43results about How to "Improve blood-brain barrier permeability" patented technology

The present invention provides combination therapies for treating a disease, disorder, or condition, and methods thereof.

A compound, which is used for the diagnosis and the prophylaxis / treatment of diseases in which prion protein is accumulated, or specific staining of abnormal prion protein in samples, represented by the formula (I) or (II): or a salt or solvate thereof.

A method and device selectively and reversibly disrupts the blood-brain barrier (BBB) in a selected volume of the brain without the need for exogenous agents. The method and device employ low intensity directed ultrasound (LODUS) that is safe, reduces the danger of cavitation and thermal tissue damage, and is able to expose small or large regions of the brain to achieve a desired therapeutic or prophylactic effect.

The present invention relates to a method of increasing blood brain barrier permeability in a subject. This method involves selecting a subject who would benefit from increased blood brain barrier permeability and subjecting the selected subject to a treatment. That treatment increases adenosine level and / or bioavailability, modulates adenosine receptors, and / or increases CD73 level and / or activity under conditions effective to increase blood brain barrier permeability in the subject. Methods of decreasing blood brain barrier permeability in a subject, treatment of a subject for a disorder or condition of the central nervous system, and screening compounds effective in increasing blood brain barrier permeability, as well as pharmaceutical agents are also disclosed.

Certain substances (e.g., large molecules) that ordinarily cannot traverse the blood brain barrier can be introduced into the brain by applying an alternating electric field to the brain for a period of time, wherein the frequency of the alternating electric field is selected so that application of the alternating electric field increases permeability of the blood brain barrier. In some embodiments, the frequency of the alternating electric field is less than 190 kHz (e.g., 100 kHz). Once the permeability of the blood brain barrier has been increased, the substance is able to cross the blood brain barrier.

Certain substances (e.g., large molecules) that ordinarily cannot traverse the blood brain barrier can be introduced into the brain by applying an alternating electric field to the brain for a period of time, wherein the frequency of the alternating electric field is selected so that application of the alternating electric field increases permeability of the blood brain barrier. In some embodiments, the frequency of the alternating electric field is less than 190 kHz (e.g., 100 kHz). Once the permeability of the blood brain barrier has been increased, the substance is able to cross the blood brain barrier.

Disclosed are compositions and methods related to improving pharmacological properties of bioactive compounds targeting nervous system.

The present invention provides a process for purifying a monoterpene or sesquiterpene having a purity greater than about 98.5% (w / w). The process comprises the steps of derivatizing the monoterpene (or sesquiterpene) to produce a monoterpene (or sesquiterpene) derivative, separating the monoterpene (or sesquiterpene) derivative, and releasing the monoterpene (or sesquiterpene) from the derivative. Also encompassed by the scope of the present invention is a pharmaceutical composition comprising a monoterpene (or sesquiterpene) having a purity greater than about 98.5% (w / w). The purified monoterpene can be used to treat a disease such as cancer. The present monoterpene (or sesquiterpene) may be administered alone, or may be co-administered with radiation or other therapeutic agents, such as chemotherapeutic agents.

The invention concerns a pseudopeptide compounds selected among the set constituted by:(i) the compounds of formula (I):in which:A1 represents a single bond, D-Arg or L-Lys;A2 represents L-Pro or trans-4-hydroxy-L-Pro (4Hyp);A3 represents L-Phe or L-thienylalanine (Thi);Y represents a hydrogen atom or a C1-C3 alkyl group;X represents a sulphur or oxygen atom; and,(ii) their additive salts. The invention also concerns the preparation and use of this compound and its additive salts in therapy.

The invention relates to compositions, methods and kits for the treatment of cancer. ATP-dependent potassium channel agonists, salts thereof, or chemical analogs thereof, for example, minoxidil sulfate, have been found to possess anti-neoplastic properties. Administering minoxidil sulfate may prolong the life of a cancer patient; for example, a patient with a brain tumor.

