CN113181181A - Application of piperine in preparation of medicine for preventing and/or treating hyperuricemia - Google Patents
Application of piperine in preparation of medicine for preventing and/or treating hyperuricemia Download PDFInfo
- Publication number
- CN113181181A CN113181181A CN202110597429.3A CN202110597429A CN113181181A CN 113181181 A CN113181181 A CN 113181181A CN 202110597429 A CN202110597429 A CN 202110597429A CN 113181181 A CN113181181 A CN 113181181A
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- CN
- China
- Prior art keywords
- piperine
- hyperuricemia
- uric acid
- medicament
- preparation
- 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.)
- Pending
Links
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- WVWHRXVVAYXKDE-UHFFFAOYSA-N piperine Natural products O=C(C=CC=Cc1ccc2OCOc2c1)C3CCCCN3 WVWHRXVVAYXKDE-UHFFFAOYSA-N 0.000 title claims abstract description 67
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Images
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4525—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K36/18—Magnoliophyta (angiosperms)
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- A61P13/00—Drugs for disorders of the urinary system
- A61P13/04—Drugs for disorders of the urinary system for urolithiasis
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
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- Physical Education & Sports Medicine (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of medicines, and discloses application of piperine in preparation of a medicine for preventing and/or treating hyperuricemia. The invention discloses the application of piperine or a derivative thereof in preparing a medicine for preventing and/or treating hyperuricemia and metabolic diseases related to the hyperuricemia for the first time, which is based on the discovery that the piperine has an inhibiting effect on URAT1 which is an important medicine target for treating the hyperuricemia, and the piperine or the derivative thereof can obviously reduce the serum uric acid level of mice with the hyperuricemia and promote the excretion of uric acid from urine, so that the hyperuricemia and the metabolic diseases related to the hyperuricemia are improved, and the piperine or the derivative thereof can be used for treating and/or treating the hyperuricemia and the metabolic diseases related to the hyperuricemia.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of piperine in preparation of a medicine for preventing and/or treating hyperuricemia.
Background
Hyperuricemia is a metabolic disease with a high incidence rate after hyperlipidemia and hyperglycemia, and the main reasons of the hyperuricemia are caused by poor dietary habits, such as eating of a large amount of seafood, excessive drinking, excessive intake of big fish meat and the like. The content of purine in the food is too high, uric acid is the final metabolite of purine substances in vivo, and adenine, hypoxanthine and the like in vivo are catalyzed by xanthine oxidase in the liver to generate uric acid purine, and the uric acid purine is excessively ingested or metabolic abnormality can cause hyperuricemia, so that gout, hypertension, cardiovascular diseases, kidney diseases and the like are caused.
The current clinical choices of uric acid-lowering drugs are few, and xanthine oxidase inhibitors are the current clinical commonly used uric acid-lowering drugs which act on the liver to inhibit the generation of uric acid, such as allopurinol, febuxostat and the like. However, allopurinol is prone to cause hypersensitive response, and febuxostat is also proposed by the Food and Drug Administration (FDA) to be prone to induce cardiovascular and cerebrovascular diseases. Except for the liver, the kidney is the main part of blood uric acid excretion, the excretion of the kidney urate depends on the balance of reabsorption and excretion of the urate, the transport process relates to a series of transporters, including urate reabsorption transporter/uric acid organic anion transporter (SLC22A12, URAT1) and glucose transporter 9(SLC2A9, GLUT9) and OAT1, OAT3 and the like which promote the excretion of uric acid, and the drugs are uric acid excretion promoting drugs. The uric acid is promoted to be excreted from urine by inhibiting an supratubular transporter URAT1, such as Benzbromarone (BM), Probenecid (PB), Lesinurad (Lesinurad) and the like, but the clinical application of the drugs is limited due to large side effect, poor drug effect and the like. URAT1 is an important transporter for the kidney to reabsorb uric acid, and more than 90% of uric acid in the renal tubules is reabsorbed by URAT 1.
