Abstract: The object of the present invention is to provide a compound having a glucokinase-activating effect. A pharmaceutical composition comprising a compound represented by the general formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient: wherein X means a nitrogen atom or CR6, wherein R6 means a hydrogen atom or a halogen atom; R1 means a hydrogen atom, a C1-C6 alkyl group, a C1-C6 alkoxy group or a C1-C6 alkylthio group; R2 means a hydrogen atom or a fluorine atom; R3 means a hydrogen atom or a C1-C6 alkyl group; and one of R4 and R5 means a hydrogen atom or a C1-C6 alkyl group, and the other means a C1-C6 alkylenecarboxylic acid, a C1-C6 alkylsulfonyl group, a C1-C6 alkylcarbonyl group, or CONH2.

Abstract: A prophylactic or therapeutic agent for diabetic maculopathy, which can be administered for a long time and exhibits efficacy in a mechanism different from that of existing medicines. The invention relates to a prophylactic or therapeutic agent for diabetic maculopathy, comprising, as an active ingredient, a compound represented by the general formula: wherein X represents a halogen or a hydrogen atom, R1 and R2 concurrently or differently represent a hydrogen atom or an optionally substituted C1 to C6 alkyl group, or R1 and R2, together with a nitrogen atom bound thereto and optionally another nitrogen atom or an oxygen atom, are combined to form a 5- to 6-membered heterocycle. Preferably, the compound is (2S,4S)-6-fluoro -2?,5?-dioxospiro chroman-4,4?-imidazolidine]-2-carboxamide. The invention also provides a model animal with diabetic maculopathy produced by subjecting a diabetic animal to intraocular ischemia/reperfusion to express edema in a retinal visual cell layer or in a macula lutea.

Abstract: The present invention is regarding plants and plant storage organs thereof in which GLP-1 derivatives are accumulated, and methods of producing them. The transgenic plants and plant storage organs thereof accumulate tandem repeated GLP-1 derivatives cleavable with intestinal digestive enzyme to monomeric molecules and are produced by methods comprising: integrating into vectors linked DNAs which comprise tandem repeated DNAs encoding the GLP-1 derivative with trypsin resistance in which the amino acid in the 26th position is Gln, the amino acid in the 34th position is Asn or Asp, and C-terminal consists of Arg or Lys to produce monomeric molecules; introducing the vectors into plant cells; and redifferentiating the obtained transformants. The edible transgenic plants and plant storage organs are useful for treating diabetes and can be ingested by diabetic patients.

Abstract: The problem to be solved by the present invention is to provide a medicine which is excellent in the treatment of type 2 diabetes, diabetic complications or impaired glucose tolerance. The present invention provides a medicine characterized in that a compound represented by the following general formula (I), a salt thereof, or a solvate thereof, and at least one kind of other diabetic medicine: (wherein R1, R2, R3 and R4 are each a hydrogen atom, a trifluoromethyl group or a C1-3 alkyl group).

Abstract: A prophylactic or therapeutic agent for diabetic maculopathy, which can be administered for a long time and exhibits efficacy in a mechanism different from that of existing medicines. The invention relates to a prophylactic or therapeutic agent for diabetic maculopathy, comprising, as an active ingredient, a compound represented by the general formula: wherein X represents a halogen or a hydrogen atom, R1 and R2 concurrently or differently represent a hydrogen atom or an optionally substituted C1 to C6 alkyl group, or R1 and R2, together with a nitrogen atom bound thereto and optionally another nitrogen atom or an oxygen atom, are combined to form a 5- to 6-membered heterocycle. Preferably, the compound is (2S,4S)-6-fluoro-2?,5?-dioxospiro[chroman-4,4?-imidazolidine]-2-carboxamide. The invention also provides a model animal with diabetic maculopathy produced by subjecting a diabetic animal to intraocular ischemia/reperfusion to express edema in a retinal visual cell layer or in a macula lutea.

Abstract: The present invention provides a method for highly producing a recombinant protein in a plant storage organ and a GLP-1 derivative. The plant storage organ in which the recombinant protein is highly produced is obtained by transformation with the use of a vector which comprises a recombinant protein gene, a cytokinin-related gene, a drug-resistant gene and a removable DNA element, in which the cytokinin-related gene and the drug-resistant gene exist in the positions so that they can behave together with the DNA element, while the recombinant protein to be expressed in the plant storage organ exists in the position so that it would not behave together with the DNA element. The GLP-1 is produced by using the method, and a derivative having been stabilized against enzymatic digestion is further provided.

