CN116585261A - Pharmaceutical liquid composition, preparation method and application thereof - Google Patents
Pharmaceutical liquid composition, preparation method and application thereof Download PDFInfo
- Publication number
- CN116585261A CN116585261A CN202310558081.6A CN202310558081A CN116585261A CN 116585261 A CN116585261 A CN 116585261A CN 202310558081 A CN202310558081 A CN 202310558081A CN 116585261 A CN116585261 A CN 116585261A
- Authority
- CN
- China
- Prior art keywords
- liquid composition
- sodium
- pharmaceutical liquid
- mixture
- amino acid
- 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
- 239000000203 mixture Substances 0.000 title claims abstract description 79
- 239000007788 liquid Substances 0.000 title claims abstract description 45
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 63
- 229960005077 sodium picosulfate Drugs 0.000 claims abstract description 37
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 31
- -1 amino acid compounds Chemical class 0.000 claims abstract description 31
- GOZDTZWAMGHLDY-UHFFFAOYSA-L sodium picosulfate Chemical compound [Na+].[Na+].C1=CC(OS(=O)(=O)[O-])=CC=C1C(C=1N=CC=CC=1)C1=CC=C(OS([O-])(=O)=O)C=C1 GOZDTZWAMGHLDY-UHFFFAOYSA-L 0.000 claims abstract description 31
- 235000001014 amino acid Nutrition 0.000 claims abstract description 26
- 239000000395 magnesium oxide Substances 0.000 claims abstract description 21
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims abstract description 21
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000004471 Glycine Substances 0.000 claims abstract description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims abstract description 13
- 235000004279 alanine Nutrition 0.000 claims abstract description 13
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 claims description 13
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 13
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims description 13
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 13
- 235000010234 sodium benzoate Nutrition 0.000 claims description 13
- 239000004299 sodium benzoate Substances 0.000 claims description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 241000289690 Xenarthra Species 0.000 claims description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 239000003755 preservative agent Substances 0.000 claims description 8
- 230000002335 preservative effect Effects 0.000 claims description 8
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims description 7
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims description 7
- 229960003415 propylparaben Drugs 0.000 claims description 7
- 239000003381 stabilizer Substances 0.000 claims description 7
- 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 6
- 239000003963 antioxidant agent Substances 0.000 claims description 6
- 230000003078 antioxidant effect Effects 0.000 claims description 6
- 235000006708 antioxidants Nutrition 0.000 claims description 6
- 235000003599 food sweetener Nutrition 0.000 claims description 6
- 230000002475 laxative effect Effects 0.000 claims description 6
- 239000003765 sweetening agent Substances 0.000 claims description 6
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 5
- VEUACKUBDLVUAC-UHFFFAOYSA-N [Na].[Ca] Chemical compound [Na].[Ca] VEUACKUBDLVUAC-UHFFFAOYSA-N 0.000 claims description 5
- 239000008141 laxative Substances 0.000 claims description 5
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 claims description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 3
- 108010011485 Aspartame Proteins 0.000 claims description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 3
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 3
- 235000016623 Fragaria vesca Nutrition 0.000 claims description 3
- 240000009088 Fragaria x ananassa Species 0.000 claims description 3
- 235000011363 Fragaria x ananassa Nutrition 0.000 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 239000004376 Sucralose Substances 0.000 claims description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 3
- 229930006000 Sucrose Natural products 0.000 claims description 3
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 3
- 244000290333 Vanilla fragrans Species 0.000 claims description 3
- 235000009499 Vanilla fragrans Nutrition 0.000 claims description 3
- 235000012036 Vanilla tahitensis Nutrition 0.000 claims description 3
- 229930003268 Vitamin C Natural products 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 3
- 239000000605 aspartame Substances 0.000 claims description 3
- 235000010357 aspartame Nutrition 0.000 claims description 3
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 3
- 229960003438 aspartame Drugs 0.000 claims description 3
- 239000003599 detergent Substances 0.000 claims description 3
- 235000013399 edible fruits Nutrition 0.000 claims description 3
- 239000003205 fragrance Substances 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- 239000001508 potassium citrate Substances 0.000 claims description 3
- 229960002635 potassium citrate Drugs 0.000 claims description 3
- 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 claims description 3
- 235000011082 potassium citrates Nutrition 0.000 claims description 3
- 239000001509 sodium citrate Substances 0.000 claims description 3
- 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 claims description 3
- 235000011083 sodium citrates Nutrition 0.000 claims description 3
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 3
- 229940001584 sodium metabisulfite Drugs 0.000 claims description 3
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 3