The invention relates to compositions, methods and kits for the treatment of cancer. ATP-dependent potassium channel agonists, salts thereof, or chemical analogs thereof, for example, minoxidil sulfate, have been found to possess anti-neoplastic properties. Administering minoxidil sulfate may prolong the life of a cancer patient; for example, a patient with a brain tumor.

The present invention relates to efflux inhibitor compositions and methods of using these agents for treating conditions where the activity of efflux transporter proteins (e.g., Breast Cancer Resistance Protein (BCRP) and P-Glycoprotein (P-GP)) inhibit effective delivery of a therapeutic agent to a target tissue (e.g., brain, spinal cord, nerves, cerebrospinal fluid, testis, eyeballs, retina, inner ear, placenta, mammary gland, liver, biliary tract, kidney, intestines, lung, adrenal cortex, endometrium, hematopoietic cells, and / or stem cells).

The present invention includes methods of improving proteolytic stability of a polypeptide, comprising alkylating at least one selected from the group consisting of a N-terminus amino group, the NH group of the N-terminus first internal amide bond, another primary amino group, a thiol group and a thioether group within the polypeptide. The present invention further includes polypeptides incorporating such chemical modifications.

It is intended to provide a benzoxazole derivative or a pharmaceutically acceptable salt or solvate thereof which is useful in the early diagnosis of a conformation disease; a composition or a kit containing the same for diagnosing a conformation disease; a medical composition for treating and / or preventing a conformation disease; and so on.

Disclosed are compositions and methods related to improving pharmacological properties of bioactive compounds targeting nervous system.

It is intended to provide a benzoxazole derivative or a pharmaceutically acceptable salt or solvate thereof which is useful in the early diagnosis of a conformation disease; a composition or a kit containing the same for diagnosing a conformation disease; a medical composition for treating and / or preventing a conformation disease; and so on.

The invention provides application of a 10B-containing compound in preparation of a medicine specifically combined with a beta amyloid protein, wherein the medicine specifically combined with the beta amyloid protein can reduce or eliminate the beta amyloid protein in an irradiation process of a neutron beam transmitted by a neutron capture treatment device after the beta amyloid protein is combined, so that Alzheimer's disease is further treated. The invention provides a new method for treatment of the Alzheimer's disease.

The invention discloses a propionylation catalpol derivative, which is prepared by esterifying catalpol and propionic anhydride and also provides a corresponding preparation method and application thereof. According to the propionylation catalpol derivative disclosed by the invention, the propionic anhydride and the catalpol are subjected to esterification reaction to generate an esterification product from the esterification reaction in which all six hydroxyls or 1 to 5 hydroxyls of the catalpol partially participate, and namely, the esterification product is the full-propionylation or partial-propionylation catalpol derivative. The catalpol derivative has good anti-aging activity, blood-brain barrier permeability of the catalpol is improved, and an esterification yield can reach 96.71%;ideas are provided for researching action modes and anti-ageing action mechanisms of the catalpol derivative and target protein, reference is provided for further synthesizing anti-aging medicine withhigher activity and higher bioavailability, and later development of catalpol is facilitated.

The present invention relates to the medical use of a certain group of diphenyl urea derivatives as potassium channel blockers for treating cardiovascular diseases, an obstructive or inflammatory airway disease, urinary incontinence, psychosis, epilepsy or pain, or for facilitating the blood-brain barrier permeability for other therapeutic substances. In other aspects the invention relates to the use of these compounds in a method of therapy.

The invention discloses a sulfhydryl compound serving as a histone deacetylase inhibitor, and an application thereof. Pharmacological experiment results show that the composition has high anti-proliferative activity on various tumor cells, shows a protective effect on glutamic acid-induced neuronal cell damage on a cell model, has low toxicity to normal cells, low potential cardiotoxicity, ideal pharmacokinetic characteristics and high blood-brain barrier permeability, and has a development prospect as a high-efficiency low-toxicity antitumor or neurodegenerative disease treatment agent. The sulfhydryl compound is a compound with a structural general formula represented by formula (I) shown in the description, or a pharmaceutically acceptable salt, an ester or a prodrug thereof.

