150 results about "Brain targeting" patented technology

The invention belongs to the field of medicine, and relates to D-configuration polypeptide with high stability and capable of realizing mediated targeting of acetylcholine receptor high-expression cells and crossing corresponding barrier membranes and a nano drug delivery system thereof as well as an application in in-vivo and in-vitro brain targeting and in treatment of brain diseases and the like. Test results indicate that DCDX and the acetylcholine receptor are combined with IC50 to obtain 84.5nM which is stable in serum and tolerates hydrolysis of protease; the model drug carried by DCDX is specifically taken in by the positive cells expressing the acetylcholine receptor and has an ability of crossing the barrier formed by the kind of cells; and the nano drug delivery system made of a DCDX-modified polymer carrier material can deliver the entrapped model drug to the target tissue while the drug effect is remarkably improved. The D-configuration polypeptide DCDX provided by the invention can mediate active targeting of the drug or nano drug delivery system and has a good application prospect in the diagnosis and treatment of multiple diseases.

The invention which belongs to the biotechnical field concretely relates to a brain targeted AmB polymer micelle administration system. The brain targeted AmB polymer micelle administration system is prepared by utilizing brain targeted head base Angiopep-2 modified polymer micelles extremely having a clinical application potential, and entrapping micromolecular hydrophobic drugs. The prepared brain targeted AmB polymer micelle administration system can effectively improve the uptaking of the hydrophobic drugs on brain capillary endothelial cells, and can effectively improve the accumulation amount of the drugs in the brain and the brain entrance efficiency of the drugs especially in a noninvasive intravenous injection mode; compared with present clinical preparations of the drugs, such as AmB for injection, the system of the invention has a substantially improved brain targeting efficiency; and the constructed polymer micelle administration system can obviously reduce the hemolyticity and the cytotoxicity of the AmB. The Angiopep-2 modified brain targeted AmB polymer micelle administration system of the invention can be used to promote the accumulation of hydrophobic drugs with low brain entrance efficiencies in the brain.

The invention belongs to the field of pharmaceuticals and relates to a cascade brain-targeting drug delivery system and the application thereof. The cascade brain-targeting drug delivery system comprises a first-stage target functional molecule, a second-stage target functional molecule and a drug carrier. The cascade target drug delivery system can identify the blood-brain barrier through the first-stage target functional molecule and identify a brain lesion through the second-stage target functional molecule, so as to achieve the accurate targeting purpose, and can also accurately transfer imaging molecules or drugs to the brain lesion, so as to achieve good imaging and therapeutic effects. The cascade brain-targeting drug delivery system can be applied to prepare formulations for treatment or diagnosis of brain diseases (such as brain tumors) and nervous system diseases.

The invention belongs to the field of pharmaceutic preparations, and relates to a brain targeting drug delivery system which comprises mediated molecules, carriers and drugs, wherein the mediated molecule is fatty acid, the carrier is polycation macromolecule, the fatty acid and the polycation macromolecule are combined to form nano particles or micelles in a covalence mode, and drug loading is completed in an entrapment or absorption mode. The invention utilizes a brain targeting tracing system to perform in-vivo and in-vitro characterization, and the result shows that the drug delivery system in the invention can obviously improve the amount of the drugs entering in the brain by permeating blood brain barriers, delivery gene drugs and diagnostic drugs in the brain by spanning the blood brain barriers and perform prevention and treatment as well as diagnosis on brain diseases. The invention can avoid potential risks and complicated administration process of an invasive administration mode, has small molecular weight and no immunogenicity, and has the advantages of large administration amount, simple administration mode, strong patient compliance and the like compared with a nasal administration mode.

The invention provides an oxiracetam agent and the preparation method, which relates to medical technical field and is used to induce the drug to penetrate through blood-brain barrier and to improve treatment effects. The agent contains oxiracetam nano-particle and excipientpharmaceutical excipient. After improved, the oxiracetam nano-particle and excipientpharmaceutical excipient contains drug core and a modified layer. The drug core mainly comprises principal agent and carrier, wherein the carrier is polymer material containing amino polysaccharide with a content of 70 to 95 percent, and the principal agent is oxiracetam with a content of 5 to 30 percent. The invention adopts polymer material containing amino polysaccharide as carrier to carry the oxiracetam and endow the oxiracetam with good brain targeting function. And the invention adopts surfactant to modify the nano surface of the carrier and lengthens the recycling time of the carrier nano-granule and the nano-particle in the recycling system. Tests show that the blood-brain barrier transmittance is 24h, which is 36.75 percent higher than ordinary oxiracetam agent and greatly enhances the dosage of oxiracetam passing through the blood-brain barrier.

