Patents Assigned to Yoshitomi Pharmaceutical Industries, Ltd.
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Patent number: 6309864Abstract: A production method of a heterologous protein, comprising culturing a heterologous protein-producing host prepared by gene manipulation in a medium containing a fatty acid or a salt thereof, and a surfactant and harvesting the heterologous protein from the culture. The production amount of the heterologous protein produced by a heterologous protein-producing host can be increased. Moreover, since decomposition of the heterologous protein by an enzyme derived from the host can be inhibited, enabling large scale production of a heterologous protein.Type: GrantFiled: December 22, 1999Date of Patent: October 30, 2001Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Toyoo Ohda, Tomoshi Ohya, Shinobu Kuwae, Masao Ohyama, Kaoru Kobayashi, Yahiro Uemura
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Patent number: 6218410Abstract: A Rho kinase inhibitor is provided as a novel pharmaceutical agent, particularly as a therapeutic agent of hypertension, a therapeutic agent of angina pectoris, a suppressive agent of cerebrovascular contraction, a therapeutic agent of asthma, a therapeutic agent of peripheral circulation disorder, a prophylactic agent of immature birth, a therapeutic agent of arteriosclerosis, an anti-cancer drug, an anti-inflammatory agent, an immunosuppressant, a therapeutic agent of autoimmune disease, an anti-AIDS drug, a contraceptive, a prophylactic agent of digestive tract infection, a therapeutic agent of osteoporosis, a therapeutic agent of retinopathy and a brain function improving drug. In addition, the Rho kinase inhibitor is provided as a reagent and a diagnostic.Type: GrantFiled: April 19, 1999Date of Patent: April 17, 2001Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Masayoshi Uehata, Takashi Ono, Hiroyuki Satoh, Keiji Yamagami, Toshio Kawahara
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Patent number: 6187774Abstract: The present invention relates to a fused heterocyclic compound of the formula (I) wherein each symbol is as defined in the specification, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing a compound of the formula (I), an optical isomer thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive, and a medicament containing a compound of the formula (I), an optical isomer thereof or a pharmaceutically acceptable salt thereof. The compound of the present invention is a useful antipsychotic agent effective not only for positive symptoms centering on hallucination and delusion characteristic of the acute stage of schizophrenia, but also negative symptoms of apathy, abulia and autism.Type: GrantFiled: September 3, 1998Date of Patent: February 13, 2001Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Hiroshi Tanaka, Takanobu Kuroita, Yoshifumi Togo, Seigo Ishibuchi, Masakazu Fujio, Takashi Futamura
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Patent number: 6177059Abstract: A complex comprising a lipid and a conjugate of GPIb and lipid having a functional group, and use thereof. The GPIb-lipid complex of the present invention is extremely useful as a platelet substitute, a pharmaceutical agent for the prophylaxis and treatment of angiopathy, vascular damages and thrombosis, a diagnostic for vWF deficiency and the like, a biological or medical reagent, a reagent for screening platelet aggregation suppressant or antithrombosis, and the like. The GPIb-lipid complex of the present invention is also useful as a diagnostic for finding the location of vascular lesion or thrombus formation, or a therapeutic agent therefor, since it accumulates at vascular lesions.Type: GrantFiled: December 3, 1998Date of Patent: January 23, 2001Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Hiroshi Matsuda, Kaeko Kamide, Yasuo Amatsuji, Takashi Imagawa, Yasuo Ikeda, Mitsuru Murata
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Patent number: 6166221Abstract: The present invention provides a method for producing an optically active 4-[.alpha.-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoic acid or a pharmaceutically acceptable salt thereof, which includes subjecting a compound of the formula (I) wherein each symbol in the formula is as defined in the specification, to optical resolution by fractional crystallization to give an optically active compound thereof and subjecting the compound to hydrolysis reaction. According to this method, a resolution method useful for industrial large-scale production of the optically active compound of 4-[.alpha.-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoic acid, which is useful as a thromboxane synthetase inhibitor and an agent for the prophylaxis and treatment of diabetic complications, can be obtained.Type: GrantFiled: February 23, 2000Date of Patent: December 26, 2000Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Kazuyuki Kawasaki, Haruhito Kobayashi, Syuji Ehara, Hideaki Sato
