CN110882258A - Use of qi-tonifying pulse-restoring (freeze-dried) or ruscogenin for injection in preventing bleeding of drug-induced organ - Google Patents

Use of qi-tonifying pulse-restoring (freeze-dried) or ruscogenin for injection in preventing bleeding of drug-induced organ Download PDF

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CN110882258A
CN110882258A CN201911376667.0A CN201911376667A CN110882258A CN 110882258 A CN110882258 A CN 110882258A CN 201911376667 A CN201911376667 A CN 201911376667A CN 110882258 A CN110882258 A CN 110882258A
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ruscogenin
tonifying
injection
pulse
restoring
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寇俊萍
张媛媛
刘元恺
余伯阳
徐晗
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China Pharmaceutical University
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China Pharmaceutical University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents

Abstract

The invention discloses a new application of qi-tonifying pulse-restoring (freeze-drying) or ruscogenin for injection in preventing bleeding of drug-induced organs. The invention uses a dasatinib-induced gastrointestinal bleeding model of mice to verify the improvement effect of qi-tonifying pulse-restoring (freeze-drying) or ruscogenin for injection on dasatinib-induced gastrointestinal bleeding of mice. In addition, the invention also uses a dasatinib damage HUVEC cell model to verify the improvement effect of qi-tonifying pulse-restoring (freeze-drying) or ruscogenin for injection on cell permeability.

