33results about How to "Improve brain targeting" patented technology

A menthol derivative containing fatting acid is prepared through catalytic esterifying reaction between menthol and straight-chain or branch-chain C5-C30 fatty acid. A medicine containing said derivative is also disclosed, which has high cerebral target performance.

The present invention discloses a piperazine (piperidine) cyclohexyl derivative and applications of the piperazine (piperidine) cyclohexyl derivative in treatment of neuropsychiatric diseases. According to the present invention, the pharmacological experiment results show that the piperazine (piperidine) cyclohexyl derivative provides high affinity with a dopamine D2 receptor, a dopamine D3 receptor, a serotonin 5-HT1A receptor and a serotonin 5-HT2A receptor, provides good D3/D2 receptor selectivity and good 5-HT1A/5-HT2A receptor selectivity, and provides low affinity with alpha receptor; the in vivo test results show that the preferred compound has characteristics of good anti-schizophrenia effect, good pharmacokinetic property, low side effect, low acute toxicity and high safety, and has the development value of being adopted as the novel efficient and low-toxic anti-neuropsychiatric disease; and the piperazine (piperidine) cyclohexyl derivative is a compound represented by the structural general formula (I), or a geometric isomer, an optical isomer, a salt, a hydrate or a solvate thereof. The formula (I) is defined in the specification.

The invention relates to antitumor drugs and discloses anti-glioma drugs based on Venenum Bufonis extract and a preparation method thereof, the drugs being a bufotalin submicron emulsion and a bufotalin nanoparticle preparation, wherein the bufotalin submicron emulsion comprises Venenum Bufonis extract, medium chain triglyceride, a lecithin, poloxamer 188, glycerol, sodium oleate and injection water; the bufotalin nanoparticle preparation comprises Venenum Bufonis extract, glycerol monostearate, medium-chain fatty acid glyceride, oleic acid, a lecithin, poloxamer 188, sodium deoxycholate and injection water. Both the two preparations can combine with endothelial cells in cerebral blood capillaries, enabling the drugs to be transmitted into the brain through membranes or by means of adsorption, medication, endocytosis and transferring, cerebral targeting of the drugs is improved, and further increase of bufotalin in the brain is facilitated, and glioma resistance is achieved by inducing apoptosis and excessive autophagy of cells.

The invention discloses a dual brain-targeted prodrug with an organic-amine-modified vitamin C being a carrier. The dual brain-targeted prodrug is a structure or pharmacy acceptable salt or water compound shown in the general formula (I), wherein X represents -(CH2)n-, -C(O)-(CH2)n-C(O)-or-(CH2)m-O-, -(CH2)m-NH-, -(CH2)m-C(O)-, -c(o)-(ch2)M-, -C(O)-(CH2)m0NH-, n represents 0-6, m represents 1-4, and Drug represents medicine acting on the central nervous system. The series of prodrug can improve brain-targeted performance of the medicine and increase the concentration of the central nervous system, in this way, the treatment effect of the medicine is improved, meanwhile, medicine distributed on peripheral organs is reduced, and toxic and side effects of the medicine are reduced.

The invention belongs to the technical field of medicines and discloses invisible brain-targeted triptolide nano-liposome and a preparation method. The preparation method comprises the following steps: using nano triptolide lipidosome as a medicine carrier, and performing invisibility modification on the medicine carrier by using polyethylene glycol PEG (Polyethylene Glycol), so as to obtain invisible triptolide nano-liposome; connecting brain-targeted ligand Lf with the surface of the PET-TP nano-liposome by adopting a covalent coupling method, thereby obtaining the invisible brain-targeted triptolide nano-liposome. Through optimization of preparation processes, the invisible brain-targeted triptolide nano-liposome which is uniform in particle size distribution, relatively high in packaging rate and good in stability is successfully prepared, and related results are not available in document reports; the average particle size of the prepared Lf-PEG-TP nano-liposome is 105.98+/-2.65nm,the packaging rate of the nano-liposome is 55.96+/-2.13%, and the Lf coupling percentage of the nano-liposome is 79.26+/-3.57%.

