CN109893533B - New application of polyacetylene compounds in reducing uric acid - Google Patents
New application of polyacetylene compounds in reducing uric acid Download PDFInfo
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- CN109893533B CN109893533B CN201711286456.9A CN201711286456A CN109893533B CN 109893533 B CN109893533 B CN 109893533B CN 201711286456 A CN201711286456 A CN 201711286456A CN 109893533 B CN109893533 B CN 109893533B
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- CN
- China
- Prior art keywords
- uric acid
- polyacetylene
- pharmaceutically acceptable
- compound
- methanol
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 46
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 title claims abstract description 35
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 229940116269 uric acid Drugs 0.000 title claims abstract description 34
- 229920001197 polyacetylene Polymers 0.000 title claims abstract description 33
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 title claims abstract description 31
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Abstract
The invention belongs to the field of medicines or health-care products, and particularly relates to a new application of a polyacetylene compound in reducing uric acid. The polyacetylene compound has a structure shown in a formula (I):
R1、R2、R3and R4As defined in the description of the invention. The research of the invention finds that the polyacetylene compounds separated from the coreopsis tinctoria and the codonopsis pilosula have the activity of reducing uric acid, have no obvious toxic or side effect, and can be used for treating hyperuricemia and gout or gout complications caused by the hyperuricemia.
Description
Technical Field
The invention belongs to the field of medicines or health-care products, and particularly relates to a new application of a polyacetylene compound in reducing uric acid.
Background
Uric acid is the final metabolite of human purine compounds, and purine metabolic disorders lead to hyperuricemia. Under normal purine diet, the level of uric acid in fasting blood twice a day is higher than 416 mu mol/L in male and higher than 360 mu mol/L in female, namely hyperuricemia (hyperuricemia). Gout is crystal-related arthropathy caused by deposition of monosodium urate (MSU), is directly related to hyperuricemia caused by purine metabolic disorder and/or reduction of uric acid excretion, and is clinically mainly manifested by hyperuricemia, repeated attack of gouty acute arthritis, gouty chronic arthritis, tophus, gouty nephropathy, renal urate calculi and the like, and serious patients can have joint disability and renal insufficiency. In addition, gout is often associated with abdominal obesity, hyperlipidemia, hypertension, type ii diabetes, and cardiovascular diseases. Gout has become the second largest metabolic disease after diabetes, seriously harming human life and health. According to the recently published '2017 Chinese gout status report white paper', the number of hyperuricemia patients in China reaches 1.7 hundred million, wherein the number of gout patients exceeds 8000 ten thousand, and the annual growth rate is rapidly increased by 9.7%; the number of gout people in China is estimated to reach 1 hundred million by 2020.
At present, hyperuricemia, gout and gout complications are treated mainly by controlling uric acid in blood, and the action mechanisms of the traditional Chinese medicine mainly comprise the following two mechanisms: (1) the formation of uric acid is effectively inhibited by inhibiting the activity of Xanthine Oxidase (XO), and representative drugs comprise allopurinol, febuxostat and the like; (2) promoting the excretion of uric acid, and typical drugs include probenecid, benzbromarone, and the like. However, the toxic side effects of all of the above drugs are generally large, such as: allopurinol can cause severe toxic and side effects such as allergic reaction (the morbidity is 10-15%), hypersensitivity syndrome, bone marrow suppression and the like; probenecid and benzbromarone have the side effects of stimulating gastrointestinal tracts, causing renal colic, exciting gout acute attack and the like; febuxostat can increase the risk of cardiovascular system diseases, and Stevens-Johnson syndrome can occur in severe cases; moreover, the tolerance of the above drugs is generally low. In conclusion, these problems limit the clinical application of these drugs to some extent. Therefore, the research on novel medicines for treating gout is of great significance.
