CN111714486B - Application of polyacetylene compound - Google Patents
Application of polyacetylene compound Download PDFInfo
- Publication number
- CN111714486B CN111714486B CN201910216331.1A CN201910216331A CN111714486B CN 111714486 B CN111714486 B CN 111714486B CN 201910216331 A CN201910216331 A CN 201910216331A CN 111714486 B CN111714486 B CN 111714486B
- Authority
- CN
- China
- Prior art keywords
- compound
- hyperuricemia
- dosage ratio
- allopurinol
- febuxostat
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/336—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having three-membered rings, e.g. oxirane, fumagillin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7032—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Molecular Biology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the field of chemical medicines, and in particular relates to a novel application of a polyacetylene compound, which comprises the polyacetylene compound with a structure shown in a formula (I) and application of pharmaceutically acceptable salts, esters, prodrugs, solvates, polymorphs, hydrates or derivatives thereof in preparation of a drug for treating hyperuricemia in combination, and also provides a hyperuricemia pharmaceutical composition, which comprises the compound and one of febuxostat or allopurinol. The hyperuricemia medicine composition can play a role in reducing uric acid equivalent to or even better than hyperuricemia medicines in the prior art, but can obviously reduce toxic and side effects of the hyperuricemia medicines, improve safety, and can be used for hyperuricemia and hyperuricemia causedGout or complications of gout.
Description
Technical Field
The invention relates to the field of chemical medicine, in particular to a new application of a polyacetylene compound.
Background
Uric acid is the final metabolite of human purine compounds in the field of chemical medicine. Purine metabolic disorders lead to hyperuricemia. Under normal purine diet, men with fasting blood uric acid levels of more than 416. Mu. Mol/L for two times a day and 360. Mu. Mol/L for women are called hyperuricemia (hyperuricemia). In general, the hyperuricemia state is simply a hyperuricemia state without subjective symptoms, but if the hyperuricemia state is maintained for a long time, urate in blood will crystallize and deposit on joints, subcutaneous tissues, kidneys and other parts, and a series of clinical manifestations such as gout and gout complications occur. The recently published white paper for reporting the status of gout in China in 2017 shows that the number of patients with hyperuricemia in China reaches 1.7 hundred million, wherein the number of patients with gout exceeds 8000 ten thousand, and the annual growth rate of 9.7% per year is rapidly increasing. It is expected that the number of gout persons will reach 1 million in 2020. Gout is the second most metabolic disease in China after diabetes mellitus, and seriously endangers the life and health of people.
Currently, in the treatment of hyperuricemia, gout and complications of gout caused by hyperuricemia, uric acid in blood needs to be controlled: for uric acid excretion-promoting drugs for uric acid excretion-defective patients (90%), such as: tribromone, ramonade, and the like; drugs (mainly xanthine oxidase inhibitors) that inhibit uric acid production are suitable for patients with excessive uric acid production, such as: allopurinol and febuxostat. However, as the clinical use of these drugs increases, adverse effects are gradually exposed.
Allopurinol (allopurinol) is the earliest drug on the market for inhibiting uric acid generation, and since 1963 is applied to clinic, the allopurinol (allopurinol) is a main drug for treating chronic gout due to low price and good uric acid reducing effect. However, with the popularization of allopurinol, adverse reactions are reported to be increased gradually, and from the beginning of the 70 th century, it is reported that allopurinol can cause adverse reactions such as liver and kidney injury, leucopenia, rash and the like, has about 1.5% of allergy risks, and is seriously likely to cause lethal allergy, thereby attracting worldwide attention. Therefore, to reduce adverse reactions, it is necessary to use allopurinol from a small dose.
Febuxostat (trade name: uloric, north american pharmaceutical corporation of martial arts) is a non-purine selective xanthine oxidase inhibitor marketed in the european union at month 5 in 2008, approved by the us FDA for marketing in 2009, 3 months, and enters the chinese market in 2013 for long-term treatment of hyperuricemia accompanied by gout. Febuxostat has higher selectivity and stronger activity than other drugs for treating hyperuricemia. However, related studies and clinical practice show that febuxostat also has certain adverse reactions: common adverse reactions are liver dysfunction (3.5%), diarrhea (2.7%), headache (1.8%), nausea (1.7%), and rash (1.5%), among others. On 11 and 15 2017, the FDA issued febuxostat cardiac-related mortality risk warnings; on month 2 and 7 of 2018, CFDA issues a drug alert rapid "a preliminary result of a safety clinical trial involving 6000 gout patients, indicated that febuxostat may increase the risk of heart-related death compared to allopurinol.
The traditional medicine has larger toxic and side effects and generally lower tolerance, and limits the clinical application of the medicines to a certain extent.
Polyacetylenes (or polyacetylenes) are a relatively specific class of natural compounds, mostly having two or more conjugated triple bonds, and therefore having considerable unsaturation and high reactivity. Polyacetylenes and derivatives thereof are very important plant secondary metabolites, are widely distributed in the plant kingdom, and only asteraceae plants have been reported to have more than 750 natural polyacetylenes and derivatives thereof. Some plants (Compositae, umbelliferae, etc.) containing polyacetylene components have long been used as medicinal products, but because such components are usually less and less stable, there are few studies on the relationship between the action of a drug and the presence of polyacetylene components. With the progress of chemical and pharmacological research methods, the compounds are reported to have physiological activities of anti-inflammatory, antifungal, sensitization, anti-tumor, antimicrobial, anticonvulsant and the like.
Disclosure of Invention
The first technical problem to be solved by the invention is to overcome the defect that medicines for treating hyperuricemia have toxic and side effects in the prior art, so as to provide a polyacetylene compound with a structure shown as a formula (I) and application of pharmaceutically acceptable salts, esters, prodrugs, solvates, polymorphs, hydrates or derivatives thereof in preparing combined medicines for treating hyperuricemia.
