase, and they can be used to treat gout and produce a series of symptoms that uric acid causes by xanthine.The extract of the medicinal plants Selaginella labordei Hieron-S. Hupehensis Pamp. of these bisflavone chemical compounds that contain, selaginella delicatula Alston, CUIYUNCAO, Herba Selaginellae Involventis has preferably xanthine oxidase inhibitory activity equally, has a better dissolubility simultaneously, thereby better therapeutic effect is arranged.These bisflavone chemical compounds of experiment confirm and these extracts have lower cytotoxicity, bigger half fatality rate, thereby the using dosage of extremely safe is arranged, can be used as the anti-gout drugs exploitation.Simultaneously, these bisflavone chemical compounds have the effect of lipotropism oxidase and Cycloxygenase, can alleviate the inflammatory reaction that causes owing to the free radical that produces in the uricopoiesis process preferably, alleviate the various symptoms of gout.
The present invention is achieved through the following technical solutions:
A kind of pharmaceutical preparation of gout, it is characterized in that this pharmaceutical preparation mainly is by natural purification or do not purify or synthetic sieve S bisflavone (robustaflavone), sieve S bisflavone-4 '-methyl ether (4 '-O-methylrobustaflavone), sieve S bisflavone 7 " methyl ether (7 "-O-methylrobustaflavone), amentoflavone (amentoflavone), hinokiflavone (hinokiflavone), Sotetsuflavone (Sotetsuflavone), isocryptomerin (isocryptomerin), ginkegetin (bilobetin), ginkegetin (ginkgetin), Podocarpus imbricatus bisflavone A (7,7 "; 4 '-tri-O-methylrobustaflavone); Podocarpus imbricatus bisflavone B (7; 7 "-di-O-methylrobustaflavone), Agathisflavone (agathisflavone, be 5-acetyl-7,4-dimethoxyflavone-(6-8)-5-acetyl-7,4-dimethoxyflavone), (volkensiflavone is 5 to volkensiflavone, 7,4 '-trimethoxy-flavanone-(3-8)-5-acetyl-7,4-dimethoxyflavone), morelloflavone (morelloflavone), 2 "; 3 "-dihydro-4 '-the methoxyl group amentoflavone (2 "; "-dihydro-4 '-O-methyl Amentoflavone) etc. the bisflavone chemical compound of one or more in the bisflavone chemical compound is formed, and perhaps is made up of the medicine of above-mentioned at least a chemical compound and auxiliary element.
The pharmaceutical preparation of gout of the present invention, its contained sieve S bisflavone, sieve S bisflavone-4 '--methyl ether, amentoflavone, hinokiflavone, Sotetsuflavone, isocryptomerin, ginkegetin, ginkegetin, Podocarpus imbricatus bisflavone A, Podocarpus imbricatus bisflavone B, Agathisflavone, volkensiflavone, morelloflavone composition, 2 "; 3 "-dihydro-4 '-the methoxyl group amentoflavone, come from natural plant extracts, its natural plant extracts contains wherein a kind of bisflavones composition at least.
The contained bisflavone compound quality proportioning of the pharmaceutical preparation of gout of the present invention is: sieve S bisflavone 0~50%, sieve S bisflavone-4 '--methyl ether 0~50%, amentoflavone 0~50%, this pharmaceutical preparation contain above-mentioned wherein a kind of bisflavones composition at least.
The pharmaceutical preparation of gout of the present invention, its contained bisflavone chemical compound can be sieve S bisflavone, sieve S bisflavone-4 '--the derivant or the salt of methyl ether, amentoflavone, for example four sulphuric acid potassium salt of sieve S bisflavone.
The pharmaceutical preparation of gout of the present invention is equipped with different adjuvants, makes the dosage form of for oral administration accordingly or external with different route of administration, is used for the treatment of the various gout symptoms that hyperuricemia causes.
Dosage form of the present invention is a said dosage form on any pharmaceutics.It is said dosage form on any pharmaceutics that is mixed and made into for the above adjuvant of described bisflavone chemical compound and any pharmaceutics.
