CN114945373A - 肠外营养制剂及其制备方法 - Google Patents
肠外营养制剂及其制备方法 Download PDFInfo
- Publication number
- CN114945373A CN114945373A CN202080005038.1A CN202080005038A CN114945373A CN 114945373 A CN114945373 A CN 114945373A CN 202080005038 A CN202080005038 A CN 202080005038A CN 114945373 A CN114945373 A CN 114945373A
- Authority
- CN
- China
- Prior art keywords
- choline
- phosphatidylcholine
- parenteral
- aqueous composition
- cytidine diphosphate
- 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.)
- Granted
Links
- 235000016236 parenteral nutrition Nutrition 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims description 12
- 239000000203 mixture Substances 0.000 claims abstract description 49
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims abstract description 44
- 229960001231 choline Drugs 0.000 claims abstract description 42
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims abstract description 33
- RZZPDXZPRHQOCG-OJAKKHQRSA-M CDP-choline(1-) Chemical compound O[C@@H]1[C@H](O)[C@@H](COP([O-])(=O)OP([O-])(=O)OCC[N+](C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 RZZPDXZPRHQOCG-OJAKKHQRSA-M 0.000 claims abstract description 20
- 229960001284 citicoline Drugs 0.000 claims abstract description 20
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 claims abstract description 9
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 claims abstract description 9
- 229960003964 deoxycholic acid Drugs 0.000 claims abstract description 9
- 230000000694 effects Effects 0.000 claims abstract description 7
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 15
- 235000016709 nutrition Nutrition 0.000 claims description 13
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 12
- 239000008777 Glycerylphosphorylcholine Substances 0.000 claims description 12
- 229960004788 choline alfoscerate Drugs 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 9
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 claims description 8
- 229960003512 nicotinic acid Drugs 0.000 claims description 8
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- 235000001968 nicotinic acid Nutrition 0.000 claims description 7
- 239000011664 nicotinic acid Substances 0.000 claims description 7
- 229930003799 tocopherol Natural products 0.000 claims description 7
- 229960001295 tocopherol Drugs 0.000 claims description 7
- 239000011732 tocopherol Substances 0.000 claims description 7
- 235000010384 tocopherol Nutrition 0.000 claims description 7
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 claims description 4
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 4