The current clinical treatment guidelines for reducing uric acid indicate that the method for promoting uric acid excretion and reducing uric acid production are key points for treating hyperuricemia. Although it has been demonstrated that uric acid lowering drugs can control hyperuricemia, there are always other adverse side effects. For example, drugs that reduce uric acid production (such as AP and febuxostat) cause allergic syndrome and gastrointestinal problems, while the uric acid excretion drug BM also sustains adverse reactions such as hepatic steatosis. Therefore, there is an urgent need to develop less toxic, more effective therapeutic strategies for hyperuricemia for the anticipated future clinical applications. Modern pharmacological research shows that piperine has various pharmacological activities including antitumor, antioxidant, blood fat reducing, antiphlogistic and immunoregulation. Temporarily no relevant reports of piperine for reducing uric acid.
Disclosure of Invention
The first aspect of the present invention is to provide an application of piperine or a derivative thereof in the preparation of a medicament for preventing and/or treating hyperuricemia.
The second aspect of the present invention is directed to provide an application of piperine or a derivative thereof in the preparation of a medicament for preventing and/or treating a metabolic disease associated with hyperuricemia.
The third aspect of the invention aims at providing the application of piperine or the derivative thereof in serving as and/or preparing URAT1 inhibitor.
In a fourth aspect, the present invention is directed to a medicament.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
in a first aspect of the present invention, there is provided a use of piperine or a derivative thereof for the preparation of a medicament for the prevention and/or treatment of hyperuricemia.
Piperine (Piperine) is an alkaloid with a molecular formula of C17H19NO3Has molecular weight of 285.34 and CAS number of 94-62-2, and is present in dry nearly mature fruit or mature fruit of Piper longum of Piperaceae. The piperine is white crystal powder, has a melting point of 130-133 ℃, is dissolved in acetic acid, benzene, ethanol and chloroform, is slightly soluble in ether, and is almost insoluble in water and petroleum ether.
Preferably, the derivative comprises a pharmaceutically acceptable hydrate, solvate, polymorph, tautomer or prodrug of piperine.
Preferably, the medicament further comprises pharmaceutically acceptable auxiliary materials.
Preferably, the adjuvant is at least one of a sustained release agent, an excipient, a filler, a binder, a wetting agent, a disintegrant, an absorption enhancer, a surfactant and a lubricant.
Preferably, the dosage form of the drug is at least one of a solid formulation, a liquid formulation and a semi-solid formulation.
Preferably, the solid formulation includes tablets, granules, powders and capsules.
Preferably, the liquid formulation comprises an injection.
Preferably, the semi-solid formulation comprises an ointment and a cream.
In a second aspect of the present invention, there is provided a use of piperine or a derivative thereof for the preparation of a medicament for the prevention and/or treatment of a metabolic disease associated with hyperuricemia.
Piperine (Piperine) is an alkaloid with a molecular formula of C17H19NO3Has molecular weight of 285.34 and CAS number of 94-62-2, and is present in dry nearly mature fruit or mature fruit of Piper longum of Piperaceae. The piperine is white crystal powder, has a melting point of 130-133 ℃, is dissolved in acetic acid, benzene, ethanol and chloroform, is slightly soluble in ether, and is almost insoluble in water and petroleum ether.
Preferably, the derivative comprises a pharmaceutically acceptable hydrate, solvate, polymorph, tautomer or prodrug of piperine.
Preferably, the metabolic disease associated with hyperuricemia is at least one of acute gout, chronic gout, gouty arthritis, gout attack, uric acid nephrolithiasis, gouty nephropathy, lithangiuria and cardiovascular disease; further preferably, the metabolic disease associated with hyperuricemia is at least one of uric acid nephrolithiasis, urinary tract calculus and cardiovascular disease.
Preferably, the medicament further comprises pharmaceutically acceptable auxiliary materials.
Preferably, the adjuvant is at least one of a sustained release agent, an excipient, a filler, a binder, a wetting agent, a disintegrant, an absorption enhancer, a surfactant and a lubricant.
Preferably, the dosage form of the drug is at least one of a solid formulation, a liquid formulation and a semi-solid formulation.
Preferably, the solid formulation includes tablets, granules, powders and capsules.
Preferably, the liquid formulation comprises an injection.
Preferably, the semi-solid formulation comprises an ointment and a cream.
In a third aspect of the invention, there is provided the use of piperine or a derivative thereof as, and/or in the preparation of, a URAT1 inhibitor.
