49 results about "Flucytosine" patented technology

The present invention provides a method for producing a cytosine deaminase (CD)-expressing, 5-fluorouracil (5-FU)-resistant microorganism which can grow in anaerobic tumor tissues, can express CD, and has a resistance to 5-FU at a concentration that is at least effective for antitumor activity. More specifically, the method is a method (A) comprising performing subculture or acclimation culture of a CD-expressing microorganism which can grow in anaerobic tumor tissues, in the presence of 5-fluorocytosine (5-FC), or a method (B) comprising (1) performing subculture or acclimation culture of a microorganism which can grow in anaerobic tumor tissues and does not express CD, in the presence of 5-FU to produce a 5-FU-resistant microorganism and (2) transforming the 5-FU-resistant microorganism by introducing a CD gene. The present invention also provides the CD-expressing, 5-FU-resistant microorganism and a pharmaceutical composition comprising the microorganism.

The invention discloses a novel technology for synthesis of 5-flucytosine. The novel technology comprises that through condensation, acidification, cyclisation, fluorination and refining, 5-flucytosine is prepared from acetonitrile, formate, hydrogen chloride low-grade saturated fatty alcohol solution, urea, fluorine gas and anhydrous hydrogen fluoride as main raw materials. The 5-flucytosine has a weight yield of 1.45-1.55 (based on acetonitrile), unknown single impurity content less than 0.1%, total impurity content less than 0.2% and quality satisfying CP2010, USP36 and BP2013 quality standards.

The invention discloses a method for fluoridating and synthesizing 5-flucytosine by cytosine, which comprises the following steps: 1)under inert gas protection, adding cytosine in anhydrous hydrogen fluoride, introducing fluorine containing gas for a fluorination reaction under -5--20 DEG C, and 2)after reacting for 3-5 hours, distilling and concentrating the reaction solution, adding water for dissolving, adding alkali to adjust the pH value of the reaction solution, and separating to obtain the 5-flucytosine by cytosine. The method has the advantages of short synthesis route and good technology selectivity, no organic solvent is used during the production process, and the synthesized 5-flucytosine by cytosine has the advantages of high purity and high synthesis yield.

A nano-hybrid of 5-fluctyosine (5-FC) and hydrotalcite-like compounds (HTlc) belongs to technology field of new material and pharmaceutical preparation.5-FC / HTlc nanohybrid is synthesized by mixed salt solution of divalent metal ion trivalent metal ion and 5-fluctyosine alkali solution throug coprecipitation method, and has a chemical constitution general formula of [MII(1-x)MIIIx(OH)2](An-)a(5-FC-)b.nH2O.The inventive 5-FC / HTlc nanohybrid has simple and easy synthetic method, large drug loading dosage, certain sustained release effect compared with raw material of 5-FC, and important significance for clinical application of 5-FC.

There is described antifungal combination use of known antifungal agents such as the azoles or polyenes in combination with a lipopeptide compound antifungal agent. More particularly, the invention relates to antifungal combination use of azoles such as fluconazole, voriconazole, itraconazole, ketoconazole, miconazole, ER 30346 and SCH 56592; polyenes such as amphotericin B, nystatin, liposomal and lipid forms thereof such as Abelcet, AmBisome and Amphocil; purine or pyrimidine nucleotide inhibitors such as flucytosine; or polyoxins such as nikkomycins, in particular nikkomycin Z or nikkomycin X; other chitin inhibitors; elongation factor inhibitors such as sordarin and analogs thereof; mannan inhibitors such as predamycin, bactericidal / permeability-inducing (BPI) protein products such as XMP.97 or XMP.127; or complex carbohydrate antifungal agents such as CAN-296; with a lipopeptide compound [I] as described herein.

The disclosure provides an extended release formulation of 5- f luorocytosine. In another aspect, a method of treating a fungal disease is provided. The method comprises administering to a subject in need thereof a fungus-treating effective amount of a composition comprising 5-f luorocytosine. In yet another aspect, a method of treating a cancer is provided. The method comprises administering to a subject in need thereof a sufficient amount of an expression vector to induce expression of cytosine deaminase which is capable of converting 5-f luorocytosine to 5-f luorourcail in cells of the cancer and a cancer-treating effective amount of a composition comprising 5-f luorocytosine.

