CN115590869A - Shuganning injection and application of characteristic compound thereof in preparation of OATs (immunoglobulin of genes) inhibitor - Google Patents
Shuganning injection and application of characteristic compound thereof in preparation of OATs (immunoglobulin of genes) inhibitor Download PDFInfo
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- 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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- 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
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
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- 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
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
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- 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
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Abstract
The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a Shuganning injection and application of a characteristic compound thereof in preparation of an OATs inhibitor. Experimental research shows that the Shuganning injection and the characteristic compounds thereof, namely baicalin and oroxylin A, can inhibit OAT1 and OAT3 transporters, and the geniposide and the chlorogenic acid can inhibit the OAT3 transporters, so that the Shuganning injection and the characteristic compounds can be used for preparing OATs inhibitors for inhibiting the transporters, preparing medicines for enhancing the curative effect of medicines excreted through the kidney by inhibiting the corresponding transporters and medicines for reducing the renal toxicity caused by mercury.
Description
Technical Field
The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a Shuganning injection and application of a characteristic compound thereof in preparation of an OATs inhibitor.
Background
The kidney is one of the important excretory organs of the body, and most of the clinically used drugs need to be excreted through the kidney, wherein the main excretory organ of some drugs is the kidney. Renal proximal convoluted tubule-mediated secretion and reabsorption are important components of the renal excretion process, and the drug concentration in renal proximal convoluted tubule epithelial cells is closely related to the transporters distributed on the basal and apical membrane sides thereof. The transporters distributed on the basal membrane side of renal proximal tubular epithelial cells mainly take an uptake type transporter and mediate the transport of anion substrates from blood to the proximal tubular, and the transporters are divided into organic cation transporters and Organic Anion Transporters (OATs); the transporters distributed on the apical membrane side are mainly excluded transporters. The organic anion transporters OAT1 and OAT3 play a key role in renal excretion of drugs and metabolites thereof, the affected drugs comprise clinical common drugs such as antibiotics, proton pump inhibitors, partial antitumor drugs and the like, and the inhibition of OAT1 and OAT3 can reduce the excretion of the drugs and improve the blood concentration thereof, thereby reducing the dosage and reducing the adverse reaction caused by drug overdose. It has also been found that inhibition of OAT1 and OAT3 may also be used as a means of reducing mercury-induced renal toxicity.
Disclosure of Invention
Aiming at the technical problems, the invention provides a Shuganning injection and application of a characteristic compound thereof in preparing an OATs inhibitor. Experimental research shows that the Shuganning injection and the characteristic compounds thereof, namely baicalin and oroxylin A, can inhibit OAT1 and OAT3 transporters, and the geniposide and the chlorogenic acid can inhibit the OAT3 transporters, so that the Shuganning injection can be used for preparing the OATs inhibitor for inhibiting the transporters.
In order to achieve the purpose of the invention, the embodiment of the invention adopts the following technical scheme:
in a first aspect, the invention provides the use of shuganning injection in the preparation of an inhibitor of OATs, wherein the inhibitor of OATs is an inhibitor for inhibiting OAT1 and OAT3 transporters.
According to the invention, researches show that the Shuganning injection has a remarkable inhibiting effect on OAT1 and OAT3 transporters mainly expressed in the kidney. The inhibition effect of the Shuganning injection enables the Shuganning injection to be used for preparing OATs inhibitors for inhibiting OAT1 and OAT 3.