Description

Use of qi-tonifying pulse-restoring (freeze-dried) or ruscogenin for injection in preventing bleeding of drug-induced organ
Technical Field
The invention relates to the field of traditional Chinese medicine compound and natural medicines, in particular to qi-tonifying pulse-restoring (freeze-drying) or ruscogenin for injection for preventing side effects of bleeding of medicinal organs.
Background
Ruscogenin (RUS) is one of the main sapogenins and effective components in radix Ophiopogonis, also called Ruscus aculeatus sapogenin. Having significant Anti-inflammatory, Anti-thrombotic, Anti-tumoral, capillary permeability reducing, etc. (1) KouJ, Sun Y, Lin Y, et al, Anti-inflammatory Activities of Aqueous Extract from radial optics and Its Two Constants [ J ]. Biol phase bulb.2005, 28(7) 1234. quadrature. 1238.(2) Cheng ZH, Wu T, Yu BY. Steroidal carbohydrates from radial optics [ J ]. J. Asian Nat Prod. Res.2006,8(6) Bu. 9.(3) Kou J, TianY, Tang Y. Anti-inflammatory Activities of Aqueous Extract from radial optics and J. 9. J. Japan fibers, J. Ash. Press, J. 10. J. Ash. Press, J. 10. 9. 3) Kou J, Tian Y. blue, 9. J. biological Extract of capillary permeability, et al, J. Press, J. 10. J. 12. J. supplement, J. 10. J. 7. J. supplement, J. 7. J. 12. J. 7. J. ethanol, J. 12. ethanol, J. 12. ethanol, J. ethanol, K. 10. supplement, K. 7. ethanol, J. ethanol, 2. ethanol, J. ethanol, 2. ethanol, ethanol, the study of the mechanism of action of Russian ruscogenin on human lung cancer A549 and H460 cells [ D ] Nanjing: Nanjing university of medicine 2014, (7) Wang Kui-Wu, zhang hong, shann lianqing, et al. novel steroid front wall medicine mineral (Linn.) Baker anti-tissue-tissues, BOBODRATE RESET ARCH.2011,346(2): 258). Dasatinib is usually associated with hemorrhagic complications, phosphorylates MLC through ROCK pathway, induces F-actin structure to generate polymerization phenomenon, and leads cytoskeleton to be reconstructed; dasatinib induces the VE-cadherin structure among endothelial cells to change, increases the permeability of the endothelial cells, causes vascular leakage, and has side effects of gastrointestinal bleeding and the like. Dasatinib induces cytoskeletal remodeling through the RhoA-ROCK pathway, increases pulmonary microvascular permeability, induces side effects such as pleural effusion ((8) Dasatinib recurring systemic vascular remodeling sub-polypeptide interaction by sub-capillary occlusion non-cardiac muscular interaction in ROCK-dependent manager [ J ]. Clin Cancer Res,2017,23(21): 6697. quadrature 6707.(9) Dasguat SK, Le A, Vijayan KV, et al.Dasatinib inhibitory interaction in fibrous differentiation and proteins intestinal permeability of cellular metabolism A-ROCK [ J ]. Cancer, 2017,6(4): 10. branched polypeptide J, 9. branched polypeptide J. (III, III. J.) (III, III. F.), 2018,51(1)). Blood is the balance of qi, qi deficiency can cause blood circulation disorder, and can cause high permeability of blood capillaries, resulting in bleeding, deficiency of qi, and weakened physiological function of governing blood, and blood flows out after leaving channels, and then flows out in stomach and intestine, i.e. hematochezia. In treatment, the function of the whole body is recovered by a method of tonifying qi and invigorating qi, thereby achieving the purpose of stopping bleeding. The qi-tonifying and pulse-restoring injection (freeze-drying) is a freeze-dried powder injection prepared according to the classic famous prescription 'pulse-restoring powder', and consists of three medicines of red ginseng, dwarf lilyturf tuber and Chinese magnoliavine fruit, the formula has the efficacies of tonifying qi and blood and tonifying qi and pulse, is a representative prescription for treating deficiency of both qi and yin, is clinically used for treating cardiovascular diseases and angina pectoris with deficiency of both qi and yin, and has obvious curative effects ((12) Han JY, Li Q, MaZZ, et al effects and mechanisms of complex Chinese medicine and major in deficiency of both qi and yin on microcirculation dynamics function and organ in deficiency of both qi and yin [ J ]. Pharmacol 146, 2017,177: 173.(13) is aligned with the east of qi-tonifying and blood bias formula [ J ]. Zhonghua health-preserving, 13-13.(14) and Sun Zong blood organ protection [ J ] (2011.: clinical research [ J ] (9323, J.: clinical protection of qi-activating effect [ J ] of traditional Chinese medicine [ 10 ] for protecting blood organ.
Disclosure of Invention
The invention discloses a medical application of qi-tonifying pulse-restoring (freeze-drying) or ruscogenin for injection.
The invention relates to a qi-tonifying pulse-restoring (freeze-drying) injection product of pharmaceutical industry Limited company of Tianjin Tianshi power, and the approval document is the Chinese medicine standard Z20060463.
The Ruscogenin provided by the invention is (25R) -Ruscogenin shown as the following formula:
Figure BDA0002341168430000021
the invention discloses an application of qi-tonifying pulse-restoring (freeze-drying) or ruscogenin for injection in preparing a medicament for preventing and/or treating organ bleeding caused by medicament.
In one embodiment, the invention discloses the use of injectable qi-tonifying pulse-restoring (lyophilized) or ruscogenin in the preparation of a medicament for the prevention and/or treatment of non-steroidal anti-inflammatory drug-induced liver, brain, kidney, spleen, lung or gastrointestinal tract bleeding.
In one embodiment, the invention discloses the use of qi-tonifying pulse-restoring (lyophilized) or ruscogenin for injection in the preparation of a medicament for the prevention and/or treatment of antithrombotic-induced liver, brain, kidney, spleen, lung or gastrointestinal bleeding.
In one embodiment, the invention discloses the use of qi-tonifying pulse-restoring (lyophilized) or ruscogenin for injection in the preparation of a medicament for the prevention and/or treatment of chemotherapy-induced liver, brain, kidney, spleen, lung or gastrointestinal bleeding.
In one embodiment, the invention discloses the use of qi-tonifying pulse-restoring (lyophilized) or ruscogenin for injection in the preparation of a medicament for the prevention and/or treatment of antibacterial-induced liver, brain, kidney, spleen, lung, gastrointestinal bleeding.
In one embodiment, the invention discloses the use of qi-tonifying pulse-restoring (lyophilized) or ruscogenin for injection in the preparation of a medicament for preventing and/or treating antidepressant-induced liver, brain, kidney, spleen, lung, gastrointestinal tract bleeding.
In one embodiment, the invention discloses the use of qi-tonifying pulse-restoring (lyophilized) or ruscogenin for injection in the preparation of a medicament for the prevention and/or treatment of corticosteroid-induced liver, brain, kidney, spleen, lung, gastrointestinal bleeding.
In one embodiment, the invention discloses the use of qi-tonifying pulse-restoring (lyophilized) or ruscogenin for injection in the preparation of a medicament for the prevention and/or treatment of immunosuppressant-induced liver, brain, kidney, spleen, lung, gastrointestinal bleeding.
