CA2359652A1 - Novel prostaglandin compounds and derivatives thereof, compositions containing the same and method of using the same for the treatment of peripheral vascular disease and pulmonaryhypertension - Google Patents
Novel prostaglandin compounds and derivatives thereof, compositions containing the same and method of using the same for the treatment of peripheral vascular disease and pulmonaryhypertension Download PDFInfo
- Publication number
- CA2359652A1 CA2359652A1 CA002359652A CA2359652A CA2359652A1 CA 2359652 A1 CA2359652 A1 CA 2359652A1 CA 002359652 A CA002359652 A CA 002359652A CA 2359652 A CA2359652 A CA 2359652A CA 2359652 A1 CA2359652 A1 CA 2359652A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- compounds
- group
- pharmaceutically acceptable
- molecular weight
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 208000002815 pulmonary hypertension Diseases 0.000 title claims abstract description 35
- 208000018262 Peripheral vascular disease Diseases 0.000 title claims abstract description 30
- -1 prostaglandin compounds Chemical class 0.000 title claims description 73
- 239000000203 mixture Substances 0.000 title claims description 37
- 238000000034 method Methods 0.000 title claims description 27
- 241001465754 Metazoa Species 0.000 claims abstract description 28
- 230000037323 metabolic rate Effects 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims description 468
- 229920001223 polyethylene glycol Polymers 0.000 claims description 67
- 239000002202 Polyethylene glycol Substances 0.000 claims description 59
- 229920000642 polymer Polymers 0.000 claims description 57
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 24
- 239000001257 hydrogen Substances 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 229920000233 poly(alkylene oxides) Polymers 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 150000002148 esters Chemical class 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 150000001720 carbohydrates Chemical class 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000004185 ester group Chemical group 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 229920002307 Dextran Polymers 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000001033 ether group Chemical group 0.000 claims description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 229920002401 polyacrylamide Polymers 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims 5
- 230000000694 effects Effects 0.000 abstract description 106
- 238000001990 intravenous administration Methods 0.000 abstract description 34
- 150000003180 prostaglandins Chemical class 0.000 abstract description 28
- 230000004872 arterial blood pressure Effects 0.000 abstract description 26
- 241001494479 Pecora Species 0.000 abstract description 24
- 230000002685 pulmonary effect Effects 0.000 abstract description 20
- 238000001802 infusion Methods 0.000 abstract description 17
- 125000006239 protecting group Chemical group 0.000 abstract description 8
- 239000005555 hypertensive agent Substances 0.000 abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 50
- 210000002216 heart Anatomy 0.000 description 49
- 238000011534 incubation Methods 0.000 description 48
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 41
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- 229920001427 mPEG Polymers 0.000 description 34
- 210000004623 platelet-rich plasma Anatomy 0.000 description 31
- 230000004044 response Effects 0.000 description 31
- 239000000243 solution Substances 0.000 description 27
- 241000700159 Rattus Species 0.000 description 25
- 230000000702 anti-platelet effect Effects 0.000 description 22
- 239000003146 anticoagulant agent Substances 0.000 description 22
- 229940125773 compound 10 Drugs 0.000 description 21
- 229940125782 compound 2 Drugs 0.000 description 21
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 21
- 239000008135 aqueous vehicle Substances 0.000 description 20
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 20
- 238000007920 subcutaneous administration Methods 0.000 description 19
- 230000009471 action Effects 0.000 description 18
- 230000007423 decrease Effects 0.000 description 18
- 239000003814 drug Substances 0.000 description 18
- 238000002474 experimental method Methods 0.000 description 18
- 210000002381 plasma Anatomy 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 125000003118 aryl group Chemical group 0.000 description 17
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 16
- 238000002347 injection Methods 0.000 description 16
- 239000007924 injection Substances 0.000 description 16
- 230000009885 systemic effect Effects 0.000 description 16
- 210000004204 blood vessel Anatomy 0.000 description 15
- 229940125904 compound 1 Drugs 0.000 description 15
- 238000001914 filtration Methods 0.000 description 15
