CN109260194A - Praeruptorin A is alleviating the application in anti-tumor drug Nephrotoxicity Caused By Cisplatin - Google Patents
Praeruptorin A is alleviating the application in anti-tumor drug Nephrotoxicity Caused By Cisplatin Download PDFInfo
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- CN109260194A CN109260194A CN201811091172.9A CN201811091172A CN109260194A CN 109260194 A CN109260194 A CN 109260194A CN 201811091172 A CN201811091172 A CN 201811091172A CN 109260194 A CN109260194 A CN 109260194A
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- Prior art keywords
- praeruptorin
- cisplatin
- cis
- platinum
- cell
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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
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
-
- 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
Abstract
The invention discloses praeruptorin As to alleviate the application in anti-tumor drug Nephrotoxicity Caused By Cisplatin.Cis-platinum is considered as efficient, the broad-spectrum anti-cancer drug for treating solid tumor, is widely used in the treatment of the tumours such as cellule and non-small cell lung cancer, carcinoma of testis, oophoroma, cervical carcinoma.But cis-platinum can cause the adverse reaction of multiple histoorgans, common are kidney, liver, digestive system, hemopoietic system, ear, neurotoxicity, allergic reaction, wherein Toxicity of Kidney is adverse reaction the most serious, and at dose dependent.It is a discovery of the invention that the toxic damages of cisplatin on human renal proximal tubular cell strain HK-2 cell can be effectively relieved in praeruptorin A, therefore, praeruptorin A is expected to develop into the drug for alleviating Nephrotoxicity Caused By Cisplatin.
Description
Technical field
The invention belongs to field of medicaments, are related to the new application of known compound, and in particular to praeruptorin A is being alleviated
Application in anti-tumor drug Nephrotoxicity Caused By Cisplatin.
Background technique
Cis-platinum is to be chanced in nineteen sixty-five by American scientist Rosenberg et al..The medicine is used for clinical treatment cancer certainly
Since disease, it is considered to be efficient, the broad-spectrum anti-cancer drug for treating solid tumor are widely used in cellule and non-small cell lung cancer, testis
The treatment of the tumours such as ball cancer, oophoroma, cervical carcinoma.However though cis-platinum is clinically used widely, it is tight there are two
High problem: first is that acquired resistance, second is that tissue or organ toxicity.Cis-platinum can cause the bad anti-of multiple tissues (organ)
It answers, common are kidney, liver, digestive system, hemopoietic system, ear, neurotoxicity, allergic reaction, wherein Toxicity of Kidney is most
For serious adverse reaction, and at dose dependent.
Therefore, it is necessary to develop the drug for alleviating anti-tumor drug Nephrotoxicity Caused By Cisplatin.
Summary of the invention
It is suitable in alleviation anti-tumor drug that it is an object of the invention to overcome the deficiencies of the prior art and provide praeruptorin As
Application in platinum Nephrotoxicity Caused.
Above-mentioned purpose of the present invention is achieved through the following technical solutions:
Application of the praeruptorin A in the drug that anti-tumor drug Nephrotoxicity Caused By Cisplatin is alleviated in preparation.
It is a kind of for alleviating the pharmaceutical preparation of anti-tumor drug Nephrotoxicity Caused By Cisplatin, active constituent is Praeruptorin A B C D
Pharmaceutically acceptable dosage form is made also containing pharmaceutically acceptable carrier or excipient in element.
Further, the carrier or excipient are solid or Auxiliary Liquid Material.
Further, the dosage form is tablet, pill, paste, capsule, injection or oral solution.
The utility model has the advantages that
It is a discovery of the invention that cisplatin on human renal proximal tubular cell strain HK-2 cell can be effectively relieved in praeruptorin A
Toxic damages, therefore, praeruptorin A are expected to develop into the drug for alleviating Nephrotoxicity Caused By Cisplatin.
Detailed description of the invention
Fig. 1 is cis-platinum group concentration when being 10 μM, and the HK-2 cell survival rate of each group compares;
Fig. 2 is cis-platinum group concentration when being 20 μM, and the HK-2 cell survival rate of each group compares.
Specific embodiment
It is specific with reference to the accompanying drawings and examples to introduce essentiality content of the present invention, but guarantor of the invention is not limited with this
Protect range.
One, experimental material
People renal proximal tubular cell strain HK-2 is given by China Medicine University's pharmacokinetics experiment room.DMEM/F12
Purchased from the biological store of thickness hundred, fetal calf serum (FBS) is raw purchased from Nanjing good fortune Mace for basal medium and 0.25% pancreatin containing EDTA
Object Technology Co., Ltd. (article No. 04-001-1ACS), CCK-8 kit are purchased from green skies Bioisystech Co., Ltd (article No.
C0039), praeruptorin A (CAS 73069-25-7) is purchased from Chengdu Rui Fensi Biotechnology Co., Ltd.
Two, experimental method
1, cell culture
The strain HK-2 cell culture of people's renal proximal tubular cell contains 5%CO at 37 DEG C2Incubator in, culture solution 89%
DMEM/F12 basal medium, 10% fetal calf serum (FBS) and 1% are dual anti-.Cell is grown in 25cm culture bottle, is replaced within 2 days
Culture medium is primary, is passed on when cell grows to 90% fusion.
2, it makes up a prescription, modeling, grouping, administration, measurement
2.1 prepare the cis-platinum culture solution containing series of concentrations
Cis-platinum powder 1mg is weighed, PBS1mL, 60 DEG C of water-bath hydrotropies are added.Filtration sterilization, -20 DEG C are kept in dark place, and obtain female
Liquid, with the cell culture fluid of the mother liquor series of concentrations cis-platinum, making final concentration is respectively 10,20 μM.
