TWI603747B - 輸液製劑(一) - Google Patents
輸液製劑(一) Download PDFInfo
- Publication number
- TWI603747B TWI603747B TW105126766A TW105126766A TWI603747B TW I603747 B TWI603747 B TW I603747B TW 105126766 A TW105126766 A TW 105126766A TW 105126766 A TW105126766 A TW 105126766A TW I603747 B TWI603747 B TW I603747B
- Authority
- TW
- Taiwan
- Prior art keywords
- infusion
- chamber
- vitamin
- preparation
- chamber infusion
- Prior art date
Links
- 238000001802 infusion Methods 0.000 title claims description 381
- 238000002360 preparation method Methods 0.000 title claims description 119
- 150000001413 amino acids Chemical class 0.000 claims description 42
- 239000000203 mixture Substances 0.000 claims description 36
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 33
- 239000011591 potassium Substances 0.000 claims description 33
- 229910052700 potassium Inorganic materials 0.000 claims description 33
- 239000002960 lipid emulsion Substances 0.000 claims description 26
- 230000003204 osmotic effect Effects 0.000 claims description 26
- 235000000346 sugar Nutrition 0.000 claims description 26
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims description 25
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 claims description 21
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 claims description 19
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 18
- 239000003792 electrolyte Substances 0.000 claims description 18
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 claims description 17
- 229960002477 riboflavin Drugs 0.000 claims description 17
- 229960003495 thiamine Drugs 0.000 claims description 17
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 claims description 16
- 229930003451 Vitamin B1 Natural products 0.000 claims description 14
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 14
- 235000010374 vitamin B1 Nutrition 0.000 claims description 14
- 239000011691 vitamin B1 Substances 0.000 claims description 14
- 229930003471 Vitamin B2 Natural products 0.000 claims description 13
- 235000019164 vitamin B2 Nutrition 0.000 claims description 13
- 239000011716 vitamin B2 Substances 0.000 claims description 13
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 12
- 229940011671 vitamin b6 Drugs 0.000 claims description 12
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 claims description 11
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 claims description 11
- 235000019155 vitamin A Nutrition 0.000 claims description 11
- 239000011719 vitamin A Substances 0.000 claims description 11
- 229940045997 vitamin a Drugs 0.000 claims description 11
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 claims description 9
- 235000019158 vitamin B6 Nutrition 0.000 claims description 9
- 239000011726 vitamin B6 Substances 0.000 claims description 9
- 229930003779 Vitamin B12 Natural products 0.000 claims description 8
- 229930003316 Vitamin D Natural products 0.000 claims description 8
- 235000019163 vitamin B12 Nutrition 0.000 claims description 8
- 239000011715 vitamin B12 Substances 0.000 claims description 8
- 235000019166 vitamin D Nutrition 0.000 claims description 8
- 239000011710 vitamin D Substances 0.000 claims description 8
- 150000003710 vitamin D derivatives Chemical class 0.000 claims description 8
- 229940046008 vitamin d Drugs 0.000 claims description 8
- 238000005192 partition Methods 0.000 claims description 7
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 6
- 229930003268 Vitamin C Natural products 0.000 claims description 6
- 229930003427 Vitamin E Natural products 0.000 claims description 6
- 229930003448 Vitamin K Natural products 0.000 claims description 6
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 6
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 claims description 6
- 235000019154 vitamin C Nutrition 0.000 claims description 6
- 239000011718 vitamin C Substances 0.000 claims description 6
- 235000019165 vitamin E Nutrition 0.000 claims description 6
- 239000011709 vitamin E Substances 0.000 claims description 6
- 229940046009 vitamin E Drugs 0.000 claims description 6
- 235000019168 vitamin K Nutrition 0.000 claims description 6
- 239000011712 vitamin K Substances 0.000 claims description 6
- 150000003721 vitamin K derivatives Chemical class 0.000 claims description 6
- 229940046010 vitamin k Drugs 0.000 claims description 6
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 claims 1
- 238000005259 measurement Methods 0.000 claims 1
- 229940024606 amino acid Drugs 0.000 description 42
- 235000001014 amino acid Nutrition 0.000 description 42
- 229960003975 potassium Drugs 0.000 description 30
- 239000003925 fat Substances 0.000 description 23
- 235000019197 fats Nutrition 0.000 description 23
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 23
- 229940088594 vitamin Drugs 0.000 description 21
- 229930003231 vitamin Natural products 0.000 description 21
- 235000013343 vitamin Nutrition 0.000 description 21
- 239000011782 vitamin Substances 0.000 description 21
- 239000003995 emulsifying agent Substances 0.000 description 15
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 14
- -1 L-phenylalanine, L-cysteine Amine Chemical class 0.000 description 14
- 239000011259 mixed solution Substances 0.000 description 14
- 238000007789 sealing Methods 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 12
- 238000002156 mixing Methods 0.000 description 12
- 229910052698 phosphorus Inorganic materials 0.000 description 12
- 239000011574 phosphorus Substances 0.000 description 12
- 238000004448 titration Methods 0.000 description 12
- 150000003722 vitamin derivatives Chemical class 0.000 description 12
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 11
- 235000019152 folic acid Nutrition 0.000 description 11
- 239000011724 folic acid Substances 0.000 description 11
- 229960000304 folic acid Drugs 0.000 description 11
- 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 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Natural products SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 10
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 10
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 10
- 239000008103 glucose Substances 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- 239000002245 particle Substances 0.000 description 10
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 235000002639 sodium chloride Nutrition 0.000 description 9
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 8