The specific embodiment
The experiment of embodiment 1 bisflavone chemical compound and compositions vitro inhibition xanthine oxidase thereof
1.1 specimen material, reagent
Amentoflavone, sieve S bisflavone (robustaflavone), sieve S bisflavone-4 '--bisflavone chemical compound pure strain Hubei College Of Traditional Chinese Medicine laboratorys such as methyl ether separate the monomeric compound that obtains from the Selaginella medicinal plants, identify conclusive evidence through structure, calculate content more than 97% with normalization method.The bisflavone compound composition is the medicinal plant extract that the master that obtains through extraction from medicinal plants contains multiple bisflavone chemical compound, its general flavone content 35%~45%, its contained amentoflavone, sieve S bisflavone (robustaflavone), sieve S bisflavone-4 '--the ratio of methyl ether sees Table 1.
The portfolio ratio (mass percent) of three kinds of bisflavones in the various extracts of table 1
Compile | Compositions | Amentoflavone relative amount % | Sieve S bisflavone relative amount % | Sieve S bisflavone-4 '--methyl ether relative amount % |
2 4 8 13 | Compositions 1 compositions 2 compositionss 3 compositionss 4 | 21.37 4.19-8.41 12.55 51.17 | 8.32 16.74-21.85 12.59 15.42 | 25.58 51.33-57.36 23.37 3.54 |
Instrument and reagent D U640 spectrophotometer (Beckman Inc.USA) have kinetics/time software.Xanthine oxidase (XOD) (Sigma, lot024K3783), xanthine (Sigma, lot85H71952); Quercetin (Nat'l Pharmaceutical ﹠ Biological Products Control Institute, 10081-9906); Dimethyl sulfoxine (Amresco), all the other reagent are analytical pure.
1.2 method
1.2.1 substrate solution: form by 0.2 mM/rise xanthine solution and 0.2 mol potassium phosphate buffer (pH 7.5, contain 1 mM/rise EDTA).
1.2.2XOD vitality test: under the catalysis of xanthine oxidase, xanthine is oxidized to uric acid, and following reaction promptly takes place:
(determine by the shading value of λ=290nm) locate by the characteristic absorption peak that detects the product uric acid for the XOD vigor.Experimental technique reference literature (P.Cos, et al.Structure activity relationship and classification offlavonoids as inhibitors of xanthine oxidase and superoxide scanvengers.J.Nat.Prod., 1998,6171) method of Miao Shuing is at 290nm place spectrophotometry.Numerical value every 5 seconds in 290.0nm place record absorbance and absorbance growth amounts to 5 minutes.In any one suitably long time period, absorbance is linear in time to be increased, and slope is reaction rate (dA/min), and slope is big more, illustrates that the vigor of enzyme is strong more.
1.2.3 sample determination: plant extract is dissolved in the dimethyl sulfoxine (DMSO), obtains the sample solution (DMSO ultimate density<1%) of variable concentrations.Get in right amount and be added in the quartz colorimetric utensil.Repeat aforesaid operations, the numerical value that increases at 290nm place record absorbance every 5 seconds, 1 minute altogether.Each sample operation repetitive 3 times writes down reaction rate respectively, the suppression ratio of the calculation sample of averaging.
1.2.4 blank: repeat aforesaid operations, do not add sample and xanthine oxidase, but add the dimethyl sulfoxine with the same volume of sample, the variation of record absorbance is as blank.
1.2.5 the xanthine oxidase reference substance is measured: method is identical with sample determination, does not just add sample.
1.2.6 positive reference substance: for controlled experiment result's credibility, get Quercetin and be dissolved in the solution that obtains variable concentrations in the dimethyl sulfoxine, repeat above-mentioned experiment, calculate IC
50
1.3 result
Adopt SPSS 13.0 statistical packages to carry out date processing, earlier according to the suppression ratio of following formula calculation sample to XOD:
Suppression ratio=[1-(Rs-Ro)/(Rp-Ro)] * 100%
Rs, Ro, Rp in the formula: the reaction rate of representing sample, blank and XOD reference substance respectively.
Being dependent variable with suppression ratio (inhibitory rate) again, is that independent variable calculates regression equation with sample concentration (concentration).Because of suppression ratio and sample concentration linear, so directly be 50% sample concentration IC according to the regression equation calculation suppression ratio
50Experimental result sees Table 2.