- 235000019408 sucralose Nutrition 0.000 claims description 3
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- 235000019154 vitamin C Nutrition 0.000 claims description 3
- 239000011718 vitamin C Substances 0.000 claims description 3
- 235000005976 Citrus sinensis Nutrition 0.000 claims description 2
- 240000002319 Citrus sinensis Species 0.000 claims description 2
- 235000010358 acesulfame potassium Nutrition 0.000 claims description 2
- 229960004998 acesulfame potassium Drugs 0.000 claims description 2
- 239000000619 acesulfame-K Substances 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 229960001855 mannitol Drugs 0.000 claims description 2
- 229960004793 sucrose Drugs 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims 1
- 230000000112 colonic effect Effects 0.000 claims 1
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 claims 1
- 239000003002 pH adjusting agent Substances 0.000 claims 1
- 239000011736 potassium bicarbonate Substances 0.000 claims 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims 1
- 235000015497 potassium bicarbonate Nutrition 0.000 claims 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims 1
- 238000001556 precipitation Methods 0.000 abstract description 18
- 239000004337 magnesium citrate Substances 0.000 abstract description 10
- 229960005336 magnesium citrate Drugs 0.000 abstract description 10
- 235000002538 magnesium citrate Nutrition 0.000 abstract description 10
- PLSARIKBYIPYPF-UHFFFAOYSA-H trimagnesium dicitrate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O PLSARIKBYIPYPF-UHFFFAOYSA-H 0.000 abstract description 10
- 239000012535 impurity Substances 0.000 abstract description 9
- 230000015556 catabolic process Effects 0.000 abstract description 6
- 238000006731 degradation reaction Methods 0.000 abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- 230000000052 comparative effect Effects 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 210000001072 colon Anatomy 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 6
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 6
- 229940067596 butylparaben Drugs 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 6
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 6
- 239000001630 malic acid Substances 0.000 description 6
- 235000011090 malic acid Nutrition 0.000 description 6
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 6
- 229960002216 methylparaben Drugs 0.000 description 6
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 6
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 6
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 5
- 229910001425 magnesium ion Inorganic materials 0.000 description 5
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 5
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 229940100688 oral solution Drugs 0.000 description 4
- 229960003885 sodium benzoate Drugs 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 3
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 3
- 239000000347 magnesium hydroxide Substances 0.000 description 3
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 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 2
- GPUPHPKQQRIVKX-UHFFFAOYSA-N S(=O)(=O)(O)O.N1=C(C=CC=C1)C(C1=CC=C(C=C1)[Na])C1=CC=C(C=C1)O Chemical compound S(=O)(=O)(O)O.N1=C(C=CC=C1)C(C1=CC=C(C=C1)[Na])C1=CC=C(C=C1)O GPUPHPKQQRIVKX-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- PNFSYNAUAPBVGF-UHFFFAOYSA-M sodium;phenyl sulfate Chemical compound [Na+].[O-]S(=O)(=O)OC1=CC=CC=C1 PNFSYNAUAPBVGF-UHFFFAOYSA-M 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000010257 thawing Methods 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 206010002153 Anal fissure Diseases 0.000 description 1
- 208000016583 Anus disease Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 208000009531 Fissure in Ano Diseases 0.000 description 1
- 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 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000799 cathartic agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000002052 colonoscopy Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000013872 defecation Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 208000014617 hemorrhoid Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 235000019629 palatability Nutrition 0.000 description 1
- 230000008855 peristalsis Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- CTYRPMDGLDAWRQ-UHFFFAOYSA-N phenyl hydrogen sulfate Chemical compound OS(=O)(=O)OC1=CC=CC=C1 CTYRPMDGLDAWRQ-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010268 sodium methyl p-hydroxybenzoate Nutrition 0.000 description 1
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
- A61K9/08—Solutions
-
- 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
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- 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
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
- A61K33/08—Oxides; Hydroxides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
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Abstract
The invention relates to a liquid pharmaceutical composition, a preparation method and application thereof. The pharmaceutical liquid composition comprises water, sodium picosulfate, magnesium oxide, citric acid and amino acid compounds; the amino acid compound is selected from one or a mixture of glycine and alanine. The pharmaceutical liquid composition can effectively inhibit magnesium citrate precipitation in a wide pH range, reduces the generation of sodium picosulfate degradation impurities, and is very stable in high and low temperature environments.