Piperine (Piperine) is an alkaloid with a molecular formula of C17H19NO3Has molecular weight of 285.34 and CAS number of 94-62-2, and is present in dry nearly mature fruit or mature fruit of Piper longum of Piperaceae. The piperine is white crystal powder, has a melting point of 130-133 ℃, is dissolved in acetic acid, benzene, ethanol and chloroform, is slightly soluble in ether, and is almost insoluble in water and petroleum ether.
Preferably, the derivative comprises a pharmaceutically acceptable hydrate, solvate, polymorph, tautomer or prodrug of piperine.
In a fourth aspect of the invention, there is provided a medicament comprising the following components:
(1) piperine and/or derivatives thereof; and
(2) pharmaceutically acceptable adjuvants.
Piperine (Piperine) is an alkaloid with a molecular formula of C17H19NO3Has molecular weight of 285.34 and CAS number of 94-62-2, and is present in dry nearly mature fruit or mature fruit of Piper longum of Piperaceae. The piperine is white crystal powder, has a melting point of 130-133 ℃, is dissolved in acetic acid, benzene, ethanol and chloroform, is slightly soluble in ether, and is almost insoluble in water and petroleum ether.
Preferably, the derivative comprises a pharmaceutically acceptable hydrate, solvate, polymorph, tautomer or prodrug of piperine.
Preferably, the adjuvant is at least one of a sustained release agent, an excipient, a filler, a binder, a wetting agent, a disintegrant, an absorption enhancer, a surfactant and a lubricant.
Preferably, the dosage form of the drug is at least one of a solid formulation, a liquid formulation and a semi-solid formulation.
Preferably, the solid formulation includes tablets, granules, powders and capsules.
Preferably, the liquid formulation comprises an injection.
Preferably, the semi-solid formulation comprises an ointment and a cream.
Preferably, the medicament further comprises other medicaments for promoting uric acid excretion, inhibiting uric acid synthesis, or promoting conversion of uric acid to allantoin.
Preferably, the drug for inhibiting uric acid synthesis is at least one of allopurinol, febuxostat, topirostat, inositol and Ulodesine.
Preferably, the drug for promoting uric acid excretion is at least one of benzbromarone, rasidone, probenecid and dortinoid (dotinuad).
Preferably, the drug that promotes the conversion of uric acid to allantoin is labyrinase.
The invention has the beneficial effects that:
the invention discloses the application of piperine or a derivative thereof in preparing a medicine for preventing and/or treating hyperuricemia and metabolic diseases related to the hyperuricemia for the first time, which is based on the discovery that the piperine has an inhibiting effect on URAT1 which is an important medicine target for treating the hyperuricemia, the blood serum uric acid level of a patient with the hyperuricemia can be obviously reduced through the piperine or the derivative thereof, and the excretion of uric acid from urine is promoted, so that the hyperuricemia and the metabolic diseases related to the hyperuricemia are improved, and the piperine or the derivative thereof can be used for treating and/or treating the hyperuricemia and the metabolic diseases related to the hyperuricemia.
Drawings
FIG. 1 is a graph of dose-effect relationship between piperine and Racinradd (lesinurad) on the inhibitory effect of URAT 1: wherein A is a dose-effect relation curve chart of piperine on the inhibitory action of URAT 1; b is a dose-response plot of rasidone over URAT1 inhibition.
FIG. 2 is a graph of the effect of piperine and Ravinader on uric acid levels in serum and urine of hyperuricemic mice: wherein A is a graph of the effect of piperine and Racinadine on the level of uric acid in the serum of hyperuricemia mice; b is a graph of the effect of piperine and Racinadine on uric acid levels in the urine of hyperuricemia mice; # indicates that p is <0.001 compared to control; denotes, p <0.05 compared to model group; denotes, p <0.01 compared to model group; indicates that p <0.001 compared to the model group.
FIG. 3 is a map of pcDNA3.1(+) -EGFP-URAT1 recombinant plasmid.
Detailed Description
The present invention will be described in further detail with reference to specific examples.
The starting materials used in the examples were prepared by conventional means or purchased from commercial sources, except as otherwise specified.
The reagents or methods of preparation of the reagents in this example were as follows:
preparation of kanamycin and ampicillin: dissolving 1g kanamycin/ampicillin in sufficient ddH2And O, finally, diluting to 20mL, filtering, sterilizing, subpackaging into small parts, storing at-20 ℃, and diluting 1000 times when in use.