In a second aspect, the invention also provides an application of a characteristic compound of the Shuganning injection in preparing an OATs inhibitor, wherein the characteristic compound is at least one of baicalin, oroxylin A, geniposide or chlorogenic acid, and the OATs inhibitor is an inhibitor for inhibiting OAT1 and/or OAT3 transporters. Experiments show that the baicalin is a substrate of OAT1 and OAT3, the low-concentration baicalin has obvious inhibition effect on substrate uptake mediated by the OAT3, and the high-concentration baicalin has stronger inhibition effect on substrate uptake mediated by OAT1 and OAT3 transporters, and can be used for preparing an OATs inhibitor for inhibiting OAT1 and/or OAT 3; the oroxylin A with low concentration and high concentration has strong inhibition effect on substrate uptake mediated by OAT1 and OAT3 transporters, and can be used for preparing an inhibitor for inhibiting OAT1 and/or OAT 3; high concentration of geniposide selectively inhibits OAT3 mediated substrate uptake, and can be used to make inhibitor for inhibiting OAT 3; chlorogenic acid with low concentration has certain inhibiting effect on OAT3 mediated substrate uptake, and the inhibiting effect is increased correspondingly when the concentration is increased, and has certain inhibiting effect on OAT1 mediated substrate uptake, and can be used for preparing OATs inhibitor for inhibiting OAT1 and/or OAT 3.
In a third aspect, the present invention also provides a medicament for enhancing the therapeutic effect of a medicament excreted from the kidney, the active ingredient of the medicament comprising at least one of baicalin, oroxylin a, geniposide and chlorogenic acid.
In combination with the third aspect, the renal excretion medication includes antibiotic drugs, proton pump inhibitors, statins, valsartan, rifampicin, and renal excretion anti-neoplastic drugs.
With reference to the third aspect, when the active ingredient of the drug includes at least one of baicalin and oroxylin a, the drug is a drug that inhibits OAT1 and/or OAT3 transporters; when the active ingredient of the drug comprises at least one of geniposide and chlorogenic acid, the drug is a drug that inhibits the OAT3 transporter.
Preferably, the dosage form of the medicament is intravenous injection. The above monomers have low oral bioavailability, and the concentration required for inhibiting OAT1 and OAT3 is not easy to reach, so intravenous injection is preferably adopted.
Optionally, the medicament further comprises pharmaceutically acceptable auxiliary materials. The specific type and amount of the auxiliary materials can be selected conventionally according to the requirements of the preparation, which is not limited in the present invention.
In a fourth aspect, the invention also provides a medicament for reducing mercury-induced renal toxicity, wherein the active ingredient of the medicament comprises at least one of baicalin, oroxylin A, geniposide and chlorogenic acid.
With reference to the fourth aspect, when the active ingredient of the drug includes at least one of baicalin and oroxylin a, the drug is a drug that inhibits OAT1 and/or OAT3 transporters; when the active ingredient of the drug comprises at least one of geniposide and chlorogenic acid, the drug is a drug that inhibits the OAT3 transporter.
Preferably, the medicament is in the form of intravenous injection.
Optionally, the medicament further comprises pharmaceutically acceptable excipients. The specific type and amount of the auxiliary materials can be selected conventionally according to the requirements of the preparation, which is not limited in the present invention.
The invention has the beneficial effects that: experimental research shows that the Shuganning injection and the characteristic compounds thereof, namely baicalin and oroxylin A, can inhibit OAT1 and OAT3 transporters, and the geniposide and the chlorogenic acid can inhibit the OAT3 transporters, so that the Shuganning injection and the characteristic compounds can be used for preparing OATs inhibitors, and further can be used for preparing medicines for enhancing the curative effect of medicines excreted by kidneys by inhibiting the corresponding transporters and medicines for reducing the renal toxicity caused by mercury. When the medicine excreted by kidney is clinically used, the medicine can be matched with Shuganning injection or the medicine containing at least one of baicalin, oroxylin A, geniposide and chlorogenic acid for use, so as to reduce the administration dosage of the medicine excreted by kidney and reduce the adverse reaction of other aspects caused by the latter. When the clinical prevention and treatment of the renal toxicity caused by mercury are carried out, the specific treatment scheme and the pharmacological effects of the Shuganning injection and the compounds with the characteristics can be combined for independent medication or combined medication so as to reduce the damage of mercury to the kidney.