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Patent number: 6159471Abstract: A method for producing an immunoglobulin preparation for intravenous injection, which comprises the steps of: fractionating an immunoglobulin-containing solution with 4 to 10 w/v % of polyethylene glycol having a molecular weight of from 1,000 to 10,000, at a pH value of from 4.5 to 6.5, an ionic strength of from 0.0001 to 0.1 M and a temperature of from 0 to 4.degree. C. to recover a supernatant fraction; and concentrating the supernatant fraction at a pH of from 3.5 to 5.0.Type: GrantFiled: October 23, 1998Date of Patent: December 12, 2000Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Yutaka Hirao, Motonori Hashimoto, Tae Kitamura, Yahiro Uemura
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Patent number: 6156766Abstract: Benzamide compounds of the formula ##STR1## wherein each symbol is defined in the specification, isomers thereof and pharmaceutically acceptable acid addition salts thereof. Pharmaceutical compositions comprising a therapeutically effective amount of this compound and a pharamaceutically acceptable additive, and therapeutic agents for hypertension, therapeutic agents for angina pectoris, therapeutic agent for asthma, therapeutic agents for renal and peripheral circulatory disturbances and inhibitor of cerebral vasospasm, which comprise this compound. The compound of the present invention has strong smooth muscle relaxing action, and shows hypertensive action and cerebral.cndot.coronary vasodilating action like conventional calcium antagonists, as well as long-lasting renal and peripheral circulation improving action.Type: GrantFiled: February 18, 1999Date of Patent: December 5, 2000Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Masafumi Arita, Tadamasa Saitoh, Masanori Minoguchi, Keiji Yamagami, Hiroyuki Satoh
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Patent number: 6129925Abstract: An object of the present invention is to provide an infusion preparation set (a container filled with infusion liquids) useful for preparation of an infusion liquid containing sugars, amino acids, electrolytes, a fat emulsion and vitamins. The present invention is constituted by the use of a container having two compartments which are separated from each other by a separation means, which contains an infusion liquid comprising a fat emulsion, sugars, fat-soluble vitamins and specified water-soluble vitamins in the first compartment and an infusion liquid comprising amino acids, electrolytes and other specified water-soluble vitamins in the second compartment. An infusion preparation containing sugars, amino acids, electrolytes, a fat emulsion and vitamins can be obtained easily and aseptically upon use, by simply removing a separation means and mixing the infusion liquids included in the first and second compartments.Type: GrantFiled: March 2, 1998Date of Patent: October 10, 2000Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Takae Kido, Shigeo Ii, Shun-ichi Abe, Kazumasa Yokoyama
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Patent number: 6121329Abstract: An external preparation for topical administration which aims at inhibiting rejection reactions at organ or bone marrow transplantation or treating autoimmune diseases or allergic diseases and contains as the active ingredient 2-amino-2-(2-(4-octylphenyl)ethyl)propane-1,3-diol or a pharmaceutically acceptable acid addition salt thereof.Type: GrantFiled: August 27, 1997Date of Patent: September 19, 2000Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Tsuneo Fujii, Tadashi Mishina, Koji Teshima, Tomonori Imayoshi
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Patent number: 6090384Abstract: Disclosed is an antiallergic composition comprising, as an active ingredient, a peptide which is capable of binding to human IgE, more specifically the high-affinity immunoglobulin E receptor .alpha. chain or a soluble fragment, which is capable of binding to human IgE, or the high-affinity immunoglobulin E receptor .alpha. chain. The composition is clinically useful for blocking allergic responses.Type: GrantFiled: January 24, 1997Date of Patent: July 18, 2000Assignees: Chisei RA, Yoshitomi Pharmaceuticals Industries, Ltd.Inventors: Chisei Ra, Koji Naito, Minoru Hirama, Ko Okumura
