34 results about "Donepezil" patented technology

The invention provides donepezil sustained-release microspheres and a preparation method, a pharmaceutical preparation and application thereof. The preparation method comprises the following steps: forming a water phase (containing a surfactant, an osmotic pressure regulator and water, and regulating the pH value with a pH regulator); forming an oil phase (comprising donepezil, a carrier material and an organic solvent); and adding the oil phase into the water phase, dispersing to form a pre-emulsion, performing membrane emulsification on the pre-emulsion to form an emulsion, and finally curing, washing and freeze-drying the emulsion to obtain the donepezil sustained-release microspheres. The preparation process is stable and controllable, the batch-to-batch repeatability is good, the surface of the microsphere is smooth and complete, the particle size distribution is uniform, the size is controllable, the microsphere has high drug loading capacity, long-term stable release can be realized, the injectability is excellent, the administration frequency can be reduced, and the adverse reaction of gastrointestinal tracts can be reduced.

The invention discloses an Alzheimer's disease transnasal microneedle drug delivery system and a preparation method thereof, and relates to the technical field of biological medicine, the microneedle drug delivery system comprises a microneedle substrate and a microneedle tip; the microneedle tip comprises a medicine carrying exosome, hyaluronic acid and polyvinylpyrrolidone; the drug-loaded exosome comprises a tobacco leaf exosome, the surface of the tobacco leaf exosome is connected with brain-targeted peptide RVG29, and donepezil is wrapped in the tobacco leaf exosome. The invention further discloses a preparation method of the microneedle drug delivery system. According to the nasal microneedle drug delivery system for Alzheimer's disease, the delivery efficiency of a small molecule drug donepezil to the brain is enhanced, and the nasal microneedle drug delivery system has the advantages of being high in safety, good in curative effect and good in targeting property; the problems that in the prior art, small molecule medicine donepezil difficultly passes through the blood brain barrier and enters the central nervous system, the medicine delivery efficiency is low, the treatment effect is low, and side effects are many are solved.

The use of glutamate 2b receptor antagonists and sigma receptor agonists as antitussives to treat or prevent a cough is disclosed. In preferred embodiments, the glutamate 2b receptor antagonist is ifenprodil or radiprodil. Preferred sigma receptor agonists include fluvoxamine, fluoxetine, excitalpram, and donepezil.

The application discloses application of a drug composition of bacosol and donepezil in preparation of a drug for treating Alzheimer's disease. The application first discovers that bacosol has double-target point inhibitory activity on BACE1 and AChE. Through cell and animal model verification, the bacosol single drug and the composition can exert an anti-AD effect through a multi-target point mechanism, and the composition with a molar ratio of 1:1 to 1:10 has a significant synergistic effect, wherein the synergistic effect is the most significant when the molar ratio is 1:1. The application provides a new treatment method for Alzheimer's disease.

The present invention relates to a donepezil and tadalafil combination therapy for the prevention, treatment or amelioration of Alzheimer's disease or cognitive dysfunction. The combined administration of donepezil and tadalafil according to the present invention has an improvement effect on Alzheimer's disease or cognitive impairment superior to that of the individual administration of donepezil, and thus can be effectively used as a therapeutic or complexing agent or the like for Alzheimer's disease or cognitive impairment.

The use of glutamate 2b receptor antagonists and sigma receptor agonists as antitussives to treat or prevent a cough is disclosed. In preferred embodiments, the glutamate 2b receptor antagonist is ifenprodil or radiprodil. Preferred sigma receptor agonists include fluvoxamine, fluoxetine, excitalpram, and donepezil.

The present disclosure provides a method of preparing a drug matrix layer and a transdermal delivery system for delivering donepezil free base to patients suffering from central nervous system disorders, including dementia and Alzheimer's disease.

The invention provides an application of a donepezil or gardenia jasminoides ellis-phellodendron amurense component in preparation of a cholinergic regulation-based immune liver injury resisting medicine, and belongs to the technical field of biological medicines. The pharmaceutical composition for resisting immunological liver injury is a donepezil component or a gardenia jasminoides ellis-phellodendron amurense component. The invention solves the problems of single action target and incomplete regulation and control mechanism of the existing immunological liver injury treatment medicine, provides a treatment scheme with anti-inflammatory, anti-oxidation, liver cell apoptosis inhibition and cholinergic system regulation and control functions, explores a brand new medical application of donepezil, verifies the liver protection effect of donepezil in immunological liver injury, and provides a new application of donepezil in immunological liver injury. The application limitation is broken through; the treatment effect of the Jashima component in an immune liver injury model induced by concanavalin A is defined, a dual regulation mechanism of inhibiting AChE expression and increasing alpha7 nAChR expression is disclosed, and the application scene is expanded; a multi-dimensional regulation and control network of cholinergic anti-inflammatory pathway-NF-kappa B inflammatory pathway-hepatocyte apoptosis is constructed, and a more efficient and comprehensive treatment strategy is provided for immunological liver injury.