Table 2 bisflavone chemical compound and contain the extract of these chemical compounds
Inhibitory action (IC to xanthine oxidase
50MgL
-1)
Material | IC50(mg·L -1) |
Quercetin (reference substance) 4'-O-methylrobustaflavone robustaflavone amentoflavone composition 1 composition 2 compositions 3 compositions 4 | 0.080 61.0 0.199 3.1 10.8 4.4 14.4 19.9 |
1.4 brief summary
More than, three kinds of bisflavone chemical compounds and four kinds of Selaginella medicinal plant extracts that contain the bisflavone chemical compound have been carried out the experiment of vitro inhibition xanthine oxidase activity, found that sieve S bisflavone, amentoflavone and several Selaginella medicinal plant extract that contains the bisflavone chemical compound have higher xanthine oxidase inhibitory activity.Sieve S bisflavone 1 ' though-the inhibition activity of methyl ether xanthine oxidase is not high, and its content in extract is generally higher, and it does not reduce the activity of whole crude extract by a relatively large margin, but has increased the dissolubility of extract greatly.
The experiment of embodiment 2, bisflavone chemical compound and compositions vitro inhibition lipoxidase thereof
2.1 material, instrument and reagent
Bisflavone chemical compound and several bisflavone compound compositions are with embodiment 1.
Instrument and reagent D U640 spectrophotometer (Beckman Inc.USA) have kinetics/time software.Lipoxidase LOX (Sigma, lot118F03422), linoleic acid (Sigma, lot015K1200); Quercetin (10081-9906); Dimethyl sulfoxine and tween 20 (Tween-20 Amresco), all the other reagent are analytical pure.
2.2 method
2.2.1 test solution preparation: 3.3 mMs/rise substrate solution: get linoleic acid 157.2 microlitres, tween 20 (Tween-20) 157.2 microlitres, 10 milliliters in water adds 0.5 milliliter of 1 mol NaOH again and makes the solution clarification, add water to 25 milliliters, mix homogeneously obtains the substrate storing solution.The substrate storing solution with 0.2 mol phosphate buffer dilute 3.3 mMs/rise substrate solution, oxygenation is 2 minutes before using.
2.2.2LOX vitality test: experimental technique reference literature (Chen, AO; Whitaker, JR.Purification andcharacterization of a lipoxygenase from immature English peas[J] .J.Agri.FoodChem, 1986,34:203 ~ 211.) method of Miao Shuing, at 234nm place spectrophotometry, lipoxidase concentration is 1.08 mcg/ml, numerical value every 5 seconds in 234nm place record absorbance and absorbance growth, minute 5 minutes, absorbance is linear in time to be increased, slope is reaction rate (dA/min), and slope is big more, illustrates that the vigor of enzyme is strong more.
2.2.3 sample determination: plant extract is dissolved in the dimethyl sulfoxine (DMSO, ultimate density<1%), obtains the solution of variable concentrations.Get and be added to quartz colorimetric utensil in right amount.Repeat aforesaid operations, the numerical value that increases at 234nm place record absorbance every 5 seconds, 2 minutes altogether.Each sample operation repetitive 3 times writes down reaction rate respectively, the suppression ratio of the calculation sample of averaging.
2.2.4 blank: repeat aforesaid operations, do not add sample and LOX, but add the dimethyl sulfoxine with the same volume of sample, the variation of record absorbance is as blank.
2.2.5LOX reference substance is measured: method is identical with sample determination, does not just add sample.
2.2.6 positive reference substance: for controlled experiment result's credibility, get Quercetin and be dissolved in the solution that obtains variable concentrations among the DMSO, measure by 2.3 methods.
2.3 result
Adopt SPSS 13.0 statistical packages to carry out date processing, earlier according to the suppression ratio of following formula calculation sample: suppression ratio=[1-(Rs-Ro)/(Rp-Ro)] * 100%, Rs, Ro, Rp in the formula: the reaction rate of representing sample, blank and LOX reference substance respectively to LOX.Being dependent variable with suppression ratio (inhibitory rate) again, is that independent variable calculates regression equation with sample concentration (concentration).Linear because of suppression ratio and sample concentration, directly be 50% sample concentration IC according to the regression equation calculation suppression ratio
50, experimental result sees Table 3.
