Abstract: An object of the present invention is mainly to provide a medical skin external preparation that is suitable for treating superficial skin infections, in particular, superficial skin infections accompanied by blister or erosion, etc. For example, the present invention can provide a medical skin external preparation containing 1-cyclopropyl-8-methyl-7-[5-methyl-6-(methylamino)-3-pyridyl]-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid and/or a pharmaceutically acceptable salt thereof as an active ingredient, and an alcohol and/or a fatty acid having 12 or more carbon atoms.
Abstract: A communication apparatus and a communication method are provided. The communication apparatus includes an antenna configured to receive a wireless signal, an oscillator driven by a driving current and configured to generate an oscillating signal based on the wireless signal, a measurer configured to measure an oscillation degree of the oscillating signal, and an accumulator configured to accumulate a difference between a target value and a measurement value of the oscillation degree. A value of the wireless signal is determined based on a cumulative signal corresponding to the accumulated difference.
Abstract: It is to provide an agent for preventing or improving hearing loss, which comprises a low molecular compound which can be produced relatively easily and inexpensively as an active ingredient. One or more compounds selected from the group consisting of compounds represented by the following formulas (I0), (II), and (III) and a pharmaceutically acceptable salt of the compounds when R3 is OH are used as an agent for preventing or improving hearing loss.
Abstract: This invention relates to a method for treating atopic dermatitis, comprising administering an effective amount of N-acyltryptamine represented by Formula (I): wherein R represents a saturated aliphatic hydrocarbon group having 2 to 29 carbon atoms; or a pharmaceutically acceptable salt, hydrate or solvate thereof to a subject in need thereof.
Abstract: Disclosed are chemical entities of Formula (I), wherein R1 and Z are defined herein, as NR2B subtype selective receptor antagonists. Also disclosed are pharmaceutical compositions comprising a chemical entity of Formula (I), and methods of treating various diseases and disorders associated with NR2B antagonism, e.g., diseases and disorders of the CNS, such as depression, by administering a chemical entity of Formula (I).
Abstract: The invention relates to a gel composition containing pirfenidone, which is advantageous over other cutaneously administered pharmaceutical forms known in the prior art and which can be used in treatment for the restoration of tissues with fibrotic lesions and for the prevention of fibrotic lesions.
Type:
Grant
Filed:
February 17, 2017
Date of Patent:
August 13, 2019
Assignee:
CELL THERAPY AND TECHNOLOGY S.A. DE C.V.
Inventors:
José Agustin Rogelio Magaña Castro, Laura Vázquez Cervantes, Juan Socorro Armendáriz Borunda
Abstract: Disclosed are chemical entities of Formula (I): wherein R1 and Z are defined herein, as NR2B subtype selective receptor antagonists. Also disclosed are pharmaceutical compositions comprising a chemical entity of Formula (I), and methods of treating various diseases and disorders associated with NR2B antagonism, e.g., diseases and disorders of the CNS, such as depression, by administering a chemical entity of Formula (I).
Abstract: The invention relates to compounds of formula I: where a, R1, and R3-6 are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds of formula I are serotonin and norepinephrine reuptake inhibitors. The invention also relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.
Type:
Grant
Filed:
June 13, 2018
Date of Patent:
February 19, 2019
Assignee:
THERAVANCE BIOPHARMA R&D IP, LLC
Inventors:
Lori Jean Patterson, Eric L. Stangeland
Abstract: The present disclosure relates to tolperisone, or a pharmaceutically acceptable salt or hydrate thereof, with 10 ppm 2-methyl-1-(4-methylphenyl)-propenone (4-MMPPO) or less, methods of producing the same, as well as compositions related thereto. The disclosure further relates to methods of treating a subject with tolperisone under conditions that limit exposure of the subject to tolerable levels of 4-MMPPO.
Type:
Grant
Filed:
August 1, 2016
Date of Patent:
June 13, 2017
Assignee:
Sanochemia Pharmazeutika AG
Inventors:
Federico Gaeta, Klaus Gerdes, Stefan Welzig, Beate Katz, Jan Rothenburger, Jozsef Gungl
Abstract: The present disclosure relates to methods of administering tolperisone to subjects in need thereof. In certain aspects, the present disclosure relates to methods of administering tolperisone to subjects in need thereof, said methods limiting the exposure of the subject to 4-MMPPO.