- 239000008280 blood Substances 0.000 claims description 4
- 210000004369 blood Anatomy 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 2
- SUHOQUVVVLNYQR-MRVPVSSYSA-O glycerylphosphorylcholine Chemical compound C[N+](C)(C)CCO[P@](O)(=O)OC[C@H](O)CO SUHOQUVVVLNYQR-MRVPVSSYSA-O 0.000 claims 6
- ZWIADYZPOWUWEW-XVFCMESISA-N CDP Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O1 ZWIADYZPOWUWEW-XVFCMESISA-N 0.000 claims 2
- 230000000050 nutritive effect Effects 0.000 claims 2
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 abstract description 3
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 abstract description 3
- RZZPDXZPRHQOCG-UHFFFAOYSA-N [[5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] 2-(trimethylazaniumyl)ethyl phosphate Chemical compound OC1C(O)C(COP([O-])(=O)OP(O)(=O)OCC[N+](C)(C)C)OC1N1C(=O)N=C(N)C=C1 RZZPDXZPRHQOCG-UHFFFAOYSA-N 0.000 description 13
- SUHOQUVVVLNYQR-MRVPVSSYSA-N choline alfoscerate Chemical compound C[N+](C)(C)CCOP([O-])(=O)OC[C@H](O)CO SUHOQUVVVLNYQR-MRVPVSSYSA-N 0.000 description 13
- 238000009472 formulation Methods 0.000 description 13
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 10
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical class O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- 230000037361 pathway Effects 0.000 description 6
- 208000024172 Cardiovascular disease Diseases 0.000 description 5
- 230000004060 metabolic process Effects 0.000 description 5
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 4
- 229960004373 acetylcholine Drugs 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 230000000968 intestinal effect Effects 0.000 description 4
- 230000002503 metabolic effect Effects 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- YHHSONZFOIEMCP-UHFFFAOYSA-N 2-(trimethylazaniumyl)ethyl hydrogen phosphate Chemical compound C[N+](C)(C)CCOP(O)([O-])=O YHHSONZFOIEMCP-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 3
- 230000008499 blood brain barrier function Effects 0.000 description 3
- 210000001218 blood-brain barrier Anatomy 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 230000003920 cognitive function Effects 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000000378 dietary effect Effects 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 3
- 150000003904 phospholipids Chemical class 0.000 description 3
- 229950004354 phosphorylcholine Drugs 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 3
- 229940045145 uridine Drugs 0.000 description 3
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 102000002745 Choline Kinase Human genes 0.000 description 2