In one embodiment, the invention discloses the use of qi-tonifying pulse-restoring (lyophilized) or ruscogenin for injection in the preparation of a medicament for the prevention and/or treatment of mycophenolate mofetil-induced liver, brain, kidney, spleen, lung, gastrointestinal bleeding.
In a specific embodiment, the invention discloses the use of qi-tonifying pulse-restoring (lyophilized) or ruscogenin for injection in the preparation of a medicament for preventing and/or treating dasatinib-induced liver, brain, kidney, spleen, lung, gastrointestinal bleeding.
In a specific embodiment, the invention discloses the use of qi-tonifying pulse-restoring (lyophilized) or ruscogenin for injection in the preparation of a medicament for preventing and/or treating dasatinib-induced gastrointestinal bleeding or intestinal barrier disruption.
In a specific embodiment, the invention discloses the use of qi-tonifying pulse-restoring (lyophilized) or ruscogenin for injection in the preparation of a medicament for preventing and/or treating dasatinib-induced barrier disruption of human umbilical vein endothelial cells.
Studies show that dasatinib phosphorylates MLC through ROCK pathway, polymerization of F-actin structure is induced, cytoskeleton is reconstructed, permeability of endothelial cells is increased, and vascular leakage is caused, so that side effects such as gastrointestinal bleeding are induced, but no slow-release method is found at present. The invention uses a dasatinib-induced gastrointestinal bleeding model of mice to verify the improvement effect of qi-tonifying pulse-restoring (freeze-drying) or ruscogenin for injection on dasatinib-induced gastrointestinal bleeding of mice. In addition, the invention also uses a dasatinib-damaged HUVC cell model to verify the improvement effect of qi-tonifying pulse-restoring (freeze-drying) or ruscogenin for injection on cytoskeleton and permeability.
The improvement effect of qi-tonifying pulse-restoring injection (lyophilized) and its active ingredient (ruscogenin) on the dasatinib-induced gastrointestinal bleeding of mice is further described below with reference to the examples.
Drawings
FIG. 1 is a graph of the effects of Qi-tonifying pulse-recovering (lyophilized) for injection and on the rate of Evans blue leakage in Dasatinib-induced mouse intestinal tissue (R) ((R))
Figure BDA0002341168430000041
n=6)。##P<0.01vs. blank set; p<0.01vs. model set.
FIG. 2 Effect of ruscogenin on the Dasatinib-induced Evans blue leakage Rate in mouse intestinal tissue ((R))
Figure BDA0002341168430000042
n=6)。##P<0.01vs. blank set; p<0.01vs. model set.
FIG. 3 the effect of Qi-tonifying and pulse-recovering (lyophilized) for injection on Dasatinib-induced intestinal blood flow in mice ((lyophilized))
Figure BDA0002341168430000043
n=6)。##P<0.01vs. blank set; p<0.01vs. model set.
FIG. 4 Effect of ruscogenin on Dasatinib-induced intestinal blood flow in mice (C)
Figure BDA0002341168430000044
n=6)。##P<0.01vs. blank set; p<0.01vs. model set.
FIG. 5 is a graph showing the effect of qi-tonifying pulse-restoring (lyophilized) for injection on the induction of pathological structures of mouse small intestine tissue by dasatinib.
FIG. 6 Effect of ruscogenin on Dasatinib-induced pathological structure of mouse small intestine tissue.
FIG. 7 is a graph showing the effect of qi-tonifying and pulse-restoring (lyophilized) for injection on the content of D-lactic acid in serum of Dasatinib-induced mice ((
Figure BDA0002341168430000045
Figure BDA0002341168430000046
n=6)。##P<0.01vs. blank set; p<0.01vs. model set.
FIG. 8 Effect of ruscogenin on the content of D-lactic acid in Dasatinib-induced mouse serum ((
Figure BDA0002341168430000047
n=6)。##P<0.01vs. blank set; p<0.01vs. model set.
FIG. 9 the effect of Qi-tonifying pulse-restoring (lyophilized) for injection on the content of ALT and AST in serum of mice induced by dasatinib ((
Figure BDA0002341168430000048
n=6)。##P<0.01vs. blank set;**P<0.01vs. model set.
FIG. 10 Effect of ruscogenin dasatinib on the induction of serum ALT, AST levels in mice ((
Figure BDA0002341168430000049
n=6)。##P<0.01vs. blank set; p<0.01vs. model set.
FIG. 11 Effect of Qi-tonifying Fumai (Freeze-drying) for injection on Dasatinib-induced human umbilical vein endothelial cell barrier: (
Figure BDA00023411684300000410
n=6)。##P<0.01vs. blank set; p<0.01vs. model set.
FIG. 12 Effect of ruscogenin on Dasatinib-induced human umbilical vein endothelial cell barrier: (
Figure BDA00023411684300000411
n=6)。##P<0.01vs. blank set; p<0.01vs. model set.
Detailed Description
The present invention will be further described with reference to the following examples, which are intended to illustrate the present invention and not to limit the scope of the present invention, and all simple modifications of the preparation method of the present invention based on the idea of the present invention are within the scope of the present invention. The following examples are experimental methods without specifying specific conditions, and generally follow the methods known in the art. The test materials used in the following examples were purchased from a conventional biochemical reagent store unless otherwise specified.
YQFM in the embodiment of the invention refers to qi-tonifying and pulse-restoring for injection (freeze-drying), is a product of Jiaozi pharmaceutical industry Co., Ltd, of Tianjin Tianshi power, and has an approval document number of Chinese medicine standard Z20060463.
The RUS in the embodiment of the invention refers to Ruscogenin, which is (25R) -Ruscogenin shown in the formula:
Figure BDA0002341168430000051
example 1
The qi-tonifying pulse-restoring (freeze-drying) for injection and the active component (ruscogenin) thereof have the improvement effect on the mice gastrointestinal bleeding induced by dasatinib.
The experimental method comprises the following steps:
a) laboratory animal
The experimental animals are C57BL/6J mice, the weight is 18-22g, the SPF grade, and the experimental animals are purchased from the comparative medicine center of Yangzhou university and meet the quality standard of common experimental animals. License number: SCXK (Su) 2012-0001. Mice are raised in cages, water is freely fed, the room temperature of the raising is 23-25 ℃, the relative humidity is 40% -80%, and the experiment is started after the mice are raised adaptively for about one week.
b) Preparation of experimental medicine
Weighing 33.6mg of YQFM, adding 1mL of physiological saline solution, and fully dissolving to obtain the low-dose group drug concentration; weighing 67.1mg of YQFM, adding 1mL of physiological saline solution, and fully dissolving to obtain the concentration of the medium-dose group medicament; 134.2mg of YQFM was weighed and added to 1mL of physiological saline solution to dissolve it sufficiently, which is the high dose group drug concentration. Weighing 1mg of ruscogenin monomer, dissolving in 10ml of 5% ethanol solution, and diluting to required dosage. Accurately weighing 35mg of Evans blue solid, dissolving the Evans blue solid in 7mL of medical physiological saline, and storing the tinfoil paper in a refrigerator at 4 ℃ in a dark place for later use. 49mg of dasatinib is accurately weighed, dissolved in 50 mu L of DMSO, added with 7mL of olive oil, uniformly mixed, and then the tinfoil paper is stored in a refrigerator at 4 ℃ in a dark place.