Drawings
Fig. 1 shows the inhibitory effect of three clinically relevant concentrations of shuganning injection on transporters in example 1 of the present invention;
fig. 2 shows the concentration-dependent inhibition and median inhibition concentration of shuganning injection in example 1 of the present invention;
FIG. 3 shows the content ratio of baicalin, oroxylin A, geniposide and chlorogenic acid in 7 SLC transporter cells and EV cells in example 1 of the present invention;
FIG. 4 shows the inhibitory effect of baicalin, oroxylin A, geniposide and chlorogenic acid in the transporter in example 1 of the present invention;
FIG. 5 shows the concentration-dependent inhibition curves and IC of baicalin, oroxylin A, geniposide and chlorogenic acid in the transporter in example 1 of the present invention 50 ；
Fig. 6 shows the effect of shuganning injection on blood concentration and clearance of furosemide in example 2 of the present invention;
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The Shuganning injection has the effects of clearing away heat and toxic materials, promoting diuresis, eliminating jaundice, invigorating qi, strengthening body resistance, and protecting liver. Can be used for treating damp-heat jaundice with symptoms of yellowish complexion, fullness and distention in chest and hypochondrium, nausea, emesis, dark urine, asthenia, anorexia, and loose stool; acute and chronic viral hepatitis with the above symptoms. At present, no report of Shuganning injection as an OATs inhibitor is found.
Experimental research shows that the Shuganning injection and part of characteristic compounds thereof have different degrees of inhibition effects on OAT1 and OAT3 transporters and can be used as an OATs inhibitor, on one hand, the mechanism can be used for reducing the excretion of medicaments excreted by kidneys, improving the blood concentration of the medicaments and further reducing the dosage, and on the other hand, the mechanism can be used for reducing the renal toxicity caused by mercury.
The embodiments of the present invention are described below with reference to specific examples.
Other raw materials, reagents and the like used in the following examples were obtained commercially unless otherwise specified.
Example 1
This example provides shuganning injection and its characteristic compounds for inhibiting OAT1 and OAT 3.
1. Materials and methods
1.1 cells
Cells overexpressing OAT1, OAT3, P-gp, BCRP transporters, and the corresponding empty cells (EV).
1.2 Primary reagents
Shuganning injection (Guizhou rui and pharmaceutical Co., ltd., production batch No. 20200325).
Baicalin (alatin, 99%), oroxylin a (shanghai-source leaves, 99%), chlorogenic acid (solibao, 98%), geniposide (solibao, 98%), 6-carboxyfluorescein, rhodamine, hester reagent (Rho 123, shanghai-source leaves), probenecid (Sigma, 98%), ketoconazole (Sigma, 99%), neomycin (alatin, 95%). Other common chemicals (such as sodium chloride, etc.) were purchased from Tianjin Jiangtian chemical technology, inc.
1.3 Main instruments
Ultimate 3000 ultra high Performance liquid systems (Thermo Fisher Scientific, san Jose, calif., USA); q-active TM A hybrid quadrupole-Orbitrap mass spectrometer (Thermo Fisher Scientific, san Jose,CA, USA) intercellular superclean bench: thermo fisher (china) corporation; CO 2 2 A constant-temperature incubator: thermo fisher (china) corporation; cell counting instrument: shanghai Rui Yu biological science and technology Co., ltd; a micropipette: eppendorf (Shanghai) International trade, inc.; analytical balance: sartorius group, germany; a pH meter: sartorius group, germany; an enzyme-labeling instrument: tecan, switzerland.
1.4 Experimental methods
1.4.1 cell culture
The cells were revived and routinely cultured in DMEM containing 10% fetal bovine serum, 1% Pen/Strep, third to tenth generation cells for the experiments.
1.4.2 substrate experiments
4 characteristic compounds (baicalin, geniposide, oroxylin A and chlorogenic acid) of the Shuganning injection are selected for monomer substrate verification.
Cells overexpressing OAT1, OAT3, P-gp, BCRP transporter and corresponding EV cells were seeded in equal numbers in 12-well plates. The above 4 characteristic compound monomers were added to the cells at a final concentration of 100. Mu.M (+/-positive inhibitor) for preliminary characterization of uptake experiments. After the intake experiment is finished, cell lysate is obtained in a repeated freezing-melting mode and is used for quantifying the liquid quality. And (3) carrying out efflux verification on P-gp and BCRP cell substrates by adopting a Transwell cell chamber, and collecting liquid on two sides of the chamber for detection.
