CN1780824A - 预防和治疗内毒素相关疾病和病症的组合物和方法 - Google Patents
预防和治疗内毒素相关疾病和病症的组合物和方法 Download PDFInfo
- Publication number
- CN1780824A CN1780824A CNA2004800117700A CN200480011770A CN1780824A CN 1780824 A CN1780824 A CN 1780824A CN A2004800117700 A CNA2004800117700 A CN A2004800117700A CN 200480011770 A CN200480011770 A CN 200480011770A CN 1780824 A CN1780824 A CN 1780824A
- Authority
- CN
- China
- Prior art keywords
- composition
- antioxidant
- solution
- disaccharides
- butylated hydroxy
- 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.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 61
- 238000000034 method Methods 0.000 title claims abstract description 54
- 239000002158 endotoxin Substances 0.000 title abstract description 6
- 201000010099 disease Diseases 0.000 title abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims description 33
- 239000003963 antioxidant agent Substances 0.000 claims description 29
- 230000003078 antioxidant effect Effects 0.000 claims description 29
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 235000019282 butylated hydroxyanisole Nutrition 0.000 claims description 21
- 239000000693 micelle Substances 0.000 claims description 21
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical group COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 claims description 20
- 239000004255 Butylated hydroxyanisole Substances 0.000 claims description 19
- 229940043253 butylated hydroxyanisole Drugs 0.000 claims description 19
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 18
- 150000002016 disaccharides Chemical class 0.000 claims description 17
- 230000001986 anti-endotoxic effect Effects 0.000 claims description 16
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 claims description 16
- 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 claims description 13
- 239000008101 lactose Substances 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 13
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 claims description 11
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 9
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 9
- XRCRJFOGPCJKPF-UHFFFAOYSA-N 2-butylbenzene-1,4-diol Chemical compound CCCCC1=CC(O)=CC=C1O XRCRJFOGPCJKPF-UHFFFAOYSA-N 0.000 claims description 7
- DECIPOUIJURFOJ-UHFFFAOYSA-N ethoxyquin Chemical compound N1C(C)(C)C=C(C)C2=CC(OCC)=CC=C21 DECIPOUIJURFOJ-UHFFFAOYSA-N 0.000 claims description 7
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 claims description 7
- PODWXQQNRWNDGD-UHFFFAOYSA-L sodium thiosulfate pentahydrate Chemical compound O.O.O.O.O.[Na+].[Na+].[O-]S([S-])(=O)=O PODWXQQNRWNDGD-UHFFFAOYSA-L 0.000 claims description 7
- 208000037487 Endotoxemia Diseases 0.000 claims description 6
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 229910001415 sodium ion Inorganic materials 0.000 claims description 6
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims description 5
- 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 claims description 5
- 229930006000 Sucrose Natural products 0.000 claims description 5
- 239000005720 sucrose Substances 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 3
- 230000001954 sterilising effect Effects 0.000 claims description 3
- 238000004659 sterilization and disinfection Methods 0.000 claims description 3
- 239000003814 drug Substances 0.000 description 56
- 238000002360 preparation method Methods 0.000 description 37
- 239000000243 solution Substances 0.000 description 31
- 235000006708 antioxidants Nutrition 0.000 description 20
- 229940079593 drug Drugs 0.000 description 12
- 238000001035 drying Methods 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- 238000001802 infusion Methods 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 238000007710 freezing Methods 0.000 description 9