- 108010018888 Choline kinase Proteins 0.000 description 2
- PCDQPRRSZKQHHS-CCXZUQQUSA-N Cytarabine Triphosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 PCDQPRRSZKQHHS-CCXZUQQUSA-N 0.000 description 2
- 102000013444 Diacylglycerol Cholinephosphotransferase Human genes 0.000 description 2
- 108010051225 Diacylglycerol cholinephosphotransferase Proteins 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 2
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 229960003237 betaine Drugs 0.000 description 2
- 230000003925 brain function Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 235000018823 dietary intake Nutrition 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 235000020673 eicosapentaenoic acid Nutrition 0.000 description 2
- 229960005135 eicosapentaenoic acid Drugs 0.000 description 2
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 108010036606 glycerophosphocholine phosphodiesterase Proteins 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- UYPYRKYUKCHHIB-UHFFFAOYSA-N trimethylamine N-oxide Chemical compound C[N+](C)(C)[O-] UYPYRKYUKCHHIB-UHFFFAOYSA-N 0.000 description 2
- DVSZKTAMJJTWFG-SKCDLICFSA-N (2e,4e,6e,8e,10e,12e)-docosa-2,4,6,8,10,12-hexaenoic acid Chemical compound CCCCCCCCC\C=C\C=C\C=C\C=C\C=C\C=C\C(O)=O DVSZKTAMJJTWFG-SKCDLICFSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
- GZJLLYHBALOKEX-UHFFFAOYSA-N 6-Ketone, O18-Me-Ussuriedine Natural products CC=CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O GZJLLYHBALOKEX-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000037157 Azotemia Diseases 0.000 description 1
- 208000028399 Critical Illness Diseases 0.000 description 1
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
- 101150049660 DRD2 gene Proteins 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010017877 Gastrointestinal fistula Diseases 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010033647 Pancreatitis acute Diseases 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- MEFKEPWMEQBLKI-AIRLBKTGSA-N S-adenosyl-L-methioninate Chemical compound O[C@@H]1[C@H](O)[C@@H](C[S+](CC[C@H](N)C([O-])=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MEFKEPWMEQBLKI-AIRLBKTGSA-N 0.000 description 1
- 206010049416 Short-bowel syndrome Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 229930003537 Vitamin B3 Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 201000003229 acute pancreatitis Diseases 0.000 description 1
- 229960001570 ademetionine Drugs 0.000 description 1
- 229960001456 adenosine triphosphate Drugs 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 230000000923 atherogenic effect Effects 0.000 description 1