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 239000003002 pH adjusting agent Substances 0.000 description 8
- 230000001954 sterilising effect Effects 0.000 description 8
- 238000004659 sterilization and disinfection Methods 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 7
- 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 7
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 7
- 229930182821 L-proline Natural products 0.000 description 7
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 7
- 230000004888 barrier function Effects 0.000 description 7
- 229960002685 biotin Drugs 0.000 description 7
- 235000020958 biotin Nutrition 0.000 description 7
- 239000011616 biotin Substances 0.000 description 7
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 7
- 239000000839 emulsion Substances 0.000 description 7
- 238000011049 filling Methods 0.000 description 7
- 239000007789 gas Substances 0.000 description 7
- 239000011777 magnesium Substances 0.000 description 7
- 229910052749 magnesium Inorganic materials 0.000 description 7
- 229960003512 nicotinic acid Drugs 0.000 description 7
- 208000001297 phlebitis Diseases 0.000 description 7
- 229960002429 proline Drugs 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 235000015424 sodium Nutrition 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- 229940083542 sodium Drugs 0.000 description 7
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 7
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 6
- 239000004698 Polyethylene Substances 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 206010047095 Vascular pain Diseases 0.000 description 6
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 229960005069 calcium Drugs 0.000 description 6
- 229910052791 calcium Inorganic materials 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 229960002433 cysteine Drugs 0.000 description 6
- 238000004945 emulsification Methods 0.000 description 6
- 235000011187 glycerol Nutrition 0.000 description 6
- 239000000787 lecithin Substances 0.000 description 6
- 229940067606 lecithin Drugs 0.000 description 6
- 235000010445 lecithin Nutrition 0.000 description 6
- 235000001968 nicotinic acid Nutrition 0.000 description 6
- 239000011664 nicotinic acid Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 235000016709 nutrition Nutrition 0.000 description 6
- 229920000573 polyethylene Polymers 0.000 description 6
- 239000003549 soybean oil Substances 0.000 description 6
- 235000012424 soybean oil Nutrition 0.000 description 6
- 238000003860 storage Methods 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 235000005282 vitamin D3 Nutrition 0.000 description 6
- 239000011647 vitamin D3 Substances 0.000 description 6
- 229940021056 vitamin d3 Drugs 0.000 description 6
- 239000011701 zinc Substances 0.000 description 6
- 229910052725 zinc Inorganic materials 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 5
- SNPLKNRPJHDVJA-ZETCQYMHSA-N D-panthenol Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCCO SNPLKNRPJHDVJA-ZETCQYMHSA-N 0.000 description 5
- FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 5
- 239000004201 L-cysteine Substances 0.000 description 5
- 235000013878 L-cysteine Nutrition 0.000 description 5
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 5
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 5
- 229930182844 L-isoleucine Natural products 0.000 description 5
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 5
- 229930195722 L-methionine Natural products 0.000 description 5
- 239000004473 Threonine Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 235000000639 cyanocobalamin Nutrition 0.000 description 5
- 239000011666 cyanocobalamin Substances 0.000 description 5
- 229960002104 cyanocobalamin Drugs 0.000 description 5
- 229960002989 glutamic acid Drugs 0.000 description 5
- 239000003978 infusion fluid Substances 0.000 description 5
- 229960000310 isoleucine Drugs 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 229960004452 methionine Drugs 0.000 description 5
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 5
- 238000004806 packaging method and process Methods 0.000 description 5
- 229940101267 panthenol Drugs 0.000 description 5
- 235000020957 pantothenol Nutrition 0.000 description 5
- 239000011619 pantothenol Substances 0.000 description 5
- 230000002093 peripheral effect Effects 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 150000008163 sugars Chemical class 0.000 description 5
- 229960002898 threonine Drugs 0.000 description 5
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 4
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 4
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 4
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 4
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 4
- 229930064664 L-arginine Natural products 0.000 description 4
- 235000014852 L-arginine Nutrition 0.000 description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
- 235000019454 L-leucine Nutrition 0.000 description 4
- 239000004395 L-leucine Substances 0.000 description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 229930192627 Naphthoquinone Natural products 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- OHSHFZJLPYLRIP-BMZHGHOISA-M Riboflavin sodium phosphate Chemical compound [Na+].OP(=O)([O-])OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O OHSHFZJLPYLRIP-BMZHGHOISA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 229960003767 alanine Drugs 0.000 description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 4
- 239000011362 coarse particle Substances 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 229960003136 leucine Drugs 0.000 description 4
- 150000002791 naphthoquinones Chemical class 0.000 description 4
- 229940055726 pantothenic acid Drugs 0.000 description 4
- 235000019161 pantothenic acid Nutrition 0.000 description 4
- 239000011713 pantothenic acid Substances 0.000 description 4
- 235000008160 pyridoxine Nutrition 0.000 description 4
- 239000011677 pyridoxine Substances 0.000 description 4
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 4
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 description 4
- 239000011764 pyridoxine hydrochloride Substances 0.000 description 4
- 229960004172 pyridoxine hydrochloride Drugs 0.000 description 4
- 239000002151 riboflavin Substances 0.000 description 4
- 235000019192 riboflavin Nutrition 0.000 description 4
- 229960001153 serine Drugs 0.000 description 4
- 125000006850 spacer group Chemical group 0.000 description 4