Preparing competent cells: the whole gold Trans1-T1 is competent (cat # CD501-02), and is used for transformation of target genes after dissolving on ice before use.
Preparation of liquid E.coli culture medium: respectively weighing 5g of peptone, 5g of sodium chloride and 2.5g of yeast extract into a 500mL clean bottle, adding 500mL of ultrapure water, uniformly stirring, sterilizing at 121 ℃ for 20min, cooling to 37 ℃, adding 500 μ L of kanamycin (50mg/mL), uniformly shaking, and storing at 4 ℃ for later use.
Preparation of solid Escherichia coli culture medium: 3g of peptone, 3g of sodium chloride, 1.5g of yeast extract and 4.5g of agar are respectively weighed into a 500mL clean bottle, 300mL of ultrapure water is added, high-temperature sterilization is carried out at 121 ℃ for 20min, the solid culture medium is placed at room temperature after the sterilization is finished, 300 mu L of kanamycin (50mg/mL) is added when the culture medium is not solidified, the culture medium is uniformly shaken and poured into a sterile culture dish, and the culture medium is stored at 4 ℃ after solidification for later use.
Example 1 in vitro inhibitory Effect of Piperine on URAT1
Construction of pcDNA3.1(+) -EGFP-URAT1 recombinant plasmid
The pcDNA3.1(+) -EGFP is taken as an expression vector, a target Gene URAT1(Gene ID: 116085) is inserted to obtain pcDNA3.1(+) -EGFP-URAT1 recombinant plasmid (shown in figure 3), the recombinant plasmid is transformed into escherichia coli and cultured for 16h at 37 ℃, then a single clone is picked up and placed in the prepared liquid culture solution for culturing, and the bacteria are shaken for 16 h. After shaking, extracting plasmid, sequencing and confirming to obtain pcDNA3.1(+) -EGFP-URAT 1.
2. Polylysine coated 96-well plate
Poly-lysine PDL (0.1mg/mL) was plated in 96-well plates for 24h, and then PDL was discarded and oven-dried for 12h for use.
3. Cell transfection
Culturing HEK293T cells, inoculating HEK293T cells into PDL coated 96-well plate, standing at 37 deg.C and 5% CO when HEK293T cells grow and fuse to 90%2After culturing in an incubator for 24 hours, performing DNA-liposome complex transient transfection when the cell fusion rate is about 70-80%, specifically as follows:
to two 1.5mL EP tubes (tube No. 1 and tube No. 2), 25. mu.L of Opti medium (Gibco) were added, and to tube No. 1, 500ng of the above plasmid (pcDNA3.1(+) -EGFP-URAT1) and 1. mu.L of P3000 were addedTMMixing uniformly; add 0.75. mu.L of Lipo 3000 to tube No. 2TMSwirling tubes No. 1 and No. 2 for 10 seconds, and standing for 5 min; mixing the two tubes, vortexing for 10 s, standing for 20min, dripping into 500 μ L/hole (10 μ L/hole) of new culture medium, standing at 37 deg.C and containing 5% CO2Culturing in an incubator for 24 h.
4.14[C]Uric acid uptake assay
(1) Process for preparing piperine14[C]Uric acid uptake assay
1) Preparation of uptake buffer: the uptake buffer was formulated as follows: 140mM NaCl, 5mM KCl, 1mM MgCl2、2mM CaCl210mM HEPES and 10mM D-glucose, the pH of the uptake buffer was adjusted to 7.4 with 0.1M NaOH, and the mixture was filtered through a 0.22 μ M microporous membrane and stored at 4 ℃ for further use.
2) Preparation of drug-containing uptake buffer: the piperine stock solution (20mM) was diluted with uptake buffer to give piperine (100,50, 25, 12.5, 6.25. mu.M) at different concentrations, preferably ready for use.
3) Preparation of the composition contains14[C]Uptake buffer for uric acid and piperine: prepared with uptake buffer at a concentration of 100. mu.M14[C]Mixing uric acid solution with piperine solution dissolved in the absorption buffer solution with different concentrations in equal volume to obtain final product14[C]Uric acid (final concentration of 50. mu.M) and piperine (100,50, 25, 12.5, 6.25. mu.M) at different concentrations were ingested as a mixed solution.