Type:
Grant
Filed:
March 11, 2016
Date of Patent:
May 30, 2017
Assignee:
SANOCHEMIA PHARMAZEUTIKA AG
Inventors:
Federico Gaeta, Klaus Gerdes, Stefan Welzig, Beate Katz, Jan Rothenburger, Jozsef Gungl
Abstract: The invention relates to processes and intermediates for preparing compounds of formula I: where a, R1, and R3-6 are as defined in the specification, or a salt thereof. The compounds of formula I are serotonin and norepinephrine reuptake inhibitors.
Abstract: This invention relates to a new salt of Pridopidine, a drug substance currently in development for the treatment of Huntington's disease. More specifically the invention provides the pharmaceutically acceptable hydrobromide salt, pharmaceutical compositions comprising this salt, and uses of this salt as a drug substance.
Abstract: This invention relates to a new crystalline form of Pridopidine, a drug substance currently in development for the treatment of Huntington's disease. More specifically the invention provides polymorphic Form II of the Pridopidine hydrochloride salt, a process for the preparation of this polymorphic form, pharmaceutical compositions comprising polymorphic Form II, and methods of uses of this polymorphic form.
Type:
Grant
Filed:
September 6, 2012
Date of Patent:
April 14, 2015
Assignee:
Ivax International GmbH
Inventors:
Clas Sonesson, Thomas Pittelkow, Brian Frøstrup, Anne Zimmermann
Abstract: Crystalline forms of 4-[2-(4-methylphenylsulfanyl)-phenyl]piperidine and salts thereof are provided, e.g., for the treatment of neuropathic pain.
Type:
Application
Filed:
November 14, 2014
Publication date:
March 12, 2015
Inventors:
Benny Bang-Andersen, Andre Faldt, Tine Bryan Stensbol, Silke Miller, Heidi Lopez De Diego
Abstract: This invention relates to a new crystalline form of Pridopidine, a drug substance currently in development for the treatment of Huntington's disease. More specifically the invention provides polymorphic Form II of the Pridopidine hydrochloride salt, a process for the preparation of this polymorphic form, pharmaceutical compositions comprising polymorphic Form II, and methods of uses of this polymorphic form.
Type:
Application
Filed:
September 6, 2012
Publication date:
October 23, 2014
Applicant:
IVAX INTERNATIONAL GMBH
Inventors:
Clas Sonesson, Thomas Pittelkow, Brian Frøstrup, Anne Zimmermann
Abstract: The invention provides compounds of formula I: in salt or zwitterionic form or a pharmaceutically acceptable salt thereof, wherein R1-6, a-e and Q are as defined in the specification. These compounds are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes for preparing such compounds and methods of using such compounds to, for example, treat pulmonary disorders such as chronic obstructive pulmonary disease and asthma.
Type:
Grant
Filed:
October 22, 2013
Date of Patent:
August 12, 2014
Assignee:
Theravance Biopharma R&D IP, LLC
Inventors:
YuHua Ji, Craig Husfeld, Christopher Lange, Rick Lee, YongQi Mu
Abstract: The invention relates to processes and intermediates for preparing compounds of formula I: where a, R1, and R3-6 are as defined in the specification, or a salt thereof. The compounds of formula I are serotonin and norepinephrine reuptake inhibitors.
Abstract: The present invention relates to compounds of Formula (Ia) and pharmaceutically acceptable salts, solvates, and hydrates thereof, that are useful as a single agent or in combination with one or more pharmaceutical agents, such as, an inhibitor of DPP-IV, a biguanide, or an alpha-glucosidase inhibitor, in the treatment of, for example, a disorder selected from: a GPR119-receptor-related disorder; a condition ameliorated by increasing a blood incretin level; a metabolic-related disorder; type 2 diabetes; obesity; and complications related thereto.