- DZGWFCGJZKJUFP-UHFFFAOYSA-N tyramine Chemical compound NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 4
- 229960004441 tyrosine Drugs 0.000 description 4
- 210000003462 vein Anatomy 0.000 description 4
- JQWAHKMIYCERGA-UHFFFAOYSA-N (2-nonanoyloxy-3-octadeca-9,12-dienoyloxypropoxy)-[2-(trimethylazaniumyl)ethyl]phosphinate Chemical compound CCCCCCCCC(=O)OC(COP([O-])(=O)CC[N+](C)(C)C)COC(=O)CCCCCCCC=CCC=CCCCCC JQWAHKMIYCERGA-UHFFFAOYSA-N 0.000 description 3
- 208000010444 Acidosis Diseases 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 3
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 3
- 239000005977 Ethylene Substances 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 208000002682 Hyperkalemia Diseases 0.000 description 3
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 3
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 3
- 229960005261 aspartic acid Drugs 0.000 description 3
- 235000015165 citric acid Nutrition 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000008344 egg yolk phospholipid Substances 0.000 description 3
- 229940068998 egg yolk phospholipid Drugs 0.000 description 3
- 239000011261 inert gas Substances 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 235000019157 thiamine Nutrition 0.000 description 3
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 3
- 239000011721 thiamine Substances 0.000 description 3
- 229940042585 tocopherol acetate Drugs 0.000 description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 3
- 229960004799 tryptophan Drugs 0.000 description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 2
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 2
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 108010016626 Dipeptides Proteins 0.000 description 2
- 206010016260 Fatty acid deficiency Diseases 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- VYGQUTWHTHXGQB-FFHKNEKCSA-N Retinol Palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-FFHKNEKCSA-N 0.000 description 2
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
- 229930003270 Vitamin B Natural products 0.000 description 2
- 230000007950 acidosis Effects 0.000 description 2
- 208000026545 acidosis disease Diseases 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 229960002713 calcium chloride Drugs 0.000 description 2
- 235000011148 calcium chloride Nutrition 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 description 2
- CHFUHGDBYUITQJ-UHFFFAOYSA-L dipotassium;2,3-dihydroxypropyl phosphate Chemical compound [K+].[K+].OCC(O)COP([O-])([O-])=O CHFUHGDBYUITQJ-UHFFFAOYSA-L 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000002969 egg yolk Anatomy 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- FOYKKGHVWRFIBD-UHFFFAOYSA-N gamma-tocopherol acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 FOYKKGHVWRFIBD-UHFFFAOYSA-N 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 229960002885 histidine Drugs 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 235000011147 magnesium chloride Nutrition 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 229960003966 nicotinamide Drugs 0.000 description 2
- 235000005152 nicotinamide Nutrition 0.000 description 2
- 239000011570 nicotinamide Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 229960005190 phenylalanine Drugs 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 229960002816 potassium chloride Drugs 0.000 description 2
- 239000011600 potassium glycerophosphate Substances 0.000 description 2
- 235000000491 potassium glycerophosphate Nutrition 0.000 description 2
- 235000011118 potassium hydroxide Nutrition 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 229960002668 sodium chloride Drugs 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- 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 2
- 229960002901 sodium glycerophosphate Drugs 0.000 description 2
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 2
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
- 239000001540 sodium lactate Substances 0.000 description 2
- 235000011088 sodium lactate Nutrition 0.000 description 2
- 229940005581 sodium lactate Drugs 0.000 description 2
- REULQIKBNNDNDX-UHFFFAOYSA-M sodium;2,3-dihydroxypropyl hydrogen phosphate Chemical compound [Na+].OCC(O)COP(O)([O-])=O REULQIKBNNDNDX-UHFFFAOYSA-M 0.000 description 2
- 239000002195 soluble material Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000008347 soybean phospholipid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 229960004295 valine Drugs 0.000 description 2
- 235000019156 vitamin B Nutrition 0.000 description 2
- 239000011720 vitamin B Substances 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- SHWBOFIPOJVOTO-LBPRGKRZSA-N (2R)-2-(decylamino)-3-sulfanylpropanoic acid Chemical compound C(CCCCCCCCC)N[C@@H](CS)C(=O)O SHWBOFIPOJVOTO-LBPRGKRZSA-N 0.000 description 1
- DBPAVGWJWNLVAP-AWEZNQCLSA-N (2S)-1-decylpyrrolidine-2-carboxylic acid Chemical compound CCCCCCCCCCN1CCC[C@H]1C(O)=O DBPAVGWJWNLVAP-AWEZNQCLSA-N 0.000 description 1
- IOOMXPHYBWAZAQ-REOHCLBHSA-N (2r)-3-sulfanyl-2-(sulfanylamino)propanoic acid Chemical compound OC(=O)[C@H](CS)NS IOOMXPHYBWAZAQ-REOHCLBHSA-N 0.000 description 1
- SNNIXEGBYLWWHH-DFWYDOINSA-N (2s)-2,5-diamino-5-oxopentanoic acid;hydrochloride Chemical compound Cl.OC(=O)[C@@H](N)CCC(N)=O SNNIXEGBYLWWHH-DFWYDOINSA-N 0.000 description 1
- KWTSXDURSIMDCE-MRVPVSSYSA-N (R)-amphetamine Chemical compound C[C@@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-MRVPVSSYSA-N 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- 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 1
- QDGAVODICPCDMU-UHFFFAOYSA-N 2-amino-3-[3-[bis(2-chloroethyl)amino]phenyl]propanoic acid Chemical compound OC(=O)C(N)CC1=CC=CC(N(CCCl)CCCl)=C1 QDGAVODICPCDMU-UHFFFAOYSA-N 0.000 description 1
- 208000013824 Acidemia Diseases 0.000 description 1
- MNYPZFWUEFQZBE-HZJYTTRNSA-N C(CCCCCCC\C=C/C\C=C/CCCCC)OC(COS)COS Chemical compound C(CCCCCCC\C=C/C\C=C/CCCCC)OC(COS)COS MNYPZFWUEFQZBE-HZJYTTRNSA-N 0.000 description 1
- 239000001736 Calcium glycerylphosphate Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- ZERULLAPCVRMCO-UHFFFAOYSA-N Dipropyl sulfide Chemical compound CCCSCCC ZERULLAPCVRMCO-UHFFFAOYSA-N 0.000 description 1
- 208000003241 Fat Embolism Diseases 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 208000034767 Hypoproteinaemia Diseases 0.000 description 1
- 235000019766 L-Lysine Nutrition 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 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 1
- 235000004347 Perilla Nutrition 0.000 description 1