The invention relates to a crystal form of donepezil 1-hydroxy-2-naphthoate ((+ / -)-2-[(1-benzyl-4-piperidyl) methyl]-5, 6-dimethoxy-1-indanone 1-hydroxy-2-naphthoate), a preparation method of the crystal form and application of the donepezil 1-hydroxy-2-naphthoate. The crystal form of donepezil 1-hydroxy-2-naphthoate provided by the invention has the advantages of better stability, lower hygroscopicity, lower solubility, lower pH dependence on solubility, better preparation processability and the like, and has important value for the development of long-acting injection of the drug in the future.

The invention relates to application of a phenyl pyrimidone compound, in particular to application of the phenyl pyrimidone compound shown in a formula (I) or tautomers, pharmaceutically acceptable salts, solvates or isotope labels of the phenyl pyrimidone compound in preparation of drugs for improving or treating cognitive impairment and / or improving or treating brain vascular diseases. Through cell model and animal model test research, compared with a clinically available drug donepezil on the market and a clinically researched drug mironafil, the compound disclosed by the invention has remarkable treatment characteristics and substantive technical progress in the aspects of protecting nerve cells, improving cognitive impairment, improving brain vascular diseases, improving degenerative diseases such as Parkinson's disease and the like.

Use of a phenylpyrimidinone compound. The present invention specifically relates to use of a phenylpyrimidinone compound represented by formula (I) or a tautomer thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, or an isotopically labelled compound thereof in the preparation of a drug for ameliorating or treating cognitive impairment, and / or ameliorating or treating cerebrovascular diseases. Studies using cell and animal models have shown that compared to the commercially available clinical drug donepezil and the investigational clinical drug mirodenafil, the compound has demonstrated significant therapeutic characteristics and substantial technical advancements in terms of protecting nerve cells, ameliorating cognitive impairment, ameliorating cerebrovascular diseases, and ameliorating degenerative diseases such as Parkinson's disease.

The invention provides compositions comprising a topical formulation of donepezil and methods of use thereof for intradermal applications.

Disclosed are uses of glutamate 2b receptor antagonists and sigma receptor agonists as antitussives for treating or preventing cough. In a preferred embodiment, the glutamate 2b receptor antagonist is ifenprodil or radiprodil. Preferred sigma receptor agonists include fluvoxamine, fluoxetine, escitalopram, and donepezil.

The invention discloses aloperine derivatives as well as a preparation method and application thereof, and belongs to the technical field of medicine preparation. According to the invention, aloperine is taken as a lead compound, 3, 4-dichlorophenyl-1, 2, 3-triazole is utilized to replace a hydrogen atom at N-12 site of aloperine, and an aloperine derivative A4 is synthesized; the MTT experiment result shows that the nerve cell protection effect of aloperine is enhanced by introducing the 1, 2, 3-triazole fragment, and EC50 of A4 is 4.711 mu M and is obviously stronger than that of aloperine serving as a lead compound and that of donepezil serving as a positive control drug; a Western blot experiment shows that the A4 reduces the relative expression of a p-Tau (Thr 181) protein, a p-P38 / P38 protein, a p-ERK1 / 2 / ERK1 / 2 protein, a p-JNK / JNK protein and a p-NF-kappa B / NF-kappa B protein. The aloperine derivative A4 reduces expression of various inflammatory factors and abnormal phosphorylation of Tau protein by inhibiting an MAPK pathway, so that the aloperine derivative A4 has a high protection effect on nerve cells and has Alzheimer's disease resisting activity.

The present invention relates to the field of biotechnology, and in particular to a kind of donepezil-loaded transferrin chitosan-cyclic peptide RGD nanoparticles, a preparation method and an application thereof. The donepezil-loaded transferrin chitosan-cyclic peptide RGD nanoparticles provided by the present invention have excellent solubility and dispersibility in water, small particle size, high encapsulation rate and good sustained-release effect. Chitosan-cyclic peptide cRGD can significantly improve the drug targeting ability. When delivered to the nose and brain, chitosan prolongs nasal retention and reduces nasal mucosal toxicity, while transferrin helps cross the blood-brain barrier, and cyclic peptide RGD can accurately target and locate the lesion site. In the nanoparticles provided by the present invention, both the chitosan-cyclic peptide RGD linker and transferrin have the advantages of good biocompatibility, natural degradability and safety. It is expected to improve bioavailability by comprehensively optimizing the drug release and absorption process, and provide a new dosage form and delivery strategy for the treatment of brain diseases.