The second technical problem to be solved by the invention is to overcome the defect that the medicines for treating hyperuricemia have toxic and side effects in the prior art, so as to provide the hyperuricemia medicine composition capable of reducing the toxic and side effects while maintaining the ideal uric acid reducing effect.
The third technical problem to be solved by the invention is to overcome the defect that the medicament for treating hyperuricemia has toxic and side effects in the prior art, thereby providing the medicament for treating hyperuricemia, which can reduce the toxic and side effects while maintaining the ideal uric acid reducing effect.
The invention also provides application of the hyperuricemia pharmaceutical composition.
Therefore, the invention provides application of a polyacetylene compound with a structure shown as a formula (I) and pharmaceutically acceptable salts, esters, prodrugs, solvates, polymorphs, hydrates or derivatives thereof in preparing a combined medicament for treating hyperuricemia. Further, the hyperuricemia medicine is one of febuxostat or allopurinol.
The invention provides a hyperuricemia pharmaceutical composition, which comprises: active ingredients having a synergistic effect with hyperuricemia drugs, and hyperuricemia drugs; wherein the hyperuricemia drug is a xanthine oxidase inhibitor; the active ingredient is a polyacetylene compound with a structure shown as a formula (I) and pharmaceutically acceptable salts, esters, prodrugs, solvates, polymorphs, hydrates or derivatives thereof:
wherein, the liquid crystal display device comprises a liquid crystal display device,
is selected from->
Or->
R 1 Selected from H, OH,
Unsubstituted or substituted C 1 -C 4 Alkyl, unsubstituted or substituted C 1 -C 4 Alkenyl group,>
one of the following; r is R 1a Selected from 1 to 2R a Substituted C 1 -C 3 Alkyl of R a Selected from H, OCOCH 3 One of the following;
R 2 selected from one of H, OH, or R 1 、R 2 Forming an unsubstituted or substituted phenyl group;
R 3 selected from the group consisting of
Unsubstituted or substituted by 1 to 3R 3a Substituted C 1 -C 10 Alkyl, alkenyl, R 3a Selected from OH, & lt + & gt>
One of them.
R 4 One selected from H, OH.
The active ingredients of the hyperuricemia medicine composition have the following structures:
the hyperuricemia medicine composition is one of febuxostat or allopurinol.
The mass of the active ingredient of the hyperuricemia medicine composition accounts for 20-97% of the sum of the mass of the active ingredient and the mass of the hyperuricemia medicine.
The hyperuricemia pharmaceutical composition also comprises a pharmaceutically acceptable carrier.
The invention also provides a medicine for treating hyperuricemia, which comprises the hyperuricemia medicine composition, wherein the medicine is prepared by adding conventional auxiliary materials into the hyperuricemia medicine composition and preparing clinically acceptable tablets, capsules, pills, granules, ointment, mixture or suspension according to a conventional process.
The invention also provides application of the hyperuricemia pharmaceutical composition in preparing hyperuricemia medicines.
The application of the hyperuricemia medicine composition in preparing hyperuricemia medicines comprises gout or gout complications caused by hyperuricemia.
The application of the hyperuricemia pharmaceutical composition in preparing hyperuricemia medicaments, wherein the gout comprises acute gout or chronic gout; the gout complications comprise gouty arthritis, gout attack, gouty nephropathy or uric acid kidney stone disease.
The technical scheme of the invention has the following advantages:
1. the invention provides a hyperuricemia medicine composition, which can achieve the effect of reducing uric acid equivalent to or even better than that of hyperuricemia medicines in the prior art, but can obviously reduce the toxic and side effects of the hyperuricemia medicines in the prior art, improve the safety, and can be used for treating hyperuricemia and gout or gout complications caused by the hyperuricemia.
2. The invention provides a medicament for treating hyperuricemia, which can achieve the effect of reducing uric acid equivalent to or even better than that of hyperuricemia medicaments in the prior art, but can obviously reduce the toxic and side effects of the hyperuricemia medicaments in the prior art, improve the safety, and can be used for treating hyperuricemia and gout or gout complications caused by hyperuricemia.
Detailed Description
Example 1
The embodiment provides an extraction method and characterization of the compounds 4-7 in the active ingredients.
The ethanol, ethyl acetate, petroleum ether and methanol used in this example are all commercially available products.
Pulverizing rhizoma Atractylodis (Compositae) 100kg, soaking in 15 times of 70% ethanol water solution at 50-100deg.C for 120min, and concentrating under reduced pressure to obtain concentrated solution A; separating the concentrated solution A with low pressure D101 column (column diameter 28cm×162cm, column volume 100L), eluting with 30% and 95% ethanol-water for 4BV, and collecting 95% parts; after concentration of the fraction (solid content: about 3 kg), the fraction was separated by an LX-20SS column (column diameter: 20 cm. Times.78 cm, column volume: 25L), and 3BV was eluted with 70% and 80% ethanol-water, respectively, followed by 4BV eluted with 95% ethanol-water, and the 95% fraction was collected to obtain a crude concentrate B (solid content: about 1 kg).
The concentrate B was separated by a silica gel column (column diameter 11 cm. Times.65 cm, column volume 6L) and eluted with a gradient using petroleum ether-ethyl acetate as mobile phase according to the following procedure: the volume ratio of petroleum ether to ethyl acetate is 100:0, 50:1, 20:1, 10:1, 5:1 and 1:1 respectively, the gradient is eluted by 3BV, finally, the 3BV is eluted by ethanol water solution with the volume concentration of 95 percent, the eluent of each mobile phase is respectively collected, and the eluent is concentrated under reduced pressure to respectively obtain 7 eluates Fr.A-G.