Type:
Application
Filed:
March 30, 2012
Publication date:
January 16, 2014
Applicant:
ARENA PHARMACEUTICALS, INC.
Inventors:
Robert M. Jones, Sangdon Han, Juerg Lehmann, Lars Thoresen
Abstract: The invention relates to compounds of formula I: where a, R1, and R3-6 are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds of formula I are serotonin and norepinephrine reuptake inhibitors. The invention also relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.
Type:
Grant
Filed:
September 28, 2012
Date of Patent:
December 10, 2013
Assignee:
Theravance, Inc.
Inventors:
Lori Jean Patterson, Eric L. Stangeland, Sheila Zipfel, Daniel D. Long
Abstract: The present invention concerns novel (aza)benzhydryl ether derivatives which exhibit H4-receptor binding activity. The present invention also concerns their process of preparation and their therapeutical uses.
Type:
Application
Filed:
June 5, 2013
Publication date:
December 5, 2013
Applicant:
BIOPROJET
Inventors:
Isabelle BERREBI-BERTRAND, Xavier BILLOT, Thierry CALMELS, Marc CAPET, Stéphane KRIEF, Olivier LABEEUW, Jeanne-Marie LECOMTE, Nicolas LEVOIN, Xavier LIGNEAU
Abstract: The present invention relates to a chemical genus of biaryl substituted heterocycle inhibitors of LTA4H (leukotriene A4 hydrolase) useful for the treatment and prevention and prophylaxis of inflammatory diseases and disorders.
Type:
Grant
Filed:
June 11, 2008
Date of Patent:
December 3, 2013
Assignee:
Decode Genetics EHF
Inventors:
Vincent Sandanayaka, Jasbir Singh, Mark Gurney, Bjorn Mamat, Peng Yu, Louis Bedell, Lei Zhao, Rama K. Mishra
Abstract: The invention provides a crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine. This invention also provides pharmaceutical compositions comprising the crystalline salt, processes and intermediates for preparing the crystalline salt, and methods of using the crystalline salt to treat diseases.
Type:
Grant
Filed:
October 1, 2012
Date of Patent:
November 26, 2013
Assignee:
Theravance, Inc.
Inventors:
Lori Jean Patterson, Robert S. Chao, Miroslav Rapta
Abstract: The invention provides compounds of formula I: in salt or zwitterionic form or a pharmaceutically acceptable salt thereof, wherein R1-6, a-e and Q are as defined in the specification. These compounds are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes for preparing such compounds and methods of using such compounds to, for example, treat pulmonary disorders such as chronic obstructive pulmonary disease and asthma.
Type:
Grant
Filed:
October 6, 2010
Date of Patent:
November 26, 2013
Assignee:
Theravance, Inc.
Inventors:
YuHua Ji, Craig Husfeld, Christopher Lange, Rick Lee, YongQi Mu
Abstract: Disclosed is a benzylpiperizine compound represented by formula (1) or a pharmaceutically acceptable salt thereof, which is useful as a medicinal agent such as an antidepressant agent. (In the formula (1), R1 represents a hydrogen atom or a methyl group; R2 is a group bound in a p- or m-position relative to a methylene group and represents a chlorine atom bound in a p-position, a bromine atom bound in a p-position, a methyl group bound in a p-position, a chlorine atom bound in a m-position or a bromine atom bound to in a m-position; X represents a methylene or an oxygen atom; and n represents an integer of 1 to 3.
Abstract: The use of 4-[2-(4-methylphenylsulfanyl)phenyl]piperidine or a pharmaceutically acceptable salt thereof in the treatment of irritable bowl syndrome.
Abstract: The present invention relates to a novel use of both enantiomers of the phenylpiperidine derivative OSU6162, i.e. (?) and (+)-OSU6162 as partial agonists on 5-hydroxytryptamine (5hHT) receptors. As a result, both (?) OSU6162 and (+)-OSU6162 may be used for the treatment and/or prevention of one or more diseases associated with a need for modulation of monoaminergic neurotransmitter receptors, wherein at least one of the monoaminergic neurotransmitter receptors is a 5-hydroxytryptamine receptor (5-HT receptor). Thus, said compounds act as stabilizers not only on dopaminergic, but also on serotonergic brain signaling and will act as partial agonists on such monoaminergic neurotransmitter receptors.