Radix Codonopsis Radix Codonopsis is dried root of Radix Codonopsis pilosula (Franch.) Nannf. or Radix Codonopsis pilosula Nannf. var. modesta (Nannf.) L.T Shen or Radix Codonopsis tandshen tangshen Oliv. of Campanulaceae, collected in autumn, cleaned, sun-dried, sweet in nature and taste, flat, spleen and lung meridian entered, and can tonify middle warmer and qi, invigorate spleen and benefit lung, and can be used for treating spleen and lung deficiency heat, short breath cardiopalmus, anorexia and loose stool, cough due to phlegm, internal heat and thirst quenching, etc. However, there is no report in the prior art about the effect of radix codonopsis or the compound isolated from radix codonopsis in reducing uric acid or treating gout.
Coreopsis tinctoria, which is known as serpentium, bicolor Coreopsis tinctoria, is a head-shaped inflorescence of Coreopsis tinctoria (Kunlun Chrysanthemum) which is a kindred plant of annual herbaceous Coreopsis tinctoria of Compositae (Comosidae), is native to North America, and is introduced into China after being produced in North America. At present, modern drug effect and pharmacological research of coreopsis tinctoria mainly focuses on aspects of reducing blood sugar, blood pressure, blood fat and inflammation, and the like, for example: chinese patent document CN105520984A discloses: the coreopsis tinctoria flower extract has the effect of treating hyperuricemia, can effectively reduce the concentration of uric acid in blood, and has a certain treatment effect on metabolic diseases related to the hyperuricemia. However, the above documents do not disclose a specific active ingredient in coreopsis tinctoria extract that exerts uric acid lowering effects.
Disclosure of Invention
Therefore, the first technical problem to be solved by the invention is that no report about the effect of the radix codonopsis or the compound separated from the radix codonopsis on reducing uric acid or treating gout exists in the prior art, so that a novel application of the polyacetylene compound in reducing uric acid is provided.
The second technical problem to be solved by the invention is that the specific active ingredients which play a role in reducing uric acid in coreopsis tinctoria extract are not disclosed in the prior literature, so that a novel application of the polyacetylene compound in reducing uric acid is provided.
In order to solve the technical problems, the invention is realized by the following technical scheme:
in a first aspect, the invention provides application of a polyacetylene compound shown as a formula (I) and pharmaceutically acceptable salts, esters, prodrugs or solvates thereof in preparing medicines or health care products with uric acid reducing effect,
wherein the content of the first and second substances,
is selected from
Or
R1、R2、R3Independently of one another, selected from H, OH, CH2CH2OH、COOCH3From
At least one glycosyl residue formed in (a); r4Selected from unsubstituted or substituted by 1 to 3R4aSubstituted C1-C12Alkyl or alkenyl of, R4aSelected from OH, from
At least one glycosyl residue formed.
The terms in the claims and the specification of the present invention have the following meanings unless otherwise specified.
Alkyl refers to: fully saturated straight or branched chain hydrocarbon radicals. For example: alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3-methylhexyl, 2-dimethylpentyl, 2, 3-dimethylpentyl, n-heptyl, n-octyl, n-nonyl, n-decyl, and the like.
Alkenyl means: a linear or branched hydrocarbon group containing at least one ethylenic bond. For example: alkenyl groups include, but are not limited to, vinyl, allyl, and the like.
Preferably, the application of the polyacetylene compound shown in the formula (I) and the pharmaceutically acceptable salt, ester, prodrug or solvate thereof in preparing the medicine or health care product with the effect of reducing uric acid,
R1、R2、R3independently of one another, selected from H, OH, CH2CH2OH、COOCH3From
The monosaccharide or disaccharide residues formed.
Further preferably, the application of the polyacetylene compound shown in the formula (I) and the pharmaceutically acceptable salt, ester, prodrug or solvate thereof in preparing the medicine or health product with the effect of reducing uric acid is that the polyacetylene compound shown in the formula (I) is selected from:
further preferably, the application of the polyacetylene compound shown in the formula (I) and the pharmaceutically acceptable salt, ester, prodrug or solvate thereof in preparing the medicine or health product with the effect of reducing uric acid is that the polyacetylene compound shown in the formula (I) and the pharmaceutically acceptable salt, ester, prodrug or solvate thereof are added with conventional auxiliary materials according to the conventional process to prepare clinically acceptable tablets, capsules, powder, mixtures, pills, granules, syrups, emplastrums, suppositories, aerosols, ointments or injections.