Table 3 bisflavone chemical compound and compositions thereof are to the inhibitory action (IC of lipoxidase
50/ μ gmL
-1)
Material | IC 50(μg·mL -1) |
Compositions 1 compositions, 2 compositions 3-1 (total flavones>35%) | 5.7 6.6 8.6 |
Compositions 3-2 (total flavones>90%) compositions 4 amentoflavone sieve S bisflavone sieve S bisflavones-4 '-the methyl ether Quercetin | 13.55 11.1 3.78 4.33 9.65 0.11 |
2.4 discuss and brief summary
Lipoxidase relates to the biosynthesis path of leukotriene, prostaglandin etc. and the oxidation of induced lipolysis acid, and these also relate to processes such as inflammation, sclerosis, cancer.Experimental result shows that the extract of above-mentioned Selaginella several plant is to the IC of LOX
50Being generally less than 10 mcg/ml, having shown that all stronger LOX suppresses active, is main active site.Obtained having active multiple bisflavone chemical compound from these positions separation.Therefore these plant extracts and chemical compound also can suppress the matter oxidase when suppressing xanthine oxidase, resist inflammation and cell membrane oxidation that hyperuricemia causes, help the alleviation of symptom.
From experimental result, several bisflavone compound monomer active component have strong LOX to suppress active, but active strong a lot of unlike the above-mentioned plant crude extract that contains these compositions.The crude extract that contains bisflavone in these plants has better dissolving part energy than containing the purer total extract of these bisflavone chemical compounds, thereby has better action effect, and compositions 3 has provided clear evidence.
The pharmacodynamic experiment of anti-hyperuricemia in embodiment 3, the body
3.1 experiment material
Male mice in kunming, body weight (24 ± 2) gram is purchased the Experimental Animal Center in Hubei Province.80% ethanol extraction of certain medicinal plants, wherein general flavone content is greater than 35%, and amentoflavone, sieve S bisflavone, sieve S bisflavone-4 '--the ratio of methyl ether is 75: 15: 5 in the bisflavone chemical compound that it contained.
2, experimental technique
40 male mices are divided into 4 groups at random, every group 10, i.g every day (filling stomach). be administered once, continuous 4 days, wherein normal saline group and hyperuricemia model group every day are by 100 ml/kg dosage i.g. normal saline, the hyperuricemia model group is at preceding 2 hours ip (lumbar injection) of blood sampling oxonic acid potassium salt, and the administration group is last hour ip oxonic acid of administration potassium salt the last time.Give back approximately 2 hours for the last time from the blood sampling of animal eye socket rear vein beard, measure serum uric acid level.
The plant extract that contains the bisflavone compound composition the results are shown in Table 4 to the influence of serum uric acid level.Under this experiment condition, extract and matched group allopurinol all can significantly reduce hyperuricemia mice serum uric acid level.
Table 4 extract is to the result that influences of serum uric acid level
Group | The treatment number of animals | The mice serum uric acid level (x ± s) |
The extract for treating high dose group | 10 | 8.22±0.25** |
The normal blank group of extract for treating low dose group allopurinol treatment matched group model blank group | 10 10 10 10 | 9.40±0.15** 7.55±0.18** 12.80±0.29 7.89±0.20** |
* * P<0.01 of comparing with model blank group
These bisflavone compound compositions of above presentation of results can significantly reduce the serum uric acid level of hyperuricemia mice.
Embodiment 4, preparation embodiment 1
1, prescription is selected the pharmaceutical composition and the additives of following consumption for use, the preparation dispersible tablet
Amentoflavone 75 grams
Sieve S bisflavone 15 grams
Sieve S bisflavone-4 '--methyl ether 5 grams
Polyethylene Glycol (PEG) 6,000 900 grams
Starch an amount of (adding to 1200 grams)
Lactose 50 grams
Polyethylene pyrrole alkane ketone (PVP) 50 grams
Magnesium stearate 5 grams
Make 2000.
2, preparation
Get amentoflavone, sieve S bisflavone, sieve S bisflavone-4 '--methyl ether, polyethylene glycol 6000 with the PEG6000 heating and melting, is got it filled the thing heating for dissolving in an amount of dehydrated alcohol, join again in the carrier under the molten condition and constantly stir, make mix homogeneously, and fling to solvent, pour into rapidly then on the corrosion resistant plate of pre-cooling in 80 ℃ of stirrings, be coated with straticulation, cooling curing under-20 ℃ of conditions, finished product is stored in a few days in the exsiccator, porphyrize, cross 60 mesh sieves, add starch again, lactose, polyethylene pyrrole alkane ketone wet granulation, oven dry, granulate, add magnesium stearate etc., mixing, tabletting, coating, promptly.
Embodiment 5, preparation embodiment 2
1, prescription is selected the pharmaceutical composition and the additives of following consumption for use, the preparation capsule
Extractive of general flavone 100 grams
(extractive of general flavone contains total flavones 50%~60%, and wherein amentoflavone 30~40%,
Sieve S bisflavone 5~10%, sieve S bisflavone-4 '--methyl ether 3~8%)
Calcium carbonate 10%
Starch adds to 300 grams
Make 1000.