Wherein fr.d was separated by a silica gel column (column diameter 11cm x height 65cm, column volume 6L) and gradient eluted with petroleum ether-ethyl acetate as mobile phase according to the following procedure: the volume ratio of petroleum ether to ethyl acetate is 50:1, 30:1, 20:1, 15:1, 10:1, 5:1 and 1:1 respectively, the gradients are all eluted for 3BV, finally, the 3BV is eluted by ethanol water solution with the volume concentration of 95 percent, the eluent of each mobile phase is respectively collected, and the eluent is concentrated under reduced pressure to respectively obtain 8 eluates Fr.D1-8.
Wherein Fr.D2 is separated by ODS preparation liquid chromatography with 70% methanol-water solution to obtain compound 5; separating Fr.D4 by ODS preparation liquid chromatography with 65% methanol-water solution to obtain compounds 6 and 7 respectively; fr.d5 was separated by ODS preparative liquid chromatography on 65% by volume methanol-water solution to give compound 4.
Isolated compounds 4-6 were identified by nuclear magnetic resonance spectroscopy and the structure of the compounds was determined by data comparison with the following prior art documents:
the references to structure confirmation data for compounds 4-5 are as follows: washino T, yoshikura M, obata S.polyacetylenic compounds of Arctium lappa L [ J ]. Journal of the Agricultural Chemical Society of Japan,1986,60 (5): 377-383.
The references to structure confirmation data for compound 6 are as follows: lehner M S, steigel A, bauer R.diacetoxy-substituted polyacetylenes from atractylodes lancea [ J ]. Phytochectry, 1997,46 (6): 1023-1028.
The structure of compound 7 was identified by nuclear magnetic resonance spectroscopy using a device model Bruker AVANCE II 400 under 1H-NMR (CCl 3D,400 MHz), 13C-NMR (CCl 3D,100 MHz) and named (3Z, 5Z, 11E) -tridecet-7, 9-diyne-1,2-diacetate ((3Z, 5Z, 11E) -tridecatriene-7,9-diyne-1, 2-diacetate), and the structure confirmation data are shown in Table 1:
TABLE 1 confirmation data for Structure of Compound 7
Example 2
The embodiment provides an extraction method and characterization of the compounds 8-11 in the active ingredients.
The n-pentane, ethyl acetate, diethyl ether, ethanol and methanol used in this example are all commercially available products.
20kg of carrot was cut into small pieces, chopped with a stirrer, then extracted with 40L of n-pentane and 30L of ethyl acetate in turn at room temperature for 3 times, respectively collecting the n-pentane extract and the ethyl acetate extract, and respectively concentrating under reduced pressure to remove the organic solvent, respectively obtaining 20g of n-pentane extract (i.e., component A) and 15g of ethyl acetate extract (i.e., component B). Component B was dissolved in 35mL of a mixed solution of n-hexane and ethyl acetate, wherein the volume ratio of n-hexane to ethyl acetate was 95:5, separating and purifying by a silica gel column (column diameter 6cm multiplied by 60cm, column volume 1.7L) after dissolution, and performing gradient elution by taking a mixed solution of n-pentane and diethyl ether as a mobile phase according to the following procedure: the volume fractions of n-pentane are 95%, 80%, 70% and 50%, and finally ethanol is used for eluting, the mobile phases are respectively eluted for 3BV, and the eluates of the mobile phases are respectively collected and concentrated under reduced pressure to obtain five eluates Fr.B1-B5.
Wherein Fr.B2 is separated by ODS preparation liquid phase chromatography, and eluting with 80% methanol-water solution as mobile phase to obtain compound 8.
The Fr.B4 is separated by ODS preparation liquid phase chromatography, and the compound 9 and the compound 10 are obtained by eluting with methanol-water solution with the volume concentration of 80 percent as a mobile phase.
The Fr.B5 is separated by ODS preparation liquid chromatography, and is eluted by taking methanol-water solution with the volume concentration of 80% as a mobile phase to obtain the compound 11.
The isolated components were identified by nuclear magnetic resonance spectroscopy and the structure of the compounds was determined by data comparison with the following prior art documents:
structure confirmation data for compounds 8-9 1H NMR and 13C NMR are referred to as follows: structural and sensory characterization of compounds contributing to the bitter off-steps of carrots (Daucus carota L.) and carrotpuree.J. Agric Food Chem,2003, 51 (13), 3865-3873
Structure confirmation data 1H NMR and 13C NMR for compounds 10-11 are referenced below: structure Determination of Bisacetylenic Oxyl ipins in Carrots (Daucus carota l.) and Enantioselective Synthesis of falcarindiol. Journal of Agricultural & Food chemistry 2009, 57 (22): 11030-11040.
Example 3
This example provides a method and characterization of the extraction of compounds 12-13 from the active ingredient.
The ethanol, n-hexane, chloroform, ethyl acetate and methanol used in this example were all commercially available products.
Pulverizing 20kg of Ginseng radix, soaking and extracting with 15 times of 80% ethanol water solution at room temperature for 1 week, extracting twice, mixing the extractive solutions, concentrating under reduced pressure to remove organic solvent to obtain concentrate. The concentrate was extracted with 1-fold volume of n-hexane for 3 times, the n-hexane layers were combined, and the organic solvent was removed by concentration under reduced pressure to obtain an n-hexane extract. The n-hexane extract was subjected to ODS reversed-phase silica gel column chromatography (column diameter: 6 cm. Times.60 cm, column volume: 1.7L), and gradient elution was carried out using a mixed solution of n-hexane and ethyl acetate as a mobile phase according to the following procedure: the volume ratio of n-hexane to ethyl acetate is: 100:1, 70:1, 50:1, 30:1, 10:1, 5:1, eluting the mobile phases for 3BV respectively, collecting the eluates of the mobile phases respectively, and concentrating under reduced pressure to obtain 6 components Fr.A-F.
Wherein fr.c was eluted by silica gel column chromatography (column diameter 6cm x height 60cm, column volume 1.7L) with a mixed solution of n-hexane and ethyl acetate as mobile phase, wherein the volume ratio of n-hexane and ethyl acetate was 4:1, combining the eluates with the same components according to TLC detection results to obtain five eluates C1-5. And (3) performing ODS preparation liquid chromatography separation on Fr.C3, and eluting with 70-75% methanol-water solution as a mobile phase to obtain the compound 12.