Type:
Application
Filed:
September 20, 2011
Publication date:
August 1, 2013
Applicant:
A. CARLSSON RESEARCH AB
Inventors:
Lizzie Maria Carlsson, Angélica Kloberg, Ethan S. Burstein, Per Arvid Emil Carlsson
Abstract: The present invention provides novel deuterated analogs of Pridopidine, i.e. 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine. Pridopidine is a drug substance currently in clinical development for the treatment of Huntington's disease. In other aspects the invention relates to pharmaceutical compositions comprising a deuterated analog of Pridopidine of the invention, and to therapeutic applications of these analogs.
Abstract: Crystalline forms of 4-[2-(4-methylphenylsulfanyl)-phenyl]piperidine and salts thereof are provided e.g. for the treatment of neuropathic pain.
Abstract: This invention relates to a new salt of Pridopidine, a drug substance currently in development for the treatment of Huntington's disease. More specifically the invention provides the pharmaceutically acceptable hydrobromide salt, pharmaceutical compositions comprising this salt, and uses of this salt as a drug substance.
Abstract: The present invention is directed to a compound of formula (I) for use in a method to treat or ameliorate amyloid or tau pathologies, such as Alzheimer's disease, or symptoms thereof. The invention is also directed to new compounds of formula (I), of subformula (II), (III), (IV), or (V).
Type:
Application
Filed:
May 23, 2011
Publication date:
May 23, 2013
Applicant:
FAES FARMA, S.A.
Inventors:
Francisco Ledo Gómez, Ana Muñoz Muñoz, Carmen Pumar Durán
Abstract: 4-Fluoro-4-phenylpiperidin-1-yl ? antagonists of general structure as well as pharmaceutical compositions comprising compounds of formula I, are disclosed. These compounds and compositions are useful as treatments of conditions or diseases associated with binding opioid receptors including pain, obesity, hyperalgesia, inflammation, osteoarthritis, drug addiction, and cancer. These compounds and compositions are also useful as treatments for tardive dyskinesia.
Abstract: The invention relates to a method for producing highly pure 2,4?-dimethyl-3-piperidino-propiophenone (tolperisone) (formula I) and the pharmaceutically acceptable salts, hydrochlorides, and hydrates thereof. The method allows the content of the undesired byproduct 2-methyl-1-(4-methylphenyl) propenone (4-MMPPO) to be kept significantly lower than in previously known methods. The invention further relates to active substance formulations which contain tolperisone and are suitable, among other things, for producing combination preparations used for treating patients suffering from Alzheimer's disease. The invention also relates to topical formulations, controlled release (CR) formulations, and transdermal therapeutic systems, such as active substance patches, which contain less than 50 ppm, preferably less than 10 ppm, more preferably less than 7 ppm, and most preferably less than 3 ppm or 0 ppm (i.e.
Type:
Grant
Filed:
April 24, 2008
Date of Patent:
February 12, 2013
Assignee:
SANOCHEMIA Pharmazeutika AG
Inventors:
Stefan Welzig, Jan Rothenburger, Beate Kälz, József Gungl, Klaus Gerdes, Federico Gaeta
Abstract: A process for the manufacture of (un)substituted phenylsulfanylphenyl-piperidines comprising the use of benzyl as N-piperidine protecting group is disclosed.
Abstract: A method is provided for the treatment of sleep apnea and other conditions wherein an effective amount of crystalline 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-piperidine monohydrochloride of formula (I): optionally comprising water up to 6%, and having an X-ray diffractogram that comprises characteristic peaks (2?) at 11.2°, 19.9°, 20.7° and 34.1°±0.2° is administered to a patient in need thereof.