1.4.3 inhibition experiments
The overall inhibition evaluation of the injection is carried out according to the recommended dosage and method of the Shuganning injection specification and the determination of three clinically relevant dosages of 0.2 percent, 1 percent and 4 percent (v/v). As with the substrate experiments, uptake inhibition experiments were performed on 4 characteristic compounds individually, and 100 μ M of compound with >50% monomer inhibition was selected for dose response curve plotting in the corresponding transporters.
1.4.4 liquid quality detection
1.4.4.1 liquid phase conditions
And detecting by using an Ultimate 3000 ultrahigh-performance liquid system.
A chromatographic column: waters ACQUITY UPLC BEH C18 (250 mm. Times.4.6 mm,1.7 μm)
Mobile phase: mobile phase A0.1% v/v aqueous formic acid solution and mobile phase B acetonitrile.
The gradient elution procedure was: 0 → 6 minutes, 98%; 6 → 8 minutes, 0%; 8 → 8.5 minutes, 0% > -98% A,100% B → 2% B;8.5 → 10 minutes, 98% A → 98% A,2% B → 2% B.
Column temperature: 35 ℃;
flow rate: 0.3mL/min;
sample injection amount: 2 mu L of the solution;
temperature of the sample chamber: 15 ℃;
1.4.4.2 Mass Spectrometry conditions
By Q-active TM A hybrid quadrupole-Orbitrap mass spectrometer collects mass spectral data of the sample.
The main parameters of an electrospray ionization source (ESI source) are as follows: spray voltage, (-) -ESI of 3.0kV, and (+) -ESI of 3.5kV; sheath gas pressure, 35psi; auxiliary gas pressure, 10arb (N) 2 Purity 99.9%); purge gas pressure, 0arb; capillary temperature, 400 ℃; the auxiliary gas heats up to 450 ℃.
The Full-MS scan range is m/z100-1500, and the resolution is set to 70,000.
Data dependent scanning (dd-MS 2) is applied to acquire high quality secondary mass spectral data. The first 5 strongest precursors were automatically selected for MS/MS fragmentation by high energy collision induced dissociation (HCD). Parameters of dd-MS 2: resolution, 17,500; isolation window, 4m/z. The Normalized Collision Energy (NCE) was set to 30, 40 and 50V. All data were recorded and processed by Thermo Scientific Xcalibur 4.0 software (Thermo Fisher Scientific).
2. Experimental results and discussion
2.1 Shuganning injection
The Shuganning injection with different concentrations has different degrees of inhibition effects on transport proteins OAT1, OAT3, P-gp and BCRP, as shown in figure 1.
The Shuganning injection has the strongest inhibition effect on OAT1 and OAT3 which are mainly expressed in the kidney, and the inhibition rate on OATs under the condition of the lowest concentration (0.2%) is more than 70%;
the Shuganning injection has weak inhibition effect on two efflux transporters P-gp and BCRP of ABC family.
The data show that OAT1 and OAT3 are easily influenced by Shuganning injection, and the influence effect is far greater than that of P-gp and BCRP. The results suggest that shuganning injection can be used for preparing the drug for reducing the mercury-induced renal toxicity by inhibiting the transporters OAT1 and OAT 3.
To further explore the inhibitory effect of shuganning injection, a dose-dependent response curve of the injection was drawn and half Inhibitory Concentration (IC) was evaluated 50 ). As shown in FIG. 2, IC of Shuganning injection in OAT1 and OAT3 50 Both are less than 1 per thousand of the concentration of the injection, the inhibition effect on the efflux transporters P-gp and BCRP is weaker than that of the ingestion transporters, and the maximum blood concentration in clinical use is suggested to possibly inhibit the active secretion of the OAT1 and OAT3 of the kidney.