4)14[C]The uric acid uptake experiment comprises the following specific steps: the medium in HEK293T cells transfected with URAT1 was discarded, and the cells were washed 3 times with 200. mu.L of uptake buffer each time; adding 100 μ L of uptake buffer containing piperine (100,50, 25, 12.5, 6.25 μ M) at different concentrations (adding equal amount of uptake buffer to control group) respectively, pre-incubating for 15min, after pre-incubation, adding mixed solution containing piperine (100,50, 25, 12.5, 6.25 μ M) and uric acid (final concentration is 50 μ M) for incubation for 15min, immediately discarding the liquid in the wells, adding ice-cold DPBS buffer to wash the cells for 3 times, 200. mu.L each time, finally adding 40. mu.L of 0.1M NaOH to lyse the cells for 30min, adding 0.2mL of liquid scintillation fluid (ARC, St. Louis, MO, USA), transferring to a liquid scintillation device, recording the effect of adding piperine on the change of the radioactive value CPM, and the median Inhibitory Concentration (IC) of piperine inhibition URAT1 was calculated by nonlinear fitting.50Value). Wherein the inhibition rate calculation formula is as follows: CPM/CPM 0100% (wherein CPM is the radioactivity value upon addition of an uptake cocktail containing piperine and uric acid simultaneously, CPM0Radioactivity at the time of addition of uric acid-containing uptake buffer only).
(2) Of Lesinurad14[C]Uric acid uptake assay
1) Preparation of uptake buffer: the uptake buffer was formulated as follows: 140mM NaCl, 5mM KCl, 1mM MgCl2、2mM CaCl210mM HEPES and 10mM D-glucose, the pH of the uptake buffer was adjusted to 7.4 with 0.1M NaOH, and the mixture was filtered through a 0.22 μ M microporous membrane and stored at 4 ℃ for further use.
2) Preparation of drug-containing uptake buffer: raschindde is diluted with uptake buffer to give different concentrations of Raschindde (40,20,10,5, 2. mu.M), ready to use.
3) Preparation of the composition contains14[C]Uptake buffer for uric acid and piperine: prepared with uptake buffer at a concentration of 100. mu.M14[C]Mixing uric acid solution with Raschild solution of different concentrations dissolved in the absorption buffer solution in equal volume to obtain the final product14[C]Uric acid (final concentration of 50. mu.M) was taken in mixed solution with different concentrations of Racinadine (40,20,10,5, 2. mu.M).
4)14[C]The uric acid uptake experiment comprises the following specific steps: the medium in HEK293T cells transfected with URAT1 was discarded, and the cells were washed 3 times with 200. mu.L of uptake buffer each time; adding 100 μ L of absorption buffer containing Rasciadol (40,20,10,5,2 μ M) at different concentrations, respectively, adding equal amount of absorption buffer into control group, pre-incubating for 15min, after pre-incubation, adding mixed solution containing Racinidde (40,20,10,5,2 μ M) and uric acid (final concentration is 50 μ M) for incubation for 15min, immediately discarding the liquid in the wells, adding ice-cold DPBS buffer solution to wash the cells for 3 times, 200 μ L each time, finally adding 40 μ L of 0.1M NaOH to lyse the cells for 30min, adding 0.2mL of liquid scintillation liquid, transferring to a liquid scintillation meter to record the influence of whether Raynaud is added on the change of the radiation value CPM value, and half Inhibitory Concentration (IC) of rascinod inhibiting URAT1 was calculated by nonlinear fitting.50Value). Wherein the inhibition rate calculation formula is as follows: CPM/CPM 0100% (wherein CPM is the intake of Racinonide and uric acid simultaneouslyEmission value in mixed liquor, CPM0Radioactivity at the time of addition of uric acid-containing uptake buffer only).
The results are shown in FIG. 1: piperine and Racinadine inhibit URAT1, its IC, in a concentration-dependent manner50Values were similar, 21.46. mu.M, 16.09. mu.M, with 3 duplicate wells per concentration. Thus, piperine acts as a URAT1 inhibitor.