c) Influence of qi-tonifying pulse-restoring (freeze-drying) and ruscogenin for injection on Evans blue leakage rate of small intestine tissues of mice induced by dasatinib
The mice were divided into 5 groups including control group, model group, and YQFM (or RUS) group at three different doses. The control group was given the same volume of saline corresponding to the time point of intraperitoneal injection of the drug (YQFM or RUS) during the experiment, which was 1h before the 3d intraperitoneal injection of dasatinib (ip) continuously. On the third day, the mice of each group were injected with 70mg/kg dasatinib intraperitoneally for 0.5h, then 5mg/mL evans blue solution was injected into the tail vein, the mice were anesthetized after 2h, and 0.9% physiological saline was perfused into the heart until the mice were washed out. Taking a small intestine of 6cm, drying the small intestine by a filter paper, weighing the small intestine, placing the small intestine in liquid nitrogen for quick freezing, and performing quick freezing according to the ratio of 100mg of intestinal tissue: homogenizing with 1mL formamide, transferring to 1.5mL EP tube, incubating at 60 deg.C for 18h, centrifuging for 30min, collecting supernatant, measuring absorbance at 620nm with microplate reader, and calculating content according to Evans blue standard curve.
The experimental results are as follows:
FIG. 1 is a graph showing the effect of qi-tonifying pulse-restoring (lyophilized) for injection on the rate of evans blue leakage in small intestine tissue of dasatinib-induced mice; FIG. 2 is a graph of the effect of ruscogenin on the rate of evans blue leakage in dasatinib-induced mouse small intestine tissue; FIG. 3 is a graph showing the effect of qi-tonifying pulse-restoring (lyophilized) for injection on Dasatinib-induced small intestinal blood flow in mice; FIG. 4 is a graph of the effect of ruscogenin on Dasatinib-induced mouse small intestinal blood flow; FIG. 5 shows the effect of qi-tonifying and pulse-restoring (lyophilized) for injection on the pathological structure of small intestine tissue of Dasatinib-induced mice; FIG. 6 Effect of ruscogenin on Dasatinib-induced pathological structure of mouse small intestine tissue; FIG. 7 is a graph showing the effect of qi-tonifying and pulse-restoring (freeze-drying) for injection on the content of D-lactic acid in serum of Dasatinib-induced mice; FIG. 8 the effect of ruscogenin on the content of D-lactic acid in serum of mice induced by intraperitoneal injection of dasatinib; FIG. 9 shows the effect of injection for invigorating qi and recovering pulse (lyophilized) on the content of ALT and AST in serum of mice induced by dasatinib; FIG. 10 influence of ruscogenin on the serum ALT and AST content of mice induced by intraperitoneal injection of dasatinib.
The above experimental results show that: the qi-tonifying pulse-restoring (freeze-drying) injection and the effective component ruscogenin thereof can improve the decrease of intestinal blood flow, the damage of intestinal barrier and the intestinal bleeding caused by dasatinib, and remarkably reduce the contents of D-lactic acid, ALT and AST.
Example 2
Research on the effect of improving the barrier damage of Dasatinib-induced human umbilical vein endothelial cells by injecting qi-tonifying pulse-restoring (freeze-drying) and the effective component ruscogenin thereof.
The experimental method comprises the following steps:
a) cell culture: after HUVECs were recovered, they were cultured in 10% FBS RPMI 1640 medium. After the cells reached about 90% full, the medium was discarded and rinsed with PBS. 0.25% trypsin solution was added to the cells at 37 ℃ and the cells were digested in an incubator, microscopically observed to become round, and then the digestion solution was discarded and the digestion was stopped by adding 10% FBS-containing RPMI 1640 culture solution. The cells were blown down and transferred to a centrifuge tube and collected by centrifugation. The supernatant was discarded, and 10% FBS-containing RPMI 1640 culture medium was added to blow out a cell suspension, which was then subcultured on a new cell culture dish at 37 ℃ in a 5% CO2 incubator.
b) Transendothelial cell resistance assay: HUVECs cells 200. mu.l (3-5X 10)4One/hole) is connected into a Millicell suspended culture chamber (0.4 mu m), 600 mu l of complete culture medium is added into a 24-hole plate of an outer chamber, the complete culture medium is placed into a CO2 incubator for culture, the resistance value is measured after the cells are planted for 2h and the wall is attached, the resistance value is measured once at a fixed time point every day, and the liquid is changed every other day. Culturing at 37 deg.C under 5% CO2 for 7d, and culturing for 1-2h before experiment.
Grouping experiments:
(a) and (4) adding serum-free DMEM medium into the chamber of the blank control group for 2 hours.
(b) Building a model, adding dasatinib (final concentration of 150nM) into the chamber for 2 h.
(c) Dosing groups, chamber YQFM (RUS) for 1h and 150nM dasatinib for 2 h. After the completion, the cells were removed to determine the TEER value.
The resistance measurement procedure was as follows:
(a) and (3) correcting the resistance meter: and inserting a standard resistance electrode into the click hole, placing the mode in an ohmic gear, turning on a power supply, adjusting the meter to enable the reading to be 1000 omega, and normally not needing to be adjusted.
(b) Electrode sterilization: the measuring electrode is immersed in 75% ethanol for sterilization for 15min before use, and then placed in a clean bench for natural air drying, and the electrode is washed by culture solution.
(c) And (3) resistance measurement: the instrument mode is set in the ohm gear, and the power supply is turned on. The measuring electrode is inserted into the Millicell culture chamber to be measured, the long electrode is on the outside, the short electrode is on the inside, the electrode needs to be perpendicular to the culture dish, and the value is recorded after the reading is stable. The resistance per unit area (sample pore resistance-blank pore resistance) x effective membrane area.
The experimental results are as follows:
FIG. 11 the effect of Qi-tonifying resuscitator (lyophilized) for injection on Dasatinib-induced human umbilical vein endothelial cell barrier; FIG. 12 Effect of ruscogenin on Dasatinib-induced human umbilical vein endothelial cell barrier.
The above experimental results show that: the qi-tonifying pulse-restoring (freeze-drying) injection and the ruscogenin serving as an active ingredient thereof can improve the reduction of HUVECs permeability caused by dasatinib and play a role in protecting endothelial cells. Provides experimental basis for the qi-tonifying pulse-restoring (freeze-drying) for injection and the effective component ruscogenin thereof for preventing and treating the side effect of dasatinib, and provides pharmacological data for the clinical application and the secondary development of the dasatinib.