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Patent number: 6080738Abstract: A heterocyclic amide compound of the formula (I) ##STR1## wherein each symbol is as defined in the specification, a pharmacologically acceptable salt thereof, a pharmaceutical composition thereof and a pharmaceutical use thereof. The heterocyclic amide compound and a pharmacologically acceptable salt thereof of the present invention have superior inhibitory action on chymase group in mammals inclusive of human, and can be administered orally or parenterally. Therefore, they are useful as chymase inhibitors and can be used for the prophylaxis and treatment of various diseases caused by chymase, such as those caused by angiotensin II.Type: GrantFiled: April 22, 1999Date of Patent: June 27, 2000Assignee: Yoshitomi Pharmaceuticals Industries, Ltd.Inventors: Fumihiko Akahoshi, Atsuyuki Ashimori, Takuya Yoshimura, Masahiro Eda, Hiroshi Sakashita, Masahide Nakajima, Teruaki Imada
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Patent number: 6068995Abstract: A method for producing a desired protein, which comprises growing, by a fed-batch culture, a host cell capable of expressing the desired protein, wherein the specific growth rate of the host cell is changed from the initial rate to a predetermined one by successively changing the rate of addition of a substrate which controls the growth of the host cell. According to the mode of change of the rate of substrate addition to the medium of the present invention, optimal patterns of specific growth rate .mu. and specific production rate .rho. can be realized to optimize the fed-batch culture system. As a consequence of the realization, it is made possible to perform a high density culture of the host cell by fed-batch culture, an the desired protein can be produced efficiently in a short time.Type: GrantFiled: September 19, 1996Date of Patent: May 30, 2000Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Kaoru Kobayashi, Kenji Tomomitsu, Shinobu Kuwae, Tomoshi Ohya, Toyoo Ohda, Takao Ohmura
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Patent number: 6066739Abstract: The present invention provides a method for producing an optically active 4-[.alpha.-hydro-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoic acid or a pharmaceutically acceptable salt thereof, which includes subjecting a compound of the formula (I) ##STR1## wherein each symbol in the formula is as defined in the specification, to optical resolution by fractional crystallization to give an optically active compound thereof and subjecting the compound to hydrolysis reaction. According to this method, a resolution method useful for industrial large-scale production of the optically active compound of 4-[.alpha.-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoic acid, which is useful as a thromboxane synthetase inhibitor and an agent for the prophylaxis and treatment of diabetic complications, can be obtained.Type: GrantFiled: July 23, 1999Date of Patent: May 23, 2000Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Kazuyuki Kawasaki, Haruhito Kobayashi, Syuji Ehara, Hideaki Sato
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Patent number: 6060480Abstract: An agent for the prophylaxis or treatment of muscle tissue degeneration, containing, as an active ingredient, a quinoline compound of the formula (I): ##STR1## or a pharmaceutically acceptable salt. The prophylactic or therapeutic agent of muscle tissue degeneration of the present invention contains a quinoline compound of the formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient, and shows remarkable inhibitory or improving action on degeneration of the muscle tissues such as necrosis, fibrosis, calcification and the like. The agent is specifically useful for the prophylaxis and treatment of cardiomyopathy, muscular dystrophy, pulmonary fibrosis and the like.Type: GrantFiled: May 10, 1999Date of Patent: May 9, 2000Assignees: Yoshitomi Pharmaceutical Industries, Ltd., Asahi Glass Co., Ltd.Inventors: Norifumi Nakamura, Mamoru Koyama, Mizuo Miyazaki
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Patent number: 6015829Abstract: 1-Phenylpyrazole compounds of the formula (1): ##STR1## which is exemplified by 5-amino-1-(3-cyano-4-isobutoxyphenyl)pyrazole-4-carboxylic acid, an optical isomer thereof and a pharmaceutically acceptable salt thereof. These compounds have a xanthine oxidase inhibitory activity and are useful as therapeutic agents for diseases such as hyperuricacidemia and gout.Type: GrantFiled: September 22, 1998Date of Patent: January 18, 2000Assignee: Yoshitomi Pharmaceutical Industries, ltd.Inventors: Seigo Ishibuchi, Hiroshi Morimoto, Atsushi Fukunari, Hiroyoshi Inoue, Yoichi Naka