The conventional auxiliary materials are as follows: fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, bases, and the like. The filler comprises: starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose, sucrose, etc.; the disintegrating agent comprises: starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, low-substituted hydroxypropylcellulose, cross-linked sodium carboxymethyl cellulose, etc.; the lubricant comprises: magnesium stearate, sodium lauryl sulfate, talc, silica, and the like; the suspending agent comprises: polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methylcellulose, and the like; the adhesive comprises starch slurry, polyvinylpyrrolidone, hydroxypropyl methylcellulose, etc.; the sweetener comprises: saccharin sodium, aspartame, sucrose, sodium cyclamate, glycyrrhetinic acid, and the like; the flavoring agent comprises: sweeteners and various essences; the preservative comprises: parabens, benzoic acid, sodium benzoate, sorbic acid and its salts, benzalkonium bromide, chloroacetidine acetate, eucalyptus oil, etc.; the matrix comprises: PEG6000, PEG4000, insect wax, etc.
In a second aspect, the invention also provides application of the polyacetylene compound shown in the formula (I) and pharmaceutically acceptable salts, esters, prodrugs or solvates thereof in preparing medicines or health care products for treating gout,
wherein the content of the first and second substances,
is selected from
Or
R1、R2、R3Independently of one another, selected from H, OH, CH2CH2OH、COOCH3From
At least one glycosyl residue formed in (a);
R4selected from unsubstituted or substituted by 1 to 3R4aSubstituted C1-C12Alkyl or alkenyl of, R4aSelected from OH, from
At least one glycosyl residue formed.
Preferably, the application of the polyacetylene compound shown in the formula (I) and the pharmaceutically acceptable salt, ester, prodrug or solvate thereof in preparing medicines or health care products for treating gout,
R1、R2、R3independently of one another, selected from H, OH, CH2CH2OH、COOCH3From
The monosaccharide or disaccharide residues formed.
Further preferably, the application of the polyacetylene compound shown in the formula (I) and the pharmaceutically acceptable salt, ester, prodrug or solvate thereof in preparing the medicines or health care products for treating gout is that the polyacetylene compound shown in the formula (I) is selected from:
further preferably, the application of the polyacetylene compound shown in the formula (I) and the pharmaceutically acceptable salt, ester, prodrug or solvate thereof in preparing medicines or health care products for treating gout is that the polyacetylene compound shown in the formula (I) and the pharmaceutically acceptable salt, ester, prodrug or solvate thereof are added with conventional auxiliary materials according to the conventional process to prepare clinically acceptable tablets, capsules, powder, mixtures, pills, granules, syrups, emplastrum, suppositories, aerosols, ointments or injections.
The technical scheme of the invention has the following advantages:
the research of the invention finds that the polyacetylene compounds separated from the coreopsis tinctoria and the codonopsis pilosula have the activity of reducing uric acid, have no obvious toxic or side effect, and can be used for treating hyperuricemia and gout or gout complications caused by the hyperuricemia.
Detailed Description
In the following examples and experimental examples of the invention, lobetyolin is commercially available, and the HPLC purity is not less than 98%.
Xanthine, xanthine oxidase, allopurinol, analytically pure absolute ethanol, chloroform, methanol, ethyl acetate, distilled water, dimethyl sulfoxide, potassium dihydrogen phosphate, and dipotassium hydrogen phosphate are all commercially available products.
The apparatus used in the invention comprises a Buchi medium pressure preparation liquid phase, an Ika stirrer, a Buchi vacuum rotary evaporator, a vortex oscillator, a water bath kettle, a Biofuge Primo R multipurpose table type high-speed centrifuge, a Mettlere 240 electronic balance and a Beckman Coulter AU480 biochemical analyzer.
