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 method for measuring the content of total folic acid and derivatives thereof in vegetables synchronously and quantitatively, which comprises the following steps of: 1) extracting folic acid in the vegetables; 2) adding mouse serum conjugase into the obtained vegetable folic acid extract, incubating and centrifugating to obtain vegetable folic acid deconjugation extract; 3) performing solid phase extraction on the vegetable folic acid deconjugation extract and purifying; 4) separating four folic acid derivatives comprising tetrahydrofolic acid, 5-methyl-tetrahydrofolic acid, 5-formyl-tetrahydrofolic acid and the folic acid in the vegetables by using a chromatographic column; and 5) measuring the folic acid quantitatively. By the method, the content of the total folic acid and different folic acid derivatives can be measured synchronously.

The invention provides a composition for a skin-care product. The composition comprises the following components in parts by weight: 0.001-1 part of folic acid and / or folic acid derivative, 0-5 parts of sturgeon fish roe extract, 0-8 parts of pearl extract, and 0-15 parts of caprylic / capric triglyceride; and not all ofthe contents of the sturgeon fish roe extract, the pearl extract and the caprylic / capric triglyceride are 0. Compared with the prior art, the composition provided by the invention has the advantages that by combination of the folic acid and / or folic acid derivative with one or more of the sturgeon fish roe extract, the pearl extract and the caprylic / capric triglyceride, the synergisticeffect can be achieved and the whitening and anti-ageing effects for the skin can be improved; since the sturgeon fish roe extract, the pearl extract and the caprylic / capric triglyceride have the effects of removing free radicals and filtering ultraviolet rays, the light-heat stability of the folic acid can be enhanced, the stability of the content of the folic acid can be maintained and the acting time of the skin-care composition can be prolonged.

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 relates to a synthesis method of a highly specific folic acid complete antigen and an application of the folic acid complete antigen and belongs to the technical field of biochemical industry. The synthesis method disclosed by the invention comprises the steps of adding 6-aminocaproic acid and water-soluble carbodiimide into a vector protein solution and then reacting at a room temperature and carrying out dialysis to obtain a vector protein B modified by a linker arm, dissolving folic acid(N-{4-[(2-amino-1,4-dihydro-4-oxo-6-pteridinyl)methylamino]benzoyl}-L-glutamic acid) in dimethyl sulfoxide, adding dicyclohexyl carbodiimide and hydroxysuccinimide, reacting to obtain a folic acid derivative and then coupling the folic acid derivative with an amino group on the linker arm of the vector protein B to obtain the complete antigen. The results show that the titer of the antiserum obtained by immunizing animals with the antigen disclosed by the invention reaches up to 81000, the detection limit is 0.042ng / mL, and the half-inhibitory concentration is 0.3ng / mL. The produced antibody has high specificity and high sensitivity. The antigen or antibody disclosed by the invention is used for preparing an immunoaffinity column, establishing an enzyme linked immunosorbent assay method and colloidal gold strip rapid detection method and detecting the residue of folic acid.

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 relates to the technical field of medical analysis, in particular to a folic acid detection kit and a folic acid detection method. The kit comprises a magnetic particle suspension coatedwith a folic acid derivative, enzyme-labeled folic acid binding protein, a sample treatment solution and a chemiluminescent substrate, and the sample treatment solution comprises a sample treating fluid 1, a sample treating fluid 2 and a sample treating fluid 3. According to the kit, a specific sample treatment solution is adopted to treat a sample to be detected, folic acid and protein can be mildly separated, protein precipitation is not generated in the detection process, horse radish peroxidase is not damaged, a detection result is high in precision, the correlation with a Rogowski kit ishigh, and the detection result is accurate and reliable; and the detection speed is high, the result can be obtained within 40 minutes, and the kit is suitable for clinical detection of folic acid content.

This invention relates to an oral stabilized modified release pharmaceutical dosage form containing L-methylfolate calcium, which is primarily absorbed from proximal small intestine via a saturable human proton-coupled folate transporter (h-PCFT) mediated transport intended as monotherapy for the treatment of patients with MDDs and / or diagnosed with dysthymia, schizophrenia, or degenerative dementia of the Alzheimer type.

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.]

Described herein are methods for making folic acid derivatives, intermediates, pharmaceutical compositions and uses thereof.

