The present invention has an object of shortening the process time and reducing use of a poor solvent for solidifying a carrier (Tag)-peptide component, by removing impurities without conducting solid-liquid separation (condensation, solid-liquid separation and drying operation) of a Tag-peptide component, in an Fmoc method using a Tag for liquid phase peptide synthesis. Provided is the peptide synthesis method that includes the following steps a-d: step a: a carrier-protected amino acid, carrier-protected peptide, or a carrier-protected amino acid amide, and an N-Fmoc-protected amino acid or an N-Fmoc-protected peptide are condensed in an organic solvent or a mixed solution of organic solvents, to obtain an N-Fmoc-carrier-protected peptide, step b: a water-soluble amine is added to the reaction solution after the condensation reaction, step c: the Fmoc group is deprotected from the protected amino group in the presence of a water-soluble amine, and step d: the reaction solution is neutralized by adding an acid, and further, by adding and washing with an acidic aqueous solution, then, by liquid-liquid separation an aqueous layer is removed to obtain an organic layer.
The purpose of the present invention is to provide a method for producing leuprorelin that allows a crude product of high purity to be obtained in a shorter production period, as compared with conventional production methods. Provided is a method for producing leuprorelin, comprising the following steps a through d: step a for obtaining an N-Fmoc-protected peptide by condensing a protected amino acid or peptide and an N-Fmoc protected amino acid in an organic solvent or an organic solvent mixture; step b for adding a water-soluble amine to the reaction solution following the condensation reaction; step c for deprotecting the Fmoc group from the protected amino group in the presence of the water-soluble amine; and step d for obtaining an organic layer by adding acid to neutralize the reaction solution, additionally adding an acidic aqueous solution to wash the product, carrying out liquid separation, and then removing the aqueous layer.
The present invention is a liquid-phase peptide synthesis method that, in an Fmoc method utilizing a carrier (Tag), has the purpose of reducing processing time and cutting back on usage of poor solvents for solidification of a Tag-peptide constituent by removing impurities without performing solid/liquid separation (concentration, solid/liquid separation, and drying operations) of the Tag-peptide constituent. Provided is the peptide synthesis method that includes the following steps a–d: a. a step in which, in an organic solvent or a mixture of organic solvents, a carrier-protected amino acid, a carrier-protected peptide, or a carrier-protected amino acid amide and an N-Fmoc-protected amino acid or an N-Fmoc-protected peptide are condensed to obtain an N-Fmoc/carrier-protected peptide; b. a step in which a water-soluble amine is added to the reaction solution after the condensation reaction; c. a step in which Fmoc is deprotected from a protected amino base in the presence of the water-soluble amine; and d. a step in which the reaction solution is neutralized by adding acid and washed by adding an acidic water aqueous solution, after which separation is performed and a water layer is removed to obtain an organic layer.
C07K 1/10 - General processes for the preparation of peptides using coupling agents
C07K 1/02 - General processes for the preparation of peptides in solution
C07K 1/04 - General processes for the preparation of peptides on carriers
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
4.
Cross-linked peptides containing non-peptide cross-linked structure, method for synthesizing cross-linked peptides, and novel organic compound used in method
The purpose of the present invention is to provide a cross-linked peptide containing a novel non-peptide cross-linked structure, and a method for synthesizing the same. A cross-linked peptide having a novel non-peptide cross-linked structure, a useful intermediate for synthesizing the cross-linked peptide, and a method for synthesizing the novel cross-linked peptide and the intermediate are provided. The cross-linked peptide is characterized by having an —NR— bond in the cross-linked structure. By using the method for synthesizing the cross-linked peptide, a cross-link can be freely designed and an change can be freely made to a cross-link.
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
5.