Fr.E was purified by silica gel column chromatography (column diameter 6 cm. Times.60 cm, column volume 1.7L) using a mixture of n-hexane, chloroform and ethyl acetate as mobile phase, wherein the volume ratio of n-hexane, chloroform and ethyl acetate was 3:2:1, six eluates E1-6 were obtained. Fr.E3 was subjected to ODS preparation liquid chromatography, and eluted with 70% by volume methanol-water solution as mobile phase to give compound 13.
The isolated components were identified by nuclear magnetic resonance spectroscopy and the structure of the compounds was determined by data comparison with the following prior art documents:
structure confirmation data for compounds 12-13 1H NMR and 13C NMR are referred to as follows: polyacetylenes from the roots of cultivated-wild ginseng and their cytotoxicity in vitro, arches of Pharmacal Research,2008, 31 (2): 154-9.
Example 4
The embodiment provides a hyperuricemia medicine composition which is formed by mixing febuxostat and a compound 1 in a weight ratio of 1:5. The compound 1 used in this example is atractylin purchased from Shanghai source leaf biotechnology Co., ltd, and the structural formula of the compound 1 is as follows:
as an alternative to this embodiment, the compound 1 may be replaced with one of the compounds 2 to 15 and the febuxostat may be replaced with allopurinol.
Example 5
The embodiment provides a hyperuricemia pharmaceutical composition, which is prepared by mixing febuxostat and a compound 3 in a weight ratio of 1:15. The compound 3 used in this example was acetyl atractylin available from the company of graminaceous biotechnology, su, the structural formula of compound 3 is as follows:
as an alternative to this example, the compound 3 may be replaced with one of the compounds 1-2 and 4-15, and the febuxostat may be replaced with allopurinol.
Example 6
The embodiment provides a hyperuricemia medicine composition which is formed by mixing febuxostat and a compound 4 in a weight ratio of 1:30. The compound 4 used in this example was prepared according to example 1, the structural formula of compound 4 being as follows:
as an alternative to this example, the compound 4 may be replaced with one of the compounds 1 to 3 and the compounds 5 to 15, and the febuxostat may be replaced with allopurinol.
Example 7
The embodiment provides a hyperuricemia medicine composition which is formed by mixing febuxostat and a compound 6 in a weight ratio of 3:5. The compound 6 used in this example was prepared according to example 1, the structural formula of compound 6 being as follows:
as an alternative to this example, the compound 6 may be replaced with one of the compounds 1 to 5 and the compounds 7 to 15, and the febuxostat may be replaced with allopurinol.
Example 8
The embodiment provides a hyperuricemia pharmaceutical composition which is prepared by mixing febuxostat and a compound 7 in a weight ratio of 1:10. The compound 7 used in this example was prepared according to example 1, the structural formula of compound 7 being as follows:
as an alternative to this example, the compound 7 may be replaced with one of the compounds 1 to 6 and the compounds 8 to 15, and the febuxostat may be replaced with allopurinol.
Example 9
The embodiment provides a hyperuricemia pharmaceutical composition, which is prepared by mixing allopurinol and a compound 8 in a weight ratio of 2:1. The compound 8 used in this example was prepared according to example 2, the structural formula of compound 8 being as follows:
as an alternative to this example, the compound 8 may be replaced with one of the compounds 1 to 7 and the compounds 9 to 15, and the allopurinol may be replaced with febuxostat.
Example 10
The embodiment provides a hyperuricemia pharmaceutical composition, which is prepared by mixing allopurinol and a compound 9 in a weight ratio of 2:5. The compound 9 used in this example was prepared according to example 2, the structural formula of the compound 9 being as follows:
as an alternative to this example, the compound 9 may be replaced with one of the compounds 1 to 8 and the compounds 10 to 15, and the allopurinol may be replaced with febuxostat.
Example 11
The embodiment provides a hyperuricemia pharmaceutical composition, which is prepared by mixing allopurinol and a compound 12 in a weight ratio of 2:3. The compound 12 used in this example was prepared according to example 3, the structural formula of the compound 12 being as follows:
as an alternative to this example, the compound 12 may be replaced with one of the compounds 1 to 11 and the compounds 13 to 15, and the allopurinol may be replaced with febuxostat.
Example 12
The embodiment provides a hyperuricemia pharmaceutical composition, which is prepared by mixing allopurinol and a compound 13 in a weight ratio of 1:3. The compound 13 used in this example was prepared according to example 3, the structural formula of compound 13 being as follows:
as an alternative to this example, the compound 13 may be replaced with one of the compounds 1 to 12 and the compounds 14 to 15, and the allopurinol may be replaced with febuxostat.
Example 13
The embodiment provides a hyperuricemia pharmaceutical composition, which is prepared by mixing allopurinol and a compound 14 in a weight ratio of 4:1. Compound 14 used in this example was purchased from tuina biotechnology limited, the structural formula of compound 14 is as follows:
as an alternative to this example, the compound 14 may be replaced with one of the compounds 1 to 13 and the compound 15, and the allopurinol may be replaced with febuxostat.
Example 14
The embodiment provides a hyperuricemia pharmaceutical composition, which is prepared by mixing allopurinol and a compound 15 in a weight ratio of 4:3. The compound 15 used in this example is a dangshen acetylenic glycoside purchased from Shanghai source leaf biotechnology Co., ltd, and the structural formula of the compound 15 is as follows:
as an alternative to this embodiment, the compound 15 may be replaced with one of the compounds 1 to 14 and the allopurinol may be replaced with febuxostat.
Example 15
The present embodiment provides a pharmaceutical tablet for treating hyperuricemia.