- 244000124853 Perilla frutescens Species 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- 229930003537 Vitamin B3 Natural products 0.000 description 1
- 229930003761 Vitamin B9 Natural products 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- VLSOAXRVHARBEQ-UHFFFAOYSA-N [4-fluoro-2-(hydroxymethyl)phenyl]methanol Chemical compound OCC1=CC=C(F)C=C1CO VLSOAXRVHARBEQ-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 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 1
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 description 1
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 1
- 239000001639 calcium acetate Substances 0.000 description 1
- 235000011092 calcium acetate Nutrition 0.000 description 1
- 229960005147 calcium acetate Drugs 0.000 description 1
- 239000004227 calcium gluconate Substances 0.000 description 1
- 229960004494 calcium gluconate Drugs 0.000 description 1
- 235000013927 calcium gluconate Nutrition 0.000 description 1
- NEEHYRZPVYRGPP-IYEMJOQQSA-L calcium gluconate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O NEEHYRZPVYRGPP-IYEMJOQQSA-L 0.000 description 1
- 229940095618 calcium glycerophosphate Drugs 0.000 description 1
- UHHRFSOMMCWGSO-UHFFFAOYSA-L calcium glycerophosphate Chemical compound [Ca+2].OCC(CO)OP([O-])([O-])=O UHHRFSOMMCWGSO-UHFFFAOYSA-L 0.000 description 1
- 235000019299 calcium glycerylphosphate Nutrition 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 229960002401 calcium lactate Drugs 0.000 description 1
- 229960002079 calcium pantothenate Drugs 0.000 description 1
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229910001567 cementite Inorganic materials 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 235000012716 cod liver oil Nutrition 0.000 description 1
- 239000003026 cod liver oil Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 229940021013 electrolyte solution Drugs 0.000 description 1
- 239000008151 electrolyte solution Substances 0.000 description 1
- 229940037395 electrolytes Drugs 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
- 235000021323 fish oil Nutrition 0.000 description 1
- 229940013640 flavin mononucleotide Drugs 0.000 description 1
- 239000011768 flavin mononucleotide Substances 0.000 description 1
- FVTCRASFADXXNN-SCRDCRAPSA-N flavin mononucleotide Chemical compound OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-SCRDCRAPSA-N 0.000 description 1
- FVTCRASFADXXNN-UHFFFAOYSA-N flavin mononucleotide Natural products OP(=O)(O)OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-UHFFFAOYSA-N 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000000729 hypotrophic effect Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 210000002977 intracellular fluid Anatomy 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002506 iron compounds Chemical class 0.000 description 1
- 235000014413 iron hydroxide Nutrition 0.000 description 1
- NCNCGGDMXMBVIA-UHFFFAOYSA-L iron(ii) hydroxide Chemical compound [OH-].[OH-].[Fe+2] NCNCGGDMXMBVIA-UHFFFAOYSA-L 0.000 description 1
- 229950005223 levamfetamine Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
- 239000011654 magnesium acetate Substances 0.000 description 1
- 235000011285 magnesium acetate Nutrition 0.000 description 1
- 229940069446 magnesium acetate Drugs 0.000 description 1
- GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 1
- 239000004137 magnesium phosphate Substances 0.000 description 1
- 229960002261 magnesium phosphate Drugs 0.000 description 1
- 229910000157 magnesium phosphate Inorganic materials 0.000 description 1
- 235000010994 magnesium phosphates Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 229940091250 magnesium supplement Drugs 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 150000004667 medium chain fatty acids Chemical class 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- MWZPENIJLUWBSY-VIFPVBQESA-N methyl L-tyrosinate Chemical compound COC(=O)[C@@H](N)CC1=CC=C(O)C=C1 MWZPENIJLUWBSY-VIFPVBQESA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000007672 methylcobalamin Nutrition 0.000 description 1
- 239000011585 methylcobalamin Substances 0.000 description 1
- JEWJRMKHSMTXPP-BYFNXCQMSA-M methylcobalamin Chemical compound C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O JEWJRMKHSMTXPP-BYFNXCQMSA-M 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 235000021542 oral nutrition Nutrition 0.000 description 1
- 210000004798 organs belonging to the digestive system Anatomy 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000011772 phylloquinone Substances 0.000 description 1
- MBWXNTAXLNYFJB-LKUDQCMESA-N phylloquinone Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CCCC(C)CCCC(C)CCCC(C)C)=C(C)C(=O)C2=C1 MBWXNTAXLNYFJB-LKUDQCMESA-N 0.000 description 1
- 229920002239 polyacrylonitrile Polymers 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 229960004109 potassium acetate Drugs 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- PHZLMBHDXVLRIX-UHFFFAOYSA-M potassium lactate Chemical compound [K+].CC(O)C([O-])=O PHZLMBHDXVLRIX-UHFFFAOYSA-M 0.000 description 1
- 235000011085 potassium lactate Nutrition 0.000 description 1
- 239000001521 potassium lactate Substances 0.000 description 1
- 229960001304 potassium lactate Drugs 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- SYGDCNJESIQXKS-UHFFFAOYSA-M potassium;2,3-dihydroxypropanoate Chemical compound [K+].OCC(O)C([O-])=O SYGDCNJESIQXKS-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- NPCOQXAVBJJZBQ-UHFFFAOYSA-N reduced coenzyme Q9 Natural products COC1=C(O)C(C)=C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)C(O)=C1OC NPCOQXAVBJJZBQ-UHFFFAOYSA-N 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 235000019172 retinyl palmitate Nutrition 0.000 description 1
- 239000011769 retinyl palmitate Substances 0.000 description 1
- 229940108325 retinyl palmitate Drugs 0.000 description 1
- 235000019231 riboflavin-5'-phosphate Nutrition 0.000 description 1
- 239000010670 sage oil Substances 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- IFGCUJZIWBUILZ-UHFFFAOYSA-N sodium 2-[[2-[[hydroxy-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyphosphoryl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid Chemical compound [Na+].C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(CC(C)C)NP(O)(=O)OC1OC(C)C(O)C(O)C1O IFGCUJZIWBUILZ-UHFFFAOYSA-N 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229960004249 sodium acetate Drugs 0.000 description 1