Cross-linked peptides containing non-peptide cross-linked structure, method for synthesizing cross-linked peptides, and novel organic compound used in method
The purpose of the present invention is to provide a cross-linked peptide containing a novel non-peptide cross-linked structure, and a method for synthesizing the same. A cross-linked peptide having a novel non-peptide cross-linked structure, a useful intermediate for synthesizing the cross-linked peptide, and a method for synthesizing the novel cross-linked peptide and the intermediate are provided. The cross-linked peptide is characterized by having an —NR— bond in the cross-linked structure. By using the method for synthesizing the cross-linked peptide, a cross-link can be freely designed and an change can be freely made to a cross-link.
C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
C07K 1/00 - General processes for the preparation of peptides
C07K 1/113 - General processes for the preparation of peptides by chemical modification of precursor peptides without change of the primary structure
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
C07K 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
A61K 47/60 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
C07K 1/06 - General processes for the preparation of peptides using protecting groups or activating agents
[Problem] To provide an aqueous suspension comprising a glucocorticosteroid compound as an active ingredient. More particularly, to provide a practically usable medicinal composition that comprises a glucocorticosteroid compound as an active ingredient. [Solution] An aqueous suspension agent characterized by comprising nanoparticles of a glucocorticosteroid compound and a dispersion stabilizing agent; the aqueous suspension agent wherein the average particle diameter of the nanoparticles is 300 nm or less and the D90 particle diameter thereof is 450 nm or less; and a medicinal composition for parenteral administration, an injection, eye drops or ear drops comprising the aforesaid aqueous suspension, more particularly, eye drops for treating or preventing an inflammatory eye disease, or ear drops for treating or preventing an inflammatory ear disease.
A61K 31/57 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 31/58 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
A61K 47/32 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
The present invention pertains to a peptide synthesis reaction using a carrier which can reversibly repeat a dissolved state and an encapsulated state, wherein it is easy to solve the problem of amino acid active species which are present in a reaction system during a deprotection reaction. The present invention (1) provides a peptide synthesis method containing the following steps: a step in which an N-Fmoc protected amino acid and a peptide having a C-terminus protected by a carrier is crystallized together with changes in the composition of a solvent in which the peptide is dissolved are condensated, in the presence of a condensing agent, to obtain an N-Fmoc-C-carrier protected peptide; a step in which a C1-14 alkyl amine or hydroxylamine is added to the reaction system; a step in which the N terminal is deprotected; and a separation step in which a solvent composition having a C-carrier protected peptide dissolved therein is varied, thereby crystallizing said peptide.
C07K 1/10 - General processes for the preparation of peptides using coupling agents
C07C 43/225 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
C07C 43/23 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
C07C 217/58 - Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
8.
AQUEOUS SUSPENSION PREPARATION COMPRISING NANOPARTICLES OF MACROLIDE ANTIBACTERIAL AGENT
[Problem] The purpose of the present invention is to provide an aqueous suspension preparation that comprises a macrolide antibacterial agent as an active component. Specifically, the purpose of the present invention is to provide a pharmaceutical composition that comprises a macrolide antibacterial agent as an active component and that can be put to practical use. [Solution] The present invention provides: an aqueous suspension preparation that is characterized by comprising nanoparticles of a macrolide antibacterial agent and a dispersion stabilizer; an aqueous suspension in which the average particle size of nanoparticles is 500 nm or less and the D90 particle size is 1,500 nm or less; a parenterally administered pharmaceutical composition that comprises this aqueous suspension preparation; an injection preparation; and eye drops or ear drops, more specifically, eye drops for the treatment or prevention of inflammatory diseases of the eye or ear drops for the treatment or prevention of inflammatory diseases of the ear.
A61K 9/72 - Medicinal preparations characterised by special physical form for smoking or inhaling
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61K 47/32 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
Cross-linked peptides containing non-peptide cross-linked structure, method for synthesizing cross-linked peptides, and novel organic compound used in method
The purpose of the present invention is to provide a cross-linked peptide containing a novel non-peptide cross-linked structure, and a method for synthesizing the same. A cross-linked peptide having a novel non-peptide cross-linked structure, a useful intermediate for synthesizing the cross-linked peptide, and a method for synthesizing the novel cross-linked peptide and the intermediate are provided. The cross-linked peptide is characterized by having an —NR— bond in the cross-linked structure. By using the method for synthesizing the cross-linked peptide, a cross-link can be freely designed and an change can be freely made to a cross-link.
