CN117257803A - Application of lurasidone in preparation of drugs for treating or preventing ischemia/reperfusion injury and cytoprotective drugs - Google Patents
Application of lurasidone in preparation of drugs for treating or preventing ischemia/reperfusion injury and cytoprotective drugs Download PDFInfo
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- CN117257803A CN117257803A CN202210671569.5A CN202210671569A CN117257803A CN 117257803 A CN117257803 A CN 117257803A CN 202210671569 A CN202210671569 A CN 202210671569A CN 117257803 A CN117257803 A CN 117257803A
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- ischemia
- reperfusion injury
- lurasidone
- myocardial
- reperfusion
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Classifications
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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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to application of lurasidone in preparing a medicament for treating or preventing ischemia/reperfusion injury and a cytoprotective medicament. The invention discovers that lurasidone can obviously reduce myocardial infarction dead area and cerebral infarction volume, reduce serum creatine kinase activity, improve neurological functions, reduce myocardial cell and nerve cell death, has myocardial cell and nerve cell protection effect, and can be used for treating or preventing myocardial infarction and ischemic cerebral apoplexy.
Description
Technical Field
The invention relates to application of lurasidone (lurasidone) in preparing a medicament for treating or preventing ischemia/reperfusion injury and a cytoprotective medicament, and belongs to the field of biological medicines. The invention provides a new application and an administration mode of lurasidone, which comprise the effects of resisting heart and brain ischemia/reperfusion injury (especially myocardial infarction and ischemic cerebral apoplexy), relieving heart and brain ischemia/reperfusion injury and expanding the indication range of lurasidone.
Background
Myocardial infarction is mainly caused by ischemia and hypoxia of myocardial cells due to heart ischemia, and can cause irreversible damage of the myocardial cells. Cerebral infarction, also called ischemic stroke, is a disorder of blood supply to local brain tissue caused by various causes, resulting in ischemia, hypoxic necrosis, and loss of nerve function in the brain tissue. Ischemic stroke is a common and frequently-occurring disease seriously jeopardizing human health, and has become the first disabling and third lethal cause worldwide, and the incidence of ischemic stroke accounts for about 80% of cerebrovascular diseases.
One of the main measures of infarct therapy is to restore the infarcted tissue perfusion blood supply as soon as possible, but reperfusion therapy is often accompanied by some tissue damage. The damage caused by ischemia and reperfusion is referred to as "ischemia/reperfusion (I/R) damage". I/R injury involves multiple mechanisms such as energy metabolism disorder, calcium overload, oxidative stress, inflammatory reaction, etc., which lead to multiple death modes such as apoptosis and necrosis of cells. Research shows that the medicine can inhibit apoptosis and/or necrosis, inhibit myocardial cell and nerve cell death caused by ischemia/reperfusion, reduce the damage degree of heart and brain ischemia/reperfusion, and reduce the infarct range.
Necrosis-like apoptosis is a caspase-independent regulated cell necrosis pattern, mediated primarily by Receptor-interacting protein kinase (Receptor-interacting protein kinase, RIPK) 1, RIPK3 and mixed junction kinase domain-like protein (mixed lineage kinase domain-like, MLKL). Necrosis-like apoptosis is closely related to various cardiovascular and cerebrovascular diseases, such as heart and brain ischemia/reperfusion injury, heart failure, drug-induced myocardial toxicity, atherosclerosis, liver and kidney injury, neurodegenerative diseases, etc. Thus, inhibition of RIPK1/RIPK 3/MLKL-dependent necrosis-like apoptosis may inhibit or reduce cell death and tissue damage resulting from the above-mentioned diseases. The literature reports that the RIPK1 inhibitor, namely, the nestin-1 (Nec-1), can reduce ischemia/reperfusion injury of heart, brain, liver, kidney and the like of mice. However, nec-1 is only used as a tool medicine for animal experiments, and no clinical treatment aiming at RIPK1/RIPK3/MLKL is currently available.
Lurasidone (Lurasidone, trade name Latuda) is an atypical antipsychotic which antagonizes dopamine D2 and 5-hydroxytryptamine 2A (5-HT 2A) receptors and is useful in the treatment of schizophrenic patients, but no anti-ischemic/reperfusion injury has been reported.