Example 1
Pulverizing dried root of radix Codonopsis Lanceolatae 30kg, soaking in 5 times by weight of 95% ethanol water solution at room temperature for 3 times, extracting for one week each time, mixing extractive solutions, and concentrating by vacuum distillation until there is no alcohol smell to obtain extract. Dispersing the extract in 1 volume of distilled water, and extracting with ethyl acetate and n-butanol respectively to obtain ethyl acetate extract part 212g and n-butanol extract part 178 g.
Separating the ethyl acetate extraction part by silica gel column chromatography (100-200 meshes), performing gradient elution by using dichloromethane-methanol as an eluent (the volume ratio is 50:1-50:30), and combining the detection results by TLC to obtain five eluates Fr.1.1-Fr.1.5. Separating the Fr.1.2 eluate by silica gel column chromatography, gradient eluting with dichloromethane-methanol as eluent (volume ratio of 20:1-20:15), and mixing according to HPLC detection result to obtain Fr.1.2-1, Fr.1.2-2, and Fr.1.2-3 eluates. Wherein Fr.1.2-1 is subjected to Agilent SD-1 preparative liquid chromatography, reversed phase C18 filler chromatographic column is used as chromatographic column, and acetonitrile water solution with volume concentration of 12% is used as mobile phase for separation and purification, so as to obtain the compound 19. Fr.1.2-2 was subjected to Agilent SD-1 preparative liquid chromatography using reversed phase C18 packed column as column and acetonitrile aqueous solution 15% by volume as mobile phase to separate and purify, to obtain 56mg of Compound 17 and 18mg of Compound 18.
Fr.1.3 through Sephadex LH-20 column chromatography, using 25%, 40%, 60% and 80% methanol water solution to elute in sequence, according to HPLC detection result combining the same components, Agilent SD-1 preparing liquid phase, using reversed phase C18 filler chromatographic column as chromatographic column, 45% methanol water solution as mobile phase to purify, obtaining 38mg of compound 7 and 6mg of compound 6.
Fr.1.5 Sephadex LH-20 column chromatography, eluting with 25%, 10%, 30%, 50% and 75% volume methanol aqueous solution sequentially, combining eluates according to HPLC detection results, and subjecting to Agilent SD-1 preparative liquid chromatography to obtain compound 43mg of compound 8 by using reversed phase C18 filler chromatography column as chromatography column and 40% volume methanol aqueous solution as mobile phase.
Separating the n-butanol extraction part by using D101 macroporous resin, and performing gradient elution according to the following procedures: sequentially adding water, 30% methanol aqueous solution, 60% methanol aqueous solution and methanol, collecting eluates of mobile phases, respectively, and concentrating under reduced pressure to obtain 25g of 60% methanol aqueous solution eluate and 105g of methanol eluate. Separating and purifying the elution part of 60% methanol aqueous solution by reverse C18 column chromatography, eluting with 30%, 40%, 50%, 60% and 70% methanol aqueous solution in sequence, merging the 40% methanol aqueous solution eluent, concentrating under reduced pressure, preparing liquid chromatography by Agilent SD-1, performing isocratic elution by reverse C8 column chromatography and 25% acetonitrile aqueous solution in volume concentration, and collecting according to liquid detection spectrogram to obtain 35mg of compound 11 and 22mg of compound 9 in sequence.
Mixing the eluates with 50% methanol aqueous solution, concentrating under reduced pressure, subjecting to Agilent SD-1 preparative liquid chromatography, performing isocratic elution with reversed phase C8 chromatographic column and 30% acetonitrile aqueous solution, and collecting according to liquid phase detection spectrogram to obtain 28mg of compound 10.