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
10.
Cross-linked peptides containing non-peptide cross-linked structure, method for synthesizing cross-linked peptides, and novel organic compound used in method
The purpose of the present invention is to provide a cross-linked peptide containing a novel non-peptide cross-linked structure, and a method for synthesizing the same. A cross-linked peptide having a novel non-peptide cross-linked structure, a useful intermediate for synthesizing the cross-linked peptide, and a method for synthesizing the novel cross-linked peptide and the intermediate are provided. The cross-linked peptide is characterized by having an —NR— bond in the cross-linked structure. By using the method for synthesizing the cross-linked peptide, a cross-link can be freely designed and an change can be freely made to a cross-link.
C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
C07K 1/00 - General processes for the preparation of peptides
C07K 1/113 - General processes for the preparation of peptides by chemical modification of precursor peptides without change of the primary structure
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
C07K 14/00 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
11.
ORGANIC COMPOUND NANOPOWDER, PRODUCTION METHOD THEREFOR, AND SUSPENSION
[Problem] To easily and inexpensively provide an organic compound nanopowder while avoiding contamination by impurities for removal. [Solution] The present invention relates to an organic compound nanopowder and a production method therefor. The organic compound nanopowder comprises at least: a particulate organic compound of which the average particle diameter is 500 nm or less and the 90% diameter is less than 1500 nm; and a sugar compound made from a sugar and/or a sugar alcohol, said sugar compound having a mass ratio of at least 0.3 relative to the organic compound. The present invention also relates to a suspension that is made by dispersing the organic compound nanopowder in a liquid dispersion medium in which the organic compound is either insoluble or slightly soluble.
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
A61K 31/57 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
National Institute of Agrobiological Sciences (Japan)
Inventor
Nakamura, Makoto
Tokino, Seiji
Suzuki, Hideaki
Nagano, Tomio
Kono, Yusuke
Ishibashi, Jun
Abstract
The purpose of the present invention is to provide a polypeptide-containing polymer that can be used to manufacture an antimicrobial fiber. The purpose of the present invention is also to provide a method for polypeptide immobilization on a fiber, whereby an antimicrobial polypeptide can be immobilized on a fiber by a relatively simple means, and whereby there is little damage to the fiber, and immobilization of the polypeptide can be maintained despite repeated use. The present invention provides an antimicrobial polypeptide-containing (beetle defensin-modified polypeptide-containing) polymer that can be used to manufacture an antimicrobial fiber. By the method of the present invention, an antimicrobial polypeptide can also be easily immobilized on a fiber.
C08F 20/60 - Amides containing nitrogen in addition to the carbonamido nitrogen
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C07K 17/08 - Peptides being immobilised on, or in, an organic carrier the carrier being a synthetic polymer
NOVEL CROSS-LINKED PEPTIDES CONTAINING NON-PEPTIDE CROSS-LINKED STRUCTURE, METHOD FOR SYNTHESIZING CROSS-LINKED PEPTIDES, AND NOVEL ORGANIC COMPOUND USED IN METHOD
The purpose of the present invention is to provide novel cross-linked peptides containing a non-peptide cross-linked structure, and a method for synthesizing the same. Cross-linked peptides having a non-peptide cross-linked structure with a novel structure, a useful intermediate for synthesizing the cross-linked peptides, and a method for synthesizing the novel cross-linked peptides and the intermediate are provided. These cross-linked peptides are characterized by having an -NR- bond in the cross-linked structure. By using the method for synthesizing these cross-linked peptides, cross-links can be freely designed and changes can be freely made to the cross-links.