The invention discloses a human epithelial tissue cancer cell detection reagent and a preparation method and application thereof. The human epithelial tissue cancer cell detection reagent is preparedfrom the raw materials in proportions as follows: 0-96 parts of dimethyl sulfoxide by volume, 0-6 parts of a folic acid derivative by weight, 0-3 parts of methylene blue by weight, 0-10 parts of acetic acid by volume, 0-6 parts of ascorbic acid by weight, 0-10 parts of cyclodextrin by weight, 0-10 parts of zinc powder by weight and 0-3 parts of an antioxidant by weight. The invention further provides the preparation method and application of the human epithelial tissue cancer cell detection reagent. The human epithelial tissue cancer cell detection reagent can effectively detect epithelial tissue tumor cells, and has good specificity, high sensitivity and a good application prospect.

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.

This invention provides a process for efficient production of folic acid derivatives suitable for forming conjugates of anticancer drug with folic acid. It discloses a process comprising a step of reacting 2-amino-protected pteroylimidazole with γ-lower alkyl glutamate; and a step of reacting the resulting product with an amino compound having a reactive group which is readily reactable with a functional group of the drug.

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 present invention provides, for example, a method of inhibiting aggregation of complex particles in which a drug is adhered to lead particles, characterized by containing a lipid derivative or a fatty acid derivative of one or more substance(s) selected from sugars, peptides, nucleic acids and water-soluble polymers or a surfactant in the lead particles. Further, it provides, for example, a method of producing the complex particles in which a nucleic acid as a drug or a drug is adhered to lead particles, comprising the step of dispersing or dissolving the nucleic acid as a drug or the drug and an adhesion-competitive agent so as to be contained in a liquid in which the lead particles containing a lipid derivative or a fatty acid derivative of one or more substance(s) selected from sugars, peptides, nucleic acids and water-soluble polymers or a surfactant are dispersed, thereby allowing the nucleic acid as a drug or the drug and the adhesion-competitive agent adhered to the lead particles.

The invention discloses a pharmaceutical composition, a compound preparation as well as a preparation method and application of the pharmaceutical composition. The pharmaceutical composition comprises the following components in any ratio: a component A: at least one of dextromethorphan or pharmaceutically acceptable salts of dextromethorphan; a component B: at least one of bupropion or medicinal salt of bupropion; component C: at least one of folic acid or folic acid derivatives; and a component D: at least one of methyl donors. The mass ratio of the component A to the component B to the component C to the component D is (1-100):(1-150):(0.1-100):(5-1000). All the components of the pharmaceutical composition can generate a synergistic effect, and the pharmaceutical composition can effectively inhibit over-activation of an NMDA receptor, inhibit reuptake of 5-HT and / or NE and effectively relieve depression.

The invention belongs to the technical field of chemical compounds, and relates to a texaphyrin-folic acid conjugate as well as a preparation method and application thereof, wherein the texaphyrin-folic acid conjugate comprises texaphyrin, a texaphyrin derivative or a conjugate formed by combining a texaphyrin homolog with folic acid or an O-(alkylamino) diaminophenol derivative of a folic acid derivative through a covalent bond. The texaphyrin-folate conjugate or the texaphyrin-folate nano-particles disclosed by the invention are applied to treatment comprising radiosensitization, radiation therapy and photothermal therapy. The texaphyrin-folic acid conjugate also can be used for medical imaging comprising MRI, two-photon, SPECT, PET, CT, fluorescence and ultrasound.

The invention provides a folate receptor targeting radioactive folic acid derivative and a preparation method and application thereof, and relates to the technical field of radiolabeling. A first aspect of the invention provides a folate receptor targeting radioactive folate derivative, the radioactive folate derivative has a structure as shown in a formula 1, and radionuclide is one of 68Ga, 64Cu, Al18F, 89Zr and 177Lu. The radioactive folic acid derivative provided by the invention can be prepared into an injection for PET diagnosis or treatment of tumor of a targeted folate receptor, is lowin preparation cost, and has the advantages of high labeling rate, strong in-vivo stability and the like.