The methanol elution part is subjected to silica gel column chromatography (100-200 meshes), and gradient elution is carried out by taking a mixed solvent of dichloromethane and methanol as a mobile phase according to the following procedures: the volume ratio of dichloromethane to methanol is 10: 1 → 8: 1 → 5: 1 → 3: 1 → 1: 1, respectively obtaining five eluates, respectively concentrating under reduced pressure, and then mixing dichloromethane-methanol in a volume ratio of 8: the elution part of 1 was subjected to silica gel column chromatography (200-300 mesh), and gradient elution was carried out using a mixed solvent of dichloromethane and ethyl acetate as a mobile phase according to the following procedure: the volume ratio of dichloromethane to methanol is 5: 1 → 4: 1 → 3: 1 → 2: 1, according to the result of TLC analysis by thin layer chromatography, the three elution sites Fr.2.1, Fr.2.2 and Fr.2.3 are obtained respectively by combining and concentrating under reduced pressure. Subjecting Fr.2.1 to Agilent SD-1 preparative liquid chromatography, performing isocratic elution with reversed phase C18 filler chromatographic column as chromatographic column and 20% methanol water solution as mobile phase, and collecting eluate according to liquid phase detection spectrogram to obtain compound 152mg, compound 2 with HPLC purity of 98% or more.
Fr.2.2 is subjected to Agilent SD-1 preparative liquid chromatography, reversed phase C18 chromatographic column is used as chromatographic column, isocratic elution is carried out by using 25% methanol aqueous solution with volume concentration, and eluent is collected according to a liquid phase detection spectrogram to obtain 112mg of compound 3, wherein the HPLC purity is not less than 98%.
Structural confirmation data of the above compounds1H NMR and13c NMR references are as follows: two new polycarboxylic acids from the roots of Codonopsis tandshen Oliv, Natural products Research, 2016, 30 (20): 1-6.
C14-Polyacetylene glucosides from Codonopsis pilosula.《Journal of Asian Natural Products Research》，2015，17(6)：601.
Example 2
Soaking dried Codonopsis cordifolia (Codonopsis cordifolia) 30kg in 95% ethanol water solution 5 times the weight of the dried Codonopsis cordifolia at room temperature for 3 times, extracting for 1 week each time, mixing extractive solutions, distilling under reduced pressure, and concentrating to remove alcohol smell to obtain extract. Dispersing the extract in distilled water with the volume of 1 time, and extracting with n-butanol to obtain 151g of n-butanol extract. Separating the n-butanol extraction part by using AB-8 macroporous resin, and performing gradient elution according to the following procedures: water, a methanol aqueous solution with a volume concentration of 35%, a methanol aqueous solution with a volume concentration of 75% and methanol, respectively, and collecting eluates of the mobile phases and concentrating under reduced pressure to obtain an elution part 36g of methanol as the mobile phase. The elution part of methanol as a mobile phase was separated by silica gel column chromatography (100-200 mesh), and gradient elution was carried out with a mixed solvent of dichloromethane and methanol according to the following procedure: the volume ratio of the dichloromethane to the methanol is 10: 1 → 8: 1 → 5: 1 → 3: 1 → 1: 1, respectively collecting the eluent of each mobile phase and concentrating under reduced pressure to respectively obtain five eluates. And then, mixing dichloromethane and methanol in a volume ratio of 10: separating the eluted part of 1 by Sephadex LH-20 column chromatography with methanol as eluting solvent, and mixing the eluates according to TLC analysis result to obtain Fr.3.1 and Fr.3.2. Subjecting Fr.3.1 to Agilent SD-1 preparative liquid chromatography, isocratic eluting with reversed phase C18 chromatographic column and 50% methanol water solution, and collecting according to liquid phase detection spectrogram to obtain 265mg of compound 4 with HPLC purity of 98% or more. Fr.3.2 by Agilent SD-1 preparative liquid chromatography, isocratic elution with reversed phase C18 chromatographic column and 65% methanol water solution, and collecting according to liquid phase detection spectrogram to obtain 121mg of compound 5 with HPLC purity of 98% or more.