Disclosed are: a PET probe compound having an alkoxy group substituted by a fluorine and a hydroxy group, which is useful for the early diagnosis of a conformational disease; a pharmaceutical composition for the treatment and / or prevention of a conformational disease, which comprises the compound; and others.

The invention relates to a pharmaceutical composition of ginsenosides RG5 and RZ1 and application of the pharmaceutical composition in brain protection. Active components of the pharmaceutical composition are the ginsenosides RG5 and RZ1 and can be used for preparing a medicine for the brain protection. A pharmaceutical preparation provided by the invention contains the pharmaceutical composition of the ginsenosides RG5 and RZ1 and pharmaceutically-acceptable carriers, and is prepared into pharmaceutically-acceptable dosage forms; the pharmaceutically-acceptable carriers comprise one or more of solids, semisolids or auxiliary liquid materials; the pharmaceutically-acceptable dosage forms comprise injections, tablets, capsules, granules, pills, syrup, powder and ointment. In the pharmaceutical composition provided by the invention, the ginsenosides RG5 and RZ1 have an effect of mutually promoting the permeability of a blood brain barrier; the permeability of the blood brain barrier of the ginsenosides RG5 and RZ1 is remarkably higher than that of single ginsenosides RG5 or RZ1, therefore, the ginsenosides RG5 and RZ1 can be combined for a drug.

The invention provides a short peptide capable of realizing brain-targeting drug delivery and application of the short peptide. An amino acid sequence of the short peptide is Ile-Thr-Pro-Thr-Arg-Lys-Ser, shown as SEQ ID NO: 1. Immunofluorescence test results show that the short peptide provided by the invention has good brain-targeting drug delivery characteristic and can improve the blood-brain barrier permeability of the existing drug.

The present invention relates to a method of increasing blood brain barrier permeability in a subject. This method involves selecting a subject who would benefit from increased blood brain barrier permeability and subjecting the selected subject to a treatment. That treatment increases adenosine level and / or bioavailability, modulates adenosine receptors, and / or increases CD73 level and / or activity under conditions effective to increase blood brain barrier permeability in the subject. Methods of decreasing blood brain barrier permeability in a subject, treatment of a subject for a disorder or condition of the central nervous system, and screening compounds effective in increasing blood brain barrier permeability, as well as pharmaceutical agents are also disclosed.

The present invention relates to a serine derivative compound having improved blood-brain barrier (BBB) permeability and the use thereof, and more particularly, to a novel serine derivative compound having improved blood-brain barrier permeability compared to L-serine, and a pharmaceutical composition for preventing, treating or alleviating nervous system diseases such as cognitive disorder, intellectual disability, microcephaly, epilepsy, neurodevelopmental disorder, dementia, autism spectrum disorder, Down's syndrome, Rett's syndrome, fragile X syndrome, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, the pharmaceutical composition containing the compound as an active ingredient. The compound of Formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient for the pharmaceutical composition for preventing or treating central nervous system diseases according to the present invention exhibits significantly improved blood-brain barrier permeability, activates neuronal cell proliferation, and exhibits a neuronal protective effect of inhibiting neuronal cell death resulting from mitochondrial membrane potential damage and / or endoplasmic reticulum stress caused by oxidative stress, and exhibits improved blood-brain barrier permeability. Therefore, the compound has an excellent effect on the prevention, treatment and alleviation of central nervous system diseases such as cognitive disorder, intellectual disability, microcephaly, epilepsy, neurodevelopmental disorder, dementia, autism spectrum disorder, Down's syndrome, Rett's syndrome, fragile X syndrome, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, and thus is a highly useful invention in the pharmaceutical industry, the food industry and the livestock industry.