- BHZOKUMUHVTPBX-UHFFFAOYSA-M sodium acetic acid acetate Chemical compound [Na+].CC(O)=O.CC([O-])=O BHZOKUMUHVTPBX-UHFFFAOYSA-M 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 229960003010 sodium sulfate Drugs 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 229940063675 spermine Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 235000011044 succinic acid Nutrition 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- UIERGBJEBXXIGO-UHFFFAOYSA-N thiamine mononitrate Chemical compound [O-][N+]([O-])=O.CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N UIERGBJEBXXIGO-UHFFFAOYSA-N 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 229940040064 ubiquinol Drugs 0.000 description 1
- QNTNKSLOFHEFPK-UPTCCGCDSA-N ubiquinol-10 Chemical compound COC1=C(O)C(C)=C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)C(O)=C1OC QNTNKSLOFHEFPK-UPTCCGCDSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000019160 vitamin B3 Nutrition 0.000 description 1
- 239000011708 vitamin B3 Substances 0.000 description 1
- 235000021470 vitamin B5 (pantothenic acid) Nutrition 0.000 description 1
- 235000021467 vitamin B7(Biotin) Nutrition 0.000 description 1
- 235000019159 vitamin B9 Nutrition 0.000 description 1
- 239000011727 vitamin B9 Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- 239000004711 α-olefin Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
- A61M5/1407—Infusion of two or more substances
-
- 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
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/15—Vitamins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/175—Amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/14—Details; Accessories therefor
- A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe
- A61J1/2093—Containers having several compartments for products to be mixed
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/07—Retinol compounds, e.g. vitamin A
-
- 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
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- 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
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
-
- 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
- A61K31/352—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 condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
-
- 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
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4172—Imidazole-alkanecarboxylic acids, e.g. histidine
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4415—Pyridoxine, i.e. Vitamin B6
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A61K31/51—Thiamines, e.g. vitamin B1
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
-
- 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
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
-
- 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
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
-
- 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
- A61K31/7135—Compounds containing heavy metals
- A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K9/0029—Parenteral nutrition; Parenteral nutrition compositions as drug carriers
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
-
- 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
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- 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
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Nutrition Science (AREA)
- Mycology (AREA)
- Molecular Biology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Inorganic Chemistry (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Anesthesiology (AREA)
- Vascular Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Dispersion Chemistry (AREA)
Description
本發明係有關於一種含有糖、脂肪、胺基酸及電解質的輸液製劑。更詳細而言,本發明係有關於一種輸液製劑(高卡路里輸液製劑),其係具2室容器之輸液製劑,其中於第1室收容有糖及脂肪乳劑,於第2室收容有胺基酸及電解質者。
含有收容於具有2室之輸液袋的糖、胺基酸及電解質之輸液製劑係公知,且被廣泛地使用於病患的營養管理。
若將還原糖與胺基酸調配於同一溶液中,會有發生梅納反應而變性之問題。因此,在該輸液製劑中,為了防止還原糖與胺基酸產生梅納反應,將輸液袋之一室中含有還原糖的輸液,與在另一室中含有胺基酸的輸液各自分開收容。在使用時,將2室連通而將各液混合後,對病患投藥。為了使該混合操作得以簡便地進行,將該等2室通常是以使用時可連通的隔壁(例如易剝離封膜(easy peel seal))來
隔開。然而,屢屢發生忘記進行該連通操作而不小心僅將其中一邊液體對病患投藥的失誤。因此,就該種2室收容型的輸液製劑而言非常重要的是,要將其製成即使在發生了因使用前忘記連通操作而僅投藥收容於其中一室內之輸液的狀況下,也不會對病患造成傷害。
例如,其中一邊輸液的鉀濃度較高時,僅投藥該輸液恐有造成病患高血鉀症之疑慮。為了消除這樣的問題,研究出將鉀分2室收容,使各輸液中的鉀濃度在40mEq/L以下之輸液製劑(專利文獻1)。
又,特別是在從末梢靜脈藉由點滴投藥輸液的情況,若滲透壓過高,恐有引起血管痛或靜脈炎之疑慮。因此,即便是混合前的輸液,也期望具有適度的滲透壓(專利文獻2)。
又,長時間僅投藥含有糖、胺基酸及電解質之輸液製劑(高卡路里輸液製劑)時,恐有出現必須脂肪酸缺乏症之症狀的疑慮。藉由將脂肪乳劑與高卡路里輸液製劑合併投藥,可預防必須脂肪酸缺乏症之症狀產生。又,脂肪具有每單位重量之卡路里量高,且與糖質不同不會造成滲透壓利尿等優點。然而,將電解質輸液與脂肪乳劑混合並經過長時間後,脂肪滴的尺寸會變大,若投藥恐有引起脂肪栓塞的疑慮。因此,開發出將脂肪乳劑與電解質收容在不同的室中,使用時再進行混合並投藥之具有2室容器的輸液製劑。
更進一步而言,一般知道在施行高卡路里輸液
中,若維生素B1不足,恐有引起酸血症的疑慮,為了防止這種情況的發生,在高卡路里輸液投藥時必須補給維生素。為了省掉這樣的功夫,亦開發出預先在糖、胺基酸、電解質之外調配維生素,由大室液、中室液及小室液等3液所構成之高卡路里輸液製劑(例如,服魯卡利庫()輸液製劑等)。就該高卡路里輸液製劑而言,從維生素(特別是脂溶性維生素)的安定性問題看來,雖是採用在大室、中室及小室等3室中收容組成相異之輸液的型態,具有3室的輸液製劑卻會有再製造時及使用時費工的問題,在生產成本及使用時的麻煩方面也有問題。又,例如在服魯卡利庫()輸液製劑的說明書中就有在調劑時的注意事項中指示不要與脂肪乳劑混合。
如上所述,迄今針對各種課題所研究出的方法,雖然用來解決各個課題是有用的,但尚未開發出能解決所有課題的輸液製劑。
【專利文獻1】日本特開2004-189677號公報
【專利文獻2】日本特開2003-95937號公報
【非專利文獻1】藥理與治療24(10),2151(1996)
本發明的目的在於開發一種能將上述所有課題解決的輸液製劑。
本發明者等研究出一種輸液製劑,令人驚訝的是,其係由可連通之隔件所隔開之具有2室的輸液製劑,其中於第1室收容有包含脂肪乳劑之第1室輸液,於第2室收容有包含胺基酸及電解質之第2室輸液,前述第1室輸液實質上不含有鉀,且滲透壓比為2.0至3.0,前述第2室輸液係鉀濃度在40mEq/L以下,且滲透壓比為2.5至3.5,隔件連通時前述第1室輸液及第2室輸液之混合液的鉀濃度在16mEq/L以上;發現若為上述輸液製劑,則在保存中不會有由還原糖及胺基酸所產生的梅納反應,在保存中脂肪乳劑中的脂肪粒尺寸不會變大,且即便是在僅投藥其中一邊的輸液的情況下,也少有病患出現高鉀血症之症狀,或引起血管痛及靜脈炎的疑慮,雖然是2室容器製劑但卻能安定的調配多種維生素,由此進一步重複改良直到完成了本發明。
即,本發明包含例如以下項目之輸液製劑。
一種輸液製劑,其係具有利用可連通之隔件所隔開之2室者,其中於第1室收容有包含糖及脂肪乳劑之第1室輸液,於第2室收容有包含胺基酸及電解質之第2室輸液,前述第1室輸液係實質上不含有鉀,且滲透壓比為2.0至3.0;
前述第2室輸液係鉀濃度在40mEq/L以下,且滲透壓比為2.5至3.5;隔件連通時前述第1室輸液及第2室輸液之混合液的鉀濃度為16mEq/L以上。
如第1項之輸液製劑,其中第1室輸液之pH為4.5至6.5,且第2室輸液之pH為6.0至7.4。
如第1或2項之輸液製劑,其中第1室輸液與第2室輸液之體積比為3:2至3:5。
如第1至3項中任一項之輸液製劑,其係於第1室進一步含有維生素B1者。
如第4項之輸液製劑,其係於第1室輸液中進一步含有維生素A、維生素B6、維生素B12、維生素D、維生素E及維生素K,且於第2室輸液中進一步含有維生素C及維生素B2者。
本發明之輸液製劑係將上述課題全部解決之輸液製劑。該輸液製劑在保存中不會發生由還原糖及胺基酸所產生之梅納反應,且脂肪乳劑中的脂肪粒尺寸也不會變大。又,即使在僅投藥其中一邊的輸液時,也幾乎不會有病患出現高鉀血症症狀,或是引起血管痛及靜脈炎的情
形。進一步而言,可期待藉由維生素B1的調配來抑制酸血症發生。又,由於是形成為可調配包含脂溶性維生素之其他維生素的2室容器製劑之故,相較於具有被隔成3室以上之形態的製劑(3室容器製劑),可減輕製造時及使用時的麻煩。
以下就本發明進一步詳細地進行說明。
本發明係有關於一種具有由可連通之隔件隔開之2室的輸液製劑,其中在第1室收納有包含糖、脂肪乳劑的第1室輸液,且在第2室收納有包含胺基酸及電解質之第2室輸液。
第1室輸液
本發明所使用之第1室輸液係包含糖及脂肪乳劑。
作為調配於第1室輸液中的糖,可列舉如:葡萄糖、果糖、麥芽糖等還原糖;木糖醇、山梨醇、甘油等非還原糖等。該等之中,尤其是從血糖值管理等的點看來,係以還原糖為佳,而以葡萄糖為更佳。該等糖係可單獨使用1種,或亦可將2種以上組合使用。
在第1室輸液中糖的調配比例係宜設定在70至150g/L的範圍內。又,在本發明之輸液製劑中,第1室輸液與第2室輸液之混合液之糖濃度係例示如宜滿足50至100
g/L,較宜為50至75g/L之範圍。
又,為了預防在輸液療法施行中發生酸血症的症狀,宜在第1室輸液中調配維生素B1。作為調配於第1室輸液之維生素B1,可使用維生素B1鹽酸鹽、硫胺素硝酸鹽、丙舒硫胺、奧托硫胺等。
第1室輸液中維生素B1的調配比例係可例示如硫胺素1.5至10mg/L,宜為2至8mg/L充足的範圍。又,在本發明之輸液製劑中,第1室輸液與第2室輸液之混合液中維生素B1的濃度宜設定成以硫胺素計為滿足1至6mg/L,較宜為1.5至4mg/L之範圍者。
