NO328229B1 - Fremgangsmate for fremstilling av di (uridin 5') - tetrafosfat) og salter derav, deres anvendelse og sammensetninger inneholdende de samme - Google Patents
Fremgangsmate for fremstilling av di (uridin 5') - tetrafosfat) og salter derav, deres anvendelse og sammensetninger inneholdende de samme Download PDFInfo
- Publication number
- NO328229B1 NO328229B1 NO19996189A NO996189A NO328229B1 NO 328229 B1 NO328229 B1 NO 328229B1 NO 19996189 A NO19996189 A NO 19996189A NO 996189 A NO996189 A NO 996189A NO 328229 B1 NO328229 B1 NO 328229B1
- Authority
- NO
- Norway
- Prior art keywords
- formula
- compound
- uridine
- group
- tetraphosphate
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 45
- 150000003839 salts Chemical class 0.000 title claims description 44
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 title claims description 24
- 239000000203 mixture Substances 0.000 title claims description 21
- 230000008569 process Effects 0.000 title claims description 17
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 title claims description 12
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 title claims description 12
- 229940045145 uridine Drugs 0.000 title claims description 12
- 238000002360 preparation method Methods 0.000 title claims description 9
- 241000124008 Mammalia Species 0.000 claims abstract description 10
- 206010047791 Vulvovaginal dryness Diseases 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 46
- 238000004519 manufacturing process Methods 0.000 claims description 17
- 239000003795 chemical substances by application Substances 0.000 claims description 16
- -1 uridine nucleotide compound Chemical class 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 206010036790 Productive cough Diseases 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 230000002209 hydrophobic effect Effects 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 10
- 230000003213 activating effect Effects 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 9
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 9
- 238000000746 purification Methods 0.000 claims description 9
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 238000003786 synthesis reaction Methods 0.000 claims description 8
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- 239000003814 drug Substances 0.000 claims description 7
- 229910052708 sodium Inorganic materials 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 235000011180 diphosphates Nutrition 0.000 claims description 6
- 238000004255 ion exchange chromatography Methods 0.000 claims description 6
- 210000003802 sputum Anatomy 0.000 claims description 6
- 208000024794 sputum Diseases 0.000 claims description 6
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 239000007900 aqueous suspension Substances 0.000 claims description 5
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 5
- CNTIXUGILVWVHR-UHFFFAOYSA-N diphosphoryl chloride Chemical compound ClP(Cl)(=O)OP(Cl)(Cl)=O CNTIXUGILVWVHR-UHFFFAOYSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 5
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 5
- 230000000865 phosphorylative effect Effects 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
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- 230000004913 activation Effects 0.000 claims description 3
- 239000012190 activator Substances 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 208000000617 lacrimal duct obstruction Diseases 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 230000026731 phosphorylation Effects 0.000 claims description 3