- 230000002457 bidirectional effect Effects 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000002390 cell membrane structure Anatomy 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 235000020669 docosahexaenoic acid Nutrition 0.000 description 1
- KAUVQQXNCKESLC-UHFFFAOYSA-N docosahexaenoic acid (DHA) Natural products COC(=O)C(C)NOCC1=CC=CC=C1 KAUVQQXNCKESLC-UHFFFAOYSA-N 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 235000004626 essential fatty acids Nutrition 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 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 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 229960004956 glycerylphosphorylcholine Drugs 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002767 hepatic artery Anatomy 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 208000008384 ileus Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000007102 metabolic function Effects 0.000 description 1
- 230000037323 metabolic rate Effects 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 230000001777 nootropic effect Effects 0.000 description 1
- 235000015816 nutrient absorption Nutrition 0.000 description 1
- 235000021238 nutrient digestion Nutrition 0.000 description 1
- 235000003715 nutritional status Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 208000009852 uremia Diseases 0.000 description 1
- 235000019160 vitamin B3 Nutrition 0.000 description 1
- 239000011708 vitamin B3 Substances 0.000 description 1
- 235000008979 vitamin B4 Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Images
Classifications
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
-
- 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
- A61K31/395—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
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- 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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
-
- 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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
-
- 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
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Nutrition Science (AREA)
- Dermatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明公开了一种肠外营养水性组合物,包含脱氧胆酸、胞苷二磷酸胆碱和甘磷酸胆碱,其中,所述肠外营养还包含4.5‑5.5%(w/v)磷脂酰胆碱,其中所述磷脂酰胆碱与胞苷二磷酸胆碱和甘磷酸胆碱的组合提高胆碱生物有效性,以立即起效。
Description
技术领域
本发明大体上涉及一种肠外营养制剂及其制备方法。特别地,本发明描述了一种用于治疗心血管疾病、非酒精性脂肪肝和认知功能的肠外营养制剂及其制备方法。
背景技术
肠外营养(parenteral nutrition,简称PN)制剂对于无法通过管灌饮食或经口进食或吸收足够的食物以维持良好营养状况的患者至关重要。患者可能需要PN来治疗会影响食物摄入、营养消化或吸收的任何类型的疾病或病症。某些需要PN的疾病和病症包括但不限于短肠综合征、胃肠道瘘管、肠梗阻、危重患者和重症急性胰腺炎。