- 230000000004 hemodynamic effect Effects 0.000 description 15
- 208000001871 Tachycardia Diseases 0.000 description 14
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 13
- 102000008186 Collagen Human genes 0.000 description 13
- 108010035532 Collagen Proteins 0.000 description 13
- 229920001436 collagen Polymers 0.000 description 13
- 229940126214 compound 3 Drugs 0.000 description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
- 229940079593 drug Drugs 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 244000025254 Cannabis sativa Species 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 230000036772 blood pressure Effects 0.000 description 12
- 229960001123 epoprostenol Drugs 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 12
- 239000003981 vehicle Substances 0.000 description 12
- 230000002776 aggregation Effects 0.000 description 11
- 238000004220 aggregation Methods 0.000 description 11
- 230000002744 anti-aggregatory effect Effects 0.000 description 11
- 230000001419 dependent effect Effects 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 11
- 239000000523 sample Substances 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 229940125898 compound 5 Drugs 0.000 description 10
- 231100000673 dose–response relationship Toxicity 0.000 description 10
- 230000036593 pulmonary vascular resistance Effects 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 9
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 9
- 239000000443 aerosol Substances 0.000 description 9
- 150000001408 amides Chemical class 0.000 description 9
- 238000005259 measurement Methods 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 230000006641 stabilisation Effects 0.000 description 9
- 238000011105 stabilization Methods 0.000 description 9
- 230000006794 tachycardia Effects 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000008351 acetate buffer Substances 0.000 description 8
- 210000004072 lung Anatomy 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 230000017531 blood circulation Effects 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 230000029058 respiratory gaseous exchange Effects 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 238000009834 vaporization Methods 0.000 description 7
- 230000008016 vaporization Effects 0.000 description 7
- 208000019553 vascular disease Diseases 0.000 description 7
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 241000700157 Rattus norvegicus Species 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- IUJDSEJGGMCXSG-UHFFFAOYSA-N Thiopental Chemical compound CCCC(C)C1(CC)C(=O)NC(=S)NC1=O IUJDSEJGGMCXSG-UHFFFAOYSA-N 0.000 description 6
- 230000005540 biological transmission Effects 0.000 description 6
- 230000036760 body temperature Effects 0.000 description 6
- 210000001715 carotid artery Anatomy 0.000 description 6
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 6
- 238000010253 intravenous injection Methods 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 239000000651 prodrug Substances 0.000 description 6
- 229940002612 prodrug Drugs 0.000 description 6
- 230000000750 progressive effect Effects 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- AWLILQARPMWUHA-UHFFFAOYSA-M thiopental sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC([S-])=NC1=O AWLILQARPMWUHA-UHFFFAOYSA-M 0.000 description 6
- 210000003437 trachea Anatomy 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 208000004248 Familial Primary Pulmonary Hypertension Diseases 0.000 description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
- 230000000890 antigenic effect Effects 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 125000000524 functional group Chemical group 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 239000008363 phosphate buffer Substances 0.000 description 5
- 201000008312 primary pulmonary hypertension Diseases 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 208000037812 secondary pulmonary hypertension Diseases 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000011550 stock solution Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- KXYGKDBONOVZOM-UHFFFAOYSA-N 1h-cyclopenta[a]naphthalene Chemical class C1=CC=CC2=C3CC=CC3=CC=C21 KXYGKDBONOVZOM-UHFFFAOYSA-N 0.000 description 4
- 208000001953 Hypotension Diseases 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 230000005792 cardiovascular activity Effects 0.000 description 4
- 229920001577 copolymer Polymers 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 210000003191 femoral vein Anatomy 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 230000001077 hypotensive effect Effects 0.000 description 4
- 210000004731 jugular vein Anatomy 0.000 description 4
- 125000005647 linker group Chemical group 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 230000036962 time dependent Effects 0.000 description 4