[ formula ]
Weighing a prescribed amount of hyperuricemia pharmaceutical composition, hydroxypropyl cellulose, starch, lactose and povidone, mixing, sieving with a 60-mesh sieve for three times, and uniformly mixing; adding 10% starch slurry to obtain soft material, sieving with 24 mesh sieve, granulating, drying, adding silica gel micropowder and magnesium stearate, mixing, granulating, tabletting, and coating with film.
Example 16
The embodiment provides a capsule for treating hyperuricemia.
[ formula ]
Weighing a prescribed amount of hyperuricemia pharmaceutical composition, lactose, povidone, microcrystalline cellulose and sodium carboxymethyl starch, sieving with a 100-mesh sieve respectively, and uniformly mixing; adding hypromellose solution to obtain soft mass, sieving with 24 mesh sieve, granulating, drying in 50-60deg.C oven for about 2-3 hr, adding silica gel micropowder and magnesium stearate, mixing, granulating, and encapsulating.
The pharmaceutical compositions of the present invention may be administered by any means known in the art, including but not limited to oral, nasal, parenteral, topical, transdermal or rectal routes of administration. The pharmaceutical compositions of the present invention are preferably suitable for oral or topical administration in dosage forms such as tablets, capsules (including hard capsules, soft capsules), pills, solutions, powders or granules, suspensions, patches, and the like, and the medicaments of the present invention may be formulated into corresponding dosage forms using methods well known in the art.
As an alternative implementation manner of this embodiment, the above-mentioned pharmaceutical excipients such as microcrystalline cellulose may be replaced with other commonly used excipients, and the "conventional excipients" described in the present invention refers to pharmaceutically acceptable materials, compositions or vehicles, such as liquid or solid fillers, diluents, excipients (such as cocoa butter and plug wax), solvents or packaging materials. The pharmaceutically acceptable carrier is compatible with the other ingredients of the composition, with the mode of administration, and is not deleterious to the patient. The pharmaceutically acceptable carrier may be aqueous or non-aqueous. Conventional excipients include gelatin, for example gelatin; starches, such as corn starch, potato starch; sugars such as lactose, glucose, and sucrose; cellulosic materials and mixtures thereof, such as sodium carboxymethyl cellulose, ethyl cellulose, and cellulose acetate. Materials that may be used as pharmaceutically acceptable carriers include, but are not limited to, tragacanth, malt, talc, oils (e.g., peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, soybean oil, and the like), alcohols (e.g., propylene glycol, ethanol, glycerol, sorbitol, mannitol, polyethylene glycol, and the like), esters (e.g., ethyl oleate, ethyl laurate, agar), buffers (e.g., magnesium hydroxide, aluminum hydroxide, boric acid, and sodium borate, and phosphate buffers), alginic acid, non-heat source water, isotonic saline, ringer's solution.
Experimental example
The febuxostat, allopurinol, analytically pure grade absolute ethyl alcohol, chloroform, methanol, ethyl acetate, distilled water, dimethyl sulfoxide, monopotassium phosphate and dipotassium phosphate used in the experimental example are all commercial products; the instruments used included Buchi medium pressure preparation liquid phase, ika stirrer, buchi vacuum rotary evaporator, vortex shaker, water bath, biofuge Primo R multipurpose bench-top high-speed centrifuge, mettlerae240 electronic balance, beckman Coulter AU Biochemical analyzer.
Compounds 1 and 15 used in this experimental example were purchased from Shanghai Source leaf Biotechnology Co., ltd; compounds 2, 3, 14 were purchased from St Biotechnology Co., ltd; the remaining compounds were isolated from the corresponding plants according to examples 1-3 (HPLC > 98%).
Test animals and groupings: taking healthy male KM mice with a weight of 15-18g, which are provided by Beijing vitamin Toril Hua biotechnology Co., ltd; after 5 cages were divided, the animals were adaptively kept in a barrier system of Kaixiang biotechnology Co., ltd, for 4 days, and then, 10 animals were randomly grouped according to body weight, and each group was a blank control group (abbreviated as blank group), a hyperuricemia model group (abbreviated as model group), a positive control group (febuxostat control group or allopurinol control group), a compound control group, and a test composition group (abbreviated as test composition).
Modeling of hyperuricemia:
firstly, preparing a gastric lavage drug, and suspending febuxostat or allopurinol by using a positive control group by using a 0.5% sodium carboxymethyl cellulose (CMC-Na) solution; compound control compound 1-15 was suspended with 0.5% sodium carboxymethylcellulose (CMC-Na) solution, respectively; the test composition groups each suspended a set dose of the pharmaceutical composition with a 0.5% sodium carboxymethyl cellulose (CMC-Na) solution. Immediately after the adaptation period of the mice, the mice are subjected to gastric lavage, 1 time in the morning and 7 days in succession, and the blank control group and the hyperuricemia model group are subjected to gastric lavage by using 0.5% CMC-Na for comparison; mice were intraperitoneally molded after lavage for 0.5 hours at day 7, with a blank group intraperitoneally injected with a 0.5% sodium carboxymethylcellulose (CMC-Na) solution; the hyperuricemia model group, the positive control group, the compound control group and the tested composition group are all injected with potassium Oxazinate (OA) dissolved by CMC-Na solution, and the injection amount is 300mg/kg body weight.
The method comprises the steps of removing eyeballs of mice after intraperitoneal injection for 1.5 hours, taking blood, placing the mice at room temperature for 1 hour after blood collection, centrifuging at 3500rpm/4 ℃ for 10 minutes after blood is completely coagulated, taking serum to be separated for 5 minutes under the same condition, taking 0.2mL of serum, and detecting the levels of Uric Acid (UA), alanine Aminotransferase (ALT), glutamic oxaloacetic Aminotransferase (AST) and Creatinine (CRE) in the serum by using a biochemical analyzer, wherein the alanine Aminotransferase (ALT), glutamic oxaloacetic Aminotransferase (AST) and Creatinine (CRE) are used for representing toxic and side effects of the medicines, and the higher the content is, the greater the toxic and side effects are indicated.