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- JPJGNZQDELRZGE-UHFFFAOYSA-N (phenyl-$l^{2}-phosphanyl)benzene Chemical compound C=1C=CC=CC=1[P]C1=CC=CC=C1 JPJGNZQDELRZGE-UHFFFAOYSA-N 0.000 claims description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- OJKZEZMAPKWHTG-UHFFFAOYSA-N bis(2h-triazol-4-yl)methanone Chemical compound C=1NN=NC=1C(=O)C1=CNN=N1 OJKZEZMAPKWHTG-UHFFFAOYSA-N 0.000 claims description 2
- YYDZNOUMWKJXMG-UHFFFAOYSA-N chloro(phenyl)phosphane Chemical compound ClPC1=CC=CC=C1 YYDZNOUMWKJXMG-UHFFFAOYSA-N 0.000 claims description 2
- XGRJZXREYAXTGV-UHFFFAOYSA-N chlorodiphenylphosphine Chemical compound C=1C=CC=CC=1P(Cl)C1=CC=CC=C1 XGRJZXREYAXTGV-UHFFFAOYSA-N 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 2
- 150000003536 tetrazoles Chemical class 0.000 claims description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 claims 2
- 230000001737 promoting effect Effects 0.000 claims 2
- RSSDWSPWORHGIE-UHFFFAOYSA-N $l^{1}-phosphanylbenzene Chemical compound [P]C1=CC=CC=C1 RSSDWSPWORHGIE-UHFFFAOYSA-N 0.000 claims 1
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 34
- 239000000243 solution Substances 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- VBGNEGYAPSWNQQ-VWDXAFRGSA-N 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione [hydroxy(phosphonooxy)phosphoryl] phosphono hydrogen phosphate Chemical compound OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)n1ccc(=O)[nH]c1=O.OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)n1ccc(=O)[nH]c1=O.OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(O)=O VBGNEGYAPSWNQQ-VWDXAFRGSA-N 0.000 description 17
- DJJCXFVJDGTHFX-XVFCMESISA-N uridine 5'-monophosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 DJJCXFVJDGTHFX-XVFCMESISA-N 0.000 description 17
- DJJCXFVJDGTHFX-UHFFFAOYSA-N Uridinemonophosphate Natural products OC1C(O)C(COP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 DJJCXFVJDGTHFX-UHFFFAOYSA-N 0.000 description 16
- PGAVKCOVUIYSFO-XVFCMESISA-N UTP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-XVFCMESISA-N 0.000 description 15
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 15
- PGAVKCOVUIYSFO-UHFFFAOYSA-N uridine-triphosphate Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-UHFFFAOYSA-N 0.000 description 15
- 229910001868 water Inorganic materials 0.000 description 13
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
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- UGJCNRLBGKEGEH-UHFFFAOYSA-N sodium-binding benzofuran isophthalate Chemical compound COC1=CC=2C=C(C=3C(=CC(=CC=3)C(O)=O)C(O)=O)OC=2C=C1N(CCOCC1)CCOCCOCCN1C(C(=CC=1C=2)OC)=CC=1OC=2C1=CC=C(C(O)=O)C=C1C(O)=O UGJCNRLBGKEGEH-UHFFFAOYSA-N 0.000 description 8
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- 238000004128 high performance liquid chromatography Methods 0.000 description 7
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
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- XCCTYIAWTASOJW-XVFCMESISA-N Uridine-5'-Diphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 XCCTYIAWTASOJW-XVFCMESISA-N 0.000 description 4
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- WJFREWBMJPXLBS-UHFFFAOYSA-N n,n-dibutylbutan-1-amine;phosphono dihydrogen phosphate Chemical compound OP(O)(=O)OP(O)(O)=O.CCCCN(CCCC)CCCC WJFREWBMJPXLBS-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/10—Expectorants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/04—Artificial tears; Irrigation solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Pulmonology (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Ophthalmology & Optometry (AREA)