胆碱是一种通过膳食摄入和内源合成获得的营养。人体需要胆碱来合成对细胞膜至关重要的两种主要磷脂:磷脂酰胆碱和鞘磷脂。磷脂酰胆碱(phosphatidylcholine,简称PC)是一种含有两种脂肪酸的分子,这两种脂肪酸与包含磷酸基和胆碱的甘油骨架相连。所有植物细胞和动物细胞都需要胆碱来保持其结构完整性。此外,需要胆碱以产生乙酰胆碱,乙酰胆碱是记忆、情绪、肌肉控制以及其它大脑和神经系统功能的重要神经递质。
寄生在消化道中的肠道细菌有效地与宿主争夺膳食胆碱,因此,一部分膳食胆碱在小肠内吸收之前被肠道细菌降解为二甲胺和三甲胺,具体取决于肠道细菌的数量。该过程显著降低了胆碱生物有效性,并且人体内三甲胺水平的升高与三甲胺基尿症的发展有关。三甲胺也被肝脏代谢为氧化三甲胺,这是一种可能促进动脉粥样硬化的致动脉粥样硬化物质。氧化三甲胺与代谢、心血管和脑血管疾病有关。
本发明提出了一种营养制剂,该营养制剂经肠外给药至人体内,并因此避免肠道细菌胆碱代谢引起的问题。此外,肠外营养制剂提高了胆碱在支持脑功能方面以立即起效,并用于治疗心血管疾病和肝病的有效性。
发明内容
本发明的一个实施例提供了一种肠外营养水性组合物,包含脱氧胆酸、胞苷二磷酸胆碱和甘磷酸胆碱,其中,肠外营养还包含4.5-5.5%(w/v)磷脂酰胆碱,其中磷脂酰胆碱与胞苷二磷酸胆碱和甘磷酸胆碱的组合提高胆碱生物有效性,以立即起效。
优选地,组合物还包含0.01-0.03%(w/v)生育酚、0.01%-0.03%(w/v)烟酸和0.01%-0.03%(w/v)三磷酸腺苷。
优选地,脱氧胆酸的浓度为2.0-4.0%(w/v)。
优选地,胞苷二磷酸胆碱的浓度为0.4-0.6%(w/v)。
优选地,甘磷酸胆碱的浓度为0.4-0.6%(w/v)。
优选地,磷脂酰胆碱与胞苷二磷酸胆碱和甘磷酸胆碱的组合经肠外给药降低血液中的同型半胱氨酸水平。
本发明的一个实施例提供了一种用于制备肠外营养水性组合物的方法,包括以下步骤:混合2.0%-4.0%(w/v)脱氧胆酸与苯甲醇和乙醇;搅拌混合物直至获得清液;向混合物中加入4.5-5.5%(w/v)磷脂酰胆碱、胞苷二磷酸胆碱和甘磷酸胆碱;搅拌所得混合物,直至磷脂酰胆碱、胞苷二磷酸胆碱和甘磷酸胆碱溶解;以及用水调节规定总体积的混合物,并均匀混合所得肠外营养水性组合物,其中,在所得肠外营养水性组合物中,磷脂酰胆碱与胞苷二磷酸胆碱和甘磷酸胆碱的组合提高胆碱生物有效性,以立即起效。
优选地,方法还包括加入0.01-0.03%(w/v)生育酚、0.01%-0.03%(w/v)烟酸和0.01%-0.03%(w/v)三磷酸腺苷。
优选地,胞苷二磷酸胆碱的浓度为0.4-0.6%(w/v)。
优选地,甘磷酸胆碱的浓度为0.4-0.6%(w/v)。
在不脱离本发明的基本特征的情况下,本发明可以以其它特定形式实施。所述实施例在所有方面仅被视为说明性实施例而非限制性实施例。因此,本发明范围由所附权利要求书而不是前述描述指明。权利要求书的含义和等效范围内的所有变更均应包含在其范围内。
附图说明
为了进一步阐明本发明一些实施例的各个方面,将通过引用其特定实施例来呈现本发明的更具体的描述,如附图中所示。应当理解的是,这些附图仅描绘本发明的典型实施例,因此不应被视为对其范围的限制。本发明将通过其附图以附加特异性和细节进行描述和解释:
附图1.0示出了一种根据本发明的制备肠外营养制剂的方法。
具体实施方式
本发明大体上涉及一种肠外营养制剂及其制备方法。特别地,本发明描述了一种用于治疗心血管疾病、非酒精性脂肪肝和认知功能的肠外营养制剂。
在下文中,将根据优选实施例详细描述根据本发明提供的肠外营养制剂及其制备方法。应当理解的是,限制本发明优选实施例的描述仅是为了促进讨论本发明,并且在不脱离所附权利要求书的范围的情况下进行设想。
本发明公开了一种肠外营养制剂,包含三种主要活性成分的组合,这三种主要活性成分为:甘磷酸胆碱(α-GPC)、胞苷二磷酸胆碱(CDP胆碱)和磷脂酰胆碱。根据一优选实施例,肠外营养制剂包含一种磷脂、两种游离胆碱、胆汁酸和水,以及少量其它附加组分,例如生育酚、烟酸和三磷酸腺苷,以形成稳定的混合胶束制剂,并进一步补充了制剂在治疗心血管疾病、非酒精性脂肪肝和认知功能方面的疗效。
胆碱是一种通过膳食摄入和内源合成获得的营养,用于合成神经递质乙酰胆碱。由于胆碱通过不可逆氧化成三甲铵乙内酯和后续合成S-腺苷甲硫氨酸而充当甲基的主要膳食来源,因此它还参与甲基代谢,在肝脏中尤其如此。
口服摄入的磷脂酰胆碱易于从肠道吸收,并通过门静脉引流系统转运至肝脏进行代谢。口服补充剂的胆碱生物有效性在很大程度上受到胃肠道健康状况的影响。当胆碱静脉输注时,磷脂酰胆碱绕过肠吸收、降解过程,减少人体内三甲胺的生成,经肝动脉输送至肝脏。
肝脏是胆碱代谢的主要部位,胆碱主要以磷脂酰胆碱的形式存在,它对维持肝脏内磷脂酰胆碱的供应非常重要。
通过参考胆碱代谢链,胆碱最初通过胆碱激酶(choline kinase,简称CK)转化为胆碱磷酸,使用ATP作为磷酸供体。一种称为磷酸胆碱胞苷酰转移酶(phosphorylcholinecytidylyltransferase,简称CCT)的酶使用胞苷三磷酸(cytidinetriphosphate,简称CTP)将磷酸胆碱转化为CDP胆碱。磷酸胆碱转化为CDP胆碱是胆碱代谢链中速度最慢的一步。由于CDP胆碱是在限速步骤之后产生的胆碱形式,并且能够穿过血脑屏障到达中枢神经系统,因此它包含在本发明制剂中。
CDP胆碱不仅仅是一种胆碱来源;它含有等摩尔量的胆碱和胞苷,有助于增加人体内的血浆尿苷核苷酸和胆碱。核苷酸尿苷是突触强度和神经连接的关键因素。在本发明中,CDP胆碱用作核苷酸尿苷和益智成分的前驱体。尿苷联合CDP胆碱通过激活D1和D2受体信号促进大脑内新多巴胺受体的生长。