The invention provides application of apoptin combined peptide to treatment of Alzheimer's disease. The apoptin combined peptide used in the invention has the following amino acid sequences: MetGlyArg, LysLysArg, Arg, GIn, Arg, Arg, LeuLysProProSerLysLysArgleArgleGlyleAlaGlyleThrLeuSerLeuArg, ProArg, Thr, AlaLysArg, ArgleArg, Leu and the like. The apoptin combined peptide provided by the invention has the following amino acid sequences: MetGlyArg, LysLysLysArg, Arg, Arg and Leu. Various animal model experiments prove that after the polypeptide drug is administered through intravenous injection (with the dosage of 1mg / kg to 3mg / kg), cognitive impairment, spatial learning and memory ability of model animals with Alzheimer's disease, vascular dementia and senile dementia can be remarkably improved, and the treatment effect is superior to that of donepezil. The action mechanism comprises reduction of oxidative damage, inhibition of APP and BACE1 pathological protein expression, increase of neuron number and nissl body content, inhibition of cell apoptosis and the like. The polypeptide medicine is high in safety and remarkable in curative effect, and a new effective medicine is provided for treating the Alzheimer's disease.

This invention discloses a traditional Chinese medicine composition for treating vascular cognitive impairment, its preparation method, and its application, belonging to the field of traditional Chinese medicine technology. It includes the following raw materials: stir-fried Atractylodes macrocephala, Fritillaria thunbergii, Ligusticum chuanxiong, Salvia miltiorrhiza, Curcuma longa, Acorus tatarinowii, Polygala tenuifolia, Cornus officinalis, Cistanche deserticola, Rehmannia glutinosa, Scrophularia ningpoensis, and borneol. Preparation method: First, the volatile oil is extracted by steam distillation and encapsulated with β-cyclodextrin; then, the lipid-soluble components in Salvia miltiorrhiza and Fritillaria thunbergii are extracted with ethanol; finally, the residue is combined with the remaining medicinal materials and decocted in water for extraction. Through the combination of Fritillaria thunbergii and borneol, the dual functions of "clearing inflammation + opening the blood-brain barrier" are achieved, increasing the brain concentration of lipid-soluble components such as tanshinone IIA. It significantly improves the learning and memory abilities of rats with vascular cognitive impairment, with efficacy superior to the Western medicine donepezil, and exhibits synergistic effects on multiple targets such as inhibiting NLRP3 inflammasomes and upregulating BDNF. This invention has a simple process, is suitable for industrial production, and has significant clinical application value.

The invention particularly relates to application of a traditional Chinese medicine monomer in treatment of vascular dementia. The component of the traditional Chinese medicine monomer is astragaloside III. Animal experiments prove that the astragaloside III can improve the problem of poor spatial learning ability and memory ability of a mouse with vascular dementia, and also has a treatment effect on a brain function lesion region caused by vascular dementia. A cell hypoxia and sugar deficiency damage model is utilized to verify that the protection effect of the astragaloside III is better than that of astragaloside I and astragaloside IV, and it is verified that the astragaloside III has a synergistic effect in common administration with a positive drug donepezil.

The present application relates to the salt of donepezil derivative and its application in medicine, specifically, the present application relates to the salt of compound shown in formula (I), the salt of the compound can play the role of long-acting inhibition of acetylcholinesterase expression, thereby more long-acting prevention and / or treatment of Alzheimer's disease, wherein R 1 has the meaning described in the present application.

The invention discloses a method for detecting related substances in a memantine hydrochloride donepezil preparation. The detection method comprises the following steps: preparing and measuring a test solution and a reference solution by adopting a GC (Gas Chromatography) method, measuring a solvent acetonitrile, and respectively injecting into a gas chromatograph; and recording a chromatogram and calculating by peak area according to an external standard method. The detection method can be used for simultaneously detecting memantine impurity E, memantine impurity F, memantine impurity G, memantine impurity H and memantine impurity I in the memantine hydrochloride donepezil preparation. The method has the advantages of good sensitivity, durability, system applicability, specificity and accuracy, and qualified recovery rate.