2.2 characterizing Compounds
In the experiment of taking baicalin by SLC transporters, the ratio of the content of compounds in OAT1 and OAT3 cells to that in EV cells is 4.10 and 3.87 times respectively. As can be seen, under the current experimental conditions, baicalin is a substrate for both transporters. The content ratios of oroxylin A, geniposide and chlorogenic acid in OAT1, OAT3 and no-load cells are all lower than 2, and therefore under the current experimental conditions, oroxylin A, geniposide and chlorogenic acid are not substrates of the two transporters. As shown in fig. 3.
The above four monomers were examined for inhibition at concentrations of 10. Mu.M and 100. Mu.M, respectively, as shown in FIG. 4: baicalin showed significant inhibition (62.5%) of OAT 3-mediated substrate uptake when the compound was treated at low concentrations (10 μ M) on cells; the inhibition effect of the geniposide on OAT1 and OAT3 is not obvious; oroxylin a showed equal strength of inhibition (> 50%) of OAT1 and OAT 3; chlorogenic acid reduces the capacity of OAT3 mediated 6-CF transport by half. When the monomer is used for treating cells at high concentration (100 mu M), baicalin and oroxylin A have strong inhibition effects on substrate uptake mediated by OAT1 and OAT3 transporters; geniposide selectively inhibits OAT 3-mediated 6-CF transport, while having no significant inhibitory effect on structurally functionally similar OAT 1; chlorogenic acid has >50% inhibition in OAT 3-mediated transmembrane transport.
In combination with the above analysis, the following conclusions are drawn in this section: 1) Baicalin and oroxylin A in the injection are most likely to cause the inhibition of OAT1 and OAT3 transporters; 2) Geniposide and chlorogenic acid show strong selective inhibition of OAT3, which may depend on the compound structure and active sites on membrane proteins.
Inhibition of 100. Mu.M monomer in FIG. 4>50% of the compounds, dose-response curve plotting in the corresponding transporters and evaluation of the IC 50 . As shown in FIG. 5, IC of baicalin in OAT1 and OAT3 50 About 10 μ M; IC of geniposide in OAT3 50 About 60 μ M; oroxylin A is currently the most potent inhibitor of OAT3, with IC 50 <2 mu M; IC of chlorogenic acid in OAT3 50 About 40. Mu.M.
Example 2
This example provides the use of shuganning injection as an OATs inhibitor to enhance the therapeutic effect of furosemide. Furosemide is a potent diuretic that is transported via OATs into the kidneys for active secretion.
1. Experimental materials
Shuganning injection (Guizhou rui and pharmaceutical Co., ltd., production batch No. 20200325).
SD male rats, 200-220 g, fasted (without water deprivation) 12h before the experiment.
The male rats were randomly divided into two groups, a control group and an experimental group, with 8 rats each.
2. Dosing regimens
The rats in the control group are injected with normal saline according to the dose of 10mg/kg in the tail vein, and are injected with furosemide injection according to the dose of 10mg/kg (calculated by active ingredients) after 10 min;
the experimental group rats were injected with Shuganning injection at a dose of 10mg/kg in the tail vein, and then injected with furosemide injection at a dose of 10mg/kg (calculated by active ingredients) after 10 min.
3. Results of the experiment
As shown in FIG. 6, the plasma concentration of furosemide was increased and the clearance was decreased in the rats of the experimental group as compared with the control group.
Example 3
This example provides an intravenous injection for enhancing the therapeutic effect of a drug excreted via the kidney by inhibiting OAT1 and OAT3 transporters, the active ingredient being baicalin.
Example 4
This example provides an intravenous injection for enhancing the therapeutic effect of a drug excreted via the kidney by inhibiting OAT1 and OAT3 transporters, the active ingredient being oroxylin a.
Example 5
This example provides an intravenous injection for enhancing the therapeutic effect of a drug excreted via the kidney by inhibiting OAT1 and OAT3 transporters, the active ingredients being baicalin and oroxylin a.
Example 6
This example provides an intravenous injection for enhancing the therapeutic effect of a drug excreted via the kidney by inhibiting OAT3 transporter, the active ingredient being geniposide.