Statistical analysis is carried out on the data by Excel and SPSS, the average number and SD are calculated, the inter-group difference of each experimental group is compared after single-factor variance analysis, and compared with a blank control group, the serum uric acid level of mice in a hyperuricemia model group, a positive control group and a tested composition group is obviously improved, and obvious differences exist, so that the modeling is successful.
The doses and test results of the drugs and the drug compositions are shown in tables 2-31:
TABLE 2 influence of Compound 1 and of the composition of non-Bulbirt on hyperuricemia mice blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE)
TABLE 3 influence of Compound 1 and allopurinol composition on blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE) in hyperuricemic mice
Table 4 Effect of Compound 2 and its combination with non-Bustat on hyperuricemia mice blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE)
Table 5 Effect of Compound 2 and allopurinol composition on blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST) and Creatinine (CRE) in hyperuricemic mice
TABLE 6 influence of Compound 3 and of the composition of non-Bulbirt on hyperuricemia mice blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE)
Table 7 Effect of Compound 3 and allopurinol composition on blood uric acid level (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST) and Creatinine (CRE) of hyperuricemia mice
Table 8 Effect of Compound 4 and its combination with non-Bustat on hyperuricemia mice blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE)
Table 9 Effect of Compound 4 and allopurinol composition on hyperuricemia mice blood uric acid level (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE)
Table 10 Effect of Compound 5 and its combination with non-Bustat on hyperuricemia mice blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE)
Table 11 influence of Compound 5 and allopurinol composition on blood uric acid level (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST) and Creatinine (CRE) of hyperuricemia mice
Table 12 Effect of Compound 6 and its combination with non-Bustat on hyperuricemia mice blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE)
Table 13 Effect of Compound 6 and allopurinol composition on blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE) in hyperuricemic mice
Table 14 Effect of Compound 7 and its combination with non-Bustat on hyperuricemia mice blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE)
Table 15 Effect of Compound 7 and allopurinol composition on hyperuricemia mice blood uric acid level (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE)
Table 16 influence of Compound 8 and of the composition of non-Bulbirt on the blood uric acid level (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST) and Creatinine (CRE) of hyperuricemia mice
Effect of compound 8 of table 17 and its combination with allopurinol on hyperuricemia mice blood uric acid level (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE)
Table 18 influence of Compound 9 and its composition with non-Bustat on hyperuricemia mice blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE)
Table 19 influence of Compound 9 and allopurinol composition on blood uric acid level (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST) and Creatinine (CRE) of hyperuricemia mice
Table 20 Effect of Compound 10 and its combination with non-Bustat on hyperuricemia mice blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE)
Influence of Compound 10 of Table 21 and its combination with allopurinol on blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST) and Creatinine (CRE) in hyperuricemic mice
Table 22 influence of Compound 11 and its composition with non-Bustat on hyperuricemia mice blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE)
Effect of compound 11 of table 23 and its combination with allopurinol on hyperuricemia mice blood uric acid level (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE)
Table 24 influence of Compound 12 and of the composition of non-Bulbirt on hyperuricemia mice blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE)
Effects of Compound 12 and allopurinol in Table 25 on blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE) in hyperuricemic mice
Table 26 influence of Compound 13 and its composition with non-Bustat on hyperuricemia mice blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE)
Effects of Compound 13 of Table 27 and its combination with allopurinol on blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE) in hyperuricemic mice
Table 28 Effect of Compound 14 and its combination with non-Bustat on hyperuricemia mice blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE)
Effects of Compound 14 of Table 29 and its combination with allopurinol on blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE) in hyperuricemic mice
TABLE 30 influence of Compound 15 and of the composition of non-Bulbirt on hyperuricemia mice blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST), creatinine (CRE)
Effect of Compound 15 of Table 31 and its combination with allopurinol on blood uric acid levels (UA), alanine Aminotransferase (ALT), glutamic-oxaloacetic Aminotransferase (AST) and Creatinine (CRE) in hyperuricemic mice
(a represents P <0.05 compared with the blank group, b represents P <0.01 compared with the blank group, c represents P <0.05 compared with the hyperuricemia model group, d represents P <0.01 compared with the hyperuricemia model group, e represents P <0.05 compared with the corresponding dose compound control group, f represents P <0.01 compared with the corresponding dose compound control group, # represents P <0.05 compared with the positive control group 1, # represents P <0.01 compared with the positive control group 1, # represents P <0.05 compared with the positive control group 2, and P <0.01 compared with the positive control group 2.
As can be derived from the above-described table results,
1. the compound disclosed by the invention can obviously reduce serum uric acid level of hyperuricemia mice, has statistical significance compared with hyperuricemia model groups, and can be used as a potential uric acid reducing drug for treating hyperuricemia.
2. The low-dose febuxostat/allopurinol and the compound are combined and then used, and the febuxostat/allopurinol compound has stronger uric acid reducing effect at various dosage ratios, and has statistical significance compared with a hyperuricemia model group.
3. The compound provided by the invention is combined with low-dose febuxostat and/or allopurinol, and has stronger uric acid reducing effect than the single use of the compound at the corresponding dose, and has statistical significance.
4. Compared with the corresponding positive medicine control group 1, the uric acid reducing effect of the test combination 1 is better than that of the corresponding positive control group 1 (febuxostat/allopurinol), and the ALT, AST, CRE value in each test combination 1 is obviously lower than that of the corresponding positive control group 1, so that the test combination 1 has statistical significance.
5. Compared with the corresponding positive medicine control group 2, the uric acid reducing effect of the tested combination group 2 is better than that of the corresponding positive control group 1 (febuxostat/allopurinol), and the ALT, AST, CRE value in each tested combination group 2 is obviously lower than that of the corresponding positive medicine control group 2, so that the method has statistical significance.