In the present invention, unless otherwise indicated, "lurasidone" is understood to mean "one of a compound of lurasidone or a semisynthetic derivative thereof or one of their salts (salts of a compound or salts of semisynthetic derivatives) or one of their esters (esters of a compound or esters of semisynthetic derivatives) or one of their ester salts (salts of esters of a compound or salts of esters of semisynthetic derivatives).
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide the application of lurasidone in preparing a medicament for treating or preventing ischemia/reperfusion injury; the second object of the invention is to provide the application of lurasidone in preparing cytoprotective medicines.
In order to solve the technical problems, the technical scheme of the invention is as follows:
the use of lurasidone in the preparation of a medicament for the treatment or prevention of ischemia/reperfusion injury and a cytoprotective medicament.
The structural formula of the lurasidone compound is shown as formula I, and the molecular formula is C 28 H 36 N 4 O 2 S。
Further, the ischemia/reperfusion injury includes one or more of myocardial ischemia/reperfusion injury, brain ischemia/reperfusion injury, liver ischemia/reperfusion injury, kidney ischemia/reperfusion injury, lung ischemia/reperfusion injury and intestinal ischemia/reperfusion injury.
Further, the myocardial ischemia/reperfusion injury comprises one or more of chronic myocardial ischemia syndrome and myocardial infarction.
Further, the chronic myocardial ischemia syndrome comprises one or more of latent coronary heart disease, stable angina and ischemic cardiomyopathy.
Further, the myocardial ischemia/reperfusion injury comprises myocardial infarction.
Further, the cerebral ischemia/reperfusion injury includes ischemic stroke (also referred to as cerebral infarction).
Based on the same inventive concept, the invention also provides application of lurasidone in preparing cytoprotective drugs.
Further, the cytoprotective drug means a drug having an effect of preventing, inhibiting or treating damage, denaturation or dysfunction of tissues, organs and cells.
Further, the cytoprotective medicine refers to a medicine for preventing, inhibiting or treating cardiovascular system diseases, nervous system diseases, ophthalmic diseases, respiratory system diseases and digestive system diseases; preferably, the cells include one or more of cardiomyocytes and nerve cells.
Further, the organ comprises one or more of brain, lung, heart, blood vessel, kidney, intestine, pancreas, skin, eye, cornea.
Further, the cytoprotective drug is a drug for use in myocardial ischemia/reperfusion injury and/or cerebral ischemia/reperfusion injury.
The inventor discovers that lurasidone can reduce the death of cardiac muscle cells and nerve cells caused by myocardial ischemia and cerebral ischemia, obviously reduce the dead body (area) of myocardial ischemia and cerebral ischemia, reduce the activity of serum creatine kinase, improve neurological functions, reduce the death of cardiac muscle cells and nerve cells, has the protection effect of cardiac muscle cells and nerve cells, and has the effect of relieving the damage of myocardial ischemia and cerebral ischemia/reperfusion compared with the current common cardiovascular and cerebrovascular medicaments.
Further, the administration mode of the medicine is one or more of intramuscular injection, subcutaneous injection, intravenous injection, intraperitoneal injection, oral administration, sublingual administration, intralesional or intracerebral or implantable delivery and spray administration, preferably intramuscular injection, subcutaneous injection and intravenous injection.
Further, the drug is administered by intramuscular, subcutaneous or intravenous injection.
Further, the medicine can be prepared into any pharmaceutically acceptable dosage form.
Further, the dosage form comprises one of injection, capsule, tablet, granule, suspension, emulsion, spray, powder, liposome, oral liquid and dripping pill, wherein the preferred dosage form is injection.
Optionally, lurasidone is a pharmaceutically acceptable salt thereof, wherein the pharmaceutically acceptable salt is a pharmaceutically common salt, and further, the salt is one or more selected from acetate, hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, benzoate, fumarate, maleate, succinic acid, tartaric acid, citrate, oxalic acid, glyoxylic acid, aspartic acid, tartrate, 2, 5-dihydroxybenzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, selenosulfonate, hydroquinonesulfonate and p-toluenesulfonate.
The research of the inventor finds that the lurasidone can specifically down regulate the expression and phosphorylation level of RIPK1, RIPK3 and MLKL, can be used as inhibitors of RIPK1, RIPK3 and MLKL, can inhibit apoptosis of cell necrosis and can reduce cell death.
