NZ519550A - Calcium dicarboxylate ethers, methods of making same, and treatment of vascular disease and diabetes therewith - Google Patents
Calcium dicarboxylate ethers, methods of making same, and treatment of vascular disease and diabetes therewithInfo
- Publication number
- NZ519550A NZ519550A NZ519550A NZ51955001A NZ519550A NZ 519550 A NZ519550 A NZ 519550A NZ 519550 A NZ519550 A NZ 519550A NZ 51955001 A NZ51955001 A NZ 51955001A NZ 519550 A NZ519550 A NZ 519550A
- Authority
- NZ
- New Zealand
- Prior art keywords
- compound
- carboxy
- methyl
- hexyloxy
- ray powder
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 44
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 title claims description 42
- 239000011575 calcium Substances 0.000 title claims description 29
- 229910052791 calcium Inorganic materials 0.000 title claims description 26
- 238000011282 treatment Methods 0.000 title claims description 15
- 208000019553 vascular disease Diseases 0.000 title claims description 15
- 150000002170 ethers Chemical class 0.000 title claims description 13
- 206010012601 diabetes mellitus Diseases 0.000 title claims description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 91
- ZJKZKKPIKDNHDM-UHFFFAOYSA-L calcium;6-(5-carboxylato-5-methylhexoxy)-2,2-dimethylhexanoate Chemical compound [Ca+2].[O-]C(=O)C(C)(C)CCCCOCCCCC(C)(C)C([O-])=O ZJKZKKPIKDNHDM-UHFFFAOYSA-L 0.000 claims abstract description 50
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 46
- 239000013078 crystal Substances 0.000 claims abstract description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 212
- 229910001868 water Inorganic materials 0.000 claims description 89
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 88
- 239000012453 solvate Substances 0.000 claims description 80
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 55
- 235000019441 ethanol Nutrition 0.000 claims description 51
- 238000001035 drying Methods 0.000 claims description 39
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 38
- 239000002253 acid Substances 0.000 claims description 36
- 239000002904 solvent Substances 0.000 claims description 36
- 239000007787 solid Substances 0.000 claims description 35
- -1 1-butvl Chemical class 0.000 claims description 32
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 24
- 239000012265 solid product Substances 0.000 claims description 24
- 238000010992 reflux Methods 0.000 claims description 23
- 239000000292 calcium oxide Substances 0.000 claims description 22
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 claims description 22
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 18
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 claims description 16
- 238000010438 heat treatment Methods 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- SDMBRCRVFFHJKR-UHFFFAOYSA-N 6-(5-carboxy-5-methylhexoxy)-2,2-dimethylhexanoic acid Chemical compound OC(=O)C(C)(C)CCCCOCCCCC(C)(C)C(O)=O SDMBRCRVFFHJKR-UHFFFAOYSA-N 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 238000010626 work up procedure Methods 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- ZQNPDAVSHFGLIQ-UHFFFAOYSA-N calcium;hydrate Chemical compound O.[Ca] ZQNPDAVSHFGLIQ-UHFFFAOYSA-N 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 6
- 239000000969 carrier Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- LUUSKZKEUDPIHB-UHFFFAOYSA-L calcium 2,2-dimethylhexanoate hydrate Chemical compound O.[Ca++].CCCCC(C)(C)C([O-])=O.CCCCC(C)(C)C([O-])=O LUUSKZKEUDPIHB-UHFFFAOYSA-L 0.000 claims description 2