Structural confirmation data of the above compounds1H NMR and13c NMR references are as follows: three New polysaccharides from the edit Roots of codenopsis cordifolia, Helvetica Chimica Acta, 2008, 91 (1): 90-96.
Example 3
Taking 100kg of coreopsis tinctoria medicinal material, crushing, soaking and extracting with 15 times volume of 70% ethanol aqueous solution, concentrating under reduced pressure to remove organic solvent, extracting the concentrated solution with 1 time volume of ethyl acetate for 3 times, combining ethyl acetate layers, concentrating under reduced pressure to remove organic solvent to obtain ethyl acetate extraction part. Separating the ethyl acetate extraction part by ODS reverse phase silica gel column chromatography, and performing gradient elution with methanol-water mixed solvent at 1mL/min according to the following procedure: the volume fractions of methanol were 10%, 30%, 45%, 60%, 80%, 90%, and 100% in this order, to give 6 eluates fr.a to G, respectively.
Performing silica gel column chromatography separation on Fr.B, and performing gradient elution with ethyl acetate-ethanol mixed solvent as mobile phase according to the volume ratio of 30:1 → 7:3 to obtain 5 eluates Fr.B-1-5. And Fr and B2 are eluted by gel column chromatography with 20% methanol water solution as mobile phase to obtain compounds 12 and 13. And Fr, B3 is eluted by gel column chromatography with 20% methanol water solution by volume as a mobile phase to obtain the compound 14. And Fr, B4 is eluted by gel column chromatography with 30% methanol water solution as mobile phase to respectively obtain compounds 15 and 16.
Structural confirmation data of the above compounds1H NMR and13c NMR references are as follows: c14-polyacetylene glycosides from the capitula of Corynebacterium and its anti-inflammatory activity against COX-2. 93-97.
Research on chemical components of polyacetylene in anthocephalus fasciatus, 2016 and 47 (11): 1834-1837.
Experimental example 1Research on uric acid reducing effect of compound of the invention
1. Experimental Material
240 healthy male KM mice, weighing 15-18g, were provided by Shanghai Ling Biotech limited; after 5 cages of the strain were treated in separate cages, the strain was kept in a barrier system for 4 days.
2. Experimental methods
2.1 Experimental groups
220 mice with concentrated body weight are selected from 240 mice and are randomly and averagely divided into 22 groups according to the body weight, and each group comprises 10 mice, namely a blank control group, a model control group, a positive control group and an experimental group 1-19.
2.2 methods of administration
After the adaptation period, the mice were administered by gavage for 7 days, with gavage being performed 1 time in the morning every day.
Experimental groups 1 to 19 groups to which the compounds prepared in examples 1 to 3 were administered 1 to 1930 mg/kg, respectively, were suspended with 0.5% sodium carboxymethylcellulose (CMC-Na) solution, respectively; febuxostat 2.5mg/kg is given to the positive control group, and the febuxostat is suspended by 0.5% sodium carboxymethylcellulose (CMC-Na) solution; both the blank control group and the model control group are subjected to intragastric perfusion by using 0.5% sodium carboxymethylcellulose (CMC-Na) solution; each group was administered by continuous gavage for 7 days.
After the administration by gavage for 0.5 hour on the 7 th morning, the mice of each group were subjected to abdominal injection for hyperuricemia modeling. Wherein the blank control group is administered with 0.5% sodium carboxymethylcellulose (CMC-Na) solution via intraperitoneal injection; 300mg/kg of Potassium Oxonate (OA) was injected into each of the model control group, the positive control group and the experimental groups 1 to 19, and dissolved in CMC-Na solution.
3. Experimental data detection and processing
3.1 detection index
After 1.5 hours of intraperitoneal injection, each group of mice is removed of eyeballs for blood sampling, the blood sampling volume is not less than 0.5mL, the mice are placed at room temperature for about 1 hour after blood sampling, the mice are centrifuged for 10 minutes at 3500rpm/4 ℃ after the blood is completely coagulated, serum is taken and is separated for 5 minutes under the same condition, and then 0.2mL of serum is taken to detect UA value through a biochemical analyzer.