又,第1室輸液中所調配之脂肪乳劑係將油脂使用乳化劑將水分散而調製成的水中油型乳劑。該脂肪乳劑的調製係可遵循一般方法進行。例如,可在水中加入油脂及乳化劑後,攪拌來調製粗乳化液,接著再利用高壓乳化法等慣用方法將粗乳化液乳化來調製。
就油脂而言,可適宜地使用食用油。例如植物油(大豆油、橄欖油、棉籽油、葵花籽油、玉米油、椰子油、紫蘇油、蘇子油等)、魚油(鱈魚肝油等)、中鏈脂肪酸三酸甘油酯(碳數8-10之脂肪酸的三酸甘油酯)[市售商品名:「Panasate」(日本油脂社製)、「ODO」(日清製油社製)、「COCONARD」(花王社製)、「Miglyol」(三葉貿易公司)等]、化學合成三酸甘油酯類[2-亞油醯基-1,3-二辛醯基甘油(8L8)、2-亞油醯基-1,3-二癸醯基甘油(10L10)等]等。該等係可單獨地使用1種,或亦可將2種以上組合使用。
作為乳化劑係可使用例如在製劑學上可容許之各種乳化劑。例如卵黄磷脂質(卵黄卵磷脂)、氫化卵黄磷脂質、大豆磷脂質(大豆卵磷脂)、氫化大豆磷脂質等,又可例示如非離子性界面活性劑等。該等係可單獨地使用1種,或亦可將2種以上組合使用。
特佳的油脂及特佳的乳化劑係可分別舉例如大豆油及卵黄磷脂質(卵黄卵磷脂)。特別是若使用卵黄卵磷脂等卵磷脂,則如後所述亦可成為磷源而為適宜。
在脂肪乳劑之調製中所使用之油脂及乳化劑的使用比例,係只要能獲得水中油型脂肪乳劑即可而無特別限定。通常,係以油脂在所獲得之脂肪乳劑中呈0.5至6 w/v%左右,宜為1至5 w/v%左右的比例來使用。又,乳化劑係由在所獲得脂肪乳劑中通常呈0.01至2 w/v%左右,宜為0.05至1 w/v%左右之範圍內來使用。
本發明之特別合適的脂肪乳劑之製法的一個具體例係如下所述。即,在水中加入油脂及乳化劑,且一併加入選自甘油及葡萄糖之至少1種物質,其後,攪拌來調製粗乳化液,接著,將粗乳化液藉由高壓乳化法等慣用的方法進行乳化。在採用高壓乳化法的情況中,該方法係可藉由使用例如Manton-Gaulin勻漿機等的乳化機,使粗乳化液在20至700Kg/cm2左右的條件下,通過2至50次左右,宜為3至20次左右來進行。又,在本方法中,甘油及/或葡萄糖在乳化時存在即可,例如,亦可在使用油脂與乳化劑調製而成的粗乳化液中添加甘油及/或葡萄糖來進行乳化。甘油
及/或葡萄糖的使用量通常係適合設成令所獲得之脂肪乳劑含有30至70w/v%左右,宜為40至60w/v%左右的甘油及/或葡萄糖。
又,可視需要再進一步添加各種添加劑,前述各種添加劑係一般所知可於脂肪乳劑中添加調配者。作為添加劑,可舉例如pH調整劑。作為pH調整劑係在鹽酸等的酸,或氫氧化鈉、氫氧化鉀等鹼之外,可使用有機酸或胺基酸。作為有機酸係可例示如醋酸、乳酸、檸檬酸、蘋果酸、琥珀酸等。又,作為胺基酸,可例示如L-組胺酸、L-離胺酸等。該等之中,油溶性材料係可在構成乳化液之油性成分中預先混合來利用。水溶性材料可混合於注射用水中,或可添加調配於所獲得之脂肪乳劑的水相中。該等添加調配量係可適宜地設定,例如可與迄今所知的該等添加調配量相同。
第1室輸液中的脂肪乳劑之調配比例,換算成油脂量係0.5至6 w/v%,宜為1至5 w/v%,較宜為2至5 w/v%。又,本發明之輸液製劑中,第1室輸液與第2室輸液之混合液中的脂肪乳劑量,換算成油脂量為0.25至6 w/v%,宜為0.5至3 w/v%,較宜為1至2.5 w/v%。
就第1室輸液的pH而言,在4.5至6.5之範圍內即可,較宜可例示如5.0至6.5。若在該pH範圍內,在第1室輸液中,可謀求脂肪乳劑與維生素B1的安定化。就第1室輸液之pH調整而言,係使用鹽酸、醋酸、冰醋酸、乳酸、蘋果酸、檸檬酸、氫氧化鈉、氫氧化鉀等pH調整劑來實施。又,
作為pH調整劑亦可使用L-組胺酸。
又,第1室輸液從進一步提高維生素B1安定性的觀點看來,宜將滴定酸度設為1以下。再者,滴定酸度係將溶液100mL中和至pH7.4所需之0.1mol/L氫氧化鈉溶液的mL量值。
作為第1室輸液的溶媒,通常可使用注射用的蒸餾水。
本發明的輸液製劑中,就第1室輸液的液量而言,係可依據該輸液製劑的總液量或第2室輸液的液量等來適宜設定。
第1室輸液係實質上不含有鉀。實質上不含有鉀係意味著不調配含有鉀的化合物。
又,第1室輸液的滲透壓比係設為2.0至3.0左右。在此,滲透壓比係指相對於生理食鹽水之滲透壓的比(即,將生理食鹽水的滲透壓設為1時的相對比)。再者,輸液的滲透壓比除非有特別提到,否則即指相對於生理食鹽水的滲透壓的比。
第2室輸液
本發明所使用之第2室輸液含有胺基酸及電解質。
就第2室輸液所調配之胺基酸而言,只要是使用於以對生物體之營養補給為目的之胺基酸輸液者即可。本發明中,胺基酸係通常以游離胺基酸的狀態來使用,但亦可為藥學上所容許的鹽、酯類、N-醯基衍生物二肽之形態。第2室輸液所調配之游離胺基酸的具體例係可例示如L-白
胺酸、L-異白胺酸、L-纈胺酸、L-離胺酸、L-蘇胺酸、L-色胺酸、L-甲硫胺酸、L-苯丙胺酸、L-半胱胺酸、L-酪胺酸、L-精胺酸、L-組胺酸、L-丙胺酸、L-脯胺酸、L-絲胺酸、甘胺酸、L-天門冬胺酸、L-麩胺酸等。又,胺基酸的鹽類,具體而言係可例示如L-精胺酸鹽酸鹽、L-半胱胺酸鹽酸鹽、L-麩胺酸鹽酸鹽、L-組胺酸鹽酸鹽、L-離胺酸鹽酸鹽等無機酸鹽;L-離胺酸醋酸鹽、L-離胺酸蘋果酸鹽等有機酸鹽等。胺基酸之酯類,具體而言係可例示如:L-酪胺酸甲酯、L-甲硫胺酸甲酯、L-甲硫胺酸乙酯等。胺基酸的N-醯基體具體而言係可例示如N-醯基-L-半胱胺酸、N-醯基-L-色胺酸、N-醯基-L-脯胺酸等。胺基酸的二肽具體而言係可例示如:L-酪胺醯基-L-酪胺酸、L-丙胺醯基-L-酪胺酸、L-精胺醯基-L-酪胺酸、L-酪胺醯基-L-精胺酸等。特別是L-半胱胺酸,作為醯基半胱胺酸調配時在安定性的點上很適合。該等胺基酸係可單獨地使用1種,但從營養補給的觀點看來,宜將2種以上組合使用。較佳係可例示如至少包含全部必須胺基酸(即,L-白胺酸、L-異白胺酸、L-纈胺酸、L-離胺酸、L-蘇胺酸、L-色胺酸、L-甲硫胺酸、L-苯丙胺酸、L-組胺酸等9種胺基酸)者。
第2室輸液中胺基酸的調配比例,以游離胺基酸之總量例示,宜為40至120g/L,較宜為50至100g/L之範圍。又,本發明之輸液製劑中,第1室輸液與第2室輸液之混合液的胺基酸濃度宜設定成以游離胺基酸總量計為滿足10至50g/L較宜為滿足20至30g/L之範圍。
又,調配於第2室輸液中的胺基酸組合及調配比例之適宜例之一係如下所述。亦即,以游離胺基酸換算計,L-白胺酸:5至15g/L、L-異白胺酸:3至9g/L、L-纈胺酸:3至9g/L、L-離胺酸:3至12g/L、L-蘇胺酸:1.2至6g/L、L-色胺酸:0.3至3g/L、L-甲硫胺酸:0.6至4.8g/L、L-苯丙胺酸:1.8至9g/L、L-半胱胺酸:0.1至1.8g/L、L-酪胺酸:0.06至1.2g/L、L-精胺酸:3至12g/L、L-組胺酸:1.2至6g/L、L-丙胺酸:3至9g/L、L-脯胺酸:1.2至6g/L、L-絲胺酸:0.6至4.2g/L、甘胺酸:1.2至6g/L、L-天門冬胺酸:0.12至1.8g/L、及L-麩胺酸:0.12至1.8g/L。
又,本發明之輸液製劑中,第1室輸液與第2室輸液之混合液的胺基酸濃度之適宜例之一係如下所述。即,以遊離胺基酸換算計L-白胺酸:3至9g/L、L-異白胺酸:1.5至4.5g/L、L-纈胺酸:1.5至4.5g/L、L-離胺酸:1.5至5g/L、L-蘇胺酸:0.6至3g/L、L-色胺酸:0.15至1.5g/L、L-甲硫胺酸:0.3至2.4g/L、L-苯丙胺酸:0.85至4.5g/L、L-半胱胺酸:0.03至0.9g/L、L-酪胺酸:0.03至0.6g/L、L-精胺酸:1.5至5g/L、L-組胺酸:0.6至3g/L、L-丙胺酸:1.5至4.5g/L、L-脯胺酸:0.6至3g/L、L-絲胺酸:0.3至2.1g/L、甘胺酸:0.6至3g/L、L-天門冬胺酸:0.06至0.9g/L、及L-麩胺酸:0.06至0.9g/L。
調配於第2室輸液中之電解質係指可在輸液領域使用的電解質,具體而言係包含於體液(例如血液、細胞內液)中的電解質(體液電解質)。也可說是生理學上重要的電
解質。更具體而言,可例示如鉀、鈣、鈉、鎂、磷、鋅、氯等。再者,本發明的輸液製劑中,該等電解質係以不調配在第1室輸液中為佳。特別是鉀,為了避免因高濃度鉀之投藥所造成的危險性,故雖然在2室輸液製劑的情況下通常會調配至兩邊輸液中,但在本發明之輸液製劑係僅調配於第2室輸液中。
作為鉀供給源,係可例示如氯化鉀、醋酸鉀、檸檬酸鉀、甘油磷酸鉀、硫酸鉀、乳酸鉀等。該等之中尤其是甘油磷酸鉀因為亦可成為磷供給源故為適宜。該等鉀供給源亦可為水合物形態。鉀係以在第2室輸液之濃度呈40mEq/L以下(宜為25至40mEq/L)之方式來調配。又,本發明之輸液製劑中,第1室輸液與第2室輸液之混合液的鉀濃度係16mEq/L以上(宜為16至25mEq/L,較宜為16至20mEq/L)。
作為鈣的供給源,可例示如葡萄糖酸鈣、氯化鈣、甘油磷酸鈣、乳酸鈣、泛酸鈣、醋酸鈣等鈣鹽。又,鈣鹽亦可為水合物形態(例如葡萄糖酸鈣水合物等)。鈣係以在第2室輸液中濃度呈15mEq/L以下(宜為6至12mEq/L)的方式調配。又,在本發明的輸液製劑中,第1室輸液與第2室輸液之混合液的鈣濃度為9mEq/L以下(宜為3至6mEq/L)。
作為鈉供給源,可例示如氯化鈉、乳酸鈉、醋酸鈉、硫酸鈉、甘油磷酸鈉、檸檬酸鈉、乳酸鈉等鈉鹽。又,在本發明之輸液製劑中,調配磷、鈣及/或鎂時,為了防止
該等產生沉澱,宜使用檸檬酸鈉來作為鈉供給源(之一部分)。又,鈉供給源亦可為水合物形態。鈉對第2室輸液之調配比例係可例示如在第2室輸液中為50至100mEq/L,宜為40至80mEq/L。又,本發明之輸液製劑中,第1室輸液與第2室輸液之混合液的鈉濃度宜設定為可滿足呈25至50mEq/L,宜為30至40mEq/L之範圍。
作為鎂供給源,可例示如硫酸鎂、氯化鎂、醋酸鎂等。又,鎂供給源亦可為水合物形態。鎂對第2室輸液的調配比例係可例示如在第2室輸液中為1至20mEq/L,宜為5至15mEq/L。又,在本發明之輸液製劑中,第1室輸液與第2室輸液之混合液的鎂濃度宜設定為可滿足呈0.5至10mEq/L,宜為6mEq/L之範圍。
作為磷供給源,由於若使用無機鹽會產生磷酸鈣及磷酸鎂的沉澱,故宜使用例如甘油磷酸鈉、甘油磷酸鉀等有機鹽。又,在第1室中使用卵磷脂來作為乳化劑時,該卵磷脂亦可成為磷供給源。僅以來自該卵磷脂的磷便能涵蓋必要量之磷時,便無需在第2室調配磷,而不會產生磷酸鈣等的沉澱故為佳。磷對第2室輸液之調配比例係可例示如在第2室輸液中為0至20mmol/L。又,在發明的輸液製劑中,第1室輸液與第2室輸液之混合液的磷濃度宜設定為可滿足呈1至20mmol/L,宜為5至10mmol/L之範圍。
作為鋅供給源,可例示如硫酸鋅、氯化鋅等。又,鋅供給源亦可為水合物形態。鋅對第2室輸液之調配比例係可例示如在第2室輸液中為2.5至15μmol/L。又,在發明的
輸液製劑中,第1室輸液與第2室輸液之混合液的鋅濃度宜設定為可滿足呈1.5至9μmol/L之範圍。
作為氯供給源,可例示如氯化鈉、氯化鉀、氯化鎂、氯化鈣等。氯對第2室輸液之調配比例係可例示如在第2室輸液中為50至100mEq/L,宜為40至80mEq/L。又,在本發明的輸液製劑中,第1室輸液與第2室輸液之混合液的氯濃度宜設定為可滿足呈25至60mEq/L,宜為30至40mEq/L之範圍。
第2室輸液宜視需要藉由pH調整劑將pH調整成6.0至7.4,宜為6.5至7.2。作為pH調整劑,係可使用與關於第1室輸液所記載者相同者。特別是檸檬酸因可抑制磷酸鈣的析出,故可適宜地使用。藉由使第2室輸液滿足上述pH範圍,可謀求L-半胱胺酸、L-麩胺酸等易起化學變化的胺基酸之安定化,更能將與第1室輸液混合後之混合液的pH維持在後述之最適範圍內。
就第2室輸液的溶劑而言,通常亦可使用注射用蒸餾水。
本發明之輸液製劑中,第2室輸液之滲透壓比係呈2.5至3.5左右。
又,亦可視需要在本發明之輸液製劑中調配安定劑。就調配於本發明之輸液製劑中的安定劑而言,可例示如亞硫酸氫鈉等亞硫酸鹽。為了避免第1室輸液中所包含之維生素B1分解,亞硫酸鹽係調配於第2室輸液中。第2室輸液之亞硫酸鹽的調配量係可例示如20至50mg/L之範圍。
在本發明之輸液製劑中,除了維生素B1以外亦可調配多種維生素。即便非為3室或4室輸液製劑,在2室輸液製劑中可安定地調配維生素的點亦為本發明之輸液製劑的特徵之一。就維生素而言,有水溶性維生素與脂溶性維生素。在本發明之輸液製劑中,脂溶性維生素係調配於第1室輸液中。又,水溶性維生素係可調配於第1室輸液、第2室輸液之任一者中。惟,如前所述,維生素B1係調配於第1室輸液中。
作為調配於本發明之輸液製劑中的水溶性維生素,可列舉如維生素B群、維生素C。就維生素B群而言,除維生素B1(硫胺素)外尚可列舉如維生素B2(核黃素)、維生素B3(菸鹼酸)、維生素B5(泛酸)、維生素B6、維生素B7(生物素)、維生素B9(葉酸)、維生素B12(氰鈷銨素)等。又,就脂溶性維生素而言,係可列舉如維生素A、維生素D(特別是膽鈣化固醇)、維生素E、維生素K等。
調配維生素C(抗壞血酸)時,可調配在第1室輸液及第2室輸液中任一者或兩者中,但以調配在第2室輸液中為佳。維生素C調配於第2室輸液中時,第2室輸液之維生素C的調配比例係可例示如50至500mg/L,宜為100至400mg/L。又,本發明之輸液製劑中,第1室輸液與第2室輸液之混合液的維生素C的濃度宜設定為滿足以下範圍:通常為25至250mg/L,宜為50至200mg/L,較宜為40至100mg/L。
就維生素B2而言,可使用核黃素、核黃素磷酸酯鈉、黃素單核苷酸等。在調配維生素B2時,可調配於第1
室輸液及第2室輸液中任一者或兩者中。惟,為了避免因維生素B2與葉酸之反應所造成之葉酸的不安定化,宜將該等成分分開收容。例如,在第1室輸液中調配有葉酸時,維生素B2宜被調配在第2室輸液中。維生素B2調配在第2室輸液中時,第2室輸液之維生素B2的調配比例通常以核黃素計可例示如2.5至15mg/L,宜為4至8mg/L。又,本發明之輸液製劑中,第1室輸液與第2室輸液之混合液的維生素B2濃度係宜設定成滿足通常以核黃素計為0.5至10mg/L,宜為0.5至3mg/L之範圍。
作為維生素B6係可使用吡哆醇、吡哆醇鹽酸鹽等吡哆醇的鹽等。調配維生素B6時,雖可於第1室輸液及第2室輸液之任一者中皆可,但由於維生素B6與維生素B2共存時會變得對光非常不安定之故,宜與維生素B2調配於不同處。將維生素B6調配於第1室輸液中時,第1室輸液之維生素B6的調配比例係可例示如通常以吡哆醇計為2至10mg/L,宜為2.5至5mg/L。又,本發明之輸液製劑中,第1室輸液與第2室輸液之混合液的維生素B6濃度係宜設定成滿足通常以吡哆醇計為1至10mg/L,宜為1.5至3.5mg/L之範圍。
調配葉酸時,雖可調配於第1室輸液及第2室輸液之任一者或兩者中,但以調配於第1室輸液中為佳。將葉酸調配在第1室輸液中時,第1室輸液之葉酸調配比例係可例示如通常0.1至0.8mg/L,宜為0.2至0.5mg/L。又,本發明之輸液製劑中,第1室輸液及第2室輸液之混合液的葉酸濃
度係宜設定成滿足通常為0.1至0.7mg/L,宜為0.2至0.4mg/L之範圍。