The invention discloses a croton acylated catapol derivative which is prepared by esterifying catalpol and crotonic anhydride. The invention provides a corresponding preparation method and application, and the preparation method comprises the following steps: 1) dissolving catalpol into triethylamine, adding a catalyst 4-dimethylaminopyridine, adding crotonic anhydride under protection of nitrogengas, reacting for 12-36 hours at a temperature of 30-90 DEG C, and drying triethylamine by distilling to obtain a product, wherein a molar ratio of crotonic anhydride to catalpol is (6-18) to 1, anda molar ratio of 4-dimethylaminopyridine to catalpol is 1 to (9.5-10.5); and 2) dissolving the product in the step 1) into dichloromethane, adding an alkaline agent, standing and layering, discardingan upper-layer water phase, drying an organic phase to remove water, drying dichloromethane by distilling, purifying and separating, evaporating-drying, and filtering to obtain the catapol derivative.The catapol derivative has good anti-ageing activity, improves blood-brain barrier permeability of catapol, and has an esterification rate of 99.16%.

A leukotriene C4 and D4 antagonist is used to treat or inhibit brain inflammation and sepsis by acting to inhibit increased capillary permeability and white blood cell extravasation. Potential candidate compounds can be screened in a non-human mammal before or after administration of an inflammation inducing agent into the subarachnoid space by determining their ability to inhibit increased capillary permeability and white blood cell extravasation.

The invention discloses a croton acylated catapol derivative which is prepared by esterifying catalpol and crotonic anhydride. The invention provides a corresponding preparation method and application, and the preparation method comprises the following steps: 1) dissolving catalpol into triethylamine, adding a catalyst 4-dimethylaminopyridine, adding crotonic anhydride under protection of nitrogengas, reacting for 12-36 hours at a temperature of 30-90 DEG C, and drying triethylamine by distilling to obtain a product, wherein a molar ratio of crotonic anhydride to catalpol is (6-18) to 1, anda molar ratio of 4-dimethylaminopyridine to catalpol is 1 to (9.5-10.5); and 2) dissolving the product in the step 1) into dichloromethane, adding an alkaline agent, standing and layering, discardingan upper-layer water phase, drying an organic phase to remove water, drying dichloromethane by distilling, purifying and separating, evaporating-drying, and filtering to obtain the catapol derivative.The catapol derivative has good anti-ageing activity, improves blood-brain barrier permeability of catapol, and has an esterification rate of 99.16%.

The invention discloses a functional platelet bionic intelligent carrier and its anti-ischemic stroke application. The biomimetic carrier is composed of platelet membrane-coated polymer nanoparticles loaded with neuroprotective agent ZL006e, Tat membrane-penetrating peptide, a substrate peptide segment that can be cleaved by thrombin, and a thrombolytic protein conjugate. The carrier system has the characteristics of good biocompatibility, can effectively prolong the circulation time in the body, and can target the microthrombus at the lesion site of ischemic stroke, and release thrombolytic drugs. At the same time, the exposed Tat wears Membrane peptides mediate neuroprotective agents to increase the permeability of the blood-brain barrier, and use pH as an intelligent drug release switch to respond to the pH-mediated degradation of the lesion, so that the drug can be released quickly at the cerebral ischemic lesion, maximizing the curative effect and reducing the blood pressure. toxic side effect.

The invention discloses a class of 8-substituted 1,6-diazabenzanthrone derivatives, a synthesis method and application thereof. The derivative has a structure shown in the following formula (I), and its synthesis method is: the compound shown in the formula (II) is nitrated, and the compound shown in the formula (III) obtained reacts with sodium sulfide in the first organic solvent to obtain The compound shown in formula (Ⅳ); react it with DMF-DMA in the second organic solvent, add ammonium chloride and weak acid reaction after the reaction is completed, and the whole reaction is carried out under the protection of atmosphere, and the compound shown in gained formula (Ⅴ) Then react with the acid chloride shown in formula (VI) in the third organic solvent to obtain the corresponding crude product of the target compound; the compounds of the structure shown in the formula (I) to formula (VI) are respectively as follows: wherein, n =1~3;R 2 for‑N(CH 3 ) 2 ,-NEt 2 ,