3.2 statistical analysis
Statistical analysis of the data was performed using Excel and SPSS, mean and SD calculated, and differences between groups were compared after one-way anova.
4. Results of the experiment
The effect on serum uric acid levels in hyperuricemic mice is shown in table 1.
TABLE 1 Effect on serum uric acid levels in hyperuricemic mice (mean, μmol/L)
| Sample (I) | Uric acid (mu mol/L) | Sample (I) | Uric acid (mu mol/L) |
| Blank control group | 52.36 | Experimental group 10 | 72.37** |
| Model control group | 149.73## | Experimental group 11 groups | 85.53* |
| Positive control group | 38.49** | Experimental group 12 groups | 75.68** |
| Experimental group 1 group | 65.62** | Experimental group 13 groups | 74.48** |
| Experimental group 2 groups | 72.33** | Experimental group 14 groups | 73.17** |
| Experimental group 3 groups | 69.91** | Experimental group 15 | 70.26** |
| Experimental group 4 groups | 70.28** | Experimental group 16 groups | 69.42** |
| Experimental group 5 groups | 77.39** | Experimental group 17 | 71.53** |
| Experimental group 6 | 89.74* | Experimental group 18 | 88.76* |
| Experimental group 7 groups | 63.39** | Experimental group 19 | 73.79** |
| Experimental group 8 | 90.29* | ||
| Experimental group 9 | 73.36** |
Note:**representing P compared to the hyperuricemia model group<0.01 (t-test);*representing P compared to the hyperuricemia model group<0.05；##Indicates P in comparison with the blank control group<0.01。
As can be seen from Table 1: (1) compared with a blank control group, the serum of the mouse of the model control group has obviously increased uric acid (P <0.01) and has obvious difference, which indicates that the model modeling of the hyperuricemia model is successful;
(2) the reduction in serum uric acid levels in the mice of experimental groups 1-19 was significantly different (P <0.01 or P <0.05) compared to the model control group.
5. Conclusion of the experiment
The polyacetylene compounds separated from the coreopsis tinctoria and the codonopsis pilosula can obviously reduce the serum uric acid level of mice with hyperuricemia, have statistical significance compared with a hyperuricemia model group, and can be used as potential uric acid reducing drugs for treating the hyperuricemia.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.
Claims (4)
1. The application of a polyacetylene compound and pharmaceutically acceptable salts thereof as the only active ingredient in the preparation of medicines with the effect of reducing uric acid is characterized in that the polyacetylene compound is selected from a formula I or a formula II, wherein:
Ⅰ
Ⅱ。
2. the application of the polyacetylene compound and the pharmaceutically acceptable salt thereof as the only active ingredients in the preparation of the medicines with the uric acid reducing effect according to the claim 1, characterized in that the polyacetylene compound and the pharmaceutically acceptable salt thereof are added with conventional auxiliary materials according to the conventional process to prepare clinically acceptable tablets, capsules, powders, mixtures, pills, granules, syrups, emplastrums, suppositories, aerosols, ointments or injections.
3. The application of a polyacetylene compound and pharmaceutically acceptable salts thereof as the only active ingredient in preparing medicines for treating gout is characterized in that the polyacetylene compound is selected from a formula I or a formula II, wherein:
Ⅰ
Ⅱ。
4. the application of the polyacetylene compounds and the pharmaceutically acceptable salts thereof as the only active ingredients in the preparation of the medicines for treating gout as claimed in claim 3, wherein the polyacetylene compounds and the pharmaceutically acceptable salts thereof are prepared into clinically acceptable tablets, capsules, powders, mixtures, pills, granules, syrups, emplastrums, suppositories, aerosols, ointments or injections by adding conventional auxiliary materials according to a conventional process.
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