- ZSXJMJATFFOPJZ-UHFFFAOYSA-L calcium;6-(5-carboxylato-5-methylhexoxy)-2,2-dimethylhexanoate;ethanol Chemical compound [Ca+2].CCO.[O-]C(=O)C(C)(C)CCCCOCCCCC(C)(C)C([O-])=O ZSXJMJATFFOPJZ-UHFFFAOYSA-L 0.000 claims 4
- ABFJKGBWBUJVSQ-UHFFFAOYSA-L calcium 2,2-dimethylhexanoate ethanol Chemical compound [Ca++].CCO.CCCCC(C)(C)C([O-])=O.CCCCC(C)(C)C([O-])=O ABFJKGBWBUJVSQ-UHFFFAOYSA-L 0.000 claims 3
- HYRHCZQDONUBBM-UHFFFAOYSA-L calcium 6-(5-carboxylato-5-methylhexoxy)-2,2-dimethylhexanoate methanol Chemical compound [Ca++].CO.CC(C)(CCCCOCCCCC(C)(C)C([O-])=O)C([O-])=O HYRHCZQDONUBBM-UHFFFAOYSA-L 0.000 claims 1
- 238000005406 washing Methods 0.000 claims 1
- 159000000007 calcium salts Chemical class 0.000 description 65
- 239000000047 product Substances 0.000 description 54
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 26
- 238000003756 stirring Methods 0.000 description 25
- 239000011541 reaction mixture Substances 0.000 description 20
- 102100040214 Apolipoprotein(a) Human genes 0.000 description 18
- 101710115418 Apolipoprotein(a) Proteins 0.000 description 18
- 235000002639 sodium chloride Nutrition 0.000 description 18
- 238000004128 high performance liquid chromatography Methods 0.000 description 17
- 238000013019 agitation Methods 0.000 description 16
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 15
- 239000000843 powder Substances 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 14
- 238000009616 inductively coupled plasma Methods 0.000 description 12
- 238000004448 titration Methods 0.000 description 12
- 108010010234 HDL Lipoproteins Proteins 0.000 description 11
- 102000015779 HDL Lipoproteins Human genes 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 239000003826 tablet Substances 0.000 description 11
- 238000011005 laboratory method Methods 0.000 description 10
- 210000002381 plasma Anatomy 0.000 description 10
- 230000008569 process Effects 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 9
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 8
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 7
- 239000000920 calcium hydroxide Substances 0.000 description 7
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 7
- 235000011116 calcium hydroxide Nutrition 0.000 description 7
- 235000012000 cholesterol Nutrition 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 241000282693 Cercopithecidae Species 0.000 description 6
- 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 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- 238000010926 purge Methods 0.000 description 6
- 238000008214 LDL Cholesterol Methods 0.000 description 5
- 108010007622 LDL Lipoproteins Proteins 0.000 description 5
- 102000007330 LDL Lipoproteins Human genes 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 229920002261 Corn starch Polymers 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 208000032928 Dyslipidaemia Diseases 0.000 description 4
- 108010023302 HDL Cholesterol Proteins 0.000 description 4
- 102000004877 Insulin Human genes 0.000 description 4
- 108090001061 Insulin Proteins 0.000 description 4
- 102000004895 Lipoproteins Human genes 0.000 description 4
- 108090001030 Lipoproteins Proteins 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 239000007958 cherry flavor Substances 0.000 description 4
- 239000008120 corn starch Substances 0.000 description 4
- 229940099112 cornstarch Drugs 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 229940125396 insulin Drugs 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 238000013341 scale-up Methods 0.000 description 4