There is described antifungal combination therapy comprising the use of known antifungal agents such as the azoles or polyenes in combination with a pneumocandin derivative antifungal agent. More particularly, the invention relates to antifungal combination therapy comprising the use of azoles such as fluconazole, voriconazole, itraconazole, ketoconazole, miconazole, ER 30346, SCH 56592; polyenes such as amphotericin B, nystatin or liposomal and lipid forms thereof such as Abelcet, AmBisome and Amphocil; purine or pyrimidine nucleotide inhibitors such as flucytosine; or polyoxins such as nikkomycins, in particular nikkomycin Z or other chitin inhibitors, elongation factor inhibitors such as sordarin and analogs thereof, mannan inhibitors such as predamycin, bactericidal / permeability-inducing (BPI) protein products such as XMP.97 or XMP.127 or complex carbohydrate antifungal agents such as CAN-296 in combination with a pneumocandin derivative as described herein.

Disclosed are methods of detecting and treating a cancer such as an ovarian cancer using stem cells. Detection methods include administering a plurality of labeled stem cells to a subject having, or suspected of having, a cancer; and detecting the distribution of the stem cells. In some configurations, the label can be a nanoparticle such as a mono-crystalline iron oxide, which can be detected by magnetic resonance imaging. Treatment methods include administering a plurality of stem cells comprising a therapeutic agent such as an enzyme which activates a prodrug. In some configurations, the stem cells harbor a nucleic acid sequence encoding a cytosine deaminase, the cells express the enzyme, and the treatment further includes administering the prodrug 5-fluorocytosine, which is converted by the cytosine deaminase to the cytotoxic metabolite, 5-fluorouracil (5-FU).

The invention discloses a method for fluoridating and synthesizing 5-flucytosine by cytosine, which comprises the following steps: 1)under inert gas protection, adding cytosine in anhydrous hydrogen fluoride, introducing fluorine containing gas for a fluorination reaction under -5--20 DEG C, and 2)after reacting for 3-5 hours, distilling and concentrating the reaction solution, adding water for dissolving, adding alkali to adjust the pH value of the reaction solution, and separating to obtain the 5-flucytosine by cytosine. The method has the advantages of short synthesis route and good technology selectivity, no organic solvent is used during the production process, and the synthesized 5-flucytosine by cytosine has the advantages of high purity and high synthesis yield.

The invention belongs to the technical field of chemical synthesis of medicines and relates to a preparation method of 5-flucytosine. The preparation method comprises the following steps: utilizing ethyl formate and methyl chloroformate to synthesize 2-chloro-3-oxo methyl propionate, then utilizing oxymethylisourea to close rings to obtain pyrimidine rings, utilizing potassium fluoride to substitute chlorine on the pyrimidine rings, utilizing phosphorus oxytrichloride to substitute hydroxyl groups on the pyrimidine rings, then adding ammonia water to lead chloride to be substituted with aminogroups, and hydrolyzing under an acid condition to obtain a product, namely the 5-flucytosine. The preparation method has the beneficial effects that the methyl chloroacetate is adopted for substituting methyl fluoroacetate to be used as a synthetic raw material of the 5-flucytosine, so that the use of highly-toxic chemicals such as the methyl fluoroacetate is avoided; simultaneously, since the price of the methyl chloroacetate is much lower than the price of the methyl fluoroacetate, the production cost can be saved; by utilization of the synthetic route provided by the invention, the higher-purity 5-flucytosine can be prepared without need of complex aftertreatment steps; simultaneously, the preparation method has higher overall yield and obvious industrial value and is worthy of being promoted and used on a large scale.

The present invention obtains a brand-new 5-fluorocytosine derivative, and uses the 5-fluorocytosine derivative to prepare a highly immunogenic 5-fluorocytosine artificial antigen, and then immunizes experimental animals to obtain a high-titer anti-antigenic antigen. 5-fluorocytosine-specific antibody; meanwhile, use the 5-fluorocytosine derivative to prepare a 5-fluorocytosine enzyme-labeled conjugate. The 5-fluorocytosine immunoassay reagent containing the above-mentioned anti-5-fluorocytosine specific antibody and 5-fluorocytosine enzyme-labeled conjugate can realize the automatic determination of 5-fluorocytosine content on a fully automatic biochemical analyzer , can high-throughput, rapid and accurate determination of 5-fluorocytosine content in biological samples, and has the advantages of simple operation, high sensitivity, strong specificity, accurate results, etc., effectively reducing the cost of 5-fluorocytosine detection, It is beneficial to widely popularize and use clinically.

A process for the resolution of a racemic mixture of nucleoside enantiomers that includes the step of exposing the racemic mixture to an enzyme that preferentially catalyzes a reaction in one of the enantiomers. The nucleoside enantiomer (−)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane is an effective antiviral agent against HIV, HBV, and other viruses replicating in a similar manner.