National University Corporation Tokyo Medical and Dental University (Japan)
Inventor
Kono, Yusuke
Fujita, Shuji
Okumoto, Mari
Nakae, Takashi
Suzuki, Hideaki
Maeda, Miki
Ohya, Keiichi
Aoki, Kazuhiro
Abstract
The purpose of this invention is to provide novel peptide that mimics a TNF receptor loop peptide (WP9QY peptide) having improved properties. More specifically, to provide an osteoporosis therapeutic agent containing a peptide, which has more desirable properties, that mimics the WP9QY peptide. A novel peptide that mimics a TNF receptor loop peptide, which has inhibitory activity against osteoclast differentiation, and which has a cross-linked structure having -NR- in a cross-linked structure, is provided. A pharmaceutical composition containing the peptide and an osteoclast growth inhibitor that uses the peptide is also provided.
The invention relates to a novel use of the antimuscarinic agent glycopyrrolate, for example the salt glycopyrronium bromide. In particular, the invention relates to glycopyrrolate for use as a heart rate lowering agent and more particularly, but not exclusively, for use in patients suffering from respiratory conditions such as chronic obstructive pulmonary disease.
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
A reagent for organic synthesis with which a chemical reaction can be conducted in a liquid phase and unnecessary compound(s) can be easily separated at low cost from the liquid phase after completion of the reaction. The reagent for organic synthesis reversibly changes from a liquid-phase state to a solid-phase state with changes in solution composition and/or solution temperature, and is for use in organic synthesis reactions. This reagent for organic syntheses facilitates process development. With the reagent, research on and development of, e.g., medicines through, e.g., compound library synthesis, etc. can be accelerated. It can hence contribute to technical innovations in the biochemical industry and chemical industry.
C07C 43/205 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring the aromatic ring being a non-condensed ring
C07C 275/30 - Derivatives of urea, i.e. compounds containing any of the groups the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by halogen atoms, or by nitro or nitroso groups
C07C 211/01 - Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
C07C 69/96 - Esters of carbonic or haloformic acids
C07C 69/76 - Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a six-membered aromatic ring
C07C 229/28 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and containing rings
C07C 265/12 - Derivatives of isocyanic acid having isocyanate groups bound to carbon atoms of six-membered aromatic rings
C07D 233/60 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms
C07D 487/02 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups in which the condensed system contains two hetero rings
A61K 31/535 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
18.
COMPOSITE ORGANIC COMPOUND POWDER FOR MEDICAL USE, METHOD FOR PRODUCING SAME AND SUSPENSION OF SAME
A safe medical agent which is low in contamination by a pulverizing medium, while having improved bioavailability. A method for producing a composite organic compound powder for medical use, which comprises a step of mixing a poorly water-soluble crystalline organic compound powder, a physiologically acceptable salt, a physiologically acceptable polyol and a carboxyvinyl polymer and pulverizing the organic compound powder, and a step of removing at least the salt and the polyol during or after the pulverization.
A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
A61K 31/405 - Indole-alkanecarboxylic acidsDerivatives thereof, e.g. tryptophan, indomethacin
A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
A61K 31/4174 - Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
19.
Carrier for separation, method for separation of compound, and method for synthesis of peptide using the carrier
A carrier for use for separation purpose and a method for separation of a compound enable a chemical reaction to be performed in a liquid phase, a compound of interest to be separated from the liquid phase after the completion of the reaction readily, the separated compound to be evaluated by structural analysis or the like while the compound is being bound to the carrier, and the compound to be separated from the carrier readily. A carrier for separation is also provided which has a reaction site capable of reacting with other compound(s) on a benzene ring, and a long-chain group having a specified carbon atom(s) at each of the ortho-position and the para-position of the reaction site through an oxygen atom.