Description
Technical Field
The invention relates to the technical field of pharmaceutical preparations, in particular to a pharmaceutical liquid composition, a preparation method and application thereof.
Background
The sodium picosulfate has the structure shown in the formula (1), is a laxative synthesized by De Angeli company in Italy in the 60 th century, has a mild laxative effect on the mucous membrane of large intestine, and can be used for constipation of various forms and relieving defecation pain caused by hemorrhoids, anal fissure and the like.
The compound sodium picosulfate contains sodium picosulfate, magnesium oxide and citric acid, and is a dual cathartic agent, wherein the sodium picosulfate directly acts on colon mucous membrane to stimulate colon peristalsis; magnesium oxide reacts with citric acid to form magnesium citrate solution, which is an osmotic laxative, and can increase intestinal water. The medicine can be used for preparing intestinal tract cleaning before colonoscopy and X-ray examination.
Compound sodium picosulfate oral granule of Hui LingThe powder is marketed in FDA lot at the earliest of 7 and 16 in 2012, and is mixed with cold water before administration. However, when the drug is dissolved in water, some patients may feel inconvenient, and some patients who cannot recognize how to properly use may drink water after putting the powder into the mouth. In this case, the exothermic reaction that occurs when the powder is dissolved in water may burn the patient's mouth.
The compound sodium picosulfate oral solution solves the problem, but in the liquid preparation, magnesium oxide and citric acid are easy to react to generate magnesium citrate, and the magnesium citrate is easy to precipitate, so that the liquid preparation is unstable.
There has been reported a liquid pharmaceutical composition containing sodium picosulfate, magnesium oxide and citric acid, which is a liquid preparation in which the amount of precipitate tends to be reduced when the pH of the drug is kept low, however, in this case, sodium picosulfate is caused to becomeUnstable and produces impurity A (4- [ (pyridin-2-yl) (4-hydroxyphenyl) methyl)]Sodium phenyl sulfate). When malic acid is used as precipitation inhibitor, stable compound sodium picosulfate oral solution can be obtained when pH is controlled between 4.1-5.4, and the product (CLENPIQ) TM ) Has been marketed as a colon cleanser. The report also shows that malic acid can form a cyclic complex with magnesium ions, and the complex has good stability, so that the precipitation of magnesium hydroxide can be inhibited, and the effect of inhibiting the precipitation is better than that of other carboxylic acids. However, the liquid pharmaceutical composition requires a pH of 4.1 to 5.4, is very narrow in range, is unstable in a low-temperature environment, and has a high requirement on storage conditions.
Disclosure of Invention
Based on the above, the present invention aims to provide a pharmaceutical liquid composition which can effectively inhibit magnesium citrate precipitation in a wide pH range, reduce the generation of sodium picosulfate degradation impurities, and is very stable in both high and low temperature environments.
The technical proposal is as follows:
a pharmaceutical liquid composition comprising water, sodium picosulfate, magnesium oxide, citric acid, and an amino acid compound;
the amino acid compound is selected from glycineAnd alanine->One or a mixture of both.
In one embodiment, the molar ratio of sodium picosulfate, magnesium oxide, citric acid, and amino acid compound is (0.001-0.1): (10-200): (10-150): (10-200).
In one embodiment, the pharmaceutical liquid composition has a pH of 3.0 to 8.0.
In one embodiment, the pharmaceutical liquid composition further comprises pharmaceutically acceptable excipients.
In one embodiment, the auxiliary material is selected from one or more of a stabilizer, a preservative, a sweetener, a pH regulator, a fragrance and an antioxidant.
In one embodiment, the stabilizer is selected from one or both of disodium edentate and calcium sodium edentate.
In one embodiment, the preservative is selected from one or more of sodium benzoate, methylparaben, ethylparaben, propylparaben and butylparaben.
In one embodiment, the sweetener is selected from one or more of sucralose, sucrose, acesulfame k, mannitol, and aspartame.
In one embodiment, the pH regulator is selected from one or more of sodium hydroxide, potassium hydroxide, ammonia solution, triethanolamine, potassium citrate, sodium bicarbonate and sodium citrate.