- 230000008014 freezing Effects 0.000 description 9
- 238000009472 formulation Methods 0.000 description 8
- 238000011068 loading method Methods 0.000 description 8
- 238000012423 maintenance Methods 0.000 description 8
- 206010040047 Sepsis Diseases 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 206010040070 Septic Shock Diseases 0.000 description 6
- 239000000443 aerosol Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000036303 septic shock Effects 0.000 description 6
- 231100000284 endotoxic Toxicity 0.000 description 5
- 230000002346 endotoxic effect Effects 0.000 description 5
- 238000010525 oxidative degradation reaction Methods 0.000 description 5
- 239000000825 pharmaceutical preparation Substances 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000004108 freeze drying Methods 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000002685 pulmonary effect Effects 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 239000003053 toxin Substances 0.000 description 4
- 231100000765 toxin Toxicity 0.000 description 4
- 210000003462 vein Anatomy 0.000 description 4
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 3
- 206010052428 Wound Diseases 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 239000003637 basic solution Substances 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 210000002216 heart Anatomy 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000008215 water for injection Substances 0.000 description 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-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
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 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
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 2
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 2
- UQONAEXHTGDOIH-AWEZNQCLSA-N O=C(N1CC[C@@H](C1)N1CCCC1=O)C1=CC2=C(NC3(CC3)CCO2)N=C1 Chemical compound O=C(N1CC[C@@H](C1)N1CCCC1=O)C1=CC2=C(NC3(CC3)CCO2)N=C1 UQONAEXHTGDOIH-AWEZNQCLSA-N 0.000 description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 210000004351 coronary vessel Anatomy 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 229940126534 drug product Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 208000024908 graft versus host disease Diseases 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 229940127557 pharmaceutical product Drugs 0.000 description 2
- 235000010388 propyl gallate Nutrition 0.000 description 2
- 238000012827 research and development Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.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 WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 1
- 101710099705 Anti-lipopolysaccharide factor Proteins 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 238000012752 Hepatectomy Methods 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010033647 Pancreatitis acute Diseases 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 201000003229 acute pancreatitis Diseases 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229940124572 antihypotensive agent Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000002612 cardiopulmonary effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 208000009190 disseminated intravascular coagulation Diseases 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- ZXQYGBMAQZUVMI-GCMPRSNUSA-N gamma-cyhalothrin Chemical compound CC1(C)[C@@H](\C=C(/Cl)C(F)(F)F)[C@H]1C(=O)O[C@H](C#N)C1=CC=CC(OC=2C=CC=CC=2)=C1 ZXQYGBMAQZUVMI-GCMPRSNUSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000002650 immunosuppressive therapy Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical group O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000989 no adverse effect Toxicity 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000008249 pharmaceutical aerosol Substances 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 210000001147 pulmonary artery Anatomy 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 208000037922 refractory disease Diseases 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000012859 sterile filling Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/739—Lipopolysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/203—Retinoic acids ; Salts thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/18—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by etherified hydroxyl radicals
