44 results about "Infarct volume" patented technology

The invention discloses a GRPAK / tetrahydroglyoxaline / RGD ternary conjugate as well as a preparation method and application of the GRPAK / tetrahydroglyoxaline / RGD ternary conjugate. According to the preparation method, L-Lys is served as a link arm, and 1, 3-dioxo-2-[(4-peracetic acid) phenyl]-4, 4, 5, 5-tetramethyl tetrahydroglyoxaline, the GRPAK pentapeptide with a thrombolytic effect, and RGD tetrapeptide with an antithrombosis effect are integrally linked, thus obtaining the GRPAK / tetrahydroglyoxaline / RGD ternary conjugate as shown in formula I. The GRPAK / tetrahydroglyoxaline / RGD ternary conjugate disclosed by the invention has high activity on removing NO free radical, excellent thrombolytic activity and antithrombosis activity; as in-vivo apoplexy activity shown, the GRPAK / tetrahydroglyoxaline / RGD ternary conjugate can effectively protect the neurologic function of a rat subjected to apoplexy, and reduces the brain infarct volume of the rat subjected to apoplexy, and has high apoplexy resisting activity, and can be prepared into a clinical medicine for treating apoplexy or cerebral infarction.

The present invention is based on the discoveries that PAN-811 (1) reduces infarct volume, suppresses brain edema and decreases mortality associated with ischemia; (2) blocks veratridine-induced swelling and neuronal cell death; (3) chelates free calcium and inhibits MMP-9 activity; and (4) blocks calcium-induced neuronal cell death and suppresses glutamate-induced calcium influx into neuronal cells. More particularly, the present invention relates to methods for treating, ameliorating or preventing vasogenic and / or cytotoxic brain edema, by administering to a subject in need thereof certain thiosemicarbazone compounds or pharmaceutically acceptable salts thereof. An example of such a thiosemicarbazone is 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (PAN-811).

The present invention discloses a thrombolysis oligopeptide-imidazolidine binary conjugate, a preparation method and uses thereof. According to the present invention, L-Lys is adopted as a linking arm to link 1,3-dioxy-2-[(4-oxyacetic acid)phenyl]-4,4,5,5-tetramethylimidazoline, ARPAK having a thrombolysis effect, GRPAK, RPAK or PAK to obtain the thrombolysis oligopeptide-imidazolidine binary conjugate represented by a formula I or II, wherein the thrombolysis oligopeptide-imidazolidine binary conjugate integrally has characteristics of nanometer structure, BBB crossing, thrombolysis and NO removing. The thrombolysis oligopeptide-imidazolidine binary conjugate has high NO free radical clearance activity, excellent thrombolysis activity and excellent antithrombosis activity. In vivo anti-stroke activity test results show that: with the thrombolysis oligopeptide-imidazolidine binary conjugate, nerve functions of stroke rats can be effectively protected, brain infarct volume of the stroke rats can be reduced, excellent anti-stroke activity is provided, and the thrombolysis oligopeptide-imidazolidine binary conjugate can be prepared into a clinical drug for brain infarction treatment.

The invention relates to a novel nicotinic acid derivative and an application thereof and further relates to the application of the nicotinic acid derivative in preparation of medicine and pharmaceutic preparation for disease prevention or treatment, especially for prevention or treatment of stroke diseases. Experiments prove that the nicotinic acid derivative has a direct protection function on neurons on a cell model and substantially reduces the hindbrain infarct volume of a mouse with ischemic stroke in an animal model. Therefore, the application of the nicotinic acid derivative with the novel chemical structural formula in preparation of the medicine for prevention or treatment of the stroke diseases is provided. The nicotinic acid derivative contains a nicotinic acid pharmacophore as well as pharmacophores aiming at other pathogenic mechanisms, and the nicotinic acid derivative has better stroke disease prevention or / and treatment effect than the prototype drug nicotinic acid.

The invention discloses an application of 5,7-dihydroxy-4'-methoxy flavone preparation extracted from snow lotus in preparation of a medicament for treating ischemic stroke. By effectively extracting the 5,7-dihydroxy-4'-methoxy flavone preparation from the snow lotus and establishing an ischemia reperfusion model of a mouse, the influence of acacetin on the infarct volume and the neurologic impairment caused by ischemia reperfusion injury of the mouse is observed. The study carried out by establishing an SH-SY5Y cell OGD model, testing the cell viability and the cell apoptosis, and demonstrating the integral level of the acacetin shows that the acacetin has the effect of significantly reducing the infarct volume, improving the neurologic function score, promoting the cell survival and reducing the cell apoptosis, clarifies that the acacetin has a neurologic protection effect on the cerebral ischemia reperfusion injury and proves that the 5,7-dihydroxy-4'-methoxy flavone preparation can be well applied to preparing the medicament for treating ischemic stroke and has wide application value.

