36 results about "Folic Acid Derivative" patented technology

Disclosed is a polymer conjugate of folic acid or a folic acid derivative, wherein an amide bond is not used. The compound has chemical stability and adequate drug release rate in the living organism. Specifically disclosed is a polymer conjugate of folic acid or a folic acid derivative, wherein a substituent represented by formula (I) is bonded to a carboxy group of a block copolymer which is composed of a polyethylene glycol and a polymer having a carboxy group in a side chain, or a pharmacologically acceptable salt thereof.[In the formula, A represents a monocyclic or fused aromatic group; G represents an optionally substituted (C1-C6) alkylene group; Y represents a hydrogen atom or a substituent; and E represents a residue of folic acid or a folic acid derivative.]

The invention discloses a preparation method of a folic acid sulfhydrylation derivative. The preparation method comprises the following steps that -SH in thiol is protected to obtain a derivative of thiol, so that sulfydryl having high reaction activity is protected; then, in the presence of a catalyst and a dehydrating agent, esterification reaction is carried out between hydroxyl on the protected thiol derivative and folic acid, so that a modified folic acid derivative is obtained; a carbon sulphur bond in the folic acid derivative is broken through reduction reaction; sulfydryl is formed again in a product, and therefore, the target product, namely sulfhydrylation folic acid, is obtained. According to the preparation method disclosed by the invention, trityl chloride is replaced by triphenylcarbinol; the disadvantages of difficulty in separation of products and lower product yield are overcome; the product yield is increased; in the esterification reaction, a solid catalyst (macroporous cation exchange resin) is adopted, so that the separation efficiency of products is greatly improved; micromolecules, such as 4-dimethylamino-pyridine (DMAP), are adopted in normal biological preparation; the micromolecules are easily dissolved in a solvent and difficult to separate.

The invention provides a folic acid alkylated derivative, specifically stearylamine derivative I of folic acid and stearic acid derivative II of folic acid, which consist of the amino group of folic acid and the carboxyl group of stearic acid, or the carboxyl group of folic acid and stearic acid The coupling reaction of the amino group of the amine is synthesized. The folic acid alkylated derivatives provided by the present invention can prepare folic acid-modified lipid nanoparticles, so as to achieve the purpose of folic acid modification of lipid nanoparticles, through the affinity of the alkyl chain in the derivative and the lipid material, and Through the folic acid receptor-mediated pathway overexpressed on the surface of tumor cells, the cellular uptake of lipid nanoparticles is accelerated, thereby improving the anti-tumor targeting of the lipid nanoparticle anti-tumor drug delivery system, which can be used in the preparation of folic acid-modified loaded anti-tumor Applications of drug solid lipids and nanostructured lipid carriers in drug delivery systems. The structural formula of the compound of the present invention is.

The invention discloses an epithelial tissue staining reagent. The epithelial tissue staining reagent comprises components in percentage by weight as follows: 0.5%-15% of folic acid derivatives, 0.02%-10% of methylene blue, 0.1%-5% of horseradish peroxidase, 2%-10% of aminogalactose, 2%-10% of N-phthaloyl chitosan oligosaccharide, 2%-6% of medical glacial acetic acid and the balance of deionized water, wherein the folic acid derivatives preferably adopt one or more of 5,6,7,8-tetrahydrofolic acid, histidine N-acetyl-2-ethanediamide folic acid and cysteamine modified folic acid. The epithelial tissue staining reagent has the advantages as follows: the raw materials don't have irritation to skin and tract mucosa; the specificity is better; the selected folic acid derivatives are more easily combined with a folic acid receptor; saccharide derivatives have good reducibility and good solubility and are easy to prepare.

The invention belongs to the medical field and discloses folic acid dimer compound combined with folate receptor targeting and an application thereof. The compound is X2-Y-Z-A, wherein X2 is lysine and folic acid connecting dimer or lysine and folic acid derivative connecting dimer; Y is conjugate with (polyethylene glycol or polyethylene glycol derivative) m-lysine structure, and m is equal to 1, 2, 3, 4 or 5; Z is DOTA, NOTA, CB-TE2A, DTPA, NODAGA, the like substance or the derivative thereof; A is radionuclide, magnetic resonance imaging agent, chemical medicine or chemical medicine-loaded nano particle; the X, Y, Z and A are connected by covalent bond. The compound can be used for preparing tumor targeted imaging and treatment medicine, and the compound can effectively improve the gathering of the radionuclide in the tumor and metastasis thereof and improve the diagnosis efficiency and treatment effect.

The invention discloses a deoxyglucose-modified folic acid derivative and its synthesis and application. The derivative is a novel compound formed by combining folic acid and deoxyglucose through chemical bonds——FA‑2‑DG . In the derivative, aminoethanol is used as a connecting arm between folic acid and deoxyglucose, the carboxyl of folic acid is connected with the amino group of aminoethanol to form an amide bond; the hydroxyl group of aminoethanol is connected with the hydroxyl group of deoxyglucose to form a glycoside bond. This connection method neither destroys the structure and function of folic acid and deoxyglucose itself, nor affects the recognition of folic acid by folate receptors. At the same time, the introduction of a connecting arm of two carbon atoms can also increase the distance between the two molecules of folic acid and deoxyglucose. The distance is more suitable for the hydrolysis of glycosidase to release deoxyglucose with anti-tumor activity. The derivative FA‑2‑DG can be used as a drug plastid to load drugs based on its structural features.

The invention relates to a sulfhydrylated folic acid and a preparation method thereof, and belongs to the field of organic synthesis technology. The preparation method comprises a step of oxidizing a sulfhydryl group in a sulfhydryl compound comprising two functional groups (a hydroxy group and a sulfhydryl group) into a disulphur bond to obtain a multifunctional disulphur compound; a step of subjecting the disulphur compound and folic acid (FA) to an esterification reaction; and a step of breaking the disulphur bond by using a reductant to prepare a folic acid derivative containing a free sulfhydryl group. The folic acid derivative can be combined with metal nanoparticles by forming a firm sulphur-metal bond (S-Me), and therefore surface modification of the folic acid to the metal nanoparticles is produced. The sulfhydrylated folic acid and the preparation method have advantages of simple preparation technology and low cost. The structural formula of the sulfhydrylated folic acid is shown as the following formula.