2.2 prepare the praeruptorin A solution containing series of concentrations
It weighs praeruptorin A to be dissolved in dimethyl sulfoxide, the monomer mother liquor of 50mM is made, 4 DEG C are kept in dark place.Face use
Before, taking appropriate mother liquor culture medium dilution to be configured to praeruptorin A concentration is 40,80 μM.
2.3 modelings, grouping, administration, measurement
The HK-2 cell of logarithmic growth phase collects cell after 0.25% trypsin digestion, is inoculated in the training of 96 hole cells
Support plate, every hole about 5.0 × 104A cell, if the treatment of blank group, control group, cis-platinum group and praeruptorin A combination cis-platinum
Group, wherein blank group not inoculating cell, every group of 3-6 multiple holes.After cell is adherent, inhales and abandon old culture medium, blank group and control
Group still gives conventional medium, and cis-platinum group changes the culture medium containing 10,20 μM of concentration cis-platinums into, and praeruptorin A combination is suitable
The treatment group of platinum changes the culture medium containing 10,20 μM of cis-platinums of 40,80 μM of praeruptorin As and concentration into, continues to cultivate 48h, change
Culture medium containing 10%WST-8 measures absorbance value under 450nm wavelength after incubator is incubated for 2h.It is thin by the measurement of WST-8 method
Born of the same parents' survival rate, i.e. cell survival rate (%)=(administration group-blank group)/(control group-blank group) × 100%.
2.4 data processing
All data are indicated with means standard deviation, are imported data to GraphPadPrism data processing software, are used bilateral
Non-paired t test statistical discrepancy, whether the praeruptorin A for comparing various concentration, which can improve HK-2 cell caused by cis-platinum, is deposited
Motility rate reduces.P < 0.05 is significant difference.
Three, experimental result
Compared with the control group, the cis-platinum of 10 μM of concentration significantly reduces the survival rate of HK-2 cell, p < 0.0001, with * * * * table
Show.Compared with cis-platinum group, after 40 μM and 80 μM of praeruptorin As combination cis-platinums, the survival rate of HK-2 cell, p can be significantly improved
< 0.0001, it is indicated with ####.As a result as shown in table 1 and Fig. 1.
When 1 cis-platinum group concentration of table is 10 μM, the HK-2 cell survival rate of each group compares
Compared with the control group, the cis-platinum of 20 μM of concentration significantly reduces the survival rate of HK-2 cell, p < 0.0001, with * * * * table
Show.Compared with cis-platinum group, after 40 μM and 80 μM of praeruptorin As combination cis-platinums, the survival rate of HK-2 cell, p can be significantly improved
< 0.0001, it is indicated with ####.As a result as shown in table 2 and figure 2.
When 2 cis-platinum group concentration of table is 20 μM, the HK-2 cell survival rate of each group compares
The above results show that cisplatin on human renal proximal tubular cell strain HK-2 cell can be effectively relieved in praeruptorin A
Toxic damages, therefore, praeruptorin A is expected to develop into the drug for alleviating Nephrotoxicity Caused By Cisplatin.
The effect of above-described embodiment is specifically to introduce essentiality content of the invention, but those skilled in the art should know
Protection scope of the present invention should not be confined to the specific embodiment by road.
Claims (4)
1. application of the praeruptorin A in the drug that anti-tumor drug Nephrotoxicity Caused By Cisplatin is alleviated in preparation.
2. a kind of for alleviating the pharmaceutical preparation of anti-tumor drug Nephrotoxicity Caused By Cisplatin, it is characterised in that: active constituent is white
Pharmaceutically acceptable dosage form is made also containing pharmaceutically acceptable carrier or excipient in flower dl-Praeruptorin A.
3. pharmaceutical preparation according to claim 2, it is characterised in that: the carrier or excipient are auxiliary for solid or liquid
Material.
4. pharmaceutical preparation according to claim 2, it is characterised in that: the dosage form is tablet, pill, paste, capsule, note
Penetrate agent or oral solution.
Priority Applications (1)
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CN201811091172.9A CN109260194B (en) | 2018-09-19 | 2018-09-19 | Application of praeruptorin A in preparation of medicine for relieving nephrotoxicity caused by antitumor drug cisplatin |
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CN201811091172.9A CN109260194B (en) | 2018-09-19 | 2018-09-19 | Application of praeruptorin A in preparation of medicine for relieving nephrotoxicity caused by antitumor drug cisplatin |
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CN109260194B CN109260194B (en) | 2021-03-02 |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111281956A (en) * | 2020-04-07 | 2020-06-16 | 中南民族大学 | Application of Uyghur medicine compound clinical application in preparation of medicine for relieving kidney injury caused by cisplatin |
-
2018
- 2018-09-19 CN CN201811091172.9A patent/CN109260194B/en active Active
Non-Patent Citations (3)
Title |
---|
PENG-JIU YU等: "Praeruptorin A Inhibits Lipopolysaccharide-induced Inflammatory Response in Murine Macrophages through Inhibition of NF-kB Pathway Activation", 《PHYTOTHERAPY RESEARCH》 * |
张森: "圆锥绣球提取物总香豆素苷治疗急慢性肾损伤的药效和作用机制研究", 《中国博士学位论文全文数据库 医药卫生科技辑》 * |
邱清华: "白花前胡甲素通过调控Bcl-2/Bax、Caspase9、Caspase3的表达对大鼠缺血再灌注的保护作用", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111281956A (en) * | 2020-04-07 | 2020-06-16 | 中南民族大学 | Application of Uyghur medicine compound clinical application in preparation of medicine for relieving kidney injury caused by cisplatin |
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