The invention provides a brain-targeted water soluble drug carrier as well as a preparation method and application thereof. An LDL (low density lipoprotein) receptor of an endothelial cell of blood-brain barrier is selected as a transmission water soluble drug to treat a target spot of central nervous system diseases, and chitosan with very good biocompatibility is taken as a drug carrier material to research a low-toxicity efficient water soluble drug nano brain-targeted preparation. The brain-targeted water soluble drug carrier can be used for strengthening brain targeting of water soluble drugs, strengthening the curative effect, lowering the toxic and side effect, and improving the bioavailability.

The invention discloses a dual-brain-targeting prodrug commonly modified by glucose and vitamin C; the dual-brain-targeting prodrug is the structure shown in a general formula (I) or pharmaceuticallyacceptable salts and aquo-complex; the formula is as shown in the specification. In which, X represents -(CH2)a , C(O) (CH2)a C(O) or (CH2)b O , (CH2)b NH , C(O) (CH2)b O , C(O) (CH2)b NH ; a represents 0-6, b represents 1-4; Y represents (CH2)n , C(O) (CH2)n C(O) or C(O) (CH2)m , (CH2)m C(O) ; n represents 0-6, m represents 1-4; Drug represents a drug applied to a central nerve system.A series of prodrug can improve the brain targeting property and pivot concentration, so as to enhance the drug effect; meanwhile, the drug distribution at a peripheral organ is reduced, and the toxic and side effects of the drug are reduced.

The invention discloses a chitosan-oligosaccharide-modified self-carrying type carrier-free nasal cavity nano preparation brain-targeted delivery system and a preparation method thereof. The system includes hydrophobic micro-molecule drugs, polyethylene glycol derivatives and chitosan oligosaccharide which have a neuroprotective effect. The invention also provides a preparation method of the nasalcavity nano preparation brain-targeted delivery system. The preparation method includes the steps of 1, preparing nano-particle freeze-dried powder; 2, stirring the freeze-dried powder and chitosan oligosaccharide in isotonic normal saline before use to form a nasal cavity preparation with good membrane permeability. The system is simple in preparation method and can improve the hydrophobicity ofthe micro-molecule drugs, reduce the toxicity and enhance the ne neuroprotective effect. The system is free of carriers, biodegradation problems and accumulation of toxin. The drug carrying rate reaches 25 percent or above, a permeable membrane has good absorption performance after being modified by chitosan oligosaccharide, and the drugs are delivered into the brain with high targeting property.The application modes of the dosage form include nasal dripping, spray and the like, the operation is simple, convenience is provided for patients who have taken the drugs for a long time, and the system has a good application prospect in the aspect of treating nervous system diseases.

The invention discloses a method for preparing nano-liposome marked by colloidal gold and loaded with a PD (pharmacodynamics) medicine. The method comprises the following steps: dispersing lecithin and a cholesterol and ethanol solution in a PBS (Phosphate Buffer Solution) containing colloidal gold and levodopa or amantadine PD therapeutic medicine under specific conditions, then adding the PBS solution into a water bath to stir, completely volatilizing the ethanol and then performing appropriate ultrasonic treatment to prepare the nano-liposome. The prepared nano-liposome marked by colloidal gold and loaded with the PD medicine is small in particle diameter and excellent in stability; meanwhile, the nano-liposome is located and marked by the gold, thereby improving the stability of the PD medicine, improving the bioavailability, reducing the usage amount of the medicine and reducing the toxicity. The preparation method is simple to operate; the reaction is easy to control; the product, namely the nano-liposome can be used for researching the medicine administration effect of the nano-levodopa or amantadine liposome, improving the toxic and side effects of the levodopa or the amantadine and enhancing the brain targetability. The product also can be used as a probe which is used for researching a cerebral metabolism pathway of the nano-liposome.