Example 7
This example provides an intravenous injection for enhancing the therapeutic effect of a drug excreted via the kidney by inhibiting OAT3 transporters, the active ingredient being chlorogenic acid.
Example 8
This example provides an intravenous injection for enhancing the therapeutic effect of a drug excreted via the kidney by inhibiting OAT3 transporter, the active ingredients being geniposide and chlorogenic acid.
Example 9
This example provides an intravenous injection for reducing mercury-induced nephrotoxicity by inhibiting OAT1 and OAT3 transporters, the active ingredient being baicalin.
Example 10
This example provides an intravenous injection for reducing mercury-induced nephrotoxicity by inhibiting OAT1 and OAT3 transporters, the active ingredient being oroxylin a.
Example 11
This example provides an intravenous injection for reducing mercury-induced nephrotoxicity by inhibiting OAT1 and OAT3 transporters, with baicalin and oroxylin a as active ingredients.
Example 12
This example provides an intravenous injection for reducing mercury-induced nephrotoxicity by inhibiting OAT3 transporters, the active ingredient being geniposide.
Example 13
This example provides an intravenous injection for reducing mercury-induced renal toxicity by inhibiting OAT3 transporters, the active ingredient being chlorogenic acid.
Example 14
This example provides an intravenous injection for reducing mercury-induced nephrotoxicity by inhibiting OAT3 transporters, the active ingredients being geniposide and chlorogenic acid.
The above description is intended to be illustrative of the preferred embodiment of the present invention and should not be taken as limiting the invention, but rather, the invention is intended to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention.
Claims (9)
1. The application of the Shuganning injection in preparing the OATs inhibitor is characterized in that the OATs inhibitor is an inhibitor for inhibiting OAT1 and OAT3 transporters.
2. The application of the characteristic compound of the Shuganning injection in preparing the OATs inhibitor is characterized in that the characteristic compound is at least one of baicalin, oroxylin A, geniposide or chlorogenic acid, and the OATs inhibitor is an inhibitor for inhibiting OAT1 and/or OAT3 transporters.
3. A medicine for enhancing the curative effect of medicine excreted from kidney is characterized in that the active component of the medicine comprises at least one of baicalin, oroxylin A, geniposide and chlorogenic acid.
4. The medicament of claim 3, wherein the renally excreted drug comprises an antibiotic drug, a proton pump inhibitor, a statin, valsartan, rifampicin, and a renally excreted antineoplastic agent.
5. The drug according to claim 3, wherein when the active ingredient of the drug comprises at least one of baicalin and oroxylin A, the drug is a drug that inhibits OAT1 and/or OAT3 transporters.
6. The drug of claim 3, wherein the drug is a drug that inhibits the OAT3 transporter when the active ingredient of the drug comprises at least one of geniposide and chlorogenic acid.
7. A medicine for reducing renal toxicity caused by mercury is characterized in that the active ingredients of the medicine comprise at least one of baicalin, oroxylin A, geniposide and chlorogenic acid.
8. The agent for reducing mercury-induced renal toxicity according to claim 7, wherein when the active ingredient of the agent comprises at least one of baicalin and oroxylin A, the agent is an agent that inhibits OAT1 and/or OAT3 transporters.
9. The drug for reducing mercury-induced nephrotoxicity according to claim 7, wherein when the active ingredient of the drug includes at least one of geniposide and chlorogenic acid, the drug is a drug that inhibits OAT3 transporters.
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| CN105769998A (en) * | 2016-04-14 | 2016-07-20 | 佛山市科之康医药科技有限公司 | Application of Danhong injection as uptake type transporter OATP inhibitor |
Non-Patent Citations (2)
| Title |
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| 麻景梅等: "茵栀黄化学成分及药理作用研究进展", 《亚太传统医药》, vol. 17, no. 4, pages 202 - 206 * |
| 黄龙等: "舒肝宁注射液对于氯丙嗪引起的新型组织工程肝构建的胆汁淤积型药物性肝损伤模型的影响", 《临床肝胆病杂志》, vol. 38, no. 3, pages 587 - 593 * |
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