Type:
Grant
Filed:
June 7, 2012
Date of Patent:
January 15, 2013
Assignee:
Bioprojet
Inventors:
Manuel Raga, Juan Sallares, Marta Guerrero, Antonio Guglietta, Jean-Michel Arrang, Jean-Charles Schwartz, Holger Stark, Walter Schunack, Xavier Ligneau, Jeanne-Marie Lecomte, Charon Ganellin
Abstract: The present application describes modulators of MIP-1? or CCR-1 of formula (I) or stereoisomers or prodrugs or pharmaceutically acceptable salts thereof, wherein n, ring A, T, V, X, R1, R2 and R8, are defined herein. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and transplant rejection using modulators of formula (I) are disclosed.
Abstract: The invention provides compounds represented by the general formula I wherein the substituents are defined in the application. The compounds are useful in the treatment of an affective disorder, including depression, anxiety disorders including general anxiety disorder and panic disorder and obsessive compulsive disorder.
Type:
Application
Filed:
February 6, 2012
Publication date:
November 29, 2012
Applicant:
H. LUNDBECK A/S
Inventors:
Thomas Ruhland, Garrick P. Smith, Benny Bang-Anderson, Ask Puschl, Ejner Knud Moltzen, Kim Andersen
Abstract: The invention provides a crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine. This invention also provides pharmaceutical compositions comprising the crystalline salt, processes and intermediates for preparing the crystalline salt, and methods of using the crystalline salt to treat diseases.
Type:
Grant
Filed:
November 13, 2009
Date of Patent:
November 6, 2012
Assignee:
Theravance, Inc.
Inventors:
Lori Jean Patterson, Robert S. Chao, Miroslav Rapta
Abstract: The invention relates to compounds of formula I: where a, R1, and R3-6 are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds of formula I are serotonin and norepinephrine reuptake inhibitors. The invention also relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.
Type:
Grant
Filed:
November 13, 2009
Date of Patent:
November 6, 2012
Assignee:
Theravance, Inc.
Inventors:
Lori Jean Patterson, Eric L. Stangeland, Sheila Zipfel, Daniel D. Long
Abstract: Crystalline forms of 4-[2-(4-methylphenylsulfanyl)-phenyl]piperidine and salts thereof are provided e.g. for the treatment of neuropathic pain.
Type:
Grant
Filed:
June 15, 2007
Date of Patent:
October 30, 2012
Assignee:
H. Lundbeck A/S
Inventors:
Benny Bang-Andersen, Andre Faldt, Tine Bryan Stensbol, Silke Miller, Heidi Lopez De Diego
Abstract: Disclosed is a benzylpiperizine compound represented by formula (1) or a pharmaceutically acceptable salt thereof, which is useful as a medicinal agent such as an antidepressant agent. (In the formula (1), R1 represents a hydrogen atom or a methyl group; R2 is a group bound in a p- or m-position relative to a methylene group and represents a chlorine atom bound in a p-position, a bromine atom bound in a p-position, a methyl group bound in a p-position, a chlorine atom bound in a m-position or a bromine atom bound to in a m-position; X represents a methylene or an oxygen atom; and n represents an integer of 1 to 3.
Abstract: The invention relates to new crystalline 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-piperidine monohydrochloride, the respective manufacture and methods of use, and compositions containing such a compound.
Type:
Grant
Filed:
February 6, 2006
Date of Patent:
June 26, 2012
Assignee:
Bioprojet
Inventors:
Manuel Raga, Juan Sallares, Marta Guerrero, Antonio Guglietta, Jean-Michel Arrang, Jean-Charles Schwartz, Holger Stark, Walter Schunack, Xavier Ligneau, Jeanne-Marie Lecomte, Charon Ganellin
Abstract: One aspect of the invention relates to piperidine compounds that are useful as inhibitors of monoamine transporters. The invention also relates to pharmaceutical compositions, comprising a piperidine compound of the invention. Another aspect of the present invention relates to the use of the aforementioned compounds in a method of treating a disorder of the central nervous system in a mammal.
Abstract: The present invention relates to biaryl piperidine-based renin inhibitor compounds, and their use in treating cardiovascular events and renal insufficiency.