The invention relates to the field of pharmaceutical preparations, which discloses a huperzine A solid lipid nano particle and a preparation method thereof. The huperzine A solid lipid nano particle is prepared from the following components in weight percent: 0.05-1% of huperzine A, 3-10% of lipid material, 2-10% of emulsifying agent and the balance water. The preparation method adopts a high-pressure even emulsification method to coat the huperzine A into a solid lipid nano particle so as to prepare the huperzine A solid lipid nano particle. The particle diameter of the huperzine A solid lipid nano particle prepared by the invention is 10-100nm, the medicine envelopment rate and the medicine-carrying quantity are high, and the stability is good; simultaneously, the use of an addition agent and an organic solvent which are harmful to a human body is avoided; and the bioavailability is enhanced, the brain targeting property is increased, and the dose and the toxic or side effect are small.

The invention discloses a targeting ginkgolide B solid lipid nanoparticle and a preparation method thereof. The ginkgolide B solid lipid nanoparticle targeting a blood brain barrier is prepared with an oil-in-water emulsion process by taking a ginkgolide B as a treating medicament, taking a solid lipid material as a carrier, taking a folic acid-modified surfactant as a targeting material and taking a mixture obtained by mixing a surfactant with the folic acid-modified surfactant in a certain ratio as an emulsifier. The particle diameter is 80-200 nanometers, and the polydispersion coefficient is 0.30+ / -0.10. According to the solid lipid nanoparticle, a brain targeting effect is achieved by using the folic acid-mediated phagocytosis on the surfaces of brain cells and the phagocytosis way of adsorption of a brain cell membrane by using the nanoparticle.

A blood brain barrier shuttle comprising a brain effector entity and a brain targeting peptide.

The present invention discloses a brain-targeted exosome which comprises an exosome capable of passing through blood brain barrier and a fluorescent material with an imaging function, wherein the fluorescent material is distributed in the entocoele of the exosome. The invention also discloses a preparation method of the brain-targeted exosome, and the method comprises: enabling brain-targeted neural stem cells to secret an exosome with a brain-targeted peptide; collecting and purifying the exosome; and enabling the fluorescent material to enter the entocoele of the exosome so as to obtain thebrain-targeted exosome. The brain-targeted exosome provided by the present invention is mainly formed by natural materials, has a function of passing through blood brain barrier, can overcome the problem that traditional nano-particles have low efficiency of passing through blood brain barrier and have toxic or side effect, overcomes the difficulty of brain targeting of traditional particles, andprovides a visible and accurate treatment strategy for treating brain-related diseases such as traumatic brain injury and brain tumors.

The nasal cavity administrated huperzine preparation consists of huperzine as effective medicine component, lauryl azatroketone and other infiltration promoter and other assistants. It is used for treating senile dementia and memory dysfunction and raising memory and learning capacity. It has high mucous membrane penetrating property and high brain targeting property and each administration can lead 80-500 microgram of huperzine into body.

The present invention belongs to the field of biotechnology, and is one kind of brain targeting gene transfer and release system and its preparation process. Lactoferrin is first used to modify cationic polymer by means of hydrophilic polymer, and the modified cationic polymer is then compounded with plasmid DNA by means of electrostatic effect to form the gene transfer and release system. The present invention can raise the transfection efficiency and expression efficiency of gene on brain capillary endothelial cell effectively, and raise the brain targeting property of gene transfer and release system and the expression of the gene in brain obviously after the non-invasive administration via intravenous injection. Compared with available technology, the present invention has obviously raised brain targeting effect.

The invention relates to a method for synthesizing a brain targeting head modification cyclodextrin (CD) derivative. The method comprises the following steps of: preparing an intermediate, namely, a mono-6-p-methylbenzene sulfonic acid-beta-cyclodextrin ester from beta-CD by an alkali aqueous solution method and introducing active amino into the reaction of the mono-6-p-methylbenzene sulfonic acid-beta-cyclodextrin ester to obtain amino-modified beta-cyclodextrin; and connecting the amino-modified beta-cyclodextrin with a mercapto brain targeting head through iso-functional group disubstituted polyethylene glycol derivative N-hydroxysuccinimide polyethylene glycol-maleimide maleinimide to prepare the brain targeting head modification cyclodextrin derivative. The method has the advantages that: the method for preparing the brain targeting head modification cyclodextrin derivative is simple and convenient, a reaction condition is mild and the derivative is taken as a medicament carrier and is easy for industrial production; a polyethylene glycol (PEG) long-chain structure is contained, so that long circulation effect is achieved and a carrier is prevented from being phagocytosed by a netlike endothelial system; and the structure is connected with a brain targeting head Tf or Lf, so that the brain transport rate of the structure serving as a medicament conveying carrier is increased.