The inventors of the present invention have unexpectedly found that lurasidone reduces myocardial cell and nerve cell death caused by myocardial ischemia/reperfusion and cerebral ischemia/reperfusion, significantly reduces dead (surface) areas of myocardial and cerebral ischemia stems, reduces serum creatine kinase activity and improves neurological functions, has the effect of down-regulating RIPK1, RIPK3, MLKL expression and phosphorylation levels, and has the effect of protecting myocardial cells and nerve cells. The medicine of the invention has better effect of relieving heart and cerebral ischemia/reperfusion injury than the existing commonly used cerebrovascular medicine, can be used for treating myocardial infarction and ischemic cerebral apoplexy, and has good development and application prospects.
The invention expands the indications of lurasidone, and is especially suitable for myocardial infarction, ischemic cerebral apoplexy and cytoprotection.
The invention relates to the application of lurasidone in preparing a medicament for treating or preventing ischemia/reperfusion injury, which belongs to the first disclosure, can obviously reduce myocardial infarction dead area and cerebral infarction volume, reduce serum creatine kinase activity and improve neurological functions, reduce myocardial cell and nerve cell death, has the protection effect of myocardial cells and nerve cells, is unexpected, is not related to the known application of lurasidone, does not have the related suggestion given by other existing compounds, has outstanding substantive characteristics, and has obvious progress in treating ischemia/reperfusion injury and cytoprotection.
Drawings
FIG. 1 is a graph showing the effect of lurasidone on myocardial infarction area and serum creatine kinase activity in rats in example 1; and (3) carrying out administration for 30 minutes after ischemia, detecting related indexes after 24 hours of reperfusion, and carrying out TTC staining and infarct area measurement condition graphs of myocardial tissues of rats after administration of A-lurasidone, wherein serum creatine kinase activity condition after administration of B-lurasidone.
FIG. 2 is a graph showing the effect of lurasidone on rat cerebral infarction volume and neurological function in example 2; the drug is administered after ischemia for 2 hours and 1 hour, relevant indexes are detected after the drug is refilled for 24 hours, and the drug is a-rat brain tissue TTC staining and infarct volume measuring condition diagram and B-rat neurological function scoring condition diagram.
FIG. 3 is a graph showing the effect of lurasidone on the regulation of MLKL and phosphorylated MLKL (p-MLKL) in rat brain tissues in example 2.
Detailed Description
The present invention will be described in detail with reference to examples.
The application of lurasidone in preparing medicines for treating ischemia/reperfusion injury and cytoprotective medicines.
Materials and methods:
to demonstrate the role of lurasidone in anti-ischemic/reperfusion injury and cytoprotection, applicants used a rat model of myocardial ischemia/reperfusion injury and a rat model of ischemic stroke, and treated Yu Lula with a cilidone drug at various time points after ischemia/reperfusion, and the animals were sacrificed 24 hours after reperfusion, and examined for myocardial cell injury with TTC staining and serum creatine kinase activity, and neural cell injury with neurobiological scoring and TTC staining.
Experimental medicine: lurasidone (a lurasidone compound) is purchased from reagent company and dissolved and formulated according to the company's reagent instructions.
Example 1
Animal experiment: protection of myocardial ischemia/reperfusion injury rat model by lurasidone.
Experimental animals:
healthy male SD rats weighing 250-300 g. The experimental animals are raised for one week in the environment with the temperature of 25 ℃ and the relative humidity of 60 percent and free drinking water and timing and quantification, and then are dosed according to the grouping requirements of the experiment.
The method for establishing the myocardial ischemia/reperfusion model of the rat comprises the following steps: SPF-grade Sprague-Dawley rats were anesthetized with 3% sodium pentobarbital (0.1 mL/kg) and then fixed to a rat plate, and the cervical and left chest hairs were removed. The rat limb was connected to an electrocardiograph and the change in the electrocardiogram of the rat during the operation was observed. The neck muscles were blunt-separated, the trachea was exposed, a "T" cut was made in the trachea, and the other end of the hose connected to the ventilator was inserted into the rat trachea and secured with a wire. The ventilator parameters were set to a tidal volume of 7mL/kg, at a frequency of 53 beats per minute. After the rat breathes smoothly, the muscles of each layer are blunt-separated by hemostatic forceps at the third and fourth intercostals of the left chest, the sternum is fixed, and the pericardium is gently opened to expose the whole heart. After the heart beat is recovered, the heart is rapidly extruded, an obvious left coronary vein can be observed between the pulmonary artery cone and the left auricle, the left anterior descending branch of the coronary artery is ligated by using a 5-0 suture line through a section of plastic hose, or a needle is penetrated from a position 2-3mm below the left auricle to a position below the pulmonary artery cone, and the heart is rapidly reset and rapidly ligated. The electrocardiogram change of the rat is monitored, ST segment is raised, and indexes such as the whitening of the apex and the like can be observed visually at the same time to judge myocardial infarction. After 1 hour of ischemia, the plastic hose at the ligation of the heart is cut off, the ligature is broken, and the heart resumes blood perfusion. After 3 hours of reperfusion, the sternum at the chest was cut open and 2-3mL of blood was collected from the apex of the heart.
After the apex of the heart is sampled, the heart is taken out, all myocardial tissues above the ligation are cut off, and the right ventricle and the ventricular septum are removed. Freezing at-20deg.C for 30min, taking out, cutting heart into pieces with uniform thickness, adding 1% TTC dye solution (PBS), and incubating at 37deg.C for 15min. After the staining is finished, removing the staining solution, washing once with PBS, fixing the 4% paraformaldehyde for 24 hours, taking out the heart slices, observing the staining condition and photographing. Infarcted areas appear white, myocardial infarction areas and risk Area areas were determined by ImageJ software, and the percentage of Infarct Area (ratio of Infarct Area to risk Area) per slice was calculated.
Experimental grouping: experimental animals were randomly divided into 4 groups, namely:
sham group (Sham group): performing an operation on the rat heart, but not performing vessel ligation;
myocardial ischemia/reperfusion group (I/R group): ligating anterior descending branch of left coronary artery for 1 hr, trimming, and reperfusion for 3 hr;
lurasidone + myocardial ischemia/reperfusion group (Lurasidone + I/R) Lurasidone (15 mg/kg of Lurasidone administered) was given by intraperitoneal injection 30min after myocardial ischemia in rats.
Vehicle + myocardial ischemia/reperfusion group (Vehicle + I/R): the same volume of vehicle was administered 30min after myocardial ischemia in rats.
Blood and myocardial tissue were collected and the relevant index was determined: rat myocardial infarction area determination and serum creatine kinase activity detection.
Serum Creatine Kinase activity (CK activity) assay
After the ischemia/reperfusion operation, the apex of the heart was sampled 1-2mL,3000rpm,4℃and the supernatant was collected after centrifugation for 10min and stored at-40 ℃. The serum CK activity was determined according to the instructions of the commercial kit as follows: dissolving 10mL R2 in a bottle of R1 to prepare a working solution, adding 4 μL serum into 200 μL CK reagent kit working solution, incubating for 2min at 37 ℃, setting the wavelength under an enzyme label instrument to 340nm, and reading absorbance at 0, 1, 2 and 3min respectivelyA 0 ，A 1 ，A 2 ，A 3 The change in average absorbance per minute (. DELTA.A) was calculated, and the concentration of CK in serum (U/L) was calculated.
Experimental results:
lurasidone has effects of resisting myocardial ischemia/reperfusion injury of rats, reducing myocardial tissue infarct area of rats, reducing serum creatine kinase activity, and reducing myocardial cell death.
As shown in a in fig. 1, 30 minutes of ischemia administration of lurasidone is effective in reducing myocardial tissue infarct size caused by ischemia/reperfusion of the rat heart; as shown in B in fig. 1, administration of lurasidone significantly reduced serum creatine kinase activity, data expressed as mean ± standard deviation, n=6, P < 0.01vs Sham, ## P＜0.01vs I/R。
conclusion of experiment:
lurasidone can reduce death of rat myocardial cells, lighten myocardial ischemia/reperfusion injury, has the function of protecting myocardial cells, and can be applied to preparing medicaments for treating myocardial ischemia/reperfusion injury.
Example 2
Animal experiment: protection of rat models for ischemic stroke by lurasidone.