Example 2 in vivo Deuricemic study of piperine
1. Male Kunming mice (20 ± 2g, purchased at southern medical university animal laboratories) were kept under standard conditions (temperature 25 ± 1 ℃ and humidity 50 ± 10% in a controlled room, with 12 hours light/dark cycles) allowing the mice to freely eat the laboratory diet and water. The mice were randomly divided into 4 groups of 6 mice each (blank, model, piperine dose (10mg/kg BW/d), positive drug group (lesinurad)). A blank group, a model group of sodium carboxymethylcellulose (CMC-Na) solution, an administration group of piperine (10mg/kg), lesinurad (2.5mg/kg), a seventh day model group, a piperine dose group (10mg/kg BW/d), a positive drug group (lesinurad) (2.5mg/kg) are respectively administered to the administration groups every day, 350mg/kg PO is initially administered to the modeling agent to construct Hyperuricemia model mice (see the specific methods: X.Wu, M.Wakamiya, S.Vaishnaval, et al, Hyperuricemia and urate neuropathology in urate oxidase-differentiation mice, Proc Natl Acad Sci S A,1994,91,742-746.), the drugs are injected into the abdominal cavity after one hour, the drugs are injected into the abdominal cavity after 7 days, the last uric acid-reducing drugs are administered for 30 minutes, and then orbital blood is obtained after 7 days. And the mice are placed into a metabolism cage to collect urine for 4 hours for measuring uric acid. The content of uric acid in urine and serum of the mice is detected, and the result is shown in figure 2: piperine and Racinadine can significantly reduce the level of uric acid in blood serum of mice with hyperuricemia and promote the excretion of uric acid from urine.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (10)
1. Application of piperine or its derivatives in preparing medicine for preventing and/or treating hyperuricemia is provided.
2. Application of piperine or a derivative thereof in preparing a medicament for preventing and/or treating metabolic diseases related to hyperuricemia.
3. Use according to claim 2, characterized in that: the metabolic diseases related to hyperuricemia comprise acute gout, chronic gout, gouty arthritis, gout attack, uric acid nephrolithiasis, gouty nephropathy, lithangiuria and cardiovascular diseases.
4. Use of piperine or a derivative thereof as and/or in the preparation of URAT1 inhibitors.
5. Use according to any one of claims 1 to 4, characterized in that:
the derivatives include pharmaceutically acceptable hydrates, solvates, polymorphs, tautomers or prodrugs of piperine.
6. Use according to any one of claims 1 to 3, characterized in that:
the medicine also comprises pharmaceutically acceptable auxiliary materials.
7. Use according to claim 6, characterized in that:
the pharmaceutically acceptable auxiliary materials are at least one of sustained release agent, excipient, filler, adhesive, wetting agent, disintegrating agent, absorption enhancer, surfactant and lubricant.
8. Use according to claim 7, characterized in that:
the dosage form of the medicament is at least one of solid preparation, liquid preparation and semi-solid preparation.
9. A medicament comprising the following components:
(1) piperine and/or derivatives thereof; and
(2) pharmaceutically acceptable adjuvants.
10. The medicament of claim 9, wherein:
the medicament also comprises other medicaments for promoting the excretion of uric acid, inhibiting the synthesis of uric acid or promoting the conversion of uric acid into allantoin.
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| CN116570584A (en) * | 2023-05-08 | 2023-08-11 | 广州白云山医药集团股份有限公司白云山制药总厂 | Application of salinomycin in preparing medicament for reducing uric acid and/or treating hyperuricemia |
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2021
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| Title |
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| EVAN PRINCE SABIN等: "A Role of Piperine on Monosodium Urate Crystal-Induced Inflammation—An Experimental Model of Gouty Arthritis", 《INFLAMMATION》 * |
| LAILATUL FITRIA等: "Analysis of Allopurinol, Cucurbitacin B, Morindine, and Piperine as Xanthine", 《JOURNAL OF SMART BIOPROSPECTING AND TECHNOLOGY》 * |
| YUSUF ANDRIANA等: "Biological Activities and Chemical Constituents of Essential Oils from Piper cubeba Bojer and Piper nigrum L.", 《MOLECULES》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN116570584A (en) * | 2023-05-08 | 2023-08-11 | 广州白云山医药集团股份有限公司白云山制药总厂 | Application of salinomycin in preparing medicament for reducing uric acid and/or treating hyperuricemia |
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