- 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 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 206010016717 Fistula Diseases 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 208000017170 Lipid metabolism disease Diseases 0.000 description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 231100000517 death Toxicity 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000003028 elevating effect Effects 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000001044 red dye Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 108010028554 LDL Cholesterol Proteins 0.000 description 2
- 108010033266 Lipoprotein(a) Proteins 0.000 description 2
- 102000057248 Lipoprotein(a) Human genes 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 229920001214 Polysorbate 60 Polymers 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 108010062497 VLDL Lipoproteins Proteins 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
- 210000001789 adipocyte Anatomy 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 210000000941 bile Anatomy 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000010961 commercial manufacture process Methods 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 229960001681 croscarmellose sodium Drugs 0.000 description 2
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000003608 fece Anatomy 0.000 description 2
- 230000003890 fistula Effects 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 208000037803 restenosis Diseases 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 239000007916 tablet composition Substances 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- UZWFWTGDUXLNKR-UHFFFAOYSA-N 8-(4-methylpentan-2-yl)-3,7-dihydropurine-2,6-dione Chemical compound N1C(=O)NC(=O)C2=C1N=C(C(C)CC(C)C)N2 UZWFWTGDUXLNKR-UHFFFAOYSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 101150102415 Apob gene Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 241000282553 Macaca Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical class CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920002472 Starch Polymers 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
- 108010069201 VLDL Cholesterol Proteins 0.000 description 1
- JOAISNMPBNLOCX-UHFFFAOYSA-N [Ca].CCO Chemical compound [Ca].CCO JOAISNMPBNLOCX-UHFFFAOYSA-N 0.000 description 1
- FVOVJUPBNYMIDL-UHFFFAOYSA-K [Na+].[Na+].[Na+].OCC(O)CO.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O Chemical compound [Na+].[Na+].[Na+].OCC(O)CO.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FVOVJUPBNYMIDL-UHFFFAOYSA-K 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000000923 atherogenic effect Effects 0.000 description 1
- 102000023732 binding proteins Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- NESOLGQVJMYTRB-UHFFFAOYSA-L calcium hexanoate hydrate Chemical compound O.[Ca++].CCCCCC([O-])=O.CCCCCC([O-])=O NESOLGQVJMYTRB-UHFFFAOYSA-L 0.000 description 1
- RNCQGJUPJDXLAI-UHFFFAOYSA-L calcium;2,2-dimethylhexanoate Chemical compound [Ca+2].CCCCC(C)(C)C([O-])=O.CCCCC(C)(C)C([O-])=O RNCQGJUPJDXLAI-UHFFFAOYSA-L 0.000 description 1
- BSJIICUVGMPYSD-UHFFFAOYSA-L calcium;hexanoate Chemical compound [Ca+2].CCCCCC([O-])=O.CCCCCC([O-])=O BSJIICUVGMPYSD-UHFFFAOYSA-L 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000010981 drying operation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000006377 glucose transport Effects 0.000 description 1
- 229930182480 glucuronide Natural products 0.000 description 1
- 150000008134 glucuronides Chemical class 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical class CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000007884 metabolite profiling Methods 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