作為維生素B12係可使用氰鈷銨素、乙酸羥鈷胺、甲基鈷胺素等。調配維生素B12時,雖可調配於第1室輸液及第2室輸液之任一者或兩者中皆可,但以調配在第1室輸液中為佳。將維生素B12調配於第1室輸液中時,第1室輸液之維生素B12的調配比例係可例示如2至10μg/L,宜為2.5至5μg/L。又,本發明之輸液製劑中,第1室輸液與第2室輸液之混合液的維生素B12濃度係宜設定成滿足通常為0.5至10mg/L,宜為0.5至3mg/L之範圍。
作為菸鹼酸係例如可適宜地使用菸鹼醯胺。調配菸鹼酸時,雖可調配於第1室輸液及第2室輸液之任一者或兩者中皆可,但以調配於第2室輸液中為佳。菸鹼酸調配於第2室輸液中時,第2室輸液之菸鹼酸的調配比例係可例示如10至100mg/L,宜為20至50mg/L。又,又,在本發明之輸液製劑中,第1室輸液與第2室輸液之混合液的菸鹼酸濃度係宜設定為滿足通常5至50mg/L,宜為5至20mg/L之範圍。
作為泛酸,係可適宜地使用泛醇。調配泛酸時,雖可調配於第1室輸液及第2室輸液之任一者或兩者中皆可,但宜調配於第2室輸液中。泛酸調配於第2室輸液中時,第2室輸液之泛酸的調配比例係可例示如以泛醇計為5至30mg/L,宜為10至20mg/L。又,在本發明之輸液製劑中,第1室輸液與第2室輸液之混合液的泛醇濃度係宜設定成滿足
通常2.5至15mg/L,宜為5至10mg/L之範圍。
調配生物素時,雖可調配於第1室輸液及第2室輸液之任一者或兩者中皆可,但以調配於第2室輸液中為佳。生物素調配於第2室輸液中時,第2室輸液之生物素的調配比例係可例示如10至100μg/L,宜為20至80μg/L。又,在本發明之輸液製劑中,第1室輸液與第2室輸液之混合液的生物素濃度亦設定成滿足通常1至50μg/L,宜為10至40μg/L之範圍。
作為維生素A,可適宜地使用棕櫚酸視黃酯。又,可使用將其溶解在油中所形成的維生素A油。維生素A係脂溶性維生素,可調配於第1室輸液中。第1室輸液之維生素A的調配比例係可例示如1000至5000IU/L,宜為2000至4000IU/L。又,在本發明之輸液製劑中,第1室輸液與第2室輸液之混合液的維生素A濃度亦宜設定成滿足通常500至2500IU/L,宜為1000至2000IU/L之範圍。再者,IU為國際單位。亦可稱為維生素A單位。
作為維生素D係可使用膽鈣化固醇(維生素D3)。維生素D係脂溶性維生素,可調配於第1室輸液中。第1室輸液之維生素D的調配比例係可例示如2至10μg/L,宜為2.5至5μg/L。又,在本發明之輸液製劑中,第1室輸液與第2室輸液之混合液的維生素D濃度係宜設定成滿足通常0.5至10μg/L,宜為0.5至3μg/L之範圍。
作為維生素E,可適宜地使用生育酚乙酸酯。維生素E係脂溶性維生素,可調配於第1室輸液中。第1室輸液
之維生素E的調配比例係可例示如2至50mg/L,宜為5至20mg/L。又,在本發明之輸液製劑中,第1室輸液與第2室輸液之混合液的維生素D濃度係宜設定成滿足通常1至25mg/L,宜為2.5至10mg/L之範圍。
作為維生素K,葉萘醌(維生素K1)。維生素A為脂溶性維生素,可調配於第1室輸液中。第1室輸液之維生素K的調配比例係可例示如50至2500μg/L,宜為80至2000μg/L。又,在本發明之輸液製劑中,第1室輸液與第2室輸液之混合液的維生素K濃度係宜設定成滿足通常20至1200μg/L,宜為30至1000μg/L之範圍。
再者,作為第1室輸液組成及第2室輸液組成之適宜的1例,係可例示如以下的組成。
〔第1室輸液〕
精製大豆油:10-50g/L
葡萄糖:70-150g/L
維生素B1鹽酸鹽:3-10mg/L
吡哆醇鹽酸鹽:3-7mg/L
氰鈷銨素:2.5-5μg/L
葉酸:0.2-0.5mg/L
維生素A油:2000-4000IU/L
膽鈣化固醇:2.5-5μg/L
生育酚乙酸酯:5-20mg/L
葉萘醌:80-2000μg/L
〔第2室輸液〕
L-白胺酸:5-15g/L
L-異白胺酸:3-9g/L
L-纈胺酸:3-9g/L
L-離胺酸鹽酸鹽:3.5-15g/L
L-蘇胺酸:1.2-6g/L
L-色胺酸:0.3-3g/L
L-甲硫胺酸:0.6-4.8g/L
醯基半胱胺酸:0.13-2.4g/L
L-苯丙胺酸:1.8-9g/L
L-酪胺酸:0.06-1.2g/L
L-精胺酸:3-12g/L
L-組胺酸:1.2-6g/L
L-丙胺酸:3-9g/L
L-脯胺酸:1.2-6g/L
L-絲胺酸:0.6-4.2g/L
甘胺酸:1.2-6g/L
L-天門冬胺酸:0.12-1.8g/L
L-麩胺酸:0.12-1.8g/L
鈉:40-80mEq/L
鉀:25-40mEq/L
鈣:6-12mEq/L
鎂:5-15mEq/L
氯:40-80mEq/L
磷:0-20mmoL/L
鋅:2.5-15μmol/L
核黃素磷酸酯鈉:5-10mg/L
抗壞血酸:0.1-0.4g/L
生物素:20-80μg/L
菸鹼醯胺:20-50mg/L
泛醇:9-19mg/L
再者,第1室輸液及第2室輸液兩者皆可依循公知的輸液製造方法來製造。例如,可使上述各輸液成分溶解於注射用蒸餾水中來製造。脂溶性成分係例如宜如上所述經乳化後再使用。
第1室輸液與第2室輸液之混合液
本發明之輸液製劑係在使用時才將第1室輸液與第2室輸液混合來使用。第1室輸液與第2室輸液之混合液,為了抑制血管痛或靜脈炎之發生來提高安全性,期許其pH值為6至7.4,宜為6.5至7.0,滴定酸度為1至10、滲透壓比為2至3。
又,在本發明之輸液製劑中,就第1室輸液與第2室輸液之體積比而言,雖可視前述第1室輸液與第2室輸液之液量等來適宜設定,但從所含有之各成分的安定性及各室的滲透壓之設定的觀點看來,係可舉例如(第1室輸液:第2室輸液)之體積比呈(3:2至3:5)之體積比。
又,該混合液之熱量宜為450至750kcal/L,較宜為500至650kcal/L。該熱量中,脂肪所占比例宜為40%以下,較宜為20至40%。又,該熱量中,糖、脂肪及胺基酸所占比例宜為糖:40至60%、脂肪:20至40%、胺基酸:10
至30%;更宜為糖:45至55%、脂肪:25至35%、胺基酸:15至25%。
再者,大約的熱量係可對各成分之調配量(g)各自乘上糖4、脂肪9、胺基酸4來獲得。也就是說,糖1g的熱量係約4kcal,脂質1g的熱量係約9kcal,胺基酸1g的熱量係約4kca,可基於此來求取熱量。上述「該混合液之熱量」之記載係基於藉由該計算所算出之值。
再者,作為該混合液之各成分組成之適宜例之1,係可例示如以下的組成。
輸液製劑的使用態樣
本發明之輸液製劑係經口攝取不充分且在輕度的低蛋白血症或低度的低營養狀態下或在侵犯期(invasive phase)時,以手術前後之病患的營養管理為目的來使用,尤其是可適宜地使用於手術後或因消化器官疾病而難以經口進行營養補給的病患(宜為接受了消化器官切除手術之病患)的營養管理之目的。藉由將本發明之輸液製劑在手術後1至14日期間,宜為手術後1至3日期間對病患投藥,可健全地保持病患的營養狀態。投藥量及投藥速度係可在考慮各病患之症狀及年齡等後進行適宜設定。特別是,本發明之輸液製劑僅以上述投藥期間、該輸液製劑,便能健全地保持病患的營養狀態。
本發明之輸液製劑係宜從末梢靜脈投藥。即,本發明之輸液製劑宜為末梢靜脈投藥用輸液製劑。通常,從末梢靜脈投藥輸液時,若輸液的滲透壓過高,恐有引起血管痛及靜脈炎的疑慮,若為本發明之輸液製劑則不會有這種疑慮,故在從末梢靜脈投藥時,本發明之輸液製劑的該效果便能獲得很好的發揮。
輸液容器
作為收容第1室輸液與第2室輸液之容器,只要是具有可連通之2室者便無特別限定,可舉例如藉由易剝離封膜來形成隔壁者(日本專利特開平2-4671號公報、實開平5-5138號公報等)、將室間以夾子夾住藉以形成隔壁者(日本專利特開昭63-309263號公報等)、在隔壁上設有可開封之各種連通
手段而成者(日本專利特公昭63-20550號公報等)等以可連通之隔壁隔開的2室容器(輸液袋)。該等之中,隔壁以易剝離封膜(easy peel seal)來形成的輸液袋因適合大量生產,又連通作業亦容易故為佳。又,作為上述容器的材質,係可列舉醫療用容器等所慣用之各種透氣性塑膠,例如聚乙烯、聚丙烯、聚氯乙烯、交聯乙烯/乙烯基醋酸共聚物、乙烯/α-烯烴共聚物,該等各聚合物的摻合物或積層體等的柔軟性塑膠。
對上述容器之第1室輸液及第2室輸液的填充、收容係可依循常法來進行,可舉例如將各輸液在惰性氣體環境下填充至各室中後,施以栓塞,並加熱滅菌之方法。在此,加熱滅菌係可採用高壓蒸氣滅菌、熱水浴滅菌等採用方法,並能視需要在二氧化碳、氮等惰性氣體環境中進行。
進一步,為了確實地防止收容於上述容器中之第1室輸液及第2室輸液變質、氧化等,宜將容器與脫氧劑一起以氧障蔽性外裝袋來包裝。尤其是,在採用隔壁由易剝離封膜所形成之輸液袋作為容器時,該輸液袋宜以不會因外壓使隔壁連通的方式在易剝離封膜部分經折疊的狀態,例如宜在易剝離封膜部分以經對折的狀態來包裝。又,亦可視需要來進行惰性氣體填充包裝等。
作為適合上述包裝之氧障蔽性外裝袋的材質,可使用一般所廣泛使用之各種材質的薄膜、薄片等。其具體例係可舉例如:乙烯/乙烯醇共聚物、聚二氯亞乙烯、聚丙烯腈、聚乙烯醇、聚醯胺、聚酯等,或由包含該等之至少1
種的材質所構成之薄膜、薄片等。
又,作為脫氧劑係可使用各種公知物,例如以氫氧化鐵、氧化鐵、碳化鐵等鐵化合物為有效成分者,或使用低分子酚與活性碳者。其代表性的市售商品的商品名係可列舉如「AGELESS」(三菱瓦斯化學社製)、「MOJURAN」(日本化藥社製)、「SEQUL」(日本曹達社製)、「TAMOTSU」(王子化工社製)、「KEEPIT」(Dorency社製)等。
以下具體地說明本發明,但本發明非受下述各例所限定者。
實施例1 輸液製劑的調製
1. 第1室輸液之調製
依照表2所示之組成,將精製大豆油、精製卵黄卵磷脂及葡萄糖加入水中,利用乳化機進行粗乳化後,以高壓乳化機(Manton-Gaulin)進行精乳化,在加水將全量調整為250ml。又,使用pH調整劑(L-組胺酸及鹽酸)將pH調整成約6.0。如此所獲得之第1室輸液的滲透壓比為3.0,滴定酸度為0.5。
2. 第2室輸液之調製
依照表3所示之組成,將各胺基酸、電解質及安定劑(亞硫酸氫鈉)溶解於注射用蒸餾水中,調製胺電解質液。進一步,將該液的pH以冰醋酸調整成6.7,使全量成為250mL,調製第2室輸液。如此所獲得之第2室輸液的滲透壓比為3.0,鉀濃度為40mEq/L。
3. 充填/包裝
將以上述方式所獲得之第1室輸液250mL及第2室輸液250mL,分別填充至各室由易剝離封膜區隔之聚乙烯製2室容器的各室中,進行各室空間部的氮置換,密封後,按常法進行高壓蒸氣滅菌。其後,將容器在易剝離封膜部折疊,與脫氧劑(商品名「AGELESS」;三菱瓦斯化學社製)一起封入多層障蔽薄膜(商品名「BOVLON」;NSR社製)的外裝袋中,獲得輸液製劑。再者,將該輸液製劑之第1室輸液與第2室輸液混合後之混合液(將組成表示於表4)係pH為6.7、滴定酸度7、鉀濃度20mEq/L。又,在混合後3天期間的保存中,粒徑0.5μm以上之粗大粒子的體積係USP(美國藥典)規格之0.05%以下,脂肪粒子安定。粒徑係使用ACCUSIZER 780(PERTICLE SIZING SYSTEM社製)來測定。
實施例2 輸液製劑的調製
1. 第1室輸液之調製
除了表2的成分之外,進一步以與實施例1相同的方式調製將維生素B1鹽酸鹽0.96mg調配而得之液劑250ml,來製作第1室輸液。再者,該第1室輸液之pH值約調整為6.0。又,該第1室輸液的滲透壓比為3,滴定酸度為0.5。
2. 第2室輸液的調製
以與實施例1相同的方式來製作第2室輸液。
3. 充填/包裝
將以上述方式所獲得之第1室輸液250mL及第2室輸液250mL,分別填充至各室由易剝離封膜區隔之聚乙烯製2室容器的各室中,進行各室空間部的氮置換,密封後,按常法進行高壓蒸氣滅菌。其後,將容器在易剝離封膜部折疊,與脫氧劑(商品名「AGELESS」;三菱瓦斯化學社製)一起封入多層障蔽薄膜(商品名「BOVLON」;NSR社製)的外裝袋中,獲得輸液製劑。再者,將該輸液製劑之第1室輸液與第2室輸液混合後之混合液(將組持表示於表5)係pH為6.7,滴定酸度為7,鉀濃度為20mEq/L。又,在混合後3天期間的保存中,粒徑0.5μm以上之粗大粒子的體積係0.05%以下,脂肪粒子安定。
實施例3 輸液製劑的調製
1. 第1室輸液的調製
在表2的成分之外,進一步以與實施例1相同的方式調製將維生素A油2.75mg(825維生素A單位)、膽鈣化固醇1.25μg、生育酚乙酸酯2.5mg、葉萘醌1mg、維生素B1鹽酸鹽0.96mg、吡哆醇鹽酸鹽1.23mg、氰鈷銨素1.25μg及葉酸0.1mg調配而得之液劑250ml,來製作第1室輸液。再者,維生素A油、膽鈣化固醇、生育酚乙酸酯、葉萘醌係預先溶解於精製大豆油中再使用。該第1室輸液之pH值約調整為6.0。又,該第1室輸液的滲透壓比為3,滴定酸度為0.5。
2. 第2室輸液的調製
除了表3的成分,進一步以與實施例1相同的方式調製將抗壞血酸25mg、生物素15μg、菸鹼醯胺10mg、泛醇3.5mg及核黃素磷酸酯鈉1.15mg調配而得之液劑250ml,來製作第2室輸液。滲透壓比為3、鉀濃度為40mEq/L。又pH經調整至6.7。
3. 充填/包裝
將以上述方式所獲得之第1室輸液250mL及第2室輸液250mL,分別填充至各室由易剝離封膜區隔之聚乙烯製2室容器的各室中,進行各室空間部的氮置換,密封後,按常法進行高壓蒸氣滅菌。其後,將容器在易剝離封膜部折疊,與脫氧劑(商品名「AGELESS」;三菱瓦斯化學社製)一起封入多層障蔽薄膜(商品名「BOVLON」;NSR社製)的外裝袋中,獲得輸液製劑。再者,將該輸液製劑之第1室輸
液與第2室輸液混合後之混合液(將組成表示於表6),pH為6.7,滴定酸度為7,鉀濃度為20mEq/L。又,在混合後3天期間的保存中,粒徑0.5μm以上之粗大粒子的體積係0.05%以下,脂肪粒子安定。
再者,將該輸液製劑(第1室輸液及第2室輸液尚未混合)在室溫下保存6個月後,將第1室輸液或第2室輸液中所含有的各維生素成分量,使用HPLC來測定後,可獲得下面表7所示之結果。從該結果可確認,若為該輸液製劑,則各維生素成分即便在6個月後仍安定地存在。
實施例4 輸液製劑的調製
1. 第1室輸液的調製
在表2的成分之外,進一步以與實施例3相同的方式調製將維生素A油2.75mg(825維生素A單位)、膽鈣化固醇1.25μg、生育酚乙酸酯2.5mg、葉萘醌37.55μg、維生素B1鹽酸鹽1.92mg、吡哆醇鹽酸鹽1.82mg、及氰鈷銨素1.25μg、葉酸0.15mg調配而得之液劑300ml,來製作第1室輸液。此時,
pH值調整為約6.0。又,滲透壓比為2.5,滴定酸度為0.5。
2. 第2室輸液的調製
除了表3的成分,進一步以與實施例3相同的方式調製將維生素C(抗壞血酸)50mg、生物素15μg、菸鹼醯胺10mg、泛醇3.5mg及維生素B2(磷酸核黃素鈉)1.15mg調配而得之液劑250ml,來製作第2室輸液。此時,pH經調整至6.7。滲透壓比為3.0,鉀濃度為40mEq/L。
3. 充填/包裝