A reagent for organic synthesis with which a chemical reaction can be conducted in a liquid phase and unnecessary compound(s) can be easily separated at low cost from the liquid phase after completion of the reaction. The reagent for organic synthesis reversibly changes from a liquid-phase state to a solid-phase state with changes in solution composition and/or solution temperature, and is for use in organic synthesis reactions. This reagent for organic syntheses facilitates process development. With the reagent, research on and development of, e.g., medicines through, e.g., compound library synthesis, etc. can be accelerated. It can hence contribute to technical innovations in the biochemical industry and chemical industry.
C07C 43/205 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring the aromatic ring being a non-condensed ring
C07C 321/06 - Thiols having mercapto groups bound to acyclic carbon atoms of a saturated carbon skeleton containing rings
C07C 217/58 - Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
C07C 217/60 - Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
C07C 217/62 - Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
Disclosed is a method for producing pulverized particles of a crystalline organic compound which is poorly water soluble. Also disclosed is a pulverized organic compound particle produced by such a method. Specifically disclosed is a method for producing a poorly water-soluble organic compound particle for medical use, which is characterized in that a poorly water-soluble organic compound for medical use is mixed with a physiologically acceptable salt and a physiologically acceptable polyol, and subjected to wet milling. Also specifically disclosed is a poorly water-soluble organic compound particle for medical use, which is produced by sucha production method.
A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
A61K 31/4174 - Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
A61K 31/4422 - 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
A61K 31/56 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids
A61K 31/57 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
23.
AMINOALCOHOL DERIVATIVES AND THEIR THERAPEUTIC USE
A compound of formula (1 ) Including pharmaceutically acceptable salts thereof, wherein: R1 is aryl or heteroaryl optionally substituted with R8; R2 is H or alkyl or CH2 (when forming part of a ring with R3, R4 or R5); R3 is H, alkyl, CH2OH or CH2OR6 and can be part of a ring with R2; R4 is H, alkyl, CH2OH or CH2OR6 and can be part of a ring with R2; R5 is H, alkyl, CH2OH or CH2OR6 and can be part of a ring with R2; R6 is H, alkyl, COH, COOR9, CON(R9)2, COR9, COR10, COR11, P(O)nR9, P(O)nR10S(O)nR10 or S(O)nR9 and can be part of a ring with R2, R3, R4 or R5; R7 is H, alkyl, COOR9, COOR11, COR9 or CON(R9)2, and can be part of a ring with R2, R3, R4, R5 or R6; R8 is alkyl, CF3, OR9, OCOR9, CONH2, CN, F, Cl, Br, I, N(R9)2, NO2, NHCHO, NHCONH2, NHSO2R9, CON(R9)2, S(O)nR9, CH2OH Or OCON(R9)2; R9 is H, alkyl or cycloalkyl; R10 is aryl or heteroaryl (optionally substituted with R8) or a four to seven membered ring (which is optionally substituted with R8 and can contain one or more additional heteroatoms selected from the list O, S(O)n and NR9); R11 is alkyl optionally substituted with R8 or R10; and n is O, 1 or 2; provided that when R3, R4 or R5 is CH2OH then R6 is not H, and that when R7 is H and R3, R4 and R5 are alkyl then R6 is not H. is of therapeutic use in the treatment of a condition associated with T-cell proliferation or that is mediated by pro- and/or anti-inflammatory cytokines.
C07C 219/22 - Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings
C07D 309/08 - Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
A61K 31/351 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
24.
ACAT INHIBITORS AND THEIR USE IN THE PREVENTION OR TREATMENT OF FIBROSIS
The present invention relates to the use of ACAT inhibitors, {e.g. F-1394, Avasimibe (CI-1011), Pactimibe (CS505), Efluimibe (F12511), Eldacimibe, NTE 122, AS-183, KW-3033, E5324, FY087, FCE27677, CI-976, K-604, TEI6522, Octimibate, FR179254, and S 58-035, or mixtures thereof), compositions comprising the same, and methods for preventing or treating fibrosis, for preventing or reducing collagen deposition in a tissue, and in the prevention and reduction of excessive fibrous connective tissue
A61K 31/357 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61P 43/00 - Drugs for specific purposes, not provided for in groups
25.