2, preparation
Get extractive of general flavone, calcium carbonate, starch, wet granulation, oven dry, granulate is crossed 80 mesh sieves, dry granulation, granulate, fill is in capsule, promptly.
Embodiment 6, preparation embodiment 3
Prescription sieve S bisflavone (content 90%) 50 grams
Polyethylene Glycol (PEG) 4000+ lecithin 900 grams
Starch an amount of (adding to 1200 grams)
Lactose 50 grams
Polyethylene pyrrole alkane ketone 50 grams
Magnesium stearate 5 grams
Make 2000.
2, preparation
Taking polyethylene glycol 4000, lecithin heating and melting are got it filled the thing heating for dissolving in an amount of dehydrated alcohol, join in the carrier under the molten condition constantly to stir again, and make mix homogeneously, and fling to solvent in 80 ℃ of stirrings, topple over being coated with straticulation then rapidly, cooling curing under-20 ℃ of conditions, finished product is stored in a few days in the exsiccator, and porphyrize is crossed 120 mesh sieves, add starch, lactose again, polyethylene pyrrole alkane ketone wet granulation, oven dry, granulate adds magnesium stearate etc., mixing, tabletting, coating, promptly.
Claims (5)
1, a kind of pharmaceutical preparation of gout, it is characterized in that this pharmaceutical preparation mainly is by natural purification or that do not purify or synthetic sieve S bisflavone, sieve S bisflavone-4 '-methyl ether, sieve S bisflavone 7 " methyl ethers; amentoflavone; hinokiflavone; Sotetsuflavone; isocryptomerin; ginkegetin, ginkegetin, Podocarpus imbricatus bisflavone A, Podocarpus imbricatus bisflavone B, Agathisflavone, volkensiflavone, morelloflavone, 2 "; 3 "-dihydro-4 '-one or more bisflavone chemical compound in the methoxyl group amentoflavone chemical compound forms, perhaps is made up of the medicine of above-mentioned at least a bisflavone chemical compound and auxiliary element.
2, the pharmaceutical preparation of gout according to claim 1, it is characterized in that sieve S bisflavone that it is contained, sieve S bisflavone-4 '-methyl ether, amentoflavone, hinokiflavone, Sotetsuflavone, isocryptomerin, ginkegetin, ginkegetin, Podocarpus imbricatus bisflavone A, Podocarpus imbricatus bisflavone B, Agathisflavone, volkensiflavone, the morelloflavone composition, 2 "; 3 "-dihydro-4 '-the methoxyl group amentoflavone, come from natural plant extracts, its natural plant extracts contains wherein a kind of bisflavones composition at least.
3, anti-gout drugs preparation according to claim 1, the mass ratio that it is characterized in that the bisflavone compound mixture that it is contained is: sieve S bisflavone 0~50%, sieve S bisflavone-4 ' monomethyl ether 0~50%, amentoflavone 0~50%, this pharmaceutical preparation contain said mixture or contain above-mentioned wherein a kind of bisflavones composition at least.
4, the pharmaceutical preparation of gout according to claim 1 is characterized in that this medicament form of pharmaceutical preparation is a said dosage form on any pharmaceutics.
5, the pharmaceutical preparation of gout according to claim 1 is characterized in that this medicament form of pharmaceutical preparation, is said dosage form on any pharmaceutics that is mixed and made into by the above adjuvant of described bisflavone chemical compound and any pharmaceutics.
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CN106074636A (en) * | 2016-07-19 | 2016-11-09 | 中南民族大学 | The application of people face fruit leaf extract and preparation method |
CN106074636B (en) * | 2016-07-19 | 2019-11-15 | 中南民族大学 | The application of people face fruit leaf extract and preparation method |
CN107021946A (en) * | 2017-06-02 | 2017-08-08 | 中山火炬职业技术学院 | A kind of compound and its preparation and application with antitussive effect |
CN107021946B (en) * | 2017-06-02 | 2020-04-03 | 中山火炬职业技术学院 | Compound with cough relieving effect and preparation and application thereof |
CN116808083A (en) * | 2023-07-11 | 2023-09-29 | 海南热带海洋学院 | Application of selaginella total flavone in preparing medicament for treating hyperuricemia |
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