Inventors:
Daniel J. McKay, Melissa Arbour, Renee Aspiotis, Austin Chen, Pierre-Andre Fournier, Michel Gallant, Yongxin Han, Helene Juteau, Patrick Lacombe, Sebastien Laliberte, Sophie Lauzon, Carmela Molinaro, Paul O'Shea, Yeeman Ramtohul, Daniel Simard, Dwight MacDonald, Bruce Mackay, Christophe Mellon, Krista Morley, Chit Tsui, Sarah Jennifer Dolman, Greg Hughes, Jacob Janey
Abstract: The present patent application concerns compounds of formula (I) with R1 and R2 taken together with the nitrogen atom to which they are attached, form a mono or bicyclic saturated nitrogen-containing ring; their preparation and their use as a H3 receptor ligand for treating e.g. CNS disorders like Alzheimer's disease.
Type:
Grant
Filed:
April 25, 2006
Date of Patent:
December 13, 2011
Assignee:
Bioprojet
Inventors:
Isabelle Bertrand, Marc Capet, Jeanne-Marie Lecomte, Nicolas Levoin, Xavier Ligneau, Olivia Poupardin-Olivier, Philippe Robert, Jean-Charles Schwartz, Olivier Labeeuw
Abstract: Use of a compound of formula (A), wherein: W is a residue which imparts antagonistic and/or agonistic activity at histamine H3-receptors when attached to an imidazole ring in 4(5) position; R1 and R2 may be identical or different and represent each independently a lower alkyl or cycloalkyl, or taken together with the nitrogen atom to which they are attached, a saturated nitrogen-containing ring (i) as defined, a non-aromatic unsaturated nitrogen-containing ring (ii) as defined, a morpholino group, or a N-substituted piperazino group as defined for preparing medicaments acting as antagonists and/or agonists at the H3-receptors of histamine.
Type:
Application
Filed:
December 15, 2010
Publication date:
November 17, 2011
Inventors:
Jean-Charles SCHWARTZ, Jean-Michel ARRANG, Monique GARBARG, Jeanne-Marie LECOMTE, Xavier LIGNEAU, Walter G. SCHUNACK, Holger STARK, Charon Robin GANELLIN, Fabien LEURQUIN, Elz Sigurd
Abstract: Compounds of general formula (I) in which R1, m, X, n, Y and R3 have any of the meanings given in the specification, have affinity for sigma receptors and are useful in the treatment of disorders of the central nervous system.
Abstract: The present invention relates to new piperidine modulators of dopamine receptors, pharmaceutical compositions thereof, and methods of use thereof.
Abstract: The present invention provides a photoresist composition having a sulfonium salt comprising an anion represented by the formula (IA): wherein R1 and R2 independently represent a hydrogen atom, a C1-C12 aliphatic hydrocarbon group, a C3-C20 saturated cyclic hydrocarbon group, a C6-C20 aromatic hydrocarbon group or a C7-C21 aralkyl group, and the aliphatic hydrocarbon group, the saturated cyclic hydrocarbon group, the aromatic hydrocarbon group and the aralkyl group can have one or more substituents selected from the group consisting of a hydroxyl group, a cyano group, a fluorine atom, a trifluoromethyl group and a nitro group, and one or more —CH2— in the aliphatic hydrocarbon group can be replaced by —O— or —CO—, or R1 and R2 are bonded each other to form a C4-C20 nitrogen-containing ring together with the nitrogen atom to which they are bonded, an acrylic resin having an acid-labile group and being insoluble or poorly soluble in an aqueous alkali solution but becoming soluble in an aqueous alkali solutio
Abstract: The present invention relates to an aralkyl alcohol piperidine derivative and use as antidepressant thereo. The said aralkyl alcohol piperidine derivative has a triple inhibition effect on the reuptaking of 5-HT, NA and DA. The derivative may be administered to the patient in need of such treatment in the form of composition by oral administration, injection and the like.
Type:
Application
Filed:
June 8, 2009
Publication date:
June 30, 2011
Applicants:
JIANGSU GOWORTH INVESTMENT CO. LTD, SHANGHAI INSTITUTE OF PHARMACEUTICAL INDUSTRY
Inventors:
Jianqi Li, Kai Gao, Wangping Cai, Yongyong Zheng