Claims (6)

1. The application of qi-tonifying pulse-restoring or ruscogenin for injection in preparing medicines for preventing and/or treating organ bleeding caused by medicament.
2. The use according to claim 1, wherein the Ruscogenin is (25R) -Ruscogenin of the following structural formula,
Figure FDA0002341168420000011
3. the application of qi-tonifying pulse-restoring or ruscogenin for injection in preparing medicines for preventing and/or treating non-steroidal anti-inflammatory drugs, antithrombotic drugs, chemotherapeutic drugs, antibacterial drugs, antidepressants, corticosteroids, immunosuppressive agents or mycophenolate mofetil-induced liver, brain, kidney, spleen, lung and gastrointestinal tract bleeding.
4. The application of qi-tonifying pulse-restoring or ruscogenin for injection in preparing medicines for preventing and/or treating liver, brain, kidney, spleen, lung and gastrointestinal bleeding induced by dasatinib.
5. The application of qi-tonifying pulse-restoring or ruscogenin for injection in preparing medicines for preventing and/or treating dasatinib-induced gastrointestinal bleeding or intestinal barrier disruption.
6. The application of qi-tonifying pulse-restoring or ruscogenin for injection in preparing a medicament for preventing and/or treating dasatinib-induced human umbilical vein endothelial cell barrier damage.
CN201911376667.0A 2019-12-27 2019-12-27 Use of qi-tonifying pulse-restoring (freeze-dried) or ruscogenin for injection in preventing bleeding of drug-induced organ Pending CN110882258A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110934878A (en) * 2019-12-30 2020-03-31 中国药科大学 Ruscogenin for preventing and treating PM2.5Medical application of body organ injury caused by
CN112843070A (en) * 2021-03-26 2021-05-28 中国药科大学 Application of ruscogenin in preparing medicine for preventing and treating cerebral hemorrhage