The invention discloses a multimeric protein having the effect of brain targeting, and a preparation method and usage thereof. The method comprises the steps: firstly, expressing cholera toxin B subunit and a fusion protein EGFP-CTA2-TAT of three proteins: an enhanced green fluorescent protein, a cholera toxin A subunit and cell-penetrating peptide in escherichia coli by incompatible double plasmid systems to obtain CTB gene by PCR amplification; cloning the gene segment into a carrier pET-28a to obtain a recombinant plasmid pET-28a-CTB; using wild type CTA2, EGFP and TAT amino acid sequences as templates, inserting 3 enzyme cutting sites and linkers between EGFP and CTA2, and optimizing to obtain codons suitable for expression in escherichia coli; cloning the gene segment into a carrier PET-22b (+) to obtain recombinant plasmid PET-22b-EGFP-CTA2-TAT; using different resistances of PET-28a-CTB and PET-22b-EGFP-CTA2-TAT, and co-transforming the different resistances of the PET-28a-CTB and the PET-22b-EGFP-CTA2-TAT into escherichia coli BL21, to obtain engineering bacteria after screening under double resistance selection pressure of penbritin and kanamycin. CTB5 / EGFP-CTA2-TAT chimeric proteins can be obtained after inducible expression of the engineering bacteria by IPTG. The invention further discloses the preparation method and usage of the protein.

The invention discloses a novel lipid material which is used for prolonging the circulation time and increasing drug targets to be transmitted to the brain. According to the novel lipid material, polyethylene glycol is used for bridging, one side of polyethylene glycol is connected with cholesterol, and the other side of polyethylene glycol is connected with glucose and vitamin C, so that the defect of the targeting capability of lipidosomes modified by single glucose or vitamin C is made up for, transfer for crossing a blood-brain and blood-brain spinal fluid dual barrier is achieved, the brain targeting of drugs is improved, and the central concentration of the drugs is increased. The novel lipid material can be used for different dosage forms including liposomes, nanoparticles and micelles, and paclitaxel liposomes prepared from the material have an obvious brain targeting function and wide application prospects.

The invention relates to a novel drug delivery system with intracerebral drug delivery characteristics. The carrier material of the drug delivery system is an amphiphilic copolymer with polyphosphate as a hydrophilic chain, and is expected to self-assemble to form a nano micelle; and the surface of the nano micelle can be bonded with a brain-targeting ligand through covalent bonds. The drug delivery system has the characteristics that one or more of low-molecular-weight chemical drugs and diagnosis drugs can be delivered to penetrate through the blood-brain barrier and enter the brain, so as to exert the effects of prevention, treatment and diagnosis; the amount of the drug penetrating through the blood-brain barrier and the intracerebral distribution of the drug are increased, thereby improving treatment and diagnosis effects; the peripheral distribution of the drug is reduced, thereby reducing overall toxic and side effects; the carrier material can be biodegraded, thereby avoiding the toxicity of the carrier material; and the particle size, surface charge and ligand modification are controllable, thereby facilitating the optimization of the carrier material.

The invention provides a novel brain targeting preparation for preventing and treating a neurodegenerative disease. The novel brain targeting preparation comprises effective dose of fusion protein of cell growth factor and TAT (transcriptional activator) cell-penetrating peptide, or fusion protein of the cell growth factor, TAT and a transferrin receptor monoclonal antibody, a protein activity protecting agent, and proper auxiliary material, wherein the fusion protein of cell growth factor and TAT cell-penetrating peptide or the fusion protein of the cell growth factor, TAT and transferrin receptor monoclonal antibody is an active ingredient. The novel brain targeting preparation disclosed by the invention has excellent performance of breaking through a blood brain barrier, and is specifically targeted to the brain; the defect that single TAT does not have cell selectivity can be overcome; a brain neurons microenvironment is regulated and controlled by the effects of neurotrophy, paracrine and the like, so as to play the roles of preventing and treating the neurodegenerative disease. The novel brain targeting preparation can be prepared into a freeze-drying preparation, a liquid preparation or an adhesive preparation and applied in an intravenous injection or nasal delivery manner.