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Patent number: 6008198Abstract: A porphyrin metal complex-albumin inclusion compound wherein a substituted porphyrin metal complex comprising, as a central, coordinated metal, a transitional metal belonging to the fourth or fifth period of the periodic law, is included in the albumin, and an oxygen carrier composition comprising said inclusion compound as an active ingredient. The compound functions as an oxygen carrier which is superior in biocompatibility, capable of adsorption and desorption of oxygen under physiological conditions, and is rather easily produced at an industrial scale.Type: GrantFiled: April 29, 1996Date of Patent: December 28, 1999Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Eishun Tsuchida, Hiroyuki Nishide, Teruyuki Komatsu
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Patent number: 6004565Abstract: The methods and compositions of the invention and the compounds used in the invention involve a novel immunosuppression mechanism, accelerated lymphocyte homing immunosuppression (ALH-immunosuppression). For example, the compound FTY720 specifically directs lymphocytes to the peripheral lymph nodes, mesenteric lymph nodes, and Peyer's patches. By reversibly sequestering lymphocytes in these tissues, the compounds can inhibit an immune response in a mammal. Understanding these mechanisms provides a novel immunosuppression therapy that can synergistically interact with other immunosuppressive compounds. Screening methods for identifying similar ALH-immunosuppression compounds are also described. The invention allows better treatments and therapies wherever an immunosuppression regimen is desired.Type: GrantFiled: September 23, 1997Date of Patent: December 21, 1999Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Kenji Chiba, Kunitomo Adachi
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Patent number: 5993863Abstract: The present invention aims at providing an alimentative infusion liquid which has improved stability and preservability and can be administered through a peripheral vein. The infusion liquid contains sugars, amino acids, electrolytes and a fat emulsion at a specific mixing ratio and has a specific pH value and a titratable acidity. The alimentative infusion liquid of the present invention containing the above-described components has good preservability without suffering from precipitation, denaturation and the like problems. Further, since the pH value is adjusted to a specific level and the titratable acidity is retained low, administration of the infusion liquid through a peripheral vein does not cause troubles such as angialiga.Type: GrantFiled: October 7, 1997Date of Patent: November 30, 1999Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Masahiro Kikuchi, Yoshihiko Okutani, Tadaaki Inoue, Ryoichiro Murashima, Shunichi Abe, Hiroshi Koshiba, Hiroshi Shibata, Shunichiro Ishii, Yoshiyasu Kawabata, Kazumasa Yokoyama
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Patent number: 5989593Abstract: A method for producing antithrombin-III from an antithrombin-III-containing aqueous solution, comprising at least one of the following steps (a) and (b): (a) heating the antithrombin-III-containing aqueous solution in the presence of a stabilizing agent so that 85% or more of the activity of antithrombin-III before the heating is maintained after the heating, and that the ratio of an antithrombin-III monomer after the heating is maintained at 95% or more; and (b) treating the antithrombin-III-containing aqueous solution with a metal chelate resin and recovering a purified antithrombin-III.Type: GrantFiled: November 19, 1997Date of Patent: November 23, 1999Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Shouji Ideno, Katsuhiro Uriyu, Yahiro Uemura
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Patent number: 5965557Abstract: A method for the prophylaxis and treatment of irritable bowel syndrome, which comprises administering a pharmaceutically effective amount of at least one compound selected from the group consisting of (.+-.)-2-(4-chlorophenyl)-5,6-dihydro-[1]benzothiepino [5,4-c]pyridazin-3(2H)-one 7-oxide, optical isomers thereof and 2-(4-chlorophenyl)-5,6-dihydro-[1]benzothiepino[5,4-c]pyridazin-3(2H)-one 7,7-dioxide to a subject in need of such prophylaxis or treatment.Type: GrantFiled: October 7, 1998Date of Patent: October 12, 1999Assignee: Yoshitomi Pharmaceuticals Industries, Ltd.Inventors: Kiyoshi Asano, Shigemi Kino, Hiroshi Yasumatsu