- 230000002792 vascular Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 206010017711 Gangrene Diseases 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000021736 acetylation Effects 0.000 description 3
- 238000006640 acetylation reaction Methods 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 230000035602 clotting Effects 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 230000000994 depressogenic effect Effects 0.000 description 3
- 230000007071 enzymatic hydrolysis Effects 0.000 description 3
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 208000021822 hypotensive Diseases 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 229920001282 polysaccharide Polymers 0.000 description 3
- 239000005017 polysaccharide Substances 0.000 description 3
- 150000004804 polysaccharides Chemical class 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 150000003815 prostacyclins Chemical class 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 210000005166 vasculature Anatomy 0.000 description 3
- 230000025033 vasoconstriction Effects 0.000 description 3
- 230000002541 vasodepressive effect Effects 0.000 description 3
- 239000003071 vasodilator agent Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 206010053567 Coagulopathies Diseases 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000004931 aggregating effect Effects 0.000 description 2
- 125000003368 amide group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000006502 antiplatelets effects Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 230000001746 atrial effect Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000036765 blood level Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 230000001120 cytoprotective effect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 238000013265 extended release Methods 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 2
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 230000006749 inflammatory damage Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000005375 photometry Methods 0.000 description 2
- 229920000151 polyglycol Polymers 0.000 description 2
- 239000010695 polyglycol Substances 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 229920001451 polypropylene glycol Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 210000001147 pulmonary artery Anatomy 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000000451 tissue damage Effects 0.000 description 2
- 231100000827 tissue damage Toxicity 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 2
- 235000019263 trisodium citrate Nutrition 0.000 description 2
- 229940038773 trisodium citrate Drugs 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- ZHZSESZYAYQFRI-UHFFFAOYSA-N 1-(2h-triazol-4-ylmethyl)cyclohexa-2,4-dien-1-ol Chemical compound C=1NN=NC=1CC1(O)CC=CC=C1 ZHZSESZYAYQFRI-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- QSGJHXSLHOHKHC-UHFFFAOYSA-N 2-(2h-triazol-4-ylmethyl)phenol Chemical compound OC1=CC=CC=C1CC1=CNN=N1 QSGJHXSLHOHKHC-UHFFFAOYSA-N 0.000 description 1
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 102100032814 ATP-dependent zinc metalloprotease YME1L1 Human genes 0.000 description 1
- 101710161876 ATP-dependent zinc metalloprotease YME1L1 Proteins 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010003226 Arteriovenous fistula Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 101100284769 Drosophila melanogaster hemo gene Proteins 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010022680 Intestinal ischaemia Diseases 0.000 description 1
- 208000035901 Ischaemic ulcer Diseases 0.000 description 1
- 208000004535 Mesenteric Ischemia Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033425 Pain in extremity Diseases 0.000 description 1
- 206010033433 Pain in jaw Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 206010040943 Skin Ulcer Diseases 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 230000000397 acetylating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 238000012382 advanced drug delivery Methods 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 206010003230 arteritis Diseases 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000002508 compound effect Effects 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- UPBDXRPQPOWRKR-UHFFFAOYSA-N furan-2,5-dione;methoxyethene Chemical compound COC=C.O=C1OC(=O)C=C1 UPBDXRPQPOWRKR-UHFFFAOYSA-N 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000005986 heart dysfunction Effects 0.000 description 1