The invention discloses a brain targeted medicine lipidosome preparation as well as a preparation method and an application thereof. The brain targeted medicine lipidosome which has an enhancement effect is prepared by taking oligopeptide with arginine residues as a target molecule and by using a thin film hydration method and a three-bottle method, and the technical problems that a conventional lipidosome preparation cannot penetrate through blood brain barrier and has no brain targeting are solved. The galenic pharmacy observation shows that the encapsulation efficiency and the particle size of the brain targeted medicine lipidosome preparation disclosed by the invention meet the medicine requirements, and compared with ordinary lipidosome, the brain targeted medicine lipidosome disclosed by the invention is good in acid sensitivity and good in stability in serum, and has in-vitro cell medicine effect and in-vivo mouse glioma medicine effect which are higher than those of long circulation Doxorubicin lipidosome.

The invention discloses a deproteinated calf blood ingredient brain targeting nanosphere preparation method, specifically comprising: according to the parts by weight, dissolving 5-30 parts of stabilizing agent in distilled water, then dissolving 5-30 parts of pluronic F-68 in distilled water, mixing the two obtained solution, shaking well, adding 50-100 parts of deproteinated calf blood extractive injection, shaking well, after constant volume, adjusting the PH value to 1-4, slowly adding 5-30 parts of polybutylcyanoacrylate while stirring; stirring for 1-6h, adjusting PH value to 6-8, stirring for 1-6h to obtain the colloid solution of deproteinated calf blood ingredient nanosphere, filtering, freeze drying; dissolving the freezedrying powder of deproteinated calf blood ingredient nanosphere, adding 5-30 parts of tween 80 and stirring for 0.5-3h to obtain deproteinated calf blood ingredient brain targeting nanophere. The invention has the advantages of simple preparation method, low cost, easy storage, short time to reach the brain, rapid blood clearance rate and the like.

The invention belongs to the technical fields of high molecular materials and pharmaceutic preparations, and relates to a pH-sensitive brain tumor two-stage targeting nano drug delivery system, and a preparation method and an application thereof. The nano drug delivery system is composed of a brain targeting functional material, a pH-sensitive tumor cell targeting functional material, an amphiphilic polymer material and an anti-tumor drug; after the nano drug delivery system crosses the blood-brain barrier and enters the brain, the nano drug delivery system is capable of responding to the slightly acidic environment of brain tumor so that the tumor cell targeting functional material molecules extends outwards to further target to the brain tumor cells. In vitro and vivo activity evaluation results indicate that the system is capable of specifically delivering the anti-tumor drug to the brain tumor part and also capable of obviously improving the accumulation of the drug in the brain tumor tissue, and has an obvious anti-brain tumor effect; and the system also has the characteristic of intelligently responding to the pathological environment to realize specifically targeted drug delivery, and thus is wide in application prospect.

The invention provides a brain-targeting neurotrophic factor fusion polypeptide for preventing and treating Alzheimer's disease, which is composed of a neurotrophic factor active peptide segment, 11 peptide and 6-aminohexanoyl (Ahx) in the middle of the neurotrophic factor active peptide segment and the 11 peptide. An amino acid sequence of the 11 peptide is YGRKKRRQRRR, and the neurotrophic factor active peptide segment comprises a brain-derived neurotrophic factor (BDNF), a nerve growth factor (NGF) or a ciliary neurotrophic factor (CNTF). The fusion polypeptide can penetrate a blood-brain barrier and can be used for preventing and treating Alzheimer's disease.

The invention discloses a brain targeting liposome and the process for preparing brain targeting liposome pharmaceutical preparation, wherein the brain targeting liposome pharmaceutical preparation comprises medicament, various synthesized or natural phosphatide with brain targeting function as liposome coating material, cephalin having brain tissue absorption accelerating agent, liposome coating material, sphingomyelin with brain tropism and immunity activation, cholestrin for liposome coating material and liposome stabilizing agent, vitamin E as anti-oxidizing agent and polyoxyethylene glycols and phosphatide derivative for extending the half-decay time of liposome pharmaceutical blood.

The invention provides a polypeptide molecule with a brain targeting function as well as a preparation method and application thereof and relates to the technical field of biomedicines. The polypeptide molecule with the brain targeting function, provided by the invention, can pass through a blood brain barrier, and the polypeptide molecule does not have immunogenicity, so that bad immune response on human bodies can be avoided. The polypeptide molecule provided by the invention also can be used as a drug-releasing carrier and can be coupled with related drugs for treating brain diseases to form a conjugate, so that the drugs for treating related brain diseases can pass through the blood brain barrier to directly act on wounds, and furthermore, the healing rate and healing speed of the related brain diseases can be effectively improved.