- 238000013508 migration Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000011020 pilot scale process Methods 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 229940083037 simethicone Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/125—Saturated compounds having only one carboxyl group and containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/235—Saturated compounds containing more than one carboxyl group
- C07C59/305—Saturated compounds containing more than one carboxyl group containing ether groups, groups, groups, or groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17782300P | 2000-01-25 | 2000-01-25 | |
| PCT/IB2001/000026 WO2001055078A1 (en) | 2000-01-25 | 2001-01-11 | Calcium dicarboxylate ethers, methods of making same, and treatment of vascular disease and diabetes therewith |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ519550A true NZ519550A (en) | 2003-11-28 |
Family
ID=22650106
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ519550A NZ519550A (en) | 2000-01-25 | 2001-01-11 | Calcium dicarboxylate ethers, methods of making same, and treatment of vascular disease and diabetes therewith |
Country Status (39)
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1481962A1 (en) * | 1997-12-12 | 2004-12-01 | Warner-Lambert Company LLC | New cholesterolemia-lowering carboxyalkylether compound |
| WO2004017952A1 (en) * | 2002-08-22 | 2004-03-04 | Warner-Lambert Company Llc | Method of treating osteoarthritis |
| CN101163668A (zh) * | 2005-04-19 | 2008-04-16 | 卫材R&D管理有限公司 | 双[(2s)-3-[3-(2s)-3-(4-氯-2-氰基苯氧基)-2-氟丙氧基]苯基]-2-异丙氧基丙酸]钙及其中间体 |
| US7816405B2 (en) | 2005-04-19 | 2010-10-19 | Eisai R&D Management Co., Ltd. | Calcium bis [(2S)-3-[3-[(2S)-3-(4-chloro-2-cyanophenoxy)-2-fluoropropoxy]phenyl ]-2-isopropoxypropionate] and intermediate thereof |
| WO2016077832A2 (en) * | 2014-11-14 | 2016-05-19 | Gemphire Therapeutics Inc. | PROCESSES AND INTERMEDIATES FOR PREPARING α,ω-DICARBOXYLIC ACID-TERMINATED DIALKANE ETHERS |
| CA3059073A1 (en) * | 2017-04-18 | 2018-10-25 | Daniela Carmen Oniciu | Gemcabene, pharmaceutically acceptable salts thereof, compositions thereof and methods of use therefor |
| CN113396138A (zh) * | 2018-10-18 | 2021-09-14 | 燿石治疗公司 | 吉卡宾、其药学上可接受的盐、其组合物和其使用方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5648387A (en) * | 1995-03-24 | 1997-07-15 | Warner-Lambert Company | Carboxyalkylethers, formulations, and treatment of vascular diseases |
| NZ503982A (en) | 1997-12-12 | 2002-03-28 | Warner Lambert Co | Statin-carboxyalkylether combinations useful for treating vascular disorders and diabetes mellitus |
-
2001
- 2001-01-11 PL PL01357076A patent/PL357076A1/xx not_active Application Discontinuation
- 2001-01-11 IL IL15054101A patent/IL150541A0/xx unknown
- 2001-01-11 BR BR0107763-5A patent/BR0107763A/pt not_active IP Right Cessation
- 2001-01-11 GE GE4872A patent/GEP20053428B/en unknown
- 2001-01-11 CA CA002397960A patent/CA2397960C/en not_active Expired - Lifetime
- 2001-01-11 NZ NZ519550A patent/NZ519550A/en unknown
- 2001-01-11 DE DE60138686T patent/DE60138686D1/de not_active Expired - Lifetime
- 2001-01-11 HU HU0204422A patent/HUP0204422A3/hu unknown
- 2001-01-11 ES ES01900037T patent/ES2324281T3/es not_active Expired - Lifetime
- 2001-01-11 EA EA200200641A patent/EA004862B1/ru not_active IP Right Cessation
- 2001-01-11 AP APAP/P/2002/002587A patent/AP2002002587A0/en unknown
- 2001-01-11 AT AT01900037T patent/ATE431326T1/de not_active IP Right Cessation
- 2001-01-11 CZ CZ20022474A patent/CZ20022474A3/cs unknown
- 2001-01-11 DK DK01900037T patent/DK1259474T3/da active
- 2001-01-11 SK SK1062-2002A patent/SK10622002A3/sk not_active Application Discontinuation