The invention discloses a [99mTc-(CNMBFA) 6]<+> complex as well as a preparation method and an application thereof. The [<99m> Tc-(CNMBFA) 6] <+> complex is obtained by two steps of synthesis of a ligand CNMBFA and preparation of the [<99m>Tc-(CNMBFA) 6]<+> complex. The complex is simple to prepare, high in radiochemical purity and good in stability, has specific uptake at a tumor part of a nude mouse with KB tumor, is relatively low in kidney uptake, reduces the injury effect on the kidney, and is a novel tumor imaging agent which is excellent in performance and is targeted to a folate receptor.

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 discloses a nano-carrier particle prepared from a sugar-modified folic acid derivative and application of the nano-carrier particle; the nano-carrier particle is a novel nano-carrier particle formed by combining folic acid and sugar together by taking a carbon chain as a connecting bridge and utilizing a chemical bond mode; the sugar comprises, but not limited to, pentose and hexose,deoxyglucose, glucose, glucosamine, fructose, lactose and the like; the sugar and the folic acid are connected through a glycosidic bond or an ester bond; and furthermore, the length of a modified carbon chain between the sugar and the folic acid can be any number between 2 and 18 carbon atoms. The nano-carrier particle in the invention can be used for loading an anti-tumour drug; the molecular weight of the anti-tumour drug is 20-2000 Daltons; the nano-carrier particle not only solves the problem of poor water solubility of folic acid and is high in stability, but also has a self-assembly property; stable nano-particles are formed; and a variety of anti-tumour drugs can be efficiently carried in a targeted manner.

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 present invention discloses a kind of folic acid derivatives and their salts for preparing antitumor medicine. The present invention discloses the application of these folic acid derivatives and their salts in preparing medicine for treating cancers. These folic acid derivatives and their salts have powerful tumor cell growth inhibiting activity.

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 discloses a deoxyglucose modified folic acid derivative as well as synthesis and an application thereof, and the derivative is a novel compound-FA-2-DG formed by combining folic acid anddeoxyglucose in a chemical bond manner. In the derivative, aminoethanol is used as a connecting arm between folic acid and deoxyglucose, and carboxyl of folic acid is connected with amino of aminoethanol to form an amido bond; hydroxyl of the aminoethanol is connected with hydroxyl of the deoxyglucose to generate glycosidic bonds. The connection mode does not destroy the structures and functionsof the folic acid and the deoxyglucose; meanwhile, a distance between two molecules of folic acid and deoxyglucose can be increased through the introduced connecting arms of the two carbon atoms, themethod is more suitable for hydrolysis of glycosidase, and deoxyglucose with anti-tumor activity is released. The derivative FA-2-DG can be used as a drug plastid for drug loading based on the structural characteristics of the derivative FA-2-DG.

The invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition for conditioning gastrointestinal functions of middle-aged and elderly people and a preparation method thereof. According to the invention, several traditional Chinese medicines such as astragalus membranaceus, atractylodes macrocephala koidz, endothelium corneum gigeriae galli, Chinese dates, donkey-hide gelatin, caulis spatholobi, white hyacinth beans and fructus amomi are used for conditioning the bodies of middle-aged and elderly people, and meanwhile,Chinese herbal medicines and folic acid derivatives are compounded, through the entrapment effect of Chinese herbal medicine plant fiber on folic acid, an appropriate combination and a dosage ratio ofChinese medicine are adopted, so that the folic acid cannot be absorbed excessively or cannot be released due to serious entrapment during the process of reaching the microenvironment of large intestines.

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 provides a composition for a skin-care product. The composition comprises the following components in parts by weight: 0.001-1 part of folic acid and / or folic acid derivative, 0-5 parts of sturgeon fish roe extract, 0-8 parts of pearl extract, and 0-15 parts of caprylic / capric triglyceride; and not all ofthe contents of the sturgeon fish roe extract, the pearl extract and the caprylic / capric triglyceride are 0. Compared with the prior art, the composition provided by the invention has the advantages that by combination of the folic acid and / or folic acid derivative with one or more of the sturgeon fish roe extract, the pearl extract and the caprylic / capric triglyceride, the synergisticeffect can be achieved and the whitening and anti-ageing effects for the skin can be improved; since the sturgeon fish roe extract, the pearl extract and the caprylic / capric triglyceride have the effects of removing free radicals and filtering ultraviolet rays, the light-heat stability of the folic acid can be enhanced, the stability of the content of the folic acid can be maintained and the acting time of the skin-care composition can be prolonged.

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.