The invention discloses a temozolomide brain-targeting pharmaceutical composition and application thereof. The pharmaceutical composition provided by the invention contains a therapeutic effective dose of temozolomide, an absorbefacient and a pharmaceutical carrier. The invention also provides a pharmaceutical composition which contains a therapeutic effective dose of temozolomide, a stabilizer and a pharmaceutical carrier. The invention further provides the application of the pharmaceutical compositions provided by the invention in the preparation of drugs for intranasal administration. The compositions provided by the invention can be used as nasal powder. The temozolomide nasal powder provided by the invention is formed by the temozolomide, the pharmaceutical carrier and the stabilizeror the absorbefacient and is a preparation which reaches the brain to treat brain tumors through the absorption of nasal mucosa.

The present invention discloses the application of toad venom extract containing more than 90% of bufolin, cinobufagin and cinobufagin in the preparation of medicines for treating human glioma. The content ratio of tobafagenin is 2:3:5, and the extract of toad venom is prepared into a nano-preparation. The bufagenin nano-preparation of the invention can increase the distribution of bufagenin in the brain and avoid being taken up by the heart, thereby improving the brain-targeting property of the drug and reducing cardiotoxicity. Compared with the common extract solution of bufogenin, the nano-preparation of bufogenin has a stronger therapeutic effect on glioma brain and less side effects, thus enhancing the use value of bufogenin and providing a new method for the treatment of glioma. new drug.

The invention belongs to the technical field of preparation of drugs, and specifically relates to quercetin-modified nano sulfur as well as a preparation method and application thereof to an anti-AD (Alzheimer's Disease) drug. According to the preparation method disclosed by the invention, quercetin is modified on nano sulfur by utilizing the microsize and a high surface energy effect of nano sulfur, not only a function of the quercetin for reducing endoplasmic reticulum stress in cells of the quercetin is utilized, but also the water solubility is improved, so that quercetin-modified nano sulfur integrating high biocompatibility and an AD treatment effect is obtained. The quercetin-modified nano sulfur is further embedded in a microbubble shell prepared from alpha-butyl cyanoacrylate by adopting a one-pot method, so that a drug preparation containing quercetin-modified nano sulfur is prepared; microbubbles of the drug preparation can be destroyed under ultrasonic action, sonoporationcan be generated, a blood brain barrier can be temporarily opened, and quercetin-modified nano sulfur can further enter the brain by penetrating through the blood brain barrier so as to take a treatment effect, so that high brain targeting performance is obtained. The preparation method of the drug preparation is simple, and products are convenient to preserve and use.

The invention discloses a brain-targeting prodrug with vitamin C as a carrier, which is a structure shown in the general formula (I) or a pharmaceutically acceptable salt or hydrate thereof, wherein X is -(CH2)n-, -C(O)-(CH2)n-C(O)- or -O-(CH2)m-, -NH-(CH2)m-, -C(O)-(CH2)m- or -NH-(CH2)m-C(O)-, n is 0- 6, and m is 1-4; Y is -(CH2)a-, -C(O)-(CH2)a-C(O)- or -O-(CH2)b-, -NH-(CH2)b-, -C(O)-(CH2)b-, -NH-(CH2)b-C(O)-, a is 0-6, and b is 1-4; and drug1 and Drug2 represent independent different or same drugs acting on the central nervous system. The invention provides a series of drugs, which can improve the brain targeting property of drugs and the central concentration of the drugs, thereby enhancing the curative effects of the drugs; and meanwhile, the distribution of drugs on peripheral organs is reduced, and the toxic or side effect of the drugs is reduced.

The invention belongs to the field of medicinal preparations, and relates to a brain-targeting delivery system. The system comprises a mediating molecule, a vector and a medicament, wherein the mediating molecule is a benzamide analog, the vector is a polycation macromolecule, and the mediating molecule and the vector are combined by a covalence mode; and the medicament is carried through an entrapping or adsorption mode. In the system, in-vivo and in-vitro brain-targeting is characterized through a tracer technique to prompt that the delivery system can span a blood brain barrier, and a genemedicament and a diagnosis medicament are delivered into a brain, so the system can be used for brain disease diagnosis and treatment. The system can avoid potential risks of an enteroinvasive administration mode and a complicated administration process, and has the advantages of large administration quantity, simple administration mode and the like; and the brain-targeting mediated molecule has the advantages of small molecular weight, low price and availability and industrialization convenience.