SALTS OF DIHYDROXYANTHRAQUINONE CARBOXYLIC ACIDS AND THEIR THERAPEUTIC USE
A compound of general formula (I): wherein Xi is H or COR1 and X2 is H or COR2 but X1 and X2 are not both H; R1 and R2 are the same or different and are each C1-4 alkyl substituted with R3, or a four to seven-membered ring which can be optionally substituted with R8 and can contain one or more additional heteroatoms selected from O, S(O)n and NR9; R3 is F, CF3, OR4, NR5R6 or S(O)nR7; R4, R5 and R6 are the same or different and are each H or C1-4 alkyl optionally substituted with R3, or NR5R6 is a C4-6 heterocycloalkyl ring containing one or more heteroatoms selected from O, NR8 and S(O)n; each n is 0-2; R7 is C1-4 alkyl; R8 is as defined for R3 or C1-4 alkyl optionally substituted with R3 or halogen; R9 is H or C1-4 alkyl; Y is NR9R10R11; and R10 and R11 are the same or different and are each H or C1-6 alkyl optionally substituted with R3 or halogen, or NR10R11 is a four to seven membered ring which can be optionally substituted with R8 or COR1, and can contain one or more additional heteroatoms selected from O, S(O)n and NR9; and hydrates thereof.
A compound containing a Tηp-aza(Phe) structure of the formula (I): wherein A is a bond, an α-amino acid or a residue of a dipeptide; R1 is hydrogen or a protective group for a terminal amino group; R2 is phenyl or phenyl substituted by one or more substitutents selected from the group consisting of a lower alkyl, a halogen, hydroxyl which may be protected, nitro, amino which may be protected and perhalo lower alkyl; R3 is hydroxyl or a protective group for a terminal carboxyl group; or a prodrug thereof that is metabolisable to form a compound as defined above; is useful for the treatment of interstitial cystitis.
A process for the racemisation of a compound which is nefopam or an analogue thereof in the form of a single enantiomer or non-racemic mixture, which comprising contacting the compound with an acid.
National University Corporation, Tokyo University of Agriculture and Technology (Japan)
JITSUBO Co., Ltd. (Japan)
Inventor
Chiba, Kazuhiro
Kim, Shokaku
Kono, Yusuke
Abstract
A reagent for organic syntheses with which a chemical reaction can be conducted in a liquid phase and unnecessary compound(s) can be easily separated at low cost from the liquid phase after completion of the reaction. The reagent for organic syntheses reversibly changes from a liquid-phase state to a solid-phase state with changes in solution composition and/or solution temperature, and is for use in organic synthesis reactions. This reagent for organic syntheses facilitates process developments. With the reagent, researches on and developments of, e.g., medicines through, e.g., compound library syntheses, etc. can be accelerated. It can hence contribute to a technical innovation in the biochemical industry and chemical industry.
C07C 41/22 - Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogenPreparation of ethers by reactions not forming ether-oxygen bonds by substitution of halogen atoms by other halogen atoms
C07C 41/26 - Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
C07C 43/225 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
C07C 43/23 - Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
C07C 67/08 - Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
C07C 217/84 - Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
C07C 265/12 - Derivatives of isocyanic acid having isocyanate groups bound to carbon atoms of six-membered aromatic rings
C07C 273/18 - Preparation of urea or its derivatives, i.e. compounds containing any of the groups the nitrogen atoms not being part of nitro or nitroso groups of substituted ureas
C07C 275/34 - Derivatives of urea, i.e. compounds containing any of the groups the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms having nitrogen atoms of urea groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
C07C 281/20 - Derivatives of carbonic acid containing functional groups covered by groups in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group the two nitrogen atoms of the functional groups being doubly-bound to each other, e.g. azoformamide
C07D 233/60 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms
A compound for therapeutic use, of the formula (I), wherein R1 is aryl or heteroaryl optionally substituted with R5; R2 is H, alkyl or CH2OH or forms part of a ring with R4; R3 is H, alkyl or CH2OH or forms part of a ring with R4; R4 is H, alkyl or (when forming part of a ring with R2 or R3) CH2; and R5 is alkyl, CF3, OH, Oalkyl, OCOalkyl, CONH2, CN, halogen, NH2, NO2, NHCHO, NHCONH2, NHSO2Me, CONH2, or SOMe; or a salt thereof.
Compounds that may be used for the treatment or prevention of a condition associated with T-cell proliferation or that is mediated by pro-inflammatory cytokines are of formula (I): wherein at least one of R1 , R2 or R3 is not H and each is independently H, alkyl, CF3, CONH2, CN, halogen, NH2, NO2, NHCHO, NHCONH2, NHSO2alkyl, SOMe, SO2NH2, Salkyl, or CH2S02alkyl; and R4 is H or alkyl; or a salt thereof.
Compounds that may be used for the treatment or prevention of a condition associated with T-cell proliferation or that is mediated by pro-inflammatory cytokines are of formula (I) or a salt thereof.
A safe medical agent which is low in contamination by a pulverizing medium, while having improved bioavailabil-ity. A method for producing a composite organic compound powder for medical use, which comprises a step of mixing a poorly water-soluble crystalline organic compound powder, a physiologically acceptable salt, a physiologically acceptable polyol and a carboxyvinyl polymer and pulverizing the organic compound powder, and a step of removing at least the salt and the polyol dur-ing or after the pulverization.
A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
A61K 31/405 - Indole-alkanecarboxylic acidsDerivatives thereof, e.g. tryptophan, indomethacin
A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
A61K 31/4174 - Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
A61K 47/32 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers
34.
ORGANIC COMPOUND NANO-POWDER, METHOD FOR PRODUCING THE SAME AND SUSPENSION
[Problem] To easily and inexpensively provide an organic compound nanopowder while avoiding contamination by impurities for removal. [Solution] The present invention relates to an organic compound nanopowder and a production method therefor. The organic compound nanopowder comprises at least: a particulate organic compound of which the average particle diameter is 500 nm or less and the 90% diameter is less than 1500 nm; and a sugar compound made from a sugar and/or a sugar alcohol, said sugar compound having a mass ratio of at least 0.3 relative to the organic compound. The present invention also relates to a suspension that is made by dispersing the organic compound nanopowder in a liquid dispersion medium in which the organic compound is either insoluble or slightly soluble.
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
A61K 31/57 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
[Problem] To provide an aqueous suspension comprising a glucocorticosteroid compound as an active ingredient. More particularly, to provide a practically usable medicinal composition that comprises a glucocorticosteroid compound as an active ingredient. [Solution] An aqueous suspension agent characterized by comprising nanoparticles of a glucocorticosteroid compound and a dispersion stabilizing agent; the aqueous suspension agent wherein the average particle diameter of the nanoparticles is 300 nm or less and the D90 particle diameter thereof is 450 nm or less; and a medicinal composition for parenteral administration, an injection, eye drops or ear drops comprising the aforesaid aqueous suspension, more particularly, eye drops for treating or preventing an inflammatory eye disease, or ear drops for treating or preventing an inflammatory ear disease.
A61K 31/57 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 31/58 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
A61K 47/32 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
Disclosed is a method for producing pulverized particles of a crystalline organic compound which is poorly water-soluble. Also disclosed is a pulverized organic compound particle produced by such a method. Specifically disclosed is a method for producing a poorly water-soluble organic compound particle for medical use, which is characterized in that a poorly water-soluble organic compound for medical use is mixed with a physiologically acceptable salt and a physiologically acceptable polyol, and subjected to wet milling. Also specifically disclosed is a poorly water-soluble organic compound particle for medical use, which is produced by such a production method.
A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
A61K 31/4174 - Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
A61K 31/4422 - 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
A61K 31/56 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids
A61K 31/57 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
patents