- 201000011200 hepatorenal syndrome Diseases 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229920006158 high molecular weight polymer Polymers 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000029226 lipidation Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000005976 liver dysfunction Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 230000005980 lung dysfunction Effects 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 206010025226 lymphangitis Diseases 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 150000002669 lysines Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000003975 mesenteric artery Anatomy 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 238000006213 oxygenation reaction Methods 0.000 description 1
- 208000003278 patent ductus arteriosus Diseases 0.000 description 1
- 208000001297 phlebitis Diseases 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 150000003173 prostaglandin H2 derivatives Chemical class 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 230000004648 relaxation of smooth muscle Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 206010042772 syncope Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 201000002282 venous insufficiency Diseases 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
- C07D307/935—Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans
- C07D307/937—Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans with hydrocarbon or substituted hydrocarbon radicals directly attached in position 2, e.g. prostacyclins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
- C07C405/005—Analogues or derivatives having the five membered ring replaced by other rings
- C07C405/0075—Analogues or derivatives having the five membered ring replaced by other rings having the side-chains or their analogues or derivatives attached to a condensed ring system
- C07C405/0083—Analogues or derivatives having the five membered ring replaced by other rings having the side-chains or their analogues or derivatives attached to a condensed ring system which is only ortho or peri condensed, e.g. carbacyclins
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12725599P | 1999-03-31 | 1999-03-31 | |
| US12725499P | 1999-03-31 | 1999-03-31 | |
| US60/127,254 | 1999-03-31 | ||
| US60/127,255 | 1999-03-31 | ||
| PCT/US2000/008240 WO2000057701A1 (en) | 1999-03-31 | 2000-03-29 | Prostaglandin compounds, compositions and methods of treating peripheral vascular disease and pulmonary hypertension |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2359652A1 true CA2359652A1 (en) | 2000-10-05 |
Family
ID=26825478
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002359652A Abandoned CA2359652A1 (en) | 1999-03-31 | 2000-03-29 | Novel prostaglandin compounds and derivatives thereof, compositions containing the same and method of using the same for the treatment of peripheral vascular disease and pulmonaryhypertension |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP1164846A1 (ko) |
| JP (1) | JP2003523935A (ko) |
| KR (1) | KR20020012169A (ko) |
| CN (1) | CN1354622A (ko) |
| AU (1) | AU4327300A (ko) |
| CA (1) | CA2359652A1 (ko) |
| WO (1) | WO2000057701A1 (ko) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6242482B1 (en) | 2000-06-05 | 2001-06-05 | United Therapeutics Corporation | Prostaglandin compounds and derivatives thereof, compositions containing the same and method of using the same for the treatment of congestive heart failure |
| EP1628654B2 (en) | 2003-05-22 | 2019-12-04 | United Therapeutics Corporation | Compounds and methods for delivery of prostacyclin analogs |
| CN101647792B (zh) * | 2003-12-16 | 2012-11-28 | 联合治疗公司 | 曲前列环素在制备治疗和预防缺血性损害的药物中的用途 |
| US20090124697A1 (en) | 2003-12-16 | 2009-05-14 | United Therapeutics Corporation | Inhalation formulations of treprostinil |
| JP5213448B2 (ja) * | 2005-03-04 | 2013-06-19 | スキャンポ・アーゲー | 末梢血管疾患の処置のための方法および組成物 |
| KR20140082649A (ko) * | 2011-08-12 | 2014-07-02 | 아센디스 파마 에이에스 | 프로스타사이클린의 서방형 조성물 |
| CN103857413A (zh) | 2011-08-12 | 2014-06-11 | 阿森迪斯药物股份有限公司 | 载体连接的曲罗尼尔前药 |
| EP3712142B1 (en) | 2013-01-11 | 2022-07-06 | Corsair Pharma, Inc. | Prodrugs of treprostinil |
| US9505737B2 (en) | 2013-01-11 | 2016-11-29 | Corsair Pharma, Inc. | Treprostinil derivative compounds and methods of using same |
| CA3125504C (en) | 2013-03-14 | 2023-10-24 | United Therapeutics Corporation | Solid forms of treprostinil |
| US20140275616A1 (en) | 2013-03-15 | 2014-09-18 | United Therapeutics Corporation | Salts of treprostinil |
| EP2978313B1 (en) | 2013-03-25 | 2018-02-21 | United Therapeutics Corporation | Process of making prostacyclin compounds with linker thiol and pegylated forms |
| WO2015061720A2 (en) | 2013-10-25 | 2015-04-30 | Insmed Incorporated | Prostacyclin compounds, compositions and methods of use thereof |
| CN106573066A (zh) | 2014-06-13 | 2017-04-19 | 联合治疗学有限公司 | 曲前列环素制剂 |
| EP3209415B1 (en) | 2014-10-20 | 2020-02-19 | United Therapeutics Corporation | Synthesis of intermediates for producing prostacyclin derivatives |