Abstract: A prophylactic or therapeutic agent for diabeticmaculopathy, which can be administered for a long time and exhibits efficacy in a mechanism different from that of existing medicines. The invention relates to a prophylactic or therapeutic agent for diabetic maculopathy, comprising, as an active ingredient, a compound represented by the general formula: wherein X represents a halogen or a hydrogen atom, R1 and R2 concurrently or differently represent a hydrogen atom or an optionally substituted C1 to C6 alkyl group, or R1 and R2, together with a nitrogen atom bound thereto and optionally another nitrogen atom or an oxygen atom, are combined to form a 5- to 6-membered heterocycle. Preferably, the compound is (2S,4S)-6-fluoro-2?,5?-dioxospiro chroman-4,4?-imidazolidine]-2-carboxamide. The invention also provides a model animal with diabetic maculopathy produced by subjecting a diabetic animal to intraocular ischemia/reperfusion to express edema in a retinal visual cell layer or in a macula lutea.

Abstract: A method for manufacturing a molded article with at one or more cores uses compression molding apparatus that includes upper and lower punches that have a double structure comprising a central punch and an outer punch that surrounds the periphery of the central punch. The central punch and the outer punch are capable of independent sliding motions and compressing operations. Molding materials are supplied for a core and an outer layer respectively. The molding materials are compressed by the punches to form molded articles that include the core. The method may be executed in a rotary compression molding machine.

Abstract: The present invention provides a protective agent for retinal nerve or optic nerve which exerts its effect through a different mechanism from that of conventional therapeutic agents and can be taken for long periods. The present invention is the protective agent for retinal nerve or optic nerve which comprises a compound with aldose reductase inhibiting activity such as the compound represented by the following general formula as an active ingredient. A preferable compound thereof is (2S,4S)-6-fluoro-2?,5?-dioxospiro[chroman-4,4?-imidazolidine]-2-carboxamide: wherein X represents a halogen atom or a hydrogen atom, R1 and R2 independently represent a hydrogen atom or an optionally substituted C1 to C6 alkyl group, or R1 and R2, together with a nitrogen atom bound thereto, or optionally another nitrogen atom or an oxygen atom, are combined to form a 5- to 6-membered heterocycle.

Abstract: The present invention provides a method for manufacturing a molding with a core by using compression molding means having upper and lower double-structured punches; the method comprising the steps of supplying molding material for the core and molding material for the outer layer respectively, the step of compression-molding the molding material for the core and/or the molding material for the outer layer, and the step of compression-molding the whole molding with a core, wherein: the step of supplying the molding material for the outer layer posterior to the step of supplying the molding material for the core is performed until a tip of the lower center punch finally takes a position protruding from a tip of the lower outer punch; and the step of compression-molding the whole molding with a core is performed with the tips of the lower center punch and the lower outer punch aligned with each other.

Abstract: This invention provides a punch comprising: a center punch and an outer punch surrounding the outer periphery of the center punch, both of which being slidable and capable of compressing; and relative position restriction means for restricting a relative position of the center and outer punches, the relative position restriction means being configured to restrict a first position in which a punch tip of the center punch is protruded from a punch tip of the outer punch and a second position in which the punch tip of the center punch is substantially coincident with the punch tip of the outer punch, and being configured to fail to restrict a third position in which the punch tip of the center punch is retracted in the punch tip of the outer punch, as well as a rotary compression molding machine provided with the double-structured punch.

Abstract: An object of the present invention is to provide a medicament as a thyroid hormone receptor ligand which is sufficient in drug efficacy and safety, and has the excellent action as a drug. The present invention provides a compound represented by the following general formula (I) or a pharmaceutically acceptable salt thereof: [wherein [Chemical Formula 2] is a single bond or a double bond; A is —CH2— or —CO—; X, Y, and Z are each independently a nitrogen atom or a carbon atom; R1 is a hydrogen atom or an aralkyl group; R2 is an alkyl group or an aralkyl group, etc.; R3 is a hydrogen atom or an alkyl group, etc.; R4 is a hydrogen atom or an alkyl group; R5 is a hydrogen atom, an alkyl group or a halo lower alkyl group, etc.; R6 is a hydrogen atom or an alkyl group; R7 is a hydrogen atom, etc.; R8 is a hydrogen atom, or an alkyl group, etc.; and E is —NHCO-G-COR12, etc. (wherein G is a single bond or an alkylene group, and R12 is a hydroxy group or an alkoxy group)].