In one embodiment, the flavoring agent is selected from one or more of orange essence, strawberry essence, orange essence, vanilla essence, and miscellaneous fruit essence.
In one embodiment, the antioxidant is selected from one or more of sodium metabisulfite and vitamin C.
The invention also provides a preparation method of the pharmaceutical liquid composition, which comprises the following steps:
mixing the water, sodium picosulfate, magnesium oxide, citric acid and amino acid compound.
In one embodiment, the mixing comprises:
mixing the magnesium oxide and citric acid in water to prepare a first mixture S1;
mixing the mixture S1 with an amino acid compound to prepare a mixture S2;
the mixture S2 was mixed with sodium picosulfate.
The invention also provides the use of a pharmaceutical liquid composition as described above for the preparation of a laxative.
The invention also provides application of the pharmaceutical liquid composition in preparing colon cleansing agents.
The invention has the following beneficial effects:
the inventor has found that glycine and/or alanine can be used as a precipitation inhibitor of the compound sodium picosulfate oral solution after a great deal of creative labor, and the effect of inhibiting precipitation is better than that of malic acid. It is hypothesized that the possible reasons are that glycine and/or alanine contain carboxyl and amino (belonging to short-chain small molecular amino acid), the oxygen atom of the carboxyl has lone pair electrons, the N atom of the amino has lone pair electrons, both can form metal organic complex with free magnesium ion, the short-chain small molecular amino acid can form annular complex with magnesium ion, and the effect of inhibiting magnesium hydroxide precipitation is good. In addition, the conditions for forming the metal organic complex are wide, the precipitation of magnesium citrate can be inhibited by glycine and/or alanine in a wide pH range (3.0-8.0), particularly in a high pH range, the generation of sodium picosulfate degradation impurity A (4- [ (pyridin-2-yl) (4-hydroxyphenyl) methyl ] phenyl sodium sulfate) is reduced, and meanwhile, the stability of the composition in high and low temperature conditions is obviously improved.
Through tests, the pharmaceutical liquid composition comprising water, sodium picosulfate, magnesium oxide, citric acid and the amino acid compound provided by the invention is very stable at the temperature of-20-60 ℃, has the same effect as a colon cleanser on the market, and has a wide application prospect.
Detailed Description
The present invention will be described in further detail with reference to specific examples. The present invention may be embodied in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.
Where the terms "comprising," "having," and "including" are used herein, it is intended to cover a non-exclusive inclusion, unless a specifically defined term is used, such as "consisting of … … only," etc., another component may be added.
The words "preferably," "more preferably," "more preferably," and the like, refer to embodiments of the invention that may provide certain benefits in some instances. However, other embodiments may be preferred under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful, nor is it intended to exclude other embodiments from the scope of the invention. That is, in the present invention, "preferable", "more preferable", etc. are merely description of embodiments or examples that are more effective, but do not limit the scope of the present invention.
In the present invention, "further", "still further", "particularly" and the like are used for descriptive purposes to indicate differences in content but should not be construed as limiting the scope of the invention.
In the present invention, "at least one" means one or more, such as one, two or more. The meaning of "plural" or "several" means at least two, for example, two, three, etc., and the meaning of "multiple" means at least two, for example, two, three, etc., unless specifically defined otherwise. In the description of the present invention, the meaning of "several" means at least one, such as one, two, etc., unless specifically defined otherwise.
When a range of values is disclosed herein, the range is considered to be continuous and includes both the minimum and maximum values for the range, as well as each value between such minimum and maximum values. Further, when a range refers to an integer, each integer between the minimum and maximum values of the range is included. Further, when multiple range description features or characteristics are provided, the ranges may be combined. In other words, unless otherwise indicated, all ranges disclosed herein are to be understood to include any and all subranges subsumed therein.
All steps of the present invention may be performed sequentially or randomly unless otherwise specified. For example, the method comprises steps (a) and (b), meaning that the method may comprise steps (a) and (b) performed sequentially, or may comprise steps (b) and (a) performed sequentially. For example, the method may further comprise step (c), meaning that step (c) may be added to the method in any order, e.g., the method may comprise steps (a), (b) and (c), steps (a), (c) and (b), steps (c), (a) and (b), etc.
Unless mentioned to the contrary, singular terms may include plural and are not to be construed as being one in number.