在该途径的最后一步,CDP胆碱通过胆碱磷酸转移酶(cholinephosphotransferase,简称CEPT)与甘油二酯(diacylglycerol,简称DAG)酯化,生成磷脂酰胆碱。诸如二十碳五烯酸(eicosapentaenoic acid,简称EPA)和二十二碳六烯酸(docosahexaenoic acid,简称DHA)之类的必需脂肪酸参与DAG的形成。磷脂酰胆碱是CDP胆碱途径的最终产物,人体和大脑中的大多数胆碱以磷脂酰胆碱的形式存在,用作胆碱的储库。磷脂酰胆碱参与极低密度脂蛋白(very low density lipoproteins,简称VLDL)的肝脏转运,并维持对所有基本生物过程至关重要的细胞膜的完整性。
通过分解磷脂酰胆碱在人体内获得α-GPC。胆碱途径中的酶反应是双向的,在制剂中强化α-GPC允许磷脂酰胆碱用于其它目的,而不是分解为胆碱。α-GPC在胆碱路径的不同点进入胆碱池,并且能够穿过血脑屏障到达中枢神经系统。在本发明中,α-GPC用作强效益智成分,可维持老化大脑对胆碱的摄取。
除了能够穿过血脑屏障直接提高中枢神经系统内乙酰胆碱的水平外,α-GPC还具有不同的作用。此外,α-GPC还用作神经元细胞磷脂生物合成的前驱体,并且进一步扩大胆碱池以产生三甲铵乙内酯,用于降低血液中的同型半胱氨酸水平。
口服α-GPC通过磷酸二酯酶在肠道黏膜中水解,然后转运至循环系统。然而,静脉给药时,它通过甘油磷酰胆碱磷酸二酯酶(glycerophosphorylcholinephosphodiesterase,简称GPCP)在大脑中氧化,以产生胆碱和甘油磷酸盐。与口服相比,经静脉给药后,α-GPC的代谢速度更快,显示两种途径的不同代谢。
基于不同动力学以及与胆碱途径的相互作用,在制剂中强化α-GPC和CDP胆碱将允许CDP胆碱途径上调以及磷脂酰胆碱循环转换;因此,提高了在乙酰胆碱合成和其它代谢功能方面的有效性。
本发明的药物制剂(肠外营养)包含以下成分:
2000–2500mg | 磷脂酰胆碱 |
250–350mg | 胞苷二磷酸胆碱 |
200–300mg | α-GPC |
1000–1500mg | 脱氧胆酸 |
10–15mg | 生育酚(维生素E) |
5–10mg | 烟酸(维生素B3) |
5–10mg | 三磷酸腺苷 |
一种用于制备肠外营养水性组合物的方法,包括以下步骤:混合0.01-0.03%(w/v)脱氧胆酸与苯甲醇和乙醇;搅拌混合物直至获得清液;向混合物中加入4.5-5.5%(w/v)磷脂酰胆碱、0.4-0.6%(w/v)胞苷二磷酸胆碱和0.4-0.6%(w/v)甘磷酸胆碱(α-GPC);向混合物中加入0.01-0.03%(w/v)生育酚、0.01-0.03%(w/v)烟酸和0.01-0.03%(w/v)三磷酸腺苷;搅拌所得混合物,直至磷脂酰胆碱、胞苷二磷酸胆碱和甘磷酸胆碱(α-GPC)溶解;以及用注射用水调节规定总体积的混合物,并均匀混合最终所得肠外营养水性组合物。
制剂含有0.8–1.0%(w/v)苯甲醇和0.24–0.26%(w/v)乙醇作为防腐剂和无菌注射用水。然后,通过过滤单元过滤最终所得肠外营养水性组合物以去除细菌细胞,然后在无菌条件下将过滤后的溶液装入瓶中,然后进行密封。
胆碱代谢链中的酶反应往往是双向的。因此,较高的CDP胆碱和α-GPC有效性使得磷脂酰胆碱可用于脂质转运,形成磷脂酰丝氨酸、鞘磷脂并支持细胞膜结构和功能,而不是分解以扩大胆碱池。
通过给予CDP胆碱、α-GPC和磷脂酰胆碱供应胆碱将在支持大脑功能和降低血液中的同型半胱氨酸水平方面立即起效。含有胆碱的组合物还专门配制用于代谢脂质,减少卒中诱导的神经损伤部位游离脂肪酸积聚并溶解血凝块。
除非上下文另有规定或特别声明相反,否则本文中所述的本发明的整数、步骤或元素为单数整数、步骤或元素,显然包含所述整数、步骤或元素的单数或复数形式。
除非上下文另有规定,否则贯穿本说明书使用的词语“包含”或变体将被理解为意味着包含规定的步骤、元素或整数或步骤、元素或整数组,但不排除任何其它步骤、元素或整数或步骤、元素或整数组。因此,在本说明书上下文中,术语“包含”具有包容性,因此应当理解为“主要包括,但不一定仅包括”。
Claims (10)
1.一种肠外营养水性组合物,包含:
脱氧胆酸;
胞苷二磷酸胆碱;以及
甘磷酸胆碱,
其特征在于,
所述肠外营养还包含4.5-5.5%(w/v)磷脂酰胆碱,其中所述磷脂酰胆碱与胞苷二磷酸胆碱和甘磷酸胆碱的组合提高胆碱生物有效性,以立即起效。
2.根据权利要求1所述的肠外营养水性组合物,其特征在于,所述组合物还包含0.01-0.03%(w/v)生育酚、0.01%-0.03%(w/v)烟酸和0.01%-0.03%(w/v)三磷酸腺苷。
3.根据权利要求1所述的肠外营养水性组合物,其特征在于,所述脱氧胆酸的浓度为2.0-4.0%(w/v)。
4.根据权利要求1所述的肠外营养水性组合物,其特征在于,所述胞苷二磷酸胆碱的浓度为0.4-0.6%(w/v)。
5.根据权利要求1所述的肠外营养水性组合物,其特征在于,所述甘磷酸胆碱的浓度为0.4-0.6%(w/v)。
6.根据权利要求1所述的肠外营养水性组合物,其特征在于,所述磷脂酰胆碱与胞苷二磷酸胆碱和甘磷酸胆碱的组合经肠外给药降低血液中的同型半胱氨酸水平。
7.一种用于制备肠外营养水性组合物(100)的方法,包括以下步骤:
(102)混合2.0%-4.0%(w/v)脱氧胆酸与苯甲醇和乙醇;
(104)搅拌所述混合物直至获得清液;
(106)向所述混合物中加入4.5-5.5%(w/v)磷脂酰胆碱、胞苷二磷酸胆碱和甘磷酸胆碱;
(110)搅拌所述混合物,直至所述磷脂酰胆碱、胞苷二磷酸胆碱和甘磷酸胆碱溶解;以及
(112)用水调节规定总体积的所述混合物,并均匀混合所得肠外营养水性组合物,
其特征在于,
在所得肠外营养水性组合物中,所述磷脂酰胆碱与胞苷二磷酸胆碱和甘磷酸胆碱的组合提高胆碱生物有效性,以立即起效。
8.根据权利要求7所述的用于制备肠外营养水性组合物的方法,其特征在于,所述方法还包括(108)加入0.01-0.03%(w/v)生育酚、0.01%-0.03%(w/v)烟酸和0.01%-0.03%(w/v)三磷酸腺苷。
9.根据权利要求7所述的用于制备肠外营养水性组合物的方法,其特征在于,所述胞苷二磷酸胆碱的浓度为0.4-0.6%(w/v)。