- Gynecology & Obstetrics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US5414797P | 1997-07-25 | 1997-07-25 | |
PCT/US1998/015445 WO1999005155A2 (fr) | 1997-07-25 | 1998-07-24 | Procede de production de masse de di(uridine 5'-tetraphosphate) et de ses sels |
Publications (3)
Publication Number | Publication Date |
---|---|
NO996189D0 NO996189D0 (no) | 1999-12-14 |
NO996189L NO996189L (no) | 2000-03-27 |
NO328229B1 true NO328229B1 (no) | 2010-01-11 |
Family
ID=21989063
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19996189A NO328229B1 (no) | 1997-07-25 | 1999-12-14 | Fremgangsmate for fremstilling av di (uridin 5') - tetrafosfat) og salter derav, deres anvendelse og sammensetninger inneholdende de samme |
Country Status (17)
Country | Link |
---|---|
US (1) | US7432252B1 (fr) |
EP (1) | EP1012154B1 (fr) |
JP (1) | JP3723227B2 (fr) |
KR (1) | KR20010013797A (fr) |
CN (1) | CN1147502C (fr) |
AT (1) | ATE261982T1 (fr) |
AU (1) | AU747196B2 (fr) |
BR (1) | BRPI9810436B1 (fr) |
CA (1) | CA2295515C (fr) |
DE (1) | DE69822482T2 (fr) |
DK (1) | DK1012154T3 (fr) |
ES (1) | ES2217569T3 (fr) |
HK (1) | HK1028613A1 (fr) |
NO (1) | NO328229B1 (fr) |
NZ (1) | NZ501696A (fr) |
PT (1) | PT1012154E (fr) |
WO (1) | WO1999005155A2 (fr) |
Families Citing this family (35)
Publication number | Priority date | Publication date | Assignee | Title |
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US6319908B1 (en) | 1996-07-03 | 2001-11-20 | Inspire Pharmaceuticals, Inc. | Method for large-scale production of di(uridine 5′-tetraphosphate) and salts thereof |
US5763447C1 (en) | 1996-07-23 | 2002-05-07 | Inspire Pharmaceuticals | Method of preventing or treating pneumonia in immobilized patients with uridine triphosphates and related compounds |
US7223744B2 (en) | 1997-02-10 | 2007-05-29 | Inspire Pharmaceuticals, Inc. | Pharmaceutical formulation comprising dinucleoside polyphosphates and salts thereof |
TW593331B (en) | 1997-07-25 | 2004-06-21 | Inspire Pharmaceuticals Inc | Method for large-scale production of di(uridine 5')-tetraphosphate and salts thereof |
KR20010013797A (ko) | 1997-07-25 | 2001-02-26 | 인스파이어 파마슈티컬스 인코퍼레이티드 | 디(우리딘 5'-테트라포스페이트) 염 및 그의 제조방법과용도 |
US6462028B2 (en) * | 1997-07-25 | 2002-10-08 | Inspire Pharmaceuticals, Inc. | Method of promoting cervical and vaginal secretions |
US6872710B2 (en) | 1997-07-25 | 2005-03-29 | Inspire Pharmaceuticals, Inc. | Di(uridine 5′)-tetraphosphate and salts thereof |
US6548658B2 (en) * | 1997-07-25 | 2003-04-15 | Inspire Pharmaceuticals, Inc. | Di-(uridine 5′)-tetraphosphate and salts thereof |
CN100354296C (zh) * | 1998-10-02 | 2007-12-12 | 雅玛山酱油株式会社 | 二尿苷四磷酸或其盐的晶体和其制备方法、以及制备该化合物的方法 |
BRPI9917911B1 (pt) * | 1998-10-02 | 2016-08-23 | Yamasa Corp | processo de produção de 5'-tetrafosfato de p1,p4 - di(uridina) ou um de seus sais |
DE60021629T2 (de) * | 1999-06-30 | 2006-01-05 | Yamasa Corp., Choshi | Dinukleotid-Kristalle |
WO2001056581A1 (fr) * | 2000-02-04 | 2001-08-09 | Kissei Pharmaceutical Co., Ltd. | Preparation en poudre pour inhalation et inhalateur de poudre contenant cette preparation |
US7018985B1 (en) | 2000-08-21 | 2006-03-28 | Inspire Pharmaceuticals, Inc. | Composition and method for inhibiting platelet aggregation |
