150 results about "Brain targeting" patented technology

A phage-displayed library of llama single heavy domain antibodies (sdAbs) was enriched for species that selectively bind to and are internalized by human cerebromicrovascular endothelial cells (HCEC). From the enriched library, two sdAbs were selected, sequenced, subcloned, and expressed as fusion proteins with c-myc-His5 tags. Similarly as phage-displayed sdAbs, these soluble tagged sdAbs were shown to selectively bind to HCEC and to transmigrate across in vitro human blood-brain barrier (BBB) model. In contrast to an unrelated llama sdAb, these sdAbs were also detected in the brain after i.v. injection into mice. These small (˜13 kDa) antibody fragments have essential characteristics of brain-specific delivery vectors and can be used to facilitate drug transport across the BBB.

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 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 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 field of medicine preparations and particularly relates to a natural nanoparticle-medicine composition for resisting Alzheimer's disease (AD) and a preparation method, property evaluation and application thereof. By recombining extracted natural lipoprotein nanoparticles and AD treatment medicine to prepare the natural nanoparticle-medicine composition, combined treatment of AD is achieved. The combined treatment is high in homologous bionic performance and safety, high in medicine loading capacity, efficient in brain targeting, high in amyloid protein affinity, capable of achieving targeting removing, mild in preparation conditions, simple in preparation process and easy in industry expanding. The natural nanoparticle-medicine composition is administrated through intravenous injection, oral taking, nasal delivery and the like, a new thought and technology is provided for the research and development of new AD medicine, and the natural nanoparticle-medicinecomposition has an important research value and promising clinical research 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.

A phage-displayed library of llama single heavy domain antibodies (sdAbs) was enriched for species that selectively bind to and are internalized by human cerebromicrovascular endothelial cells (HCEC). From the enriched library, two sdAbs were selected, sequenced, subcloned, and expressed as fusion proteins with c-myc-His5 tags. Similarly as phage-displayed sdAbs, these soluble tagged sdAbs were shown to selectively bind to HCEC and to transmigrate across in vitro human blood-brain barrier (BBB) model. In contrast to an unrelated llama sdAb, these sdAbs were also detected in the brain after i.v. injection into mice. These small (˜13 kDa) antibody fragments have essential characteristics of brain-specific delivery vectors and can be used to facilitate drug transport across the BBB.

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 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.