Abstract: The present invention provides a preventive or therapeutic agent for cerebral ischemic injury or cerebral ischemic reperfusion injury in stroke such as cerebral infarction and cerebral hemorrhage which exerts its effect through a different mechanism from that of conventional therapeutic agents and can be taken for along period. The present invention is a preventive or therapeutic agent for cerebral ischemic injury or cerebral ischemic reperfusion injury in stroke which contains 6-fluoro-2?,5?-dioxospiro[chroman-4,4?-imidazolidine]-2-carboxamide as an active ingredient. A particularly preferable compound is an optically resolved (2S,4S)-form of fidarestat.

Abstract: Disclosed herein is at least a method of preventing or treating cardiac dysfunction or myocardial injury caused by ischemia or ischemia reperfusion

Abstract: The present invention provides a method for manufacturing a molding with a core by using compression molding means having upper and lower double-structured punches; the method comprising the steps of supplying molding material for the core and molding material for the outer layer respectively, the step of compression-molding the molding material for the core and/or the molding material for the outer layer, and the step of compression-molding the whole molding with a core, wherein: the step of supplying the molding material for the outer layer posterior to the step of supplying the molding material for the core is performed until a tip of the lower center punch finally takes a position protruding from a tip of the lower outer punch; and the step of compression-molding the whole molding with a core is performed with the tips of the lower center punch and the lower outer punch aligned with each other.

Abstract: A dipeptidyl peptidase IV inhibitor which is satisfactory in respect of activity, stability and safety and has an excellent action as a pharmaceutical agent. A compound represented by the following general formula or a pharmaceutically acceptable salt thereof: wherein R1 and R2 each represents hydrogen, an optionally substituted C1-6 alkyl group, or —COOR5 whereupon R5 represents hydrogen or an optionally substituted C1-6 alkyl group, or R1, R2, and a carbon atom together represent a 3- to 6-membered cycloalkyl group, R3 represents hydrogen or an optionally substituted C6-10 aryl group, R4represents a hydrogen or a cyano group, D represents —CONR6-, —CO— or —NR6CO—, R6 represents hydrogen or an optionally substituted C1-6 alkyl group, E represents —(CH2)m— whereupon m is 1 to 3, —CH2OCH2—, or —SCH2—, n is 0 to 3, and A represents an optionally substituted bicyclic heterocyclic group or bicyclic hydrocarbon group.

Abstract: A method for ameliorating severe diabetic retinopathy in a mammal comprising administering to the subject an effective amount of a compound represented by the following general formula: wherein X represents a halogen or a hydrogen atom, R1 and R2 concurrently or differently represent a hydrogen atom or an optionally substituted C1 to C6 alkyl group, or R1 and R2, together with a nitrogen atom bound thereto and optionally another nitrogen atom or an oxygen atom, are combined to form a 5- to 6-membered heterocycle.

Abstract: A GLP-1 derivative is provided including an amino acid sequence of GLP-1 (7-35) having deletion, substitution and/or addition of one or more amino acids and having Waa-(Xaa)n-Yaa (in which Waa is Arg or Lys, Xaa is Arg or Lys, n is an integer of 0 to 14, and Yaa is Arg, Arg-NH2, Lys, Lys-NH2 or Hse) added to the C-terminus of the peptide having a GLP-1 activity. These derivatives are highly absorbable via a mucous membrane. The GLP-1 derivative can be conferred with resistance to dipeptidyl peptidase IV by substituting amino acid 8 in its GLP-1 amino acid sequence with Ser, or with resistance to trypsin by substituting amino acids 26 and 34 with Gln and Asn, respectively. The absorption efficiency of the GLP-1 derivatives via mucous membranes can be further improved by preparing a composition using a charge-regulated fat emulsion regulated to be negatively charged thereon.

Abstract: The present invention provides a rotary press that allows mass production of a molded product. The rotary press has upper and lower punches that may be split in to a plurality of split punches, a means for moving the split punches, and a means for manipulating the plurality of split punches. In addition, the rotary press also has a plurality of molding material supply-charging units for supplying and charging molding materials into the space formed by the tip portions of the split punches, a precompression molding unit and a main compression molding unit for compression-molding the molding materials supplied and charged the entire molded product, respectively. Optionally, a unit to remove residual molding material remaining on the lower punches and/or the temporary molded product may be provided.

Abstract: To manufacture a multi-core press-coated molded product efficiently and in a single step from molding materials, namely, powder or granular particles, a punch has been devised that is characterized in that the punch, consists of a center punch whose tip portion is split into two or more parts, and an outer punch enclosing the outer perimeter of the center punch, and whose tip portion fills the gap at the tip portion of the center punch, with both the center and outer punches being slidable and manipulatable for compression operation the method of manufacturing a multi-core press-coated molded product using the punch of the invention as compression molding means for at least the upper punch and preferably for both the upper and lower punches, and a rotary compression molding machine therefore is also discribed.