10.根据权利要求7所述的用于制备肠外营养水性组合物的方法,其特征在于,所述甘磷酸胆碱的浓度为0.4-0.6%(w/v)。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
MYPI2020005841A MY198026A (en) | 2020-11-06 | 2020-11-06 | Parenteral nutrition formulation and methods of preparation thereof |
MYPI2020005841 | 2020-11-06 | ||
PCT/IB2020/001100 WO2022096913A1 (en) | 2020-11-06 | 2020-12-31 | Parenteral nutrition formulation and methods of preparation thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114945373A true CN114945373A (zh) | 2022-08-26 |
CN114945373B CN114945373B (zh) | 2024-02-06 |
Family
ID=79867877
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202080005038.1A Active CN114945373B (zh) | 2020-11-06 | 2020-12-31 | 肠外营养制剂及其制备方法 |
Country Status (6)
Country | Link |
---|---|
US (1) | US20230364116A1 (zh) |
EP (1) | EP4013427A4 (zh) |
JP (1) | JP2023547772A (zh) |
CN (1) | CN114945373B (zh) |
AU (1) | AU2020476040B2 (zh) |
PH (1) | PH12021550453A1 (zh) |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070004670A1 (en) * | 1998-07-31 | 2007-01-04 | Richard Wurtman | Compositions containing citicoline, and methods of use thereof |
CN101940586A (zh) * | 2010-08-27 | 2011-01-12 | 北京中海康医药科技发展有限公司 | 一种高安全性注射用多烯磷脂酰胆碱及制备方法 |
US20110015154A1 (en) * | 2009-07-20 | 2011-01-20 | Kellermann Gottfried H | Supporting acetylcholine function |
WO2013151341A1 (en) * | 2012-04-04 | 2013-10-10 | Ami Pharm Co., Ltd. | Injectable composition comprising phosphatidylcholine and method for preparing thereof |
CN104080460A (zh) * | 2012-02-07 | 2014-10-01 | 啊美药业 | 不含脱氧胆酸钠的含磷脂酰胆碱的可注射组合物及其制备方法 |
US20170173065A1 (en) * | 2014-06-25 | 2017-06-22 | Korea Research Institute Of Bioscience And Biotechnology | Antiviral composition containing material involved in phosphatidylcholine snythesis pathway |
WO2019232044A1 (en) * | 2018-06-01 | 2019-12-05 | Baxter International Inc. | Parenteral nutrition formulation |
-
2020
- 2020-12-31 US US18/030,129 patent/US20230364116A1/en active Pending
- 2020-12-31 JP JP2023519344A patent/JP2023547772A/ja active Pending
- 2020-12-31 EP EP20870471.8A patent/EP4013427A4/en active Pending
- 2020-12-31 AU AU2020476040A patent/AU2020476040B2/en active Active
- 2020-12-31 CN CN202080005038.1A patent/CN114945373B/zh active Active
-
2021
- 2021-03-03 PH PH12021550453A patent/PH12021550453A1/en unknown
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070004670A1 (en) * | 1998-07-31 | 2007-01-04 | Richard Wurtman | Compositions containing citicoline, and methods of use thereof |
CN103599124A (zh) * | 2006-08-28 | 2014-02-26 | 麻省理工学院 | 含有cdp-胆碱的组合物及其使用方法 |