| JP6866043B2 (ja) | 2014-11-18 | 2021-04-28 | インスメッド インコーポレイテッド | トレプロスチニルプロドラッグおよびトレプロスチニル誘導体プロドラッグの製造方法 |
| US9643911B2 (en) | 2015-06-17 | 2017-05-09 | Corsair Pharma, Inc. | Treprostinil derivatives and compositions and uses thereof |
| US9394227B1 (en) | 2015-06-17 | 2016-07-19 | Corsair Pharma, Inc. | Treprostinil derivatives and compositions and uses thereof |
| WO2018058124A1 (en) | 2016-09-26 | 2018-03-29 | United Therapeutics Corporation | Treprostinil prodrugs |
| US10415080B2 (en) | 2016-11-21 | 2019-09-17 | Nanostring Technologies, Inc. | Chemical compositions and methods of using same |
| EP3498283A1 (en) | 2017-12-14 | 2019-06-19 | Ipsol AG | Glycosidic derivatives of treprostinil |
| WO2020223237A1 (en) | 2019-04-29 | 2020-11-05 | Insmed Incorporated | Dry powder compositions of treprostinil prodrugs and methods of use thereof |
| JP2022546314A (ja) | 2019-08-23 | 2022-11-04 | ユナイテッド セラピューティクス コーポレイション | トレプロスチニルプロドラッグ |
| JP2023523557A (ja) | 2020-04-17 | 2023-06-06 | ユナイテッド セラピューティクス コーポレイション | 間質性肺疾患の治療における使用のためのトレプロスチニル |
| US11793780B2 (en) | 2020-06-09 | 2023-10-24 | United Therapeutics Corporation | Prodrugs of treprosiinil |
| KR20230134480A (ko) | 2020-12-14 | 2023-09-21 | 유나이티드 쎄러퓨틱스 코포레이션 | 트레프로스티닐 프로드러그로 질환을 치료하는 방법 |
| EP4301372A1 (en) | 2021-03-03 | 2024-01-10 | United Therapeutics Corporation | A dry powder composition of trestinil and its prodrug thereof and further comprising comprising (e)-3,6-bis[4-(n-carbonyl-2-propenyl)amidobutyl]-2,5-diketopiperazine (fdkp) |
| US20230263807A1 (en) | 2022-02-08 | 2023-08-24 | United Therapeutics Corporation | Treprostinil iloprost combination therapy |
-
2000
- 2000-03-29 AU AU43273/00A patent/AU4327300A/en not_active Abandoned
- 2000-03-29 CA CA002359652A patent/CA2359652A1/en not_active Abandoned
- 2000-03-29 JP JP2000607467A patent/JP2003523935A/ja active Pending
- 2000-03-29 KR KR1020017012628A patent/KR20020012169A/ko not_active Application Discontinuation
- 2000-03-29 WO PCT/US2000/008240 patent/WO2000057701A1/en not_active Application Discontinuation
- 2000-03-29 CN CN00804756A patent/CN1354622A/zh active Pending
- 2000-03-29 EP EP00923092A patent/EP1164846A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| KR20020012169A (ko) | 2002-02-15 |
| CN1354622A (zh) | 2002-06-19 |
| JP2003523935A (ja) | 2003-08-12 |
| EP1164846A1 (en) | 2002-01-02 |
| AU4327300A (en) | 2000-10-16 |
| WO2000057701A1 (en) | 2000-10-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6242482B1 (en) | Prostaglandin compounds and derivatives thereof, compositions containing the same and method of using the same for the treatment of congestive heart failure | |
| CA2359652A1 (en) | Novel prostaglandin compounds and derivatives thereof, compositions containing the same and method of using the same for the treatment of peripheral vascular disease and pulmonaryhypertension | |
| JP6883605B2 (ja) | 治療薬のポリマーコンジュゲートの皮下送達 | |
| WO2011042450A1 (en) | Carrier linked paliperidone prodrugs | |
| US20120191039A1 (en) | Carrier linked pramipexole prodrugs | |
| KR20140082649A (ko) | 프로스타사이클린의 서방형 조성물 | |
| JPH09501652A (ja) | グリセロールエステルと組み合わせたヘパリン、ヘパリン断片またはそれらの派生物を含有する薬剤組生物 | |
| JP2001507676A (ja) | 抗血栓性有機硝酸塩 | |
| EP3643306A2 (en) | Carrier-linked prodrugs having reversible carboxylic ester linkages | |
| AU2012290987B2 (en) | Left ventricular diastolic function improving agent | |
| US20030108512A1 (en) | Modified prostaglandin compounds and analogs thereof, compositions containing the same useful for the treatment of cancer | |
| JPH07503709A (ja) | 虚血及び再潅流による組織障害を改善する方法，及び組成物 | |
| EP2928501B1 (en) | Carrier-linked prostanoid prodrugs | |
| WO2001079302A1 (fr) | Combinaison d'acide folique et de polysaccharide, son procede de preparation et composition pharmaceutique contenant cette combinaison agissant comme principe actif | |
| HUT62917A (en) | Process for producing hepqrin derivatives and pharmaceutical compositions comprising such active ingredient | |
| WO1999043736A1 (fr) | Polymeres transporteurs migrant dans des organes cibles et polymeres contenant des medicaments | |
| JP2005515982A (ja) | ２−ヒドロキシプロピル−β−シクロデキストリンによるタキソールの包接錯体 | |
| EP4245792A1 (en) | Copolymer containing poly(ethylene glycol) and poly(l-amino acid derivative), microparticles thereof, and use therefor in pharmaceutical composition | |
| JP2012526819A (ja) | 脂質−ポリマー複合体、その調製、及びその使用 | |
| JP2002543148A (ja) | カルボキシペプチダーゼｕ阻害剤とトロンビン阻害剤とを含有する医薬製剤 | |
| RU2692078C2 (ru) | Конъюгат, содержащий фолиевую кислоту и индол-3-карбинол, для медицинского применения | |
| JP4166851B2 (ja) | 新規虚血・再灌流障害抑制剤 | |
| CN117122695A (zh) | 一种靶向活化cd44分子的透明质酸功能化偶联物及制备方法和应用 | |
| US20130337053A1 (en) | Novel formulations and methods | |
| Solaro et al. | Multifunctional polymeric materials for biomedical applications |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Dead |