- C07D303/20—Ethers with hydroxy compounds containing no oxirane rings
- C07D303/22—Ethers with hydroxy compounds containing no oxirane rings with monohydroxy compounds
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Toxicology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
Abstract
Description
强度(标记要求) | 10mg管瓶 | ||
组分和质量标准(以及等级,如果适用) | 每单位数量 | % | 组分功能 |
E5564药品,Eisai标准 | 10.0mg作为游离酸,10.7mg作为四钠盐 | 0.26% | 活性成分 |
乳糖一水合物,NF | 400mg | 9.7% | 填充剂 |
磷酸,NFA | 0.98mg | 0.024% | pH调节剂 |
丁基羟基茴香醚,NFC | 0.0072mg | 0.00017% | 抗氧化剂 |
氢氧化钠,NFA | 0.30mg | 0.0073% | pH调节剂 |
注射用水,USPB | 3724mg | 90.0% | 溶剂 |
循环 | ST(℃) | P(mmHg) | PT(℃) | 塌陷 |
ABCD | -25-40到+20+20+20 | 0.10.10.10.02 | -31-31到-24-27-28 | 否是否否 |
%(重量/体积)乳糖/制剂A | 胶团尺寸(水动力学直径) |
1% | 16nm |
2% | 13nm |
5% | 8nm |
10% | 7nm |
抗氧化剂 | 时间 | 主要氧化降解物 | E5564浓度(%初始) | 备注 |
无无BHTBHTBHABHA没食子酸丙酯没食子酸丙酯维生素E醋酸酯维生素E醋酸酯抗坏血酸抗坏血酸抗坏血酸棕榈酸酯抗坏血酸棕榈酸酯亚硫酸钠亚硫酸钠硫代硫酸钠硫代硫酸钠一硫代甘油一硫代甘油 | 0小时18-22小时0小时18-22小时0小时18-22小时0小时18-22小时0-4小时18-22小时0-4小时18-22小时0-4小时18-22小时0-4小时18-22小时0-4小时18-22小时0-4小时18-22小时 | 1.126.020.770.240.680.270.380.321.344.550.080.110.150.190.130.250.090.190.130.16 | 10091.3100102.8100102.3100100.610094.210097.410092.4100101.8100100.2100101.3 | 对照快速降解有效有效有效无效无用,对氧化反应稳定但E5564-抗坏血酸反应生成新的杂质无用,对氧化反应稳定但E5564-抗坏血酸棕榈酸酯反应生成新的杂质有效有效有效 |
Claims (22)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US45202203P | 2003-03-05 | 2003-03-05 | |
US60/452,022 | 2003-03-05 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN1780824A true CN1780824A (zh) | 2006-05-31 |
Family
ID=32962682
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA2004800117700A Pending CN1780824A (zh) | 2003-03-05 | 2004-03-05 | 预防和治疗内毒素相关疾病和病症的组合物和方法 |
Country Status (12)
Country | Link |
---|---|
US (1) | US20080095786A9 (zh) |
EP (1) | EP1601661A2 (zh) |
JP (1) | JP2006519872A (zh) |
KR (1) | KR20060002795A (zh) |
CN (1) | CN1780824A (zh) |
AU (1) | AU2004218358A1 (zh) |
BR (1) | BRPI0408077A (zh) |
CA (1) | CA2516629A1 (zh) |
MX (1) | MXPA05009428A (zh) |
NO (1) | NO20054346L (zh) |
RU (1) | RU2005130771A (zh) |
WO (1) | WO2004078142A2 (zh) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030130212A1 (en) * | 1999-01-14 | 2003-07-10 | Rossignol Daniel P. | Administration of an anti-endotoxin drug by intravenous infusion |
KR100841813B1 (ko) | 2000-02-18 | 2008-06-26 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 미셀 |
EP2338497A1 (en) * | 2001-08-10 | 2011-06-29 | Eisai R&D Management Co., Ltd. | Treatment and prevention of heat shock protein-associated diseases and conditions |
US20090105130A1 (en) * | 2005-08-12 | 2009-04-23 | Astellas Pharma Inc. | Depsipeptide-containing injection solution |
KR101457418B1 (ko) * | 2009-10-23 | 2014-11-04 | 삼성전자주식회사 | 계층적 부호화 단위의 크기에 따른 비디오 부호화 방법과 그 장치, 및 비디오 복호화 방법과 그 장치 |
US9132141B2 (en) * | 2012-03-28 | 2015-09-15 | University Of Maryland, Baltimore | Administration of eritoran or pharmaceutically acceptable salts thereof to treat orthomyxovirus infections |
EP3897665A4 (en) | 2018-12-17 | 2022-09-28 | Eisai R&D Management Co., Ltd. | FORMULATION INCLUDING LIPOSOMES |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5681824A (en) * | 1995-06-05 | 1997-10-28 | Eisai Co., Ltd. | Substituted liposaccharides useful in the treatment and prevention of endotoxemia |