In summary, the febuxostat and/or allopurinol are reduced in dosage and combined with the compound provided by the invention, so that the same or better uric acid reducing effect of febuxostat and/or allopurinol can be obtained under the conventional dosage, but the febuxostat and/or allopurinol with low dosage can be combined with the compound to obviously reduce the increase of CRE, ALT, AST caused by febuxostat and/or allopurinol in terms of safety, thereby reducing toxic and side effects, and showing higher safety than the febuxostat and/or allopurinol singly used under the conventional dosage.
It is apparent that the above examples are given by way of illustration only and are not limiting of the embodiments. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. While still being apparent from variations or modifications that may be made by those skilled in the art are within the scope of the invention.
Claims (7)
1. A pharmaceutical composition for treating hyperuricemia comprising: active ingredients having synergistic effect with drugs for treating hyperuricemia and drugs for treating hyperuricemia; wherein the drug for treating hyperuricemia is one of febuxostat or allopurinol; the active ingredient is a polyacetylene compound or pharmaceutically acceptable salt thereof with the structure shown as the following:
the ratio of the pharmaceutical composition is selected from:
the dosage ratio of febuxostat and compound 1 is 1:15, 1:30, 3:5, 3:15 or 3:30;
the dosage ratio of allopurinol and compound 1 is 10:30, 20:5, 20:15 or 20:30;
the dosage ratio of febuxostat and compound 2 is 1:5, 1:30, 3:5, 3:15 or 3:30;
the dosage ratio of allopurinol and compound 2 is 10:5, 10:30, 20:5, 20:15 or 20:30;
the dosage ratio of febuxostat and compound 3 is 1:5, 1:15, 1:30, 3:5, 3:15 or 3:30;
the dosage ratio of allopurinol and compound 3 is 10:5, 20:5, 20:15 or 20:30;
the dosage ratio of the febuxostat to the compound 4 is 3:30;
the dosage ratio of allopurinol and the compound 4 is 20:30;
the dosage ratio of the febuxostat to the compound 5 is 3:15;
the dosage ratio of allopurinol and compound 5 is 20:15;
the dosage ratio of the febuxostat to the compound 6 is 3:30;
the dosage ratio of allopurinol and the compound 6 is 20:30;
the dosage ratio of the febuxostat to the compound 7 is 3:30;
the dosage ratio of allopurinol and the compound 7 is 20:30;
the dosage ratio of the febuxostat and the compound 8 is 3:15 or 3:30;
the dosage ratio of allopurinol and the compound 8 is 10:30;
the dosage ratio of the febuxostat and the compound 9 is 1:5 or 1:30;
the dosage ratio of allopurinol and compound 9 is 20:5, 20:15 or 20:30;
the dosage ratio of the febuxostat to the compound 10 is 3:30;
the dosage ratio of allopurinol and compound 10 is 20:30;
the dosage ratio of the febuxostat to the compound 11 is 3:15;
the dosage ratio of allopurinol and compound 11 is 20:15;
the dosage ratio of the febuxostat to the compound 12 is 3:15;
the dosage ratio of allopurinol and compound 12 is 20:15;
the dosage ratio of the febuxostat to the compound 13 is 3:15;
the dosage ratio of allopurinol and compound 13 is 20:15;
the dosage ratio of the febuxostat and the compound 14 is 3:30;
the dosage ratio of allopurinol and compound 14 is 20:30;
the dosage ratio of the febuxostat and the compound 15 is 3:30;
the dosage ratio of allopurinol and compound 15 is 20:30;
the proportion relation of the dosage ratio is mg/kg: mg/kg.
2. The pharmaceutical composition for treating hyperuricemia according to claim 1, further comprising a pharmaceutically acceptable carrier.
3. A medicament for treating hyperuricemia, which is characterized by comprising the pharmaceutical composition for treating hyperuricemia according to any one of claims 1-2, wherein the medicament is prepared by adding conventional auxiliary materials into the pharmaceutical composition for treating hyperuricemia and preparing clinically acceptable tablets, capsules, pills, granules, ointment, mixture or suspension according to a conventional process.
4. Use of a pharmaceutical composition for treating hyperuricemia according to claim 1 or 2 in the preparation of a medicament for treating hyperuricemia.
5. The use of a pharmaceutical composition for treating hyperuricemia according to claim 4, wherein the hyperuricemia is selected from gout or complications of gout caused by hyperuricemia.
6. The use of a pharmaceutical composition for treating hyperuricemia according to claim 5, wherein the gout is selected from acute gout or chronic gout; the gout complications are selected from gouty arthritis, gout flares or gouty nephropathy.