The invention relates to the field of medicaments, and in particular relates to a 3H-1,2-dithio-cyclopentene-3-thioketone compound and an application thereof. The 3H-1,2-dithio-cyclopentene-3-thioketone compound disclosed by the invention has a structure shown in a formula I or a formula II and is a compound with a completely-new structure. Proved by experiments, the 3H-1,2-dithio-cyclopentene-3-thioketone compound has a direct protection role on neurons on a cell model, and can obviously restrain excessive inflammatory responses of inflammatory cells in the cerebrum; and by using 3H-1,2-dithio-cyclopentene-3-thioketone, focal cerebral ischemia cerebral infarction volume of a mouse can be obviously reduced in an animal model. Therefore, the invention provides the 3H-1,2-dithio-cyclopentene-3-thioketone compound and the application of acceptable slat of the 3H-1,2-dithio-cyclopentene-3-thioketone compound on the pharmacy aspect to the preparation of medicaments for preventing or treating a cerebral apoplexy disease.

The invention provides an application of total saponins of bacopa monnieri (L.) wettst. in preparation of medicaments for resisting cerebral ischemia. The total saponins of the bacopa monnieri (L.) wettst. mainly comprise the following dammarane type triterpenoid saponin compounds: bacopaside I, bacoside A3, bacopaside II, bacopasaponin cisomer and bacopasaponin C. The invention further provides an application of the bacopaside I in preparation of a medicament for resisting cerebral ischemia. The experimental study shows that the total saponins of the bacopa monnieri (L.) wettst. and the bacopaside I have the effects of improving the behavioral symptoms caused by cerebral ischemia reperfusion injury, reducing the cerebral infarct volume and reducing the cerebral edema caused by cerebral ischemia of a rat. Therefore, the total saponins of the bacopa monnieri (L.) wettst. can be used for preparing the medicaments for preventing and treating cerebral ischemia. The medicaments for preventing and treating the cerebral ischemia are prepared from the total saponins of the bacopa monnieri (L.) wettst. or bacopaside I as the active component and medicinal accessories by adopting a conventional method. The invention further expands the function of the bacopaside I and the total saponins of the bacopa monnieri (L.) wettst. and provides the novel medicaments for preventing and treating the cerebral ischemia. The bacopaside I and the total saponins of the bacopa monnieri (L.) wettst. have high clinical application values.

The present invention discloses an RPAK / imidazolidine / RGD ternary conjugate, a preparation method and uses thereof. According to the present invention, L-Lys is adopted as a linking arm to link 1,3-dioxy-2-[(4-oxyacetic acid)phenyl]-4,4,5,5-tetramethylimidazoline, an RPAK tetrapeptide having a thrombolysis effect, and a RGD tetrapeptide having an anti-thrombosis effect to obtain the RPAK / imidazolidine / RGD ternary conjugate represented by a formula I, wherein the RPAK / imidazolidine / RGD ternary conjugate integrally has effects of BBB crossing, thrombolysis and NO removing. The RPAK / imidazolidine / RGD ternary conjugate has high NO free radical clearance activity, excellent thrombolysis activity and excellent anti-thrombosis activity. In vivo anti-stroke activity test results show that: with the RPAK / imidazolidine / RGD ternary conjugate, nerve functions of stroke rats can be effectively protected, brain infarct volume of the stroke rats can be reduced, anti-stroke activity is provided, and the RPAK / imidazolidine / RGD ternary conjugate can be adopted as a clinical drug for brain infarction treatment.

The invention relates to novel use of methylene blue (MB) in prevention of acute cerebral ischemia. MB can remarkably reduce cerebral ischemia infarction caused by permanent middle cerebral artery occlusion (middle cerebral artery occlusion MCAO) and alleviate damage of neurological function. The inventors of the invention permanently occlude middle cerebral artery of a mouse by adopting a suture method and after intraperitoneal injection of MB at the moment and at different time points after cerebral ischemia, changes on degree and ethology of permanent cerebral ischemia infarction of the mouse are observed. Researches discover that MB can remarkably reduce infarct volume caused by cerebral ischemia and improve the active ability of the mouse after cerebral ischemia. Through the method provided by the invention, moderate doses of MB are delivered for many times after cerebral ischemia can remarkably alleviate damage degree after permanent cerebral ischemia of the mouse so as to improve the active ability of the mouse after cerebral ischemia. The use of MB is expected to provide a rescue therapeutic measure to cerebral apoplexy and alleviate permanent neurological function deficit after golden treatment period.

The invention discloses an application of cholest-4-ene-3,6-dione in preparing a drug for treating or preventing neuron injury. Cholest-4-ene-3,6-dione can relieve hippocampus neuron oxidative stressinjury caused by glutamic acid, cerebellar granule neuron apoptosis injury caused by potassium deprivation and cortical neuron and cerebellar granule neuron oxidative stress injury caused by glutamicacid, also has a function of remarkably reducing infarct volume in an MACO (middle cerebral artery occlusion) model of a stroke rat and has the potential of a neuroprotective agent used for being developed into multiple acting mechanisms. Neurodegenerative diseases such as the Parkinson's disease, the Alzheimer's disease, the tau protein disease, amyotrophic lateral sclerosis and the like as wellas cerebral stroke, cerebral injury and spinal cord injury are all caused by neuron injury, and neuron injury is further aggravated. Cholest-4-ene-3,6-dione has a protection function on neuron injuryand has potential functions in drugs for treating or preventing neuron injury.

The invention provides an edaravone composition for injection, and relates to the technical field of medicine manufacturing. The main medicine of the composition comprises edaravone and melatonin, wherein the melatonin comprises a quick release part and a cyclodextrin-included slow release part. According to the edaravone composition for injection provided by the invention, the therapeutic effect of edaravone is improved, instability caused by oral administration of MT (Melatonin) is avoided and MT is quick to distribute and eliminate and the like, and the first pass effect of MT is reduced. The dosage of edaravone is reduced, and the side effect of edaravone is reduced. The design of dosage combining quick release and slow release is in accordance with secretion characteristic of MT, so that the problem of half-life period of MT is solved and the bioavailability of a product is improved. The melatonin combined with edaravone acted on nerve cells has the synergistic effect of preventing encephaledema, reducing the infarct volume and improving the neurological function.

Methods are described for the isolation and selection of a heterogeneous bone marrow cell population, called NCS-01, that is effective at treating neurodegeneration. For example, NCS-01 cells are shown to treat neurodegeneration caused by ischemia. In vivo studies demonstrate that selected NCS-01 cell populations treat neurodegeneration in a standard rat middle cerebral artery occlusion (MCAO) animal model under conditions of transient or permanent total arterial occlusion. These studies also disclose that when the neurodegeneration is caused by ischemic stroke, combining the administration of a selected NCS-01 cell population with thrombolytic agents and / or mechanical methods of clot removal leads to a decrease in the volume of infarction caused by acute onset neurodegeneration. The disclosed cell therapy promises to make a significant clinical impact on patient survival after stroke.

The invention discloses an application of (Z)-2-imino-5-(3,5-dimethoxyphenylmethylene)-1-methylimidazolidinyl-4-one in the preparation of cardiovascular drugs. Specifically, the provided compound has a prominent effect on reducing damage caused by myocardial ischemia / reperfusion; is capable of prominently reducing the infarct volume in left ventricle of myocardial ischemia rats, and is suitable for preparing drugs for preventing and / or treating cardiovascular diseases especially ischemic cardiomyopathy, myocardial ischemia / reperfusion damage, and the like.

The invention discloses a nerve injury resisting method of an ischemic brain injury animal model. The nerve injury resisting method comprises the following steps of S1, establishing the ischemic braininjury animal model; S2, performing lumbricusion administration experiment; S3, performing behavioristics testing, measuring infarct volume, and observing the influence of the lumbricusion on the expression of VEGF (vascular endothelial growth factor) and CD34 related with ischemic penumbra and angiogenesis of an ischemic brain injury mouse; observing the influence of the lumbricusion on the protein expression of related VEGF, PI3K (phosphatidyl inositol-3-kinase) and AKT (protein kinase B) factors of the PI3K-AKT signal channels of a local ischemic brain injury mouse. The nerve injury resisting method has the advantages that according to the animal experiment, the optimum dosage of the lumbricusion for realizing the nerve protection effect on the ischemic brain injury animal is determined; according to the reliable testing indexes, the lumbricusion can be used for performing nerve protection on the ischemic brain injury.

The invention relates to the medical technology field, and provides purposes of piperlongumine used for preparing a medicine preventing cerebral arterial thrombosis. Through pharmacological test of a mouse focal cerebral ischemia model, the facts are discovered that piperlongumine can improve behavior symptoms caused by mouse cerebral ischemia reperfusion injury obviously, the cerebral infarction size is reduced, and encephaledema degree of a mouse with cerebral ischemia is lowered. Thus piperlongumine can be used for preparing a medicine preventing cerebral arterial thrombosis.

A novel flavonoid derivative compound 6-CEPN can protect a brain against ischemia / reperfusion (I / R) injury by attenuating peroxynitrite-mediated mitochondrial autophagy. The infarct volume and neurological impairment score of acute ischemic stroke is significantly improved by 6-CEPN. It is found that the 6-CEPN inhibites excess mitochondrial autophagy activation during brain I / R injury, accompanied by a reduction in the production of peroxynitrite. Specifically, the 6-CEPN inhibites the expression ratio of LC3-II / I and Drp1 in the mitochondrial fraction in a dose-dependent manner, as well as the protein expression of the iNOS and NADPPH oxidase subunit p47phox.

Methods of treating brain ischema or hypoxia by using an inhibitor of cysteine-glutamate transporter (i.e. system xc−) is provided. The inhibitor includes sorafenib and a derivative thereof, erastin, and suifasalazine. These inhibitors can effectively decrease a concentration of extracellular glutamate, so that excitotoxicity to central nervous system (CNS) and a cortical infarct volume in brains can be reduced.

Small molecule agonists, partial agonists, and antagonists for the TrkA receptor are described. The compounds are gambogic amines, where the carboxylic acid group of gambogic acid (CO2H) has been replaced by an amine group (CH2NR1R2). In some embodiments, the compounds selectively bind to TrkA but not TrkB or C, robustly induce its tyrosine phosphorylation and downstream signaling activation including Akt and MAP kinases. Further, they can strongly prevent glutamate-induced neuronal cell death and provoke prominent neurite outgrowth in PC12 cells. Gambogic amines specifically interact with the cytoplasmic juxtamembrane domain of TrkA receptor and trigger its dimerization. Administration of these compounds in can substantially diminishes Kainic acid-triggered neuronal cell death and decrease infarct volume in transient middle cerebral artery occlusion (MCAO) model of stroke. Thus, these compounds can provide effective treatments for debilitating neurodegenerative diseases and provide neuroprotection from patients suffering from stroke or other ischemic events.

The invention discloses catalpol nasal drops and a preparation method and application thereof.The catalpol nasal drops are prepared from catalpol, a thickening agent, an absorption enhancer and a pH regulator, the catalpol, the thickening agent and the absorption enhancer are 10 mg / ml, the mass percentage of the thickening agent is 0.1%, the volume percentage of the absorption enhancer is 2.0%, and the pH value is 6.5-7.0; the preparation is stable in storage property under normal-temperature and dark conditions; the absorption is fast through nasal administration, the concentration in brain tissues is obviously higher than that of intravenous administration, and brain targeting is achieved; compared with oral administration and injection administration, the catalpol nasal administration dosage form can also reduce the infarct volume of brain tissues of acute cerebral ischemia patients, and can reduce the number of apoptosis of neuronal cells in a cortical region caused by cerebral ischemia injury, which shows that the catalpol nasal administration dosage form has a remarkable neuroprotective effect on the cerebral cortical region; the catalpol nasal drops have low toxicity to cilia, no obvious nasal cavity irritation is found, and the nasal administration safety is good.

The invention relates to the technical field of medicine, and the invention provides the use of smilaxamide for preparing a medicine for preventing and treating ischemic stroke. According to the pharmacological test of the focal cerebral ischemia model in mice, the present invention finds that smilaxamide can significantly improve the behavioral symptoms caused by cerebral ischemia-reperfusion injury in mice, reduce the volume of cerebral infarction, and reduce cerebral edema in mice with cerebral ischemia degree. Therefore, smilaxamide can be used to prepare medicines for preventing and treating ischemic stroke.

Disclosed is the use of (+)-2-borneol in the preparation of a drug for promoting the upregulation of the expression of sphingosine kinase-1 and / or BDNF (a brain-derived neurotrophic factor). Herein, (+)-2-borneol can be used to prepare a drug for promoting the upregulation of the expression of the sphingosine kinase-1 and / or the brain-derived neurotrophic factor. The drug can induce astrocyte spreading and migration, oligodendrocyte differentiation and survival, and neurite growth and nerve regeneration, and can promote the upregulation of the expression of the brain-derived neurotrophic factor, promote the survival of neurons and the growth of axons, inhibit the expansion of the infarct volume, and achieve the effect of repairing damage at the site of an immediate injury while preventing further expansion of the infarct area to completely treat brain damage, so that the long-term therapeutic effect thereof is significantly improved.

Provided is a manufacturing method of sutures used for MACO models of mice. The sutures are prepared by selection, preparation of material, coating of head ends and marking after coating. The suture material is a filament which is drawn with the diameter ranging from 0.065 to 0. 1 mm at the temperature of 300 DEG C and made by polytetrafluoroethylene resin. At the temperature of 350 DEG C, the surface of the above filament is coated by titanium dioxide in order to obtain the material of the sutures. Coating material, for coating the head ends, is formed by mixing 15% of silicone emulsion, 34% of polyvinylpyrrolidone, 23% of polyvinyl alcohol, 16% of polyethylene glycol, and 12% of polytetrafluoroethylene under ultrasonic concussion based on weight. The manufacturing method of the sutures used for MACO models of mice has following beneficial effects: the sutures are consistent in size and have appropriate hardness and elasticity and blunt and smooth head ends so that the sutures can smoothly enter middle cerebral arteries of mice; inserted sutures can be bent in accordance with the bending blood vessels in order to reduce mechanical damage to blood vessels; obstruction is performed more completely and reliably; the scope of cerebral ischemia is stable; cerebral infarct volume is stable; operation is carried out easily; high success rate of models is achieved; and death rate of mice is low.

A new compound (as shown in formula I) and salts thereof, which are proved to be used for treating and preventing cerebral ischemic diseases and improving sleep by experiments. When R=H, salts are respectively generated by the compound together with alkali metal sodium, magnesium, potassium or calcium and organic alkali tromethamine, diethylamine, triethylamine or the like, and have functions of treating and preventing ischemic cardiovascular and cerebrovascular diseases and improving sleep. Compared with a control group, the present invention is greater in influence on the volume of ischemic cerebral infarction and higher in plasma concentration in brain tissue; and a half-life period is obviously prolonged.

The invention relates to a new naphthalene acetamide compound as shown in formula I and the salt of the naphthalene acetamide compound.Experiments prove that the naphthalene acetamide compound can be used for treating and preventing cerebral ischemic disease and improving sleep.When R=H, the naphthalene acetamide compound can react with alkali metal such as sodium, magnesium, potassium and calcium and tromethamine, diethylamine, triethylamine and the like to generate the salt which is capable of treating and preventing the cerebral ischemic disease and improving the sleep. The influence of the naphthalene acetamide compound on ischemic cerebral infarction volume is larger than that of a control group, the blood concentration of the naphthalene acetamide compound in brain tissue is higher than that of the control group, and the half-life period is prolonged evidently.

The present invention relates to a composition containing a fruit extract of Lonicera caerulea L. var. edulis as an active ingredient for the prevention and treatment of ischemic cerebrovascular disease. The fruit extract of Lonicera caerulea L. var. edulis according to the present invention has a nerve cell-protecting effect, thereby remarkably reducing neurobehavioral impairments and infarct volume due to ischemic cerebrovascular disease. Therefore, it can be provided as a pharmaceutical composition for the prevention or treatment of ischemic cerebrovascular disease, and as a health food for the prevention or improvement of ischemic cerebrovascular disease.

Using high-throughput screening, in an oxygen-glucose deprivation (OGD) model, isoxsuprine hydrochloride was identified as a potent neuroprotective compound. In an animal middle artery occlusion (MCAO) model of transient focal ischemia, isoxsuprine significantly reduced infarct volume compared to vehicle. The invention, therefore, provides methods of treatment and pharmaceutical compositions that are useful in the treatment and prevention of a wide-variety of ischemia-related injuries, including stroke.

The invention discloses an application of a compound in preparing a medicine for treating a cerebrovascular disease. The structural formula of the compound is shown in the specification. The compound has a certain protective effect on cerebral ischemic injury, and can obviously improve neurological deficits caused by cerebral ischemia and reduces brain infarct volume.