Experimental animals: healthy male SD rats weighing 250-300 g. The experimental animals are raised for one week in the environment with the temperature of 25 ℃ and the relative humidity of 60 percent and free drinking water and timing and quantification, and then are dosed according to the grouping requirements of the experiment.
The modeling method comprises the following steps: a rat brain ischemia/reperfusion injury model was prepared by Middle Cerebral Artery Occlusion (MCAO) method. The method comprises the following steps: (1) Separating the left Common Carotid Artery (CCA), external Carotid Artery (ECA) and Internal Carotid Artery (ICA) of the rat; (2) Temporarily clamping the ECA and ICA with an ophthalmic forceps and ligating the proximal end of the CCA; (3) Placing a knotted standby silk thread at the distal end of the CCA, cutting a small opening at the lower end of the thread, inserting the bolt thread into the internal carotid artery, tightening the silk thread, releasing the arterial clamps on the ECA and the ICA, and delivering the bolt thread into the cranium along the ICA; (4) The insertion depth is about 18-20 mm from the bifurcation of the CCA when the resistance is met; (5) After 120min of ischemia, the thrombus was pulled out, the skin was sutured, and the animals were post-treated by reperfusion for 24h.
Model success criteria the neurological deficit of rat brain ischemia injury was scored using Longa "5 score". 0 point: no neurological deficit symptoms; 1, the method comprises the following steps: the right forelimb cannot be completely straightened; 2, the method comprises the following steps: the rat walks to rotate to the right; 3, the method comprises the following steps: walking and tilting to the right; 4, the following steps: can not walk spontaneously, and the consciousness is lost. 1 to 4 are divided into effective models.
Rat brain TTC staining and infarct volume determination. After rat anesthesia, the brain was rapidly removed, the olfactory bulb and hindbrain were removed, and brain tissue was cut into coronal brain slices about 2mm thick starting from frontal pole, immediately placed in 1% ttc solution and incubated at 37 ℃ for 30min in the absence of light. Then the mixture was fixed by immersing in 10% paraformaldehyde solution. The infarcted area appeared white and the non-infarcted area appeared red. And (5) arranging each group of brain slices in order and then scanning. And then measuring the infarct area of each brain slice by using imageJ, and according to the formula: the total cerebral infarct volume, i.e. the sum of all cerebral infarct volumes, was calculated by the same method as the infarct volume = [ (front infarct area of each tablet + back infarct area of each tablet)/2 ]. Times.each tablet thickness.
Western Blot (WB) detects MLKL and phosphorylated MLKL expression levels. Taking a proper amount of brain tissue, adding precooled PBS and cleaning. Adding magnetic beads into the homogenizing tube, pre-cooling on ice, and adding cleaned brain tissue into the homogenizing tube for homogenizing (70 Hz,180 s). Centrifuge at 12000rpm for 10min at 4℃to leave a supernatant. After protein concentration was measured by BCA method, 20-40 ug of protein was separated by 8-10% SDS-PAGE gel and transferred to PVDF membrane, and incubated overnight with MLKL and p-MLKL (Abcam, cambridge, UK) antibodies and β -actin (beyotide, jiangsu) antibodies, after removal of the antibodies, the membrane was washed, and after addition of the corresponding secondary antibodies, developed by Molecular Imager ChemiDoc XRS System (Bio-Rad, philiadelphia, PA) and β -actin was used as an internal reference. Protein gray values were determined by Image J software to evaluate protein expression levels.
Experimental grouping: experimental animals were randomly divided into 4 groups, namely:
sham group (Sham group): and (3) performing internal and external carotid artery separation operation without inserting a bolt wire into an artery.
Cerebral ischemia/reperfusion group (I/R group): cerebral ischemia was performed for 2h and reperfusion was performed for 24h.
Lurasidone+cerebral ischemia/reperfusion group (lurasidone+i/R): intramuscular injection of lurasidone (10 mg/kg per administration of lurasidone) was performed 2h, 1h, and 6h after ischemia.
Vehicle + cerebral ischemia/reperfusion group (Vehicle + I/R): after ischemia for 2h, reperfusion for 1h and 6h, the same volume of solvent treatment is respectively given.
Rat neurological scoring was measured and cerebral infarct volume was determined.