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Publication number Priority date Publication date Assignee Title
CN1878529A (en) * 2003-11-11 2006-12-13 若维有限公司化妆品原材料两合公司 Combined cosmetic or therapeutic preparation
CN101926931A (en) * 2009-06-24 2010-12-29 天津天士力制药股份有限公司 Application of qi-tonifying and pulse-restoring preparation in preparing medicine for treating shock and intestinal canal damage caused by endotoxin
CN107158007A (en) * 2017-05-23 2017-09-15 中国药科大学 Application of the ruscogenin isomers in medicine is prepared

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1878529A (en) * 2003-11-11 2006-12-13 若维有限公司化妆品原材料两合公司 Combined cosmetic or therapeutic preparation
CN101926931A (en) * 2009-06-24 2010-12-29 天津天士力制药股份有限公司 Application of qi-tonifying and pulse-restoring preparation in preparing medicine for treating shock and intestinal canal damage caused by endotoxin
CN107158007A (en) * 2017-05-23 2017-09-15 中国药科大学 Application of the ruscogenin isomers in medicine is prepared

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110934878A (en) * 2019-12-30 2020-03-31 中国药科大学 Ruscogenin for preventing and treating PM2.5Medical application of body organ injury caused by
CN110934878B (en) * 2019-12-30 2022-03-01 中国药科大学 Ruscogenin for preventing and treating PM2.5Medical application of body organ injury caused by
CN112843070A (en) * 2021-03-26 2021-05-28 中国药科大学 Application of ruscogenin in preparing medicine for preventing and treating cerebral hemorrhage

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Application publication date: 20200317