7. The use of a pharmaceutical composition for treating hyperuricemia according to claim 6, wherein the gouty kidney disease is selected from urolithiasis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910216331.1A CN111714486B (en) | 2019-03-20 | 2019-03-20 | Application of polyacetylene compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910216331.1A CN111714486B (en) | 2019-03-20 | 2019-03-20 | Application of polyacetylene compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111714486A CN111714486A (en) | 2020-09-29 |
| CN111714486B true CN111714486B (en) | 2023-06-20 |
Family
ID=72562581
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910216331.1A Active CN111714486B (en) | 2019-03-20 | 2019-03-20 | Application of polyacetylene compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111714486B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111714485B (en) * | 2019-03-20 | 2021-11-23 | 苏州凯祥生物科技有限公司 | Hyperuricemia pharmaceutical composition and application thereof |
| CN111714491B (en) * | 2019-03-20 | 2023-06-20 | 苏州凯祥生物科技有限公司 | Application of sesquiterpene lactone 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 |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105520984A (en) * | 2014-09-30 | 2016-04-27 | 苏州凯祥生物科技有限公司 | Novel medicinal application of coreopsis tinctoria |
| CN108697723A (en) * | 2016-01-18 | 2018-10-23 | 中央研究院 | Beggar-ticks is to increasing muscle and reducing the advantageous effect of fat |
| CN109893533A (en) * | 2017-12-07 | 2019-06-18 | 苏州凯祥生物科技有限公司 | New application of the poly- acetylene compound in anti-trioxypurine |
| CN109893538A (en) * | 2017-12-07 | 2019-06-18 | 苏州凯祥生物科技有限公司 | New application of the carbene class in anti-trioxypurine |
| CN109893517A (en) * | 2017-12-07 | 2019-06-18 | 苏州凯祥生物科技有限公司 | A kind of new application of carbene compounds for treating gout |
| CN109893521A (en) * | 2017-12-07 | 2019-06-18 | 苏州凯祥生物科技有限公司 | A kind of new application of poly- acetylene compound anti-trioxypurine |
| 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 |
-
2019
- 2019-03-20 CN CN201910216331.1A patent/CN111714486B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105520984A (en) * | 2014-09-30 | 2016-04-27 | 苏州凯祥生物科技有限公司 | Novel medicinal application of coreopsis tinctoria |
| CN108697723A (en) * | 2016-01-18 | 2018-10-23 | 中央研究院 | Beggar-ticks is to increasing muscle and reducing the advantageous effect of fat |
| CN109893533A (en) * | 2017-12-07 | 2019-06-18 | 苏州凯祥生物科技有限公司 | New application of the poly- acetylene compound in anti-trioxypurine |
| CN109893538A (en) * | 2017-12-07 | 2019-06-18 | 苏州凯祥生物科技有限公司 | New application of the carbene class in anti-trioxypurine |
| CN109893517A (en) * | 2017-12-07 | 2019-06-18 | 苏州凯祥生物科技有限公司 | A kind of new application of carbene compounds for treating gout |
| CN109893521A (en) * | 2017-12-07 | 2019-06-18 | 苏州凯祥生物科技有限公司 | A kind of new application of poly- acetylene compound anti-trioxypurine |
| 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 |
Non-Patent Citations (5)
| Title |
|---|
| Enzyme inhibitory activities of acetylene and sesquiterpene compounds in Atractylodes rhizome;Tetsuro Sakurai等;《Biol. Pharm. Bull.》;19931231;第16卷(第2期);142-145 * |
| Lipase inhibition and antiobesity effect of Atractylodes lancea;Ping Jiao等;《Planta Med》;20140331;第80卷;577-582 * |
| Tetsuro Sakurai等.Enzyme inhibitory activities of acetylene and sesquiterpene compounds in Atractylodes rhizome.《Biol. Pharm. Bull.》.1993,第16卷(第2期),142-145. * |
| 两色金鸡菊头状花序聚炔部位主要成分及指纹图谱研究;古文杰;《中国优秀硕士学位论文全文数据库 医药卫生科技辑》;20160815(第8期);E057-106 * |
| 吴惠勤等编著.理化性质.《安全风险物质高通量质谱检测技术》.华南理工大学出版社,2019,(第1版),409-411. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111714486A (en) | 2020-09-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111714486B (en) | Application of polyacetylene compound | |
| US20060233896A1 (en) | Medicinal preparation containing phenylethanoid glycosides extracted from herbaceous plant, Cistanche tubulosa (Schenk.) Wight, process of making the same, and uses of the same | |
| CN109893538B (en) | Novel application of polyacetylenes in reducing uric acid | |
| CN108440292B (en) | Sapium sebiferum element A-H, pharmaceutical composition and application thereof | |
| CN108191616B (en) | Monomer component with selective butyrylcholine esterase inhibition effect in bletilla striata and application thereof | |
| CN106008502A (en) | Alkaloid compounds with novel skeletons in purslane and extraction and separation method thereof | |
| CN114524825A (en) | Artemisia sphaerocephala lactone A-T, pharmaceutical composition thereof, and preparation method and application thereof | |
| CN111714485B (en) | Hyperuricemia pharmaceutical composition and application thereof | |
| CN111714491B (en) | Application of sesquiterpene lactone compound | |
| CN111150740A (en) | Lipid-lowering active ingredient and lipid-lowering composition in panax japonicus and application of lipid-lowering active ingredient and lipid-lowering composition | |
| CN108785316B (en) | Use of cortex Periplocae Radicis C21 steroids in preparation of IDO inhibitor | |
| CN106928299B (en) | Compound from cortex lycii radicis, preparation method and application thereof in aspect of reducing blood sugar | |
| CN111714487B (en) | Hyperuricemia pharmaceutical composition | |
| CN111617072B (en) | Hyperuricemia medicine composition and medicine for treating hyperuricemia | |
| CN109467581B (en) | Method for extracting flavonoid glycoside from lotus leaves and pharmaceutical preparation containing flavonoid glycoside from lotus leaves | |
| CN106963844B (en) | Application of tomato water-soluble saponin extract in preparation of drug or health-care product for treating hyperuricemia | |
| CN107281230B (en) | Pharmaceutical composition, preparation method thereof and application thereof in preparation of medicine for treating hypertension | |
| CN112089738A (en) | Preparation method and application of caulis sinomenii extract | |
| CN111617071B (en) | Hyperuricemia medicine composition and medicine for treating hyperuricemia | |
| EP1498131B1 (en) | Medicinal preparation containing phenylethanoid glycosides extracted from Cistanche tubulosa | |
| CN115429790B (en) | Application of isoflavone compound in preparing medicament for preventing or treating alcoholic liver injury or dispelling alcohol effect and protecting liver | |
| CN111297940A (en) | Preparation method and application of traditional Chinese medicine composition for reducing uric acid | |
| CN111943920B (en) | Phloroglucinol compound Hyperacmosin D and application thereof in preparation of antidiabetic drugs | |
| CN115745933B (en) | Artemisia rupestris sesquiterpene lactone A-N and pharmaceutical composition thereof, and preparation method and application thereof | |
| CN109575089B (en) | Acylated glucose compounds, pharmaceutical composition, preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |