Patents by Inventor Cheng-Fang Hsu

Cheng-Fang Hsu has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Publication number: 20200392134
    Abstract: A method for purifying 2-[[2-[[[3-(4-Chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]-oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiol-[1R-(exo-exo)]-hydrochloride is revealed. After medium pressure liquid chromatography and subsequent acid treatment, 2-[[2-[[[3-(4-Chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]-oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiol-[1R-(exo-exo)]-hydrochloride with high purity is obtained. The method for purifying can solve the problem that the product purity is not up to the standard for radiopharmaceuticals.
    Type: Application
    Filed: May 12, 2020
    Publication date: December 17, 2020
    Inventors: SHOW-WEN LIU, CHENG-FANG HSU, WEI-HSI CHEN, YU CHANG
  • Publication number: 20190276416
    Abstract: A method for preparing a NOTA derivative is revealed. The method includes a plurality of steps. First take 4-toluenesulfonyl chloride and diethylenetriamine to carry out tosylation reaction and obtain a first product. Then the first substitution reaction takes place upon addition of the first product with sodium methoxide to get the second product. Next take 4-toluenesulfonyl chloride to react with ethylene glycol for preparing a third product by tosylation reaction therebewteen. Then a coupling reaction between the third product and the second product is carried out to produce a fourth product. The second substitution reaction occurs involving the fourth product in the presence of sulfuric acid. Lastly take the reaction product and hydrochloric acid to have bonding reaction and obtain a final product. The method solves the water-absorption problem of the cyclic organic compound TACN, a NOTA derivative.
    Type: Application
    Filed: March 6, 2018
    Publication date: September 12, 2019
    Inventors: YU CHANG, CHENG-FANG HSU
  • Publication number: 20190106457
    Abstract: The present invention provides a method for preparing S-Bz-MAG3 as a precursor of contrast media. Thioglycolic acid and benzoyl chloride are taken for the thiol protection reaction. Next, N,N?-dicyclohexylcarbodiimide and N-hydroxysuccinimide are converted to corresponding ester compounds. The corresponding ester compounds then react with triglycine by amide bonding reaction. The product of the reaction is recrystallized using acetone, filtered, and finally flushed using flushing agent to give the final product. This is a bifunctional chelator and can be bridged with 99mTc and 186/188Re effectively and applied to nuclear medicine imaging and tumor radiotherapy. By taking advantage of fewer synthesis steps and ease of operations, complicated separation and purification reactions can be reduced and thus achieving highly productivity of S-Bz-MAG3.
    Type: Application
    Filed: October 11, 2018
    Publication date: April 11, 2019
    Inventors: Ching-Yun LEE, Yu CHANG, Cheng-Fang HSU
  • Publication number: 20180265480
    Abstract: A method for preparing a contrast agent precursor is revealed. The method includes several steps. First dissolve di-tert-butyl 2,2?-(1,4,7-triazacyclononane-1,4-diyl)diacetate, benzyl-2-bromoacetate and an alkaline compound in a first solvent to perform a bimolecular nucleophilic substitution reaction and get a product. Then dissolve the product in a second solvent to get a solution and adjust the pH value of the solution. Next add an organic solvent when the solution becomes acid and then remove a first organic layer that contains the organic solvent. Adjust the solution to become an alkaline solution and add the organic solvent again to get a second organic layer containing the organic solvent. The second organic layer contains the final product, di-tert-butyl 2,2?-{7-[2-(benzyloxy)-2-oxyethyl-(1,4,7-triazacyclononane-1,4-diyl}-diacetate.
    Type: Application
    Filed: March 15, 2017
    Publication date: September 20, 2018
    Inventors: JHE-YU LIU, YU CHANG, CHENG-FANG HSU
  • Patent number: 10059661
    Abstract: A [F-18]FEONM precursor is synthesized. 2-bromoethanol is added to further connect an atom of oxygen at an N terminal of the precursor. Four atoms of carbon can be further connected. Thus, better fat-solubility is obtained along with the increase in carbon. Positioning in brain imaging becomes better.
    Type: Grant
    Filed: July 28, 2017
    Date of Patent: August 28, 2018
    Assignee: INTITUTE OF NUCLEAR ENERGY RESEARCH, ATOMIC ENERGY COUNCIL, Executive Yuan, R.O.C.
    Inventors: Shu-Hung Lin, Sheng-Po Huang, Show-Wen Liu, Cheng-Fang Hsu, Jenn-Tzong Chen, Shiou-Shiow Farn, Wuu-Jyh Lin, Chyng-Yann Shiue
  • Patent number: 9981953
    Abstract: A contrast agent precursor is revealed. The contrast agent precursor includes a 1,4,7-Tris(carbonylmethyl)-1,4,7,10-tetraazacyclododecane that forms complexes with radioisotopes or connects to a peptide. The contrast agent precursor also includes a 2-nitroimidazole that allows the precursor to become retained in hypoxic tissues According to the features mentioned above, the contrast agent prepared by the precursor has a better binding specificity, labeling accuracy and detection sensitivity. Moreover, a method for preparing the contrast agent precursor not only solves the emulsion problem generated during conventional synthesis of intermediate products but also provides a solution to the problem of residual trifluoroacetic acid. Both the yield rate and the purity of the final product are also improved.
    Type: Grant
    Filed: January 4, 2017
    Date of Patent: May 29, 2018
    Assignee: INSTITUTE OF NUCLEAR ENERGY RESEARCH, ATOMIC ENERGY COUNCIL, EXECUTIVE YUAN, R.O.C.
    Inventors: Wen-Ching Wu, Kuei-Lin Lu, Yu Chang, Cheng-Fang Hsu
  • Publication number: 20180059072
    Abstract: A high performance liquid chromatography method for analysis of a MN diagnostic and therapeutic ligand and precursors is revealed. Polarity of eluents used during elution is changed to remove impurities. First use a first eluent with a lower ratio of acetonitrile as a mobile phase to elute analytes. Then a second eluent in which a ratio of acetonitrile is increased into 97˜99% is used to elute the analytes for at least 20 minutes. Next use the first eluent to elute the analytes for at least 60 minutes. Thus no residual impurities are left in the column and the analytes remain in the column stably. Therefore a more accurate and reproductive result is obtained.
    Type: Application
    Filed: September 1, 2016
    Publication date: March 1, 2018
    Inventors: KUEI-LIN LU, JIA-DONG TSAI, YU CHANG, CHENG-FANG HSU
  • Publication number: 20180051051
    Abstract: A method for preparing a precursor of gene expression probe is revealed. First prepare 2-deoxy-2-fluoro-3,5-di-O-benzoyl-?-D-arabinofuranosyl bromide and 2,4-bis-O-(trimethylsilyl)-5-bromouracil respectively. Then use 2-deoxy-2-fluoro-3,5-di-O-benzoyl-?-D-arabinofuranosyl bromide and 2,4-bis-O-(trimethylsilyl)-5-bromouracil to perform a coupling reaction and get a 1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-?-D-arabinofuranosyl)-5-bromouracil. Next use 1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-?-D-arabinofuranosyl)-5-bromouracil generated and hexabutylditin to perform a substitution reaction in an anhydrous 1,4-dioxane solution and get 1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-?-D-arabinofuranosyl)-5-tributylstannyl)uracil. At last carry out debenzoylation of 1-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-?-D-arabinofuranosyl)-5-tributylstannyl)uracil to get 5-tributylstannyl-1-(2-deoxy-2-fluoro-?-D-arabinofuranosyl)uracil (FSAU), a precursor of gene expression probe.
    Type: Application
    Filed: August 22, 2016
    Publication date: February 22, 2018
    Inventors: SHOW-WEN LIU, CHENG-FANG HSU, YU CHANG
  • Patent number: 9714220
    Abstract: A tetradentate organic ligand H3-MN-16Bn containing a long alkyl group, a precursor thereof, and a method for preparing the same are revealed. A precursor of H3-MN-16Bn, benzyl 16-bromohexadecanate, is obtained by esterification reaction of 16-bromohexadecanoic acid. Then bimolecular nucleophilic substitution reaction (SN2) of Benzyl 16-bromohexadecanate with nitrogen sulfide (N2S2) is carried out to get H3-MN-16Bn that is used as a standard hydrolysis metabolites of non-radioactive 185Re-complex compound.
    Type: Grant
    Filed: October 23, 2015
    Date of Patent: July 25, 2017
    Assignee: Institute of Nuclear Energy Research, Atomic Energy Council, Executive Yuan, R.O.C.
    Inventors: Jia-Dong Tsai, Yu Chang, Kuei-Lin Lu, Cheng-Fang Hsu
  • Publication number: 20170114009
    Abstract: A tetradentate organic ligand H3-MN-16Bn containing a long alkyl group, a precursor thereof, and a method for preparing the same are revealed. A precursor of H3-MN-16Bn, benzyl 16-bromohexadecanate, is obtained by esterification reaction of 16-bromohexadecanoic acid. Then bimolecular nucleophilic substitution reaction (SN2) of Benzyl 16-bromohexadecanate with nitrogen sulfide (N2S2) is carried out to get H3-MN-16Bn that is used as a standard hydrolysis metabolites of non-radioactive 185Re-complex compound.
    Type: Application
    Filed: October 23, 2015
    Publication date: April 27, 2017
    Inventors: JIA-DONG TSAI, YU CHANG, KUEI-LIN LU, CHENG-FANG HSU
  • Patent number: 9580394
    Abstract: In a benzodiazepine derivative and a method of producing the derivative, isatoic anhydride or 5-chloroisatoic anhydride is reacted with amino acid ester hydrochloride for conducting a simple cyclization to obtain a produce with a low percentage of by-product directly without requiring the complicated separation and purification processes of column chromatography, and a chlorine-containing structure of the structure can improve the lipo-solubility and chlorine ion permeability and allow a functional group of a radioisotope to be modified to maximize the effects of the pharmacological properties such as the sedative, anticonvulsant and anti-spasmodic effects on the central nervous system or the benzodiazepine derivative can be used as a contrast agent of the system with excellent effects on applications.
    Type: Grant
    Filed: March 7, 2014
    Date of Patent: February 28, 2017
    Assignee: Atomic Energy Council—Institute of Nuclear Energy Research
    Inventors: Yu Chang, Ching-Yun Lee, Tsung-Hsien Chiang, Cheng-Fang Hsu
  • Patent number: 9567315
    Abstract: A method for synthesis of 4-OH substituted anabaseine derivative which is used as an ?7 receptor agonist is revealed. A nucleophilic substitution reaction of ?-valerolactam with ethyl nicotinate is carried out to get an intermediate product. Then heat the intermediate product under reflux with concentrated hydrochloric acid to get a cyclized product-anabaseine. Next anabaseine and 4-hydroxyethoxy-2-methoxybenzaldehyde are reacted under concentrated hydrochloric acid catalysis to get a 4-OH anabaseine derivative 3-[(4-Hydroxyethoxy-2-methoxy)-benzylidene]anabaseine. The 4-OH anabaseine derivative is synthesized and prepared easily by the present invention. Not only the steps for synthesis are simplified, the yield is as high as 60%. The product can be mass-produced.
    Type: Grant
    Filed: April 22, 2016
    Date of Patent: February 14, 2017
    Assignee: Institute of Nuclear Energy Research, Atomic Energy Council, Executive Yuan, R.O.C.
    Inventors: Yu Chang, Cheng-Fang Hsu
  • Patent number: 9382202
    Abstract: A precursor for labeling therapeutic agents for liver cancer and a method for manufacturing the same are revealed. The chemical structure of the precursor has a ligand linked to complex compounds of radioisotopes. Moreover, the chemical structure of the precursor further includes a specific functional group soluble in Lipiodol or having properties of Lipiodol. Thus the radioisotopes attached to the precursor are allowed to retain in hepatic tissues of patients with liver cancer for internal radiation therapy of liver cancer.
    Type: Grant
    Filed: May 8, 2014
    Date of Patent: July 5, 2016
    Assignee: Atomic Energy Council—Institute of Nuclear Energy Research
    Inventors: Show-Wen Liu, Yu Chang, Cheng-Fang Hsu
  • Patent number: 9227931
    Abstract: A bifunctional compound and a method for manufacturing the same are revealed. The structural formula of the compound includes two main functional groups. One functional group is a diamide dithiolate (N2S2) ligand able to bind with radioisotopes. The other functional group is polybasic carboxylic acid that binds to biochemical substances. Based on properties of the above two functional groups, the compound of the present invention can be used for preparation of radiopharmaceuticals such as radiotracter for disease diagnosis or radioactive therapeutic agent for disease treatment.
    Type: Grant
    Filed: July 29, 2014
    Date of Patent: January 5, 2016
    Assignee: Atomic Energy Council—Institute of Nuclear Energy Research
    Inventors: Show-Wen Liu, Yu Chang, Cheng-Fang Hsu
  • Publication number: 20150322005
    Abstract: A precursor for labeling therapeutic agents for liver cancer and a method for manufacturing the same are revealed. The chemical structure of the precursor has a ligand linked to complex compounds of radioisotopes. Moreover, the chemical structure of the precursor further includes a specific functional group soluble in Lipiodol or having properties of Lipiodol. Thus the radioisotopes attached to the precursor are allowed to retain in hepatic tissues of patients with liver cancer for internal radiation therapy of liver cancer.
    Type: Application
    Filed: May 8, 2014
    Publication date: November 12, 2015
    Applicant: ATOMIC ENERGY COUNCIL-INSTITUTE OF NUCLEAR ENERGY RESEARCH
    Inventors: SHOW-WEN LIU, YU CHANG, CHENG-FANG HSU
  • Patent number: 9150602
    Abstract: A precursor used for labeling hepatocyte receptors and applied to radiotracers for imaging or pharmaceutical compositions for liver cancers is revealed. The precursor is a bifunctional compound. The bifunctional group includes a trisaccharide structure and a diamide dimercaptide (N2S2) ligand. The trisaccharide has high affinity to asialoglycoprotein receptors (ASGPR) on surfaces of hepatocytes while N2S2 ligand reacts with radioisotopes to form neutral complexes. Thus the precursor stays on surfaces of hepatocytes to provide radioisotope labeling or treatment effect of liver cancers.
    Type: Grant
    Filed: July 24, 2012
    Date of Patent: October 6, 2015
    Assignee: Atomic Energy Council, Institute of Nuclear Energy Research
    Inventors: Show-Wen Liu, Yu Chang, Cheng-Fang Hsu, Ming-Che Tsai, Tsung-Hsien Chiang, Yueh-Feng Deng, Kuei-Lin Lu, Chih-Yuan Lin, Da-Ming Wang, Ching-Yun Li
  • Publication number: 20150252009
    Abstract: In a benzodiazepine derivative and a method of producing the derivative, isatoic anhydride or 5-chloroisatoic anhydride is reacted with amino acid ester hydrochloride for conducting a simple cyclization to obtain a produce with a low percentage of by-product directly without requiring the complicated separation and purification processes of column chromatography, and a chlorine-containing structure of the structure can improve the lipo-solubility and chlorine ion permeability and allow a functional group of a radioisotope to be modified to maximize the effects of the pharmacological properties such as the sedative, anticonvulsant and anti-spasmodic effects on the central nervous system or the benzodiazepine derivative can be used as a contrast agent of the system with excellent effects on applications.
    Type: Application
    Filed: March 7, 2014
    Publication date: September 10, 2015
    Inventors: YU CHANG, CHING-YUN LEE, TSUNG-HSIEN CHIANG, CHENG-FANG HSU
  • Patent number: 9096623
    Abstract: A method for preparing a radiotracer precursor SnADAM is revealed. The method overcomes shortcomings of conventional synthesis methods including lower yield rate and time-consuming. Moreover, Pd/C catalyst and hydrogen gas are used to catalyze reduction reaction for avoiding the generation of a large amount of intermediate products with similar structures. Thus there is no need to perform isolation and purification processes. The yield rate of the intermediate products is also increased so that its impact on the low yield rate of the final product SnADAM is minimized. A part of the reaction is significantly accelerated by using tris(dibenzylideneacetone)-dipalladium(0) (Pd2(dba)3) as a catalyst. Thus the production time of SnADAM is shortened.
    Type: Grant
    Filed: May 8, 2014
    Date of Patent: August 4, 2015
    Assignee: Atomic Energy Council—Institute of Nuclear Energy Research
    Inventors: Ching-Yun Lee, Yu Chang, Cheng-Fang Hsu, Yueh-Feng Deng
  • Patent number: 9044519
    Abstract: A radiotracer precursor for imaging of hypoxic tissues, a radiotracer and a method for preparing the same are revealed. The radiotracer precursor, DANI, includes a nitroimidazole functional group with a feature of retention in hypoxic tissues and a bifunctional ligand able to complex with radioisotopes. Thus DANI can be used to produce radiotracers stayed in hypoxic tissues and the radiotracers are applied to medical imaging of malignant tumor with hypoxic layer.
    Type: Grant
    Filed: June 18, 2013
    Date of Patent: June 2, 2015
    Assignee: Atomic Energy Council—Institute of Nuclear Energy Research
    Inventors: Show-Wen Liu, Yu Chang, Cheng-Fang Hsu, Tsung-Hsien Chiang, Sheng-Lun Lin, Chih-Yuan Lin
  • Patent number: 9045513
    Abstract: A method for preparing a precursor used to label hepatocyte receptors is revealed. The precursor contains a bifunctional structure including trisaccharide and DTPA ligand. During synthesis processes of the precursor, silica gel columns and Reverse phase-18 (RP-18) columns are used for purification. Thus both the purification times and cost of each purification are reduced. Moreover, use diethyl ether to facilitate precipitation of products and remove a part of coupling reagent. Removing the coupling reagent helps purification of products. Furthermore, N?,N?-bis(carboxymethyl)-L-lysine hydrate and benzyl chloroformate are coupled to form a trisaccharide skeleton so as to ensure the yield rate of trisaccharide structure.
    Type: Grant
    Filed: August 10, 2012
    Date of Patent: June 2, 2015
    Assignee: Atomic Energy Council—Institute of Nuclear Energy Research
    Inventors: Chih-Yuan Lin, Yu Chang, Jen-Tsung Wang, Cheng-Fang Hsu, Wei-Ti Kuo, Hung-Wen Yu, Wuu-Jyh Lin, Mei-Hui Wang