The invention belongs to the technical field of medicine and pharmacology, and discloses a preparation method of berberine long-circulating nano-liposome BR-Lf with a brain targeting function. The preparation method comprises the following steps: preparing a PL-COOH liposome by using ammonium sulfate as a hydration medium and adopting an improved ethanol injection method; taking 2 parts by mass of PL-COOH, adding 1 part by mass of an EDC solution and 1 part by mass of an NHS solution in an ice-water bath, performing magnetic stirring and activating for 0.5 h, restoring to room temperature, adding 6 parts by mass of Lf, performing full dissolving, adding 1.4 parts by mass of TEA, performing reacting for 4 h, and terminating the reaction in the ice-water bath to obtain lactoferrin modified PEGylated blank liposome PL-Lf; and taking PL-Lf suspension, removing an external water phase through an anion-cation fiber column, adding a berberine hydrochloride BR solution according to a drug-lipid ratio of 1: 15, performing incubating at a constant temperature of 40 DEG C for at least 15 minutes, and terminating drug loading in the ice-water bath to obtain BR-Lf. By optimizing the preparation process, the BR-Lf which is uniform in particle size distribution, relatively high in encapsulation efficiency and good in stability is successfully prepared.

The invention discloses citicoline sodium brain-targeting thermosensitive gel. The citicoline sodium brain-targeting thermosensitive gel is a preparation which can be absorbed fast and has high bioavailability. The citicoline sodium brain-targeting thermosensitive gel utilizes water as a solvent and comprises solute components of 10 to 400mg/ml of citicoline sodium, 0.1 to 3.0mg/ml of Tween-80, 0.5 to 5.0mg/ml of phosphatide E80, 0.5 to 3.0mg/ml of poloxamer P188, and 5.0 to 10.0mg/ml of poloxamer P407. The invention also discloses a preparation method of the citicoline sodium brain-targetingthermosensitive gel. The citicoline sodium brain-targeting thermosensitive gel has a high drug loading amount, is uniform and stable, has good fluidity, is in a state of gel at a temperature of 33 DEG C, has good biological adhesion strength, is suitable for being applied through a nasal cavity, has a good appearance, and does not produce floating oil and layering.

The embodiment of the invention discloses a preparation method of a triptolide and berberine co-loaded invisible nano-liposome. The preparation method comprises the following steps: preparing a PEGylated blank liposome PL and a carboxyl-end blank liposome PL-COOH by taking citric acid as a hydration medium and adopting an improved ethanol injection method; adjusting the pH value of the carboxyl-terminal blank liposome PL-COOH to 7 by using hydrochloric acid, taking the gradient PEGylated blank liposome PL, and adding the gradient PEGylated blank liposome PL into a berberine hydrochloride BR solution according to a drug-lipid ratio of 1: (15-25) to obtain BR-PL and BR-PL-COOH liposome; the preparation method comprises the following steps: adding a triptolide TP solution into BR-PL and BR-PL-COOH lipidosome, incubating for at least 60 minutes at a constant temperature of 40-60 DEG C, and terminating drug loading in an ice-water bath, so as to prepare the triptolide and berberine co-loaded invisible nano-lipidosome TP-BR-PL and TP-BR-PL-COOH.

Belonging to the field of biological technology, the invention and relates to a brain targeting gene delivery system based on polymethacrylate and a preparation method thereof. A vector of the gene delivery system comprises a cationic chain segment polymethacrylate, an electrically neutral segment and a brain targeting functional base TGN in covalent connection, and the vector further conducts self-assembling with an anionic plasmid DNA into nano-micelles through electrostatic interaction. The system provided by the invention can transfer gene drugs across the blood-brain barrier into the brain to play a role. Through noninvasive intravenous injection administration test, the system significantly improves the brain targeting performance of the gene delivery system and expression of the gene in the brain; the particle size, surface charge and modification degree of targeting functional groups are controllable, so as to facilitate optimization of the gene delivery system. The gene delivery system constructed by the invention has the advantages of low cytotoxicity and high brain targeting efficiency.