US20110015154A1 (en) * | 2009-07-20 | 2011-01-20 | Kellermann Gottfried H | Supporting acetylcholine function |
CN101940586A (zh) * | 2010-08-27 | 2011-01-12 | 北京中海康医药科技发展有限公司 | 一种高安全性注射用多烯磷脂酰胆碱及制备方法 |
CN104080460A (zh) * | 2012-02-07 | 2014-10-01 | 啊美药业 | 不含脱氧胆酸钠的含磷脂酰胆碱的可注射组合物及其制备方法 |
WO2013151341A1 (en) * | 2012-04-04 | 2013-10-10 | Ami Pharm Co., Ltd. | Injectable composition comprising phosphatidylcholine and method for preparing thereof |
US20170173065A1 (en) * | 2014-06-25 | 2017-06-22 | Korea Research Institute Of Bioscience And Biotechnology | Antiviral composition containing material involved in phosphatidylcholine snythesis pathway |
WO2019232044A1 (en) * | 2018-06-01 | 2019-12-05 | Baxter International Inc. | Parenteral nutrition formulation |
Non-Patent Citations (2)
Title |
---|
KAWAMURA, T等: ""Glycerophosphocholine enhances growth hormone secretion and fat oxidation in young adults"", 《NUTRITION》, pages 1122 - 1126 * |
严希康等: ""L-a-甘油磷脂酰胆碱的研发进展"", 《上海医药》, vol. 36, no. 15, pages 68 - 73 * |
Also Published As
Publication number | Publication date |
---|---|
CN114945373B (zh) | 2024-02-06 |
JP2023547772A (ja) | 2023-11-14 |
EP4013427A1 (en) | 2022-06-22 |
EP4013427A4 (en) | 2022-09-14 |
AU2020476040B2 (en) | 2024-05-23 |
PH12021550453A1 (en) | 2021-12-13 |
US20230364116A1 (en) | 2023-11-16 |
AU2020476040A1 (en) | 2023-03-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP2934189B1 (en) | Human milk oligosaccharides to ameliorate symptoms of stress | |
DK2658403T3 (en) | NUTRITION PRODUCT FOR IMPROVING TOLERANCE, Digestion, and Absorption of Lipid-Soluble Nutrient from an Infant, Toddler, or Child | |
CN103533921B (zh) | 用于治疗神经外伤的方法 | |
EP2861226B1 (en) | Nutritional product comprising decanoic acid and octanoic acid | |
EP3574771B1 (en) | Infant formula with special lipid architecture for promoting healthy growth | |
EP4136984A1 (en) | Lipid emulsion for parenteral nutrition comprising gpc | |
BR112020023199A2 (pt) | Emulsão de lípidos para administração parenteral | |
EP4149278A1 (en) | Infant formula | |
CN114945373B (zh) | 肠外营养制剂及其制备方法 | |
WO2022096913A1 (en) | Parenteral nutrition formulation and methods of preparation thereof | |
JP3981991B2 (ja) | 水性乳化栄養組成物及びその用途 | |
JP3773210B2 (ja) | トレハロース含有脂肪乳剤 | |
CN114554873A (zh) | 包含乳磷脂和蛋磷脂的营养组合物 | |
ITMI991458A1 (it) | Biopolimeri non digeribili e/o non assorbibili chimicamente derivatizzati quali antagonisti competitivi dell'assorbimento intestinale di nut |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for 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: 40080058 Country of ref document: HK |
|
GR01 | Patent grant | ||
GR01 | Patent grant |