US6495532B1 (en) * | 1997-03-19 | 2002-12-17 | Sky High, Llc | Compositions containing lysophosphotidic acids which inhibit apoptosis and uses thereof |
US6437006B1 (en) * | 1999-09-27 | 2002-08-20 | American Cyanamid Company | Pharmaceutical carrier formulation |
CA2446356C (en) * | 2001-05-09 | 2012-07-10 | The Regents Of The University Of Michigan | Use of compositions for treating rosacea |
-
2004
- 2004-03-05 CA CA002516629A patent/CA2516629A1/en not_active Abandoned
- 2004-03-05 EP EP04718037A patent/EP1601661A2/en not_active Withdrawn
- 2004-03-05 US US10/547,599 patent/US20080095786A9/en not_active Abandoned
- 2004-03-05 MX MXPA05009428A patent/MXPA05009428A/es not_active Application Discontinuation
- 2004-03-05 AU AU2004218358A patent/AU2004218358A1/en not_active Abandoned
- 2004-03-05 BR BRPI0408077-7A patent/BRPI0408077A/pt not_active IP Right Cessation
- 2004-03-05 JP JP2006509152A patent/JP2006519872A/ja not_active Withdrawn
- 2004-03-05 CN CNA2004800117700A patent/CN1780824A/zh active Pending
- 2004-03-05 WO PCT/US2004/006713 patent/WO2004078142A2/en active Application Filing
- 2004-03-05 RU RU2005130771/15A patent/RU2005130771A/ru not_active Application Discontinuation
- 2004-03-05 KR KR1020057016441A patent/KR20060002795A/ko not_active Application Discontinuation
-
2005
- 2005-09-20 NO NO20054346A patent/NO20054346L/no not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
JP2006519872A (ja) | 2006-08-31 |
EP1601661A2 (en) | 2005-12-07 |
NO20054346L (no) | 2005-11-04 |
US20060222655A1 (en) | 2006-10-05 |
CA2516629A1 (en) | 2004-09-16 |
AU2004218358A1 (en) | 2004-09-16 |
BRPI0408077A (pt) | 2006-02-14 |
MXPA05009428A (es) | 2005-12-12 |
WO2004078142A3 (en) | 2004-12-23 |
US20080095786A9 (en) | 2008-04-24 |
WO2004078142A2 (en) | 2004-09-16 |
NO20054346D0 (no) | 2005-09-20 |
RU2005130771A (ru) | 2006-01-27 |
KR20060002795A (ko) | 2006-01-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1147472C (zh) | 具有组蛋白脱乙酰酶抑制剂活性的苯甲酰胺制剂 | |
CN1246039C (zh) | 莫西沙星/氯化钠制剂 | |
KR20160014592A (ko) | 퓨로세마이드의 피하 투여용 약학 제형 | |
CN1223347C (zh) | 注射用西洛他唑水性制剂 | |
CN1170533C (zh) | 用于肠胃外给药的药学上稳定的奥沙利铂制剂 | |
KR20150000448A (ko) | 데옥시콜린산 및 그의 염들의 제형물들 | |
CN1635880A (zh) | 双胍衍生物在制备具有瘢痕形成作用的医药产品中的应用 | |
CN1568999A (zh) | 稳定的医药用河豚毒素冷冻干燥制剂 | |
CN1283235C (zh) | 清澈稳定的丙泊酚组合物 | |
CN1780824A (zh) | 预防和治疗内毒素相关疾病和病症的组合物和方法 | |
JP6502507B2 (ja) | スルホンアミド系医薬組成物の調製方法 | |
TWI510243B (zh) | 用於治療膀胱癌的組成物及方法 | |
JP2006523723A (ja) | 医薬的に活性な化合物を調節して導入する方法 | |
JP2008507580A (ja) | 反応性酸素種およびカルボニル種を阻害し得る組成物 | |
CN1803811A (zh) | 一类硝基咪唑衍生物、制备方法及用途 | |
EP0359148A1 (en) | Benzoyl urea compound-albumin complex | |
CN1671418A (zh) | 降钙素的口服施用 | |
RU2440113C2 (ru) | Фармацевтическая композиция для инъекционного особенно целенаправленного местного применения | |
CN1070909A (zh) | 硫脲衍生物和含该硫脲衍生物的抗微生物剂和抗溃疡剂 | |
CN1843354A (zh) | 含有法罗培南的注射用药物组合物 | |
CN1210023C (zh) | 卡铂前体脂质体注射剂及其制造方法 | |
CN1091441C (zh) | 甲磺酸氨氯地平及其制法和应用 | |
WO2007016153A2 (en) | Tilmicosin formulation | |
CN1810815A (zh) | 用于治疗的硝基咪唑衍生物 | |
CN1341591A (zh) | 四水合n-[邻-(对-三甲基乙酰氧基苯磺酰胺基)苯甲酰基]甘氨酸单钠盐的溶液及其药品 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1092459 Country of ref document: HK |
|
ASS | Succession or assignment of patent right |
Owner name: WEI CAI & D MANAGEMENT CO., LTD. Free format text: FORMER OWNER: EISAI CO., LTD. Effective date: 20080314 |
|
C41 | Transfer of patent application or patent right or utility model | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20080314 Address after: Tokyo, Japan, Japan Applicant after: Eisai R. & D. Man Co., Ltd. Address before: Tokyo, Japan Applicant before: Eisai co., Ltd. |
|
C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
WD01 | Invention patent application deemed withdrawn after publication | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1092459 Country of ref document: HK |