Results:
lurasidone has effects of resisting cerebral ischemia/reperfusion injury of rats, reducing cerebral infarction volume, improving neurological deficit symptom, and reducing nerve cell death.
As shown in a in fig. 2, the I/R group had an obvious white infarct focus, and the cerebral infarction volume of the lurasidone rats was significantly reduced after ischemia 2h, reperfusion 1h, and 6h, and cerebral ischemia/reperfusion injury was significantly alleviated. As shown in fig. 2B, lurasidone significantly improved neurological deficit symptoms (n=6, P < 0.01vs Sham, ## P＜0.01vs I/R)。
as shown in fig. 3, cerebral ischemia/reperfusion induced up-regulation of rat brain tissue MLKL and p-MLKL (phosphorylated MLKL), whereas lurasidone significantly inhibited up-regulation of MLKL and p-MLKL.
Conclusion: lurasidone has the effects of inhibiting necrosis-like apoptosis, reducing nerve cell death, relieving cerebral ischemia/reperfusion injury, and can be used for preparing medicines for relieving cerebral ischemia/reperfusion injury, and treating ischemic cerebral apoplexy.
However, the present invention is not limited to ischemia/reperfusion injury of heart and brain, and the medicine is also suitable for treating ischemia/reperfusion injury of liver, kidney, lung and intestine because the ischemia/reperfusion injury of liver, kidney, lung and intestine has similarities with the ischemia/reperfusion injury mechanism of heart and brain.
The foregoing examples are set forth in order to provide a more thorough description of the present invention, and are not intended to limit the scope of the invention, since modifications of the invention in various equivalent forms will occur to those skilled in the art upon reading the present invention, and are within the scope of the invention as defined in the appended claims.
Claims (10)
1. Use of lurasidone in the manufacture of a medicament for the treatment or prevention of ischemia/reperfusion injury.
2. The use according to claim 1, wherein the ischemia/reperfusion injury comprises one or more of myocardial ischemia/reperfusion injury, cerebral ischemia/reperfusion injury, liver ischemia/reperfusion injury, kidney ischemia/reperfusion injury, lung ischemia/reperfusion injury, and intestinal ischemia/reperfusion injury.
3. The use according to claim 2, wherein the myocardial ischemia/reperfusion injury comprises one or more of chronic myocardial ischemia syndrome, myocardial infarction.
4. The use according to claim 3, wherein the myocardial ischemia/reperfusion injury comprises myocardial infarction.
5. The use according to claim 2, wherein the cerebral ischemia/reperfusion injury comprises ischemic stroke.
6. Use of lurasidone in the preparation of a cytoprotective medicament.
7. The use according to claim 6, wherein the cytoprotective drug is a drug having the effect of preventing, inhibiting or treating injury, degeneration or dysfunction of tissues, organs and cells.
8. The use according to claim 6, wherein the cytoprotective drug is a drug for preventing, inhibiting or treating cardiovascular diseases, nervous system diseases, ophthalmic diseases, respiratory system and digestive system; preferably, the cells include one or more of cardiomyocytes and nerve cells.
9. The use according to claim 7, wherein the organ comprises one or more of brain, lung, heart, blood vessel, kidney, intestine, pancreas, skin, eye, cornea.
10. The use according to claim 6, wherein the cytoprotective drug is a drug for use in myocardial ischemia/reperfusion injury and/or cerebral ischemia/reperfusion injury.
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| US20120122792A1 (en) * | 2010-11-12 | 2012-05-17 | Promentis Pharmaceuticals, Inc. | S-t-BUTYL PROTECTED CYSTEINE DI-PEPTIDE ANALOGS AND RELATED COMPOUNDS |
| US20130289277A1 (en) * | 2012-04-26 | 2013-10-31 | Dainippon Sumitomo Pharma Co., Ltd. | Medicament for treating mental and behavioural disorders |
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| US20120122792A1 (en) * | 2010-11-12 | 2012-05-17 | Promentis Pharmaceuticals, Inc. | S-t-BUTYL PROTECTED CYSTEINE DI-PEPTIDE ANALOGS AND RELATED COMPOUNDS |
| US20130289277A1 (en) * | 2012-04-26 | 2013-10-31 | Dainippon Sumitomo Pharma Co., Ltd. | Medicament for treating mental and behavioural disorders |
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