US7452870B2 (en) | 2000-08-21 | 2008-11-18 | Inspire Pharmaceuticals, Inc. | Drug-eluting stents coated with P2Y12 receptor antagonist compound |
CN1228053C (zh) * | 2001-09-11 | 2005-11-23 | 参天制药株式会社 | 含有二尿苷磷酸的滴眼液 |
KR100870104B1 (ko) * | 2005-11-28 | 2008-11-26 | 주식회사 머젠스 | 안구건조증 치료 및 예방용 조성물 |
EP2045257B1 (fr) | 2006-07-26 | 2016-08-17 | Yamasa Corporation | Procédé servant à produire un di(nucléoside pyrimidique-5'-)polyphosphate |
JP5599078B2 (ja) * | 2009-06-23 | 2014-10-01 | ヤマサ醤油株式会社 | アデノシンテトラホスフェート化合物の製造法 |
SG188482A1 (en) | 2010-09-10 | 2013-04-30 | Santen Pharmaceutical Co Ltd | Agent for treatment of dry eye characterized by combining p2y2 receptor agonist and hyaluronic acid or salt thereof, method for treating dry eye, and use of the p2y2 receptor agonist and hyaluronic acid or salt thereof |
US20140221306A1 (en) | 2010-12-28 | 2014-08-07 | Santen Pharmaceutical Co. Ltd | Ophthalmic solution comprising diquafosol, method for producing the same, and method for inhibiting formation of insoluble precipitate |
CN102146111A (zh) * | 2011-01-26 | 2011-08-10 | 北京润德康医药技术有限公司 | 一类新型二核苷酸化合物及其制备方法 |
TR201820073T4 (tr) | 2012-03-26 | 2019-01-21 | Santen Pharmaceutical Co Ltd | Diquafosol içeren göz damlası. |
US10815263B2 (en) * | 2016-10-25 | 2020-10-27 | Yamasa Corporation | Method for purifying P1,P4-di(uridine 5′-)tetraphosphate |
KR102504764B1 (ko) * | 2017-06-21 | 2023-03-02 | 주식회사 종근당 | 디뉴클레오사이드 폴리포스페이트 화합물의 제조방법 |
CN109305991B (zh) * | 2017-07-27 | 2021-02-26 | 江苏恒瑞医药股份有限公司 | 一种p1,p4-二(尿苷5’-)四磷酸钠的制备方法 |
KR20180091689A (ko) | 2017-11-06 | 2018-08-16 | 주식회사 종근당 | 무정형 디뉴클레오사이드 폴리포스페이트 화합물의 제조방법 |
JP6716800B2 (ja) | 2018-02-28 | 2020-07-01 | 参天製薬株式会社 | ジクアホソルおよびカチオン性ポリマーを含有する眼科用組成物 |
CN110540555B (zh) * | 2018-05-28 | 2023-01-24 | 江苏恒瑞医药股份有限公司 | 一种游离核苷磷酸的方法 |
CN109021049B (zh) * | 2018-06-14 | 2020-12-08 | 扬子江药业集团北京海燕药业有限公司 | 一种尿苷5′-二磷酸-苯并咪唑二钠的合成方法 |
CN113518646B (zh) | 2019-02-27 | 2023-12-12 | 参天制药株式会社 | 含有地夸磷索或其盐,乙烯基系高分子及纤维素系高分子的眼科用组合物 |
KR20200106738A (ko) | 2019-03-05 | 2020-09-15 | 주식회사 파마코스텍 | P1,p4-디(우리딘 5'-)테트라포스페이트, 이의 염 또는 이의 수화물의 신규한 제조방법 |
CN110590887B (zh) * | 2019-09-04 | 2020-12-15 | 江苏金殳医药科技有限公司 | 一种磷酸酯的制备方法 |
KR20210077946A (ko) | 2019-12-18 | 2021-06-28 | 주식회사 종근당 | 우리딘 5’-디인산(udp), 이의 염 또는 이의 수화물의 제조방법 |
KR20210110055A (ko) * | 2020-02-28 | 2021-09-07 | 주식회사 종근당바이오 | P1, p4-디(우리딘 5'-)테트라포스페이트 나트륨염 4 수화물 결정형 a의 제조방법 |
CN111662350B (zh) * | 2020-07-07 | 2022-06-07 | 南京宸翔医药研究有限责任公司 | 一种绿色化智能化高纯度地夸磷索四钠的制备方法 |
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US3639562A (en) | 1970-04-29 | 1972-02-01 | Smith Kline French Lab | Vaginal suppositories and impregnated tampons |
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US5635160A (en) | 1995-06-07 | 1997-06-03 | The University Of North Carolina At Chapel Hill | Dinucleotides useful for the treatment of cystic fibrosis and for hydrating mucus secretions |
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US5900407A (en) * | 1997-02-06 | 1999-05-04 | Inspire Pharmaceuticals, Inc. | Method of treating dry eye disease with uridine triphosphates and related compounds |
US5837861A (en) | 1997-02-10 | 1998-11-17 | Inspire Pharmaceuticals, Inc. | Dinucleotides and their use as modulators of mucociliary clearance and ciliary beat frequency |
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US5789391A (en) | 1996-07-03 | 1998-08-04 | Inspire Pharmaceuticals, Inc. | Method of treating sinusitis with uridine triphosphates and related compounds |
US5763447C1 (en) * | 1996-07-23 | 2002-05-07 | Inspire Pharmaceuticals | Method of preventing or treating pneumonia in immobilized patients with uridine triphosphates and related compounds |
WO1998015835A1 (fr) | 1996-10-08 | 1998-04-16 | Inspire Pharmaceuticals, Inc. | Procede de detection precoce du cancer des poumons par provocation de l'expectoration et analyse des crachats afin de detecter des substances associees au cancer |
US6159952A (en) | 1996-11-07 | 2000-12-12 | Inspire Pharmaceuticals, Inc. | Method of treating bronchitis with uridine triphosphate and related compounds |
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US6462028B2 (en) | 1997-07-25 | 2002-10-08 | Inspire Pharmaceuticals, Inc. | Method of promoting cervical and vaginal secretions |
KR20010013797A (ko) | 1997-07-25 | 2001-02-26 | 인스파이어 파마슈티컬스 인코퍼레이티드 | 디(우리딘 5'-테트라포스페이트) 염 및 그의 제조방법과용도 |
JP2001513568A (ja) | 1997-08-29 | 2001-09-04 | ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル | 肺疾患を治療するためのウリジン5’−ジホスフェートとその類似体の使用 |
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-
1998
- 1998-07-24 KR KR1019997011815A patent/KR20010013797A/ko active Search and Examination
- 1998-07-24 PT PT98937115T patent/PT1012154E/pt unknown
- 1998-07-24 CA CA002295515A patent/CA2295515C/fr not_active Expired - Lifetime
- 1998-07-24 JP JP51015699A patent/JP3723227B2/ja not_active Expired - Lifetime
- 1998-07-24 AT AT98937115T patent/ATE261982T1/de active
- 1998-07-24 DK DK98937115T patent/DK1012154T3/da active
- 1998-07-24 CN CNB988061996A patent/CN1147502C/zh not_active Expired - Lifetime
- 1998-07-24 ES ES98937115T patent/ES2217569T3/es not_active Expired - Lifetime
- 1998-07-24 NZ NZ501696A patent/NZ501696A/en not_active IP Right Cessation
- 1998-07-24 BR BRPI9810436A patent/BRPI9810436B1/pt not_active IP Right Cessation
- 1998-07-24 WO PCT/US1998/015445 patent/WO1999005155A2/fr active IP Right Grant
- 1998-07-24 EP EP98937115A patent/EP1012154B1/fr not_active Expired - Lifetime
- 1998-07-24 DE DE69822482T patent/DE69822482T2/de not_active Expired - Lifetime
- 1998-07-24 AU AU85903/98A patent/AU747196B2/en not_active Expired
-
1999
- 1999-12-14 NO NO19996189A patent/NO328229B1/no not_active IP Right Cessation
-
2000
- 2000-03-20 US US09/531,851 patent/US7432252B1/en not_active Expired - Fee Related
- 2000-12-14 HK HK00108028A patent/HK1028613A1/xx not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
BR9810436A (pt) | 2000-12-12 |
PT1012154E (pt) | 2004-08-31 |
EP1012154A2 (fr) | 2000-06-28 |
DE69822482D1 (de) | 2004-04-22 |
NZ501696A (en) | 2001-08-31 |
DE69822482T2 (de) | 2005-03-03 |
JP3723227B2 (ja) | 2005-12-07 |
JP2001510484A (ja) | 2001-07-31 |
AU8590398A (en) | 1999-02-16 |
CA2295515A1 (fr) | 1999-02-04 |
EP1012154B1 (fr) | 2004-03-17 |
HK1028613A1 (en) | 2001-02-23 |
AU747196B2 (en) | 2002-05-09 |
NO996189L (no) | 2000-03-27 |
KR20010013797A (ko) | 2001-02-26 |
WO1999005155A2 (fr) | 1999-02-04 |
ATE261982T1 (de) | 2004-04-15 |
ES2217569T3 (es) | 2004-11-01 |
CN1265114A (zh) | 2000-08-30 |
NO996189D0 (no) | 1999-12-14 |
DK1012154T3 (da) | 2004-07-26 |
BRPI9810436B1 (pt) | 2015-12-29 |
WO1999005155A3 (fr) | 1999-06-24 |
US7432252B1 (en) | 2008-10-07 |
CA2295515C (fr) | 2006-03-14 |
CN1147502C (zh) | 2004-04-28 |
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Legal Events
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CHAD | Change of the owner's name or address (par. 44 patent law, par. patentforskriften) |
Owner name: MERCK SHARP & DOHME CORP, US |
|
MK1K | Patent expired |