將以上述方式所獲得之第1室輸液300mL及第2室輸液250mL,分別填充至各室由易剝離封膜區隔之聚乙烯製2室容器的各室中,進行各室空間部的氮置換,密封後,按常法進行高壓蒸氣滅菌。其後,將容器在易剝離封膜部折疊,與脫氧劑(商品名「AGELESS」;三菱瓦斯化學社製)一起封入多層障蔽薄膜(商品名「BOVLON」;NSR社製)的外裝袋中,獲得輸液製劑。再者,將該輸液製劑之第1室輸液與第2室輸液混合後之混合液(將組成表示於表8),pH為6.7,滴定酸度為6,鉀濃度為18.2mEq/L。又,在混合後3天期間的保存中,粒徑0.5μm以上之粗大粒子的體積係0.05%以下,脂肪粒子安定。
比較例1 輸液製劑的調製
1. 第1室輸液的調製
依照表2所示的組成,將精製大豆油、精製卵黄卵磷脂及葡萄糖加入水中並藉由乳化機進行粗乳化後,以高壓乳化機(Manton-Gaulin)進行精乳化,進一步加入水將全量調整為350ml。又,使用pH調整劑(L-組胺酸及鹽酸)將pH調整成6.0。如此所獲得之第1室輸液的滲透壓比為2.1,滴定酸度為0.5。
2. 第2室輸液的調製
將調配表3的成分而成之液劑150ml,以與實施例1相同的方式調製,來製作第2室輸液。此時,pH經調整至6.7。滲透壓比為5,鉀濃度為67mEq/L。
3. 充填/包裝
將以上述方式所獲得之第1室輸液350mL及第2室輸液150mL,分別填充至各室由易剝離封膜區隔之聚乙烯製2室容器的各室中,進行各室空間部的氮置換,密封後,按常法進行高壓蒸氣滅菌。其後,將容器在易剝離封膜部折疊,與脫氧劑(商品名「AGELESS」;三菱瓦斯化學社製)一起封入多層障蔽薄膜(商品名「BOVLON」;NSR社製)的外裝袋中,獲得輸液製劑。再者,雖然該輸液製劑之第1室輸液與第2室輸液混合後之混合液與實施例1為完全相同的組成,但在比較例1的處方中,由於第2室的鉀濃度呈67mEq/L這樣的高濃度,在隔壁未開通就使用的情況下,就是將高濃度的鉀投藥於體內,是非常危險的。又,
第2室的滲透壓比極高高達5時亦不可忽略靜脈炎等的不良影響。
Claims (4)
- 一種輸液製劑,具有以可連通之隔件隔開之2室,其係於第1室收容有包含糖及脂肪乳劑之第1室輸液;於第2室收容有包含胺基酸及電解質之第2室輸液;前述第1室輸液實質上不含有鉀,滲透壓比為2.0至3.0;前述第2室輸液之鉀濃度在40mEq/L以下,且滲透壓比為2.5至3.5;於隔件連通時測定,前述第1室輸液與第2室輸液之混合液的鉀濃度為16mEq/L以上;且第1室輸液與第2室輸液之體積比為3:2至3:3。
- 如申請專利範圍第1項之輸液製劑,其中第1室輸液之pH為4.5至6.5,且第2室輸液之pH為6.0至7.4。
- 如申請專利範圍第1或2項之輸液製劑,其係於第1室進一步含有維生素B1。
- 如申請專利範圍第3項之輸液製劑,其係於第1室輸液中進一步含有維生素A、維生素B6、維生素B12、維生素D、維生素E及維生素K,且於第2室輸液中進一步含有維生素C及維生素B2者。
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010265611 | 2010-11-29 |
Publications (2)
Publication Number | Publication Date |
---|---|
TW201642835A TW201642835A (zh) | 2016-12-16 |
TWI603747B true TWI603747B (zh) | 2017-11-01 |
Family
ID=46171823
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW100143712A TWI597070B (zh) | 2010-11-29 | 2011-11-29 | 輸液製劑 |
TW105126766A TWI603747B (zh) | 2010-11-29 | 2011-11-29 | 輸液製劑(一) |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW100143712A TWI597070B (zh) | 2010-11-29 | 2011-11-29 | 輸液製劑 |
Country Status (13)
Country | Link |
---|---|
US (3) | US9446184B2 (zh) |
EP (2) | EP2647370B1 (zh) |
JP (2) | JP5866582B2 (zh) |
KR (1) | KR101799135B1 (zh) |
CN (3) | CN105342994B (zh) |
AU (1) | AU2011337781B2 (zh) |
CA (1) | CA2819212C (zh) |
HK (1) | HK1243004A1 (zh) |
MY (2) | MY157108A (zh) |
PH (1) | PH12015502806A1 (zh) |
SG (3) | SG10201606838VA (zh) |
TW (2) | TWI597070B (zh) |
WO (1) | WO2012073891A1 (zh) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101799135B1 (ko) * | 2010-11-29 | 2017-11-17 | 가부시키가이샤 오츠까 세이야꾸 고죠 | 수액 제제 |
WO2015001995A1 (ja) | 2013-07-01 | 2015-01-08 | 丸石製薬株式会社 | 血管痛を改善したロクロニウム製剤及びその製造方法並びに該ロクロニウム製剤を用いた血管痛の抑制・緩和方法 |
CN107898808B (zh) * | 2017-10-31 | 2021-04-27 | 华仁药业股份有限公司 | 小儿用静脉营养制剂 |
CN107802596A (zh) * | 2017-11-30 | 2018-03-16 | 哈尔滨珍宝制药有限公司 | 一种羟乙基淀粉注射液组合物及其制备方法与应用 |
GB2569997A (en) * | 2018-01-09 | 2019-07-10 | Counsell David | Improvements relating to intravenous fluids |
WO2019176996A1 (ja) | 2018-03-13 | 2019-09-19 | 株式会社大塚製薬工場 | 輸液製剤 |
EP3796883A2 (en) | 2018-05-18 | 2021-03-31 | Baxter International Inc. | Dual chamber flexible container, method of making and drug product using same |
JP7289137B2 (ja) * | 2019-08-02 | 2023-06-09 | 株式会社大塚製薬工場 | 輸液製品 |
Family Cites Families (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3610693A (en) | 1969-12-30 | 1971-10-05 | Xerox Corp | Method of making a cylindrical brush |
JPS5752455A (en) | 1980-09-16 | 1982-03-27 | Nissho Kk | Bag for transfused liquid |
JPS63309263A (ja) | 1987-06-09 | 1988-12-16 | Otsuka Pharmaceut Factory Inc | 輸液バッグ |
JP2675075B2 (ja) | 1988-06-10 | 1997-11-12 | 株式会社新素材総合研究所 | 内容物入り容器 |
JPH085708Y2 (ja) | 1990-11-20 | 1996-02-21 | 株式会社大塚製薬工場 | 輸液バッグ |
DK0671166T3 (da) * | 1991-04-26 | 2005-01-03 | Mitsubishi Pharma Corp | Næringstilförende præparater |
EP0747033B1 (en) * | 1992-10-22 | 2000-05-31 | Yoshitomi Pharmaceutical Industries, Ltd. | Transfusion liquid-containing holder and prepared transfusion liquid |
JPH06312923A (ja) * | 1993-04-30 | 1994-11-08 | Green Cross Corp:The | 末梢静脈投与用栄養輸液 |
KR100426153B1 (ko) * | 1994-04-20 | 2004-06-16 | 미쯔비시 웰 파마 가부시키가이샤 | 주입액으로충전시킨용기,주입제제및바이타민을포함하는고칼로리주입제제 |
JPH08709A (ja) | 1994-04-20 | 1996-01-09 | Green Cross Corp:The | 輸液入り容器、輸液製剤及びビタミン配合総合高カロリー輸液製剤 |
DE69929128T2 (de) | 1998-08-31 | 2006-06-29 | Nipro Corp. | Nährstoffinfusionspräparat |
JP4717170B2 (ja) * | 1998-08-31 | 2011-07-06 | ニプロ株式会社 | 栄養輸液製剤 |
JP4148632B2 (ja) | 2000-05-18 | 2008-09-10 | ニプロ株式会社 | 末梢静脈栄養輸液製剤 |
JP2003095937A (ja) | 2001-07-17 | 2003-04-03 | Otsuka Pharmaceut Factory Inc | 末梢静脈用輸液 |
JP2004189677A (ja) | 2002-12-12 | 2004-07-08 | Otsuka Pharmaceut Factory Inc | 輸液製剤 |
WO2004103375A1 (ja) | 2003-05-22 | 2004-12-02 | Otsuka Pharmaceutical Factory, Inc. | 末梢静脈投与用輸液製剤およびビタミンb1の安定化方法 |
JP4622311B2 (ja) * | 2004-05-21 | 2011-02-02 | 味の素株式会社 | 末梢静脈投与用輸液 |
JP2007137836A (ja) * | 2005-11-21 | 2007-06-07 | Ajinomoto Co Inc | 末梢静脈栄養輸液 |
KR101799135B1 (ko) * | 2010-11-29 | 2017-11-17 | 가부시키가이샤 오츠까 세이야꾸 고죠 | 수액 제제 |
-
2011
- 2011-11-28 KR KR1020137015992A patent/KR101799135B1/ko active IP Right Grant
- 2011-11-28 AU AU2011337781A patent/AU2011337781B2/en active Active
- 2011-11-28 CN CN201510815549.0A patent/CN105342994B/zh active Active
- 2011-11-28 CN CN201180056952XA patent/CN103237541A/zh active Pending
- 2011-11-28 WO PCT/JP2011/077392 patent/WO2012073891A1/ja active Application Filing
- 2011-11-28 CN CN201510815943.4A patent/CN105342995B/zh active Active
- 2011-11-28 EP EP11845978.3A patent/EP2647370B1/en active Active
- 2011-11-28 US US13/990,018 patent/US9446184B2/en active Active
- 2011-11-28 MY MYPI2013001927A patent/MY157108A/en unknown
- 2011-11-28 SG SG10201606838VA patent/SG10201606838VA/en unknown
- 2011-11-28 SG SG10201509567PA patent/SG10201509567PA/en unknown
- 2011-11-28 EP EP17164509.6A patent/EP3210598B1/en active Active
- 2011-11-28 CA CA2819212A patent/CA2819212C/en active Active
- 2011-11-28 JP JP2012546860A patent/JP5866582B2/ja active Active
- 2011-11-28 SG SG2013041249A patent/SG190915A1/en unknown
- 2011-11-28 MY MYPI2016000682A patent/MY186310A/en unknown
- 2011-11-29 TW TW100143712A patent/TWI597070B/zh active
- 2011-11-29 TW TW105126766A patent/TWI603747B/zh active
-
2015
- 2015-10-05 JP JP2015197970A patent/JP6002980B2/ja active Active
- 2015-12-17 PH PH12015502806A patent/PH12015502806A1/en unknown
- 2015-12-18 US US14/974,534 patent/US9687600B2/en active Active
-
2017
- 2017-06-20 US US15/627,783 patent/US9884149B2/en active Active
-
2018
- 2018-02-26 HK HK18102719.6A patent/HK1243004A1/zh unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TWI603747B (zh) | 輸液製劑(一) | |
JPH06209979A (ja) | 輸液入り容器及び輸液製剤 | |
JP6647656B1 (ja) | 輸液製剤 | |
AU2019234899B2 (en) | Transfusion preparation | |
JPH08709A (ja) | 輸液入り容器、輸液製剤及びビタミン配合総合高カロリー輸液製剤 | |
AU2015268572B2 (en) | Infusion preparation | |
JP2020152662A (ja) | 脂肪乳剤 |