- 2001-01-11 WO PCT/IB2001/000026 patent/WO2001055078A1/en not_active Ceased
- 2001-01-11 OA OA1200200226A patent/OA12166A/en unknown
- 2001-01-11 DZ DZ013239A patent/DZ3239A1/fr active
- 2001-01-11 JP JP2001555021A patent/JP4750995B2/ja not_active Expired - Fee Related
- 2001-01-11 CN CN01804045A patent/CN1395555A/zh active Pending
- 2001-01-11 AU AU22140/01A patent/AU2214001A/en not_active Abandoned
- 2001-01-11 EE EEP200200404A patent/EE200200404A/xx unknown
- 2001-01-11 EP EP01900037A patent/EP1259474B1/en not_active Expired - Lifetime
- 2001-01-11 KR KR1020027009519A patent/KR20020073182A/ko not_active Ceased
- 2001-01-11 MX MXPA02007223A patent/MXPA02007223A/es active IP Right Grant
- 2001-01-22 UY UY26550A patent/UY26550A1/es not_active Application Discontinuation
- 2001-01-22 SV SV2001000290A patent/SV2002000290A/es not_active Application Discontinuation
- 2001-01-23 GT GT200100015A patent/GT200100015A/es unknown
- 2001-01-23 AR ARP010100284A patent/AR029436A1/es unknown
- 2001-01-23 PA PA20018510601A patent/PA8510601A1/es unknown
- 2001-01-24 CO CO01005267A patent/CO5261537A1/es not_active Application Discontinuation
- 2001-01-24 HN HN2001000011A patent/HN2001000011A/es unknown
- 2001-01-24 TN TNTNSN01013A patent/TNSN01013A1/fr unknown
- 2001-01-24 PE PE2001000076A patent/PE20011064A1/es not_active Application Discontinuation
-
2002
- 2002-06-20 BG BG106851A patent/BG106851A/xx unknown
- 2002-06-25 IS IS6442A patent/IS6442A/is unknown
- 2002-07-22 MA MA26735A patent/MA26867A1/fr unknown
- 2002-07-23 ZA ZA200205880A patent/ZA200205880B/xx unknown
- 2002-07-24 NO NO20023526A patent/NO20023526L/no not_active Application Discontinuation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2516471C (en) | Ferric organic compounds, uses thereof and methods of making same | |
| CN101490015B (zh) | 瑞舒伐他汀锌盐 | |
| CN103502203A (zh) | 制备l-鸟氨酸苯基乙酸盐的方法 | |
| SK1302000A3 (en) | A crystalline dibenzothiazepine derivative and its use as an antipsychotic agent | |
| MX2014005362A (es) | Forma iv del clorhidrato de ivabradina. | |
| US6861555B2 (en) | Calcium dicarboxylate ethers, methods of making same, and treatment of vascular disease and diabetes therewith | |
| EP1259474B1 (en) | Calcium dicarboxylate ethers, methods of making same | |
| JP2022539911A (ja) | ピリジンスルホンアミドリン酸エステル系化合物、その製造方法及びその用途 | |
| US10155007B2 (en) | Synthesis method for improved tenofovir disoproxil fumarate using ion-exchange resin and method for preparing oral dissolving film form using the same | |
| CN106279127B (zh) | 阿法替尼酸加成盐及其晶型、其制备方法及药物组合物 | |
| CN115850220B (zh) | 稳定的盐酸胺碘酮及其制备方法和用途 | |
| CA3160501A1 (en) | Co-crystal of ketoprofen and its preparation, pharmaceutical compositions comprising the same and uses thereof | |
| CN119630666A (zh) | 取代的吡唑并[1,5-a]嘧啶-7-胺衍生物的药学上可接受的盐和多晶型物及其应用 | |
| CN112313202A (zh) | 曲前列尼尔钠盐新晶型及制备方法 | |
| CN104610208B (zh) | (1s)‑1,6‑二脱氧‑1‑[4‑甲氧基‑3‑(反式‑4‑正丙基环己基)甲基苯基]‑d‑吡喃葡萄糖的晶型a及其制备方法和应用 | |
| CN108276369B (zh) | 多硫代赤霉酸酯类化合物及其制备方法与抗肿瘤用途 | |
| HK40042103A (en) | New crystal form of treprostinil sodium salt and preparation method therefor | |
| CN115141234A (zh) | 一种克林霉素磷酸酯原料药的合成工艺 | |
| CN114195633A (zh) | 一种布洛芬杂质f的合成方法 | |
| KR840001621B1 (ko) | 글루코사민의 니코틴산유도체의 제조방법 | |
| JPH06340527A (ja) | リフィブロールの新規修飾型 | |
| HK1077580B (en) | Methods of making ferric organic compounds | |
| HK1050183A (en) | Calcium dicarboxylate ethers, methods of making same, and treatment of vascular disease and diabetes therewith |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PSEA | Patent sealed | ||
| RENW | Renewal (renewal fees accepted) |