The invention discloses a hetero-diad compound taking indanone-tetrahydrothieno [3, 2-c] pyridine as a parent body and a preparation method and application thereof, the hetero-diad compound taking indanone-tetrahydrothieno [3, 2-c] pyridine as the parent body is selected from the compounds shown in the following general formulas (I), (II) and (III), the compound takes indanone of donepezil as a parent nucleus, and the compound is selected from the compounds shown in the general formulas (I), (II) and (III). And the compound is combined with an anti-platelet functional group tetrahydrothieno [3, 2-c] pyridine through a linking group. The compound has multiple action mechanisms (inhibiting AChE, resisting Abeta aggregation, resisting platelet aggregation and improving learning and memory impairment) and high blood-brain barrier permeability, and is suitable for preventing and treating vascular dementia.

Provided herein are methods for promoting biostasis or preservation of a cell, tissue or organ during cancer treatment or for transplantation comprising contacting the cell, tissue or organ with an agonist of the δ-opioid receptor, SNC-80, an or Donepezil. Further provided herein is a method of treating a hematological neoplastic disease.

The invention provides compositions comprising a topical formulation of donepezil and methods of use thereof for intradermal applications.

A donepezil sustained-release microsphere, and a preparation method therefor, a pharmaceutical preparation, and the use thereof. The preparation method comprises the following steps: forming an aqueous phase (including a surfactant, an osmotic pressure regulator and water, and adjusting the pH value with a pH regulator); forming an oil phase (including donepezil, a carrier material and an organic solvent); adding the oil phase into the aqueous phase for dispersion to form a pre-emulsion, then carrying out membrane emulsification on the pre-emulsion to form an emulsion, and finally curing, washing and freeze-drying the emulsion to obtain the donepezil sustained-release microsphere. The preparation process is stable and controllable, with good batch-to-batch repeatability. The microspheres have smooth and intact microsphere surfaces, a uniform particle size distribution and controllable sizes, have a high drug loading capacity, can achieve long-term stable release, and have excellent injectability, so that the administration frequency can be reduced, and adverse reactions in the gastrointestinal tract can be alleviated.

The invention provides a method for treating or preventing dementia and / or neurodegenerative diseases, especially Alzheimer's disease and / or Parkinson's disease, of a GLP-1 compound and a corresponding pharmaceutical application of the GLP-1 compound. Compared with positive control drugs such as semeglutide, donepezil, rasagiline and L-dopamine, the compound shows a better improvement effect.

The present invention relates to a novel daily low dosage regimen of donepezil and its derivatives or pharmaceutically acceptable salts and / or solvates for use in the prevention and / or treatment of obsessive-compulsive disorders, in particular eating disorders. The invention also relates to a unit dosage form comprising from 0.25 mg to 2.5 mg of donepezil, derivatives or pharmaceutically acceptable salts and / or solvates thereof, in particular for use in the prevention and / or treatment of obsessive-compulsive disorders, in particular eating disorders.

The present invention relates to a novel low-dose daily administration regimen of donepezil and its derivatives, or pharmaceutically acceptable salts and / or solvates thereof, for the prevention and / or treatment of obsessive-compulsive disorders, particularly eating disorders. The present invention also relates to a unit dosage form containing 0.25 to 2.5 mg of donepezil, its derivatives, or pharmaceutically acceptable salts and / or solvates thereof, for use in the prevention and / or treatment of obsessive-compulsive disorders, particularly eating disorders.

The present disclosure provides a method of preparing a drug matrix layer and a transdermal delivery system for delivering donepezil free base to patients suffering from central nervous system disorders, including dementia and Alzheimer's disease.

A percutaneous absorption preparation for the treatment of dementia wherein the drug-containing layer contains donepezil or a pharmaceutically acceptable salt thereof as an active ingredient and a stabilizer that is either (i) a mixture of a thiocyanate salt and a compound selected from the group consisting of tea catechin, (+)-catechin, epigallocatechin gallate, ascorbic acid, and isoascorbic acid, or (ii) a mixture of monothioglycerol and a compound selected from the group consisting of tea catechin, (+)-catechin, epigallocatechin gallate, and ascorbic acid is disclosed. The percutaneous absorption preparation meets the criteria of Procedure 1 and Procedure 2 of the U.S. Pharmacopoeia in short-term stress test (70° C. 48 hours storage), long-term accelerated test 1 (40° C. relative humidity 75% 1 month storage), and long-term accelerated test 2 (40° C. relative humidity 75% 3 months storage), and exhibits improved stability for long-term preservation.