30 results about "Alpha-v beta-3" patented technology

The invention relates to a radionuclide-marked RGD polypeptide medicine and a preparation method thereof. The medicine comprises RGD polypeptide, a bifunctional Chelator and radioactive Nuclide, wherein the RGD polypeptide is RGD cyclic peptide dimer, namely E(L-c(RGDxK))2, which is synthesized by connecting a connecting agent L and an RGD polypeptide monomer and dimerizing two RGD polypeptide monomers connected with the connecting agent L; the radioactive Nuclide marks the RGD cyclic peptide dimer through the bifunctional Chelator; and a pharmacokinetic modified molecule PKM is also connected between the RGD cyclic peptide dimer and the bifunctional Chelator. The radionuclide-marked RGD polypeptide medicine is Nuclide-Chelator-PKM-E(L-c(RGDxK))2, and is a colorless and transparent liquid injection solution. The radionuclide-marked RGD polypeptide medicine is used for diagnosing and treating integrin alpha v beta 3 positive tumor.

The invention provides a 99mTc complex taking iminodiacetic acid as a difunctional chelating agent. Structure of the complex is shown as a formula (1). The complex has the advantages of simplicity in preparation, low cost, high marking rate, radiochemical purity, target to non-target ratio and tumor uptake value, long residence time and low liver-kidney background. The complex can serve as a novel photographic developer marked by technetium-99m and used for positive tumor diagnosis of intergrin alpha v beta 3 receptor to be applied in the technical field of radioactive medicinal chemistry and clinical nuclear medicine.

The invention belongs to the technical field of biomedicine production or the fields of protein polypeptide drugs and biomedical engineering, and in particular relates to a polypeptide which has high affinity with an integrin receptor and an application of the polypeptide like cancer diagnosis and treatment. The polypeptide is composed of five amino acids, and the sequence is arginine-tryptophan-arginine-asparagine-methionine (Arg-Trp-Arg-Asn-Met). On the basis of an in-vitro flow cytometry affinity determination experiment, the polypeptide disclosed by the invention has quite strong targeting on high-expression cells of the integrin receptor, and through an in-vitro laser confocal cell uptake experiment, the polypeptide can be targeted to high-expression tumor cells of the integrin receptor alpha-v-beta-3 and can basically avoid targeting on low-expression tumor cells and normal cells of the integrin receptor alpha-v-beta-3. An in-vitro cytotoxicity result shows that the 5-peptide disclosed by the invention is basically free from toxicity on cells, and the 5-peptide has a good application prospect in the diagnosis and the treatment of cancers.

The teachings provided herein generally relate to a combination therapy and are directed to pharmaceutical compositions and methods for administering a combination of an αvβ3 antagonist with an αVβ1 antagonist to a subject. The methods are for use in inhibiting, preventing, or reversing angiogenesis, as well as in treating cancer. In some embodiments, the compositions and methods include a combined administration of echistatin and VP12 (ECL12).

The invention relates to the chitosan polymer derivatives of formula I:and pharmaceutically acceptable salts and esters thereof, wherein Y, X1, X4, R1, R2, and n are defined in the detailed description and claims. The chitosan polymer derivatives of formula I bind to or associate with alpha-4-beta-1 (α4β1) and alpha-V-beta-3 (αVβ3) integrin dimers and can be used in delivery formulations to deliver drugs, nucleic acids, or other therapeutic compounds to tissues or cells expressing such integrins.

The invention relates to the chitosan polymer derivatives of formula I: and pharmaceutically acceptable salts and esters thereof, wherein Y, X1, X4, R1, R2, and n are defined in the detailed description and claims. The chitosan polymer derivatives of formula I bind to or associate with alpha-4-beta-1 (α4β1) and alpha-V-beta-3 (αVβ3) integrin dimers and can be used in delivery formulations to deliver drugs, nucleic acids, or other therapeutic compounds to tissues or cells expressing such integrins.

The invention relates to compounds of formula (I): wherein R1, R2, and n are defined in the detailed description and claims. In particular, the present invention relates to the compounds of formula (I) for use in the manufacture and delivery of conjugated moieties such as small molecules, peptides, nucleic acids, fluorescent moieties, and polymers which are linked to alpha-V-beta-3 integrin antagonists to target cells expressing alpha-V-beta-3.

The invention discloses a type of 1,3-dihydro-1-oxo-2H-isoindole compounds (I) and pharmaceutically acceptable salts thereof and also discloses application of the compounds in preparation of medicines for preventing or / and treating various symptoms or diseases such as tumor metastasis, tumor growth, solid tumor growth, angiogenesis, retinopathy, macular degeneration, osteoporosis, arthritis, smooth muscle cell migration and atherosclerosis caused by integrin alpha v beta 3 mediation. The structural formula is as shown in the specification.

The invention discloses tumor targeted cordycepin nanometer capsules and a preparation method thereof. The method comprises the following steps of firstly preparing RGD modified apolipoprotein A I(ApoAI), and then constructing nanometer capsules from the RGD modified apolipoprotein A I(ApoAI), phospholipid and cordycepin. RGD peptide is a specific ligand of an integrin alpha v beta 3, and the integrin alpha v beta 3 gene is subjected to zero expression or little expression in majority of normal organ systems and normal vascular endothelial cells, and is subjected to overexpression on the surfaces of various tumor cells and tumor regenerated blood vessel endothelial cells, so that after being subjected to RGD modification, the nanometer capsules have good targeting effects on tumors, the effective concentration of cordycepin in tumor positions can be increased, and the antitumor effects of the cordycepin can be reinforced.

The invention discloses an integrin targeted MnOL-Gd hybrid bimetallic paramagnetic nanocolloid (alpha v beta 3-MnOL-Gd NC) and application in magnetic resonance imaging (MRI) of angiogenesis. The alpha v beta 3-MnOL-Gd NC provided by the invention is obtained by coupling alpha v beta 3 targeted specific biomolecules of polyethylene glycol 2000 integrated phosphatidyl ethanolamine to the surfaces of MnOL-Gd hybrid bimetallic paramagnetic nanoparticles. Research shows that, the alpha v beta 3-MnOL-Gd NC is effective in imaging of angiogenesis, and can generate specific angiogenesis imaging high signal contrast 2 hours after injection. Therefore, the alpha v beta 3-MnOL-Gd NC disclosed by the invention can be used for T1 weighted MR molecular imaging of angiogenesis, and is free of obvious allergic reaction side effect, thus providing a new technological means for magnetic resonance imaging of angiogenesis.

The invention discloses 1,3-dihydro-1-oxo-2H-isobenzazole compounds (I) and pharmaceutically acceptable salts thereof, and also discloses preparation methods for the compounds, and uses of the compounds in preparing medicines for preventing and / or treating various diseases caused by the mediation of integrin alpha v beta 3, such as tumor metastasis, tumor growth, solid tumor growth, angiogenesis, retinopathy, macular degeneration, osteoporosis, arthritis, smooth muscle cell migration and atherosclerosis symptoms or diseases.

The invention discloses a cancer cell-targeting structural molecule and a use thereof. A molecule shown in the formula (I) reacts with a connection molecule containing a carboxyl structure and a maleimide group so that the cancer cell-targeting structural molecule is produced by a dehydration synthesis reaction of an amino group and a carboxyl group. The cancer cell-targeting structural molecule can be bonded with a sulfydryl (-SH)-modified nucleotide molecule, can be directly applied to a human body by blood vessel administration, can be specifically bonded with cancer cells expressing integrin family alpha v beta 3 acceptors or with new vessel endothelial cells in cancer tissue, can effectively penetrate a cell membrane by receptor-mediated endocytosis, and can convey the nucleotide molecule into cytoplasm. In the formula (I), n is in a range of 1-10.

The invention discloses an RGD (Arg-Gly-Asp)-like peptide PET (positron emission tomography) developing agent of targeting integrin alpha v beta 3 and a preparation method thereof. The preparation comprises the following steps of: performing 1, 3 dipolar cycloaddition reaction of nitrine and alkynyl in the terminal position on a compound B and a compound C under the catalysis of Cu (I) in a solvent to prepare a compound A. The compound A can be used for diagnosing tumors, cardiovascular diseases and other diseases, such as malignant glioma, melanoma, H22 liver cancer and the like. The invention finds that the RGD-like peptide PET developing agent can specifically target the tumors with high expression of alpha v beta 3 by studies. A marking method of the PET developing agent is simple and universal, a reaction system is stable, conditions are mild, and the radiochemical purity, the specific activity and the radiochemical yield are higher. RGD-like peptide monomers used in the preparation method are low in production cost and convenient to perform large-quantity synthesis and modification, and the used other chemical reagents are low in cost and easy to obtain.

The invention relates to a PEGylated Fe3+ / PEI genetic vector based on functional peptide R9 modification and a preparation method and application of the PEGylated Fe3+ / PEI genetic vector. The genetic vector contains polyethylene glycol modified Fe3+ / polyethyleneimine and a conjugate formed by functional peptides R9. The PEGylated Fe3+ / PEI genetic vector based on functional peptide R9 modification has the advantages that metal ions Fe3 react with PEI at first, PEG modification is carried out to form PEGylated Fe3+ / PEI, then the functional peptide R9 which has ability of improving nuclear delivery and is targeted at alpha v beta 3 is synthesized, R9 is coupled with a PEG-Fe3+ / PEI by a crosslinking technology, and therefore, a novel virogene-free vector system PEG-Fe3 + / PEI is established. On the basis of reducing PEI cytotoxicity, in-vivo targeting property and nuclear delivery ability are improved, then the transfection efficiency of the vector in vivo is improved, and an effective way is searched for final application of gene therapy on clinical treatment.

The invention discloses a dual-targeting ultrasonic contrast agent and a preparation method thereof. The contrast agent is an Integrin alpha v beta 3 / MCP-1 dual-targeting micro-vesicle, the dual-targeting micro-vesicle comprises a lipid shell and a gas inner core, and the external surface of the lipid shell is connected with an Integrin alpha v beta 3 monoclonal antibody and an MCP-1 monoclonal antibody. Through the combined application of different target spots, the targeting efficiency of the contrast agent can be effectively increased, and the degree of enrichment of the carrying genes in the target tissue can be greatly increased. In addition, the contrast agent disclosed by the invention is an ultrasonic contrast agent with double functions of development and treatment, and tumor images can be accurately observed in real time through an ultrasonic imaging system; and after gene transfection is realized through high-strength ultrasonic irradiation, the tumor gene treatment effect can be achieved.