The invention provides a pharmaceutical liquid composition which can effectively inhibit magnesium citrate precipitation in a wider pH range, reduce the generation of sodium picosulfate degradation impurities and is very stable in high and low temperature environments.
The technical proposal is as follows:
a pharmaceutical liquid composition comprising water, sodium picosulfate, magnesium oxide, citric acid, and an amino acid compound;
the amino acid compound is selected from glycineAnd alanine->One or a mixture of both.
According to research, glycine and/or alanine can be used as a precipitation inhibitor of the compound sodium picosulfate oral solution, and the effect of inhibiting precipitation is superior to that of malic acid. It is hypothesized that the possible reasons are that glycine and alanine contain carboxyl and amino groups (belonging to short-chain small molecular amino acids), the oxygen atoms of the carboxyl have lone pair electrons, the N atoms of the amino groups have lone pair electrons, both can form metal organic complexes with free magnesium ions, the short-chain small molecular amino acids can form annular complexes with the magnesium ions, and the effect of inhibiting magnesium hydroxide precipitation is good. In addition, the conditions for forming the metal organic complex are wide, the precipitation of magnesium citrate can be inhibited by glycine and/or alanine in a wide pH range (3.0-8.0), particularly in a high pH range, the generation of sodium picosulfate degradation impurity A (4- [ (pyridin-2-yl) (4-hydroxyphenyl) methyl ] phenyl sodium sulfate) is reduced, and meanwhile, the stability of the composition in high and low temperature conditions is obviously improved.
It will be appreciated that in the present invention, the amino acid compound is selected fromGlycine, orAlanine, or a mixture of glycine and alanine, such a precipitation inhibitor is capable of significantly inhibiting the precipitation of magnesium citrate and reducing the sodium picosulfate degradation impurity a (4- [ (pyridin-2-yl) (4-hydroxyphenyl) methyl)]Sodium phenylsulfate) and at the same time, the stability of the composition at high and low temperatures is significantly improved. Further, when the amino acid compound is a mixture of glycine and alanine, the molar ratio of the two is 1 (0.01-99.9), including but not limited to 1:0.01, 1:0.05, 1:0.1, 1:0.5, 1:1, 1:2, 1:5, 1:8, 1:10, 1:15, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90, 1:95, 1:99.9.
In one embodiment, the molar ratio of sodium picosulfate, magnesium oxide, citric acid, and amino acid compound is (0.001-0.1): (10-200): (10-150): (10-200), including but not limited to: 0.001:10:10: 10. 0.001:100:10: 10. 0.001:200:10: 10. 0.001:100:100: 10. 0.001:100:150: 10. 0.001:100:150: 100. 0.001:100:150: 200. 0.01:10:10: 10. 0.01:100:10: 10. 0.01:200:10: 10. 0.01:100:100: 10. 0.01:100:150: 10. 0.01:100:150: 100. 0.01:100:150: 200. 0.05:10:10: 10. 0.05:100:10: 10. 0.05:200:10: 10. 0.05:100:100: 10. 0.05:100:150: 10. 0.05:100:150: 100. 0.05:100:150: 200. 0.1:10:10: 10. 0.1:100:10: 10. 0.1:200:10: 10. 0.1:100:100: 10. 0.1:100:150: 10. 0.1:100:150:100 and 0.1:100:150:200. further, referring to the above, when the amino acid compound is a mixture of glycine and alanine, the molar ratio of the two is 1 (0.01-99.9), including but not limited to 1:0.01, 1:0.05, 1:0.1, 1:0.5, 1:1, 1:2, 1:5, 1:8, 1:10, 1:15, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90, 1:95, 1:99.9.
In one embodiment, the pharmaceutical liquid composition further comprises pharmaceutically acceptable excipients.
In one embodiment, the auxiliary material is selected from one or more of a stabilizer, a preservative, a sweetener, a pH regulator, a fragrance and an antioxidant.
In one embodiment, the stabilizer is selected from one or two of disodium edentate and calcium sodium edentate, which significantly enhances the stability and oxidation resistance of the drug. It will be appreciated that the stabilizer is selected from disodium edentate, or calcium sodium edentate, or a mixture of disodium edentate and calcium sodium edentate.
In one embodiment, the preservative is selected from one or more of sodium benzoate, methylparaben, ethylparaben, propylparaben and butylparaben, which significantly improves the preservative and storage properties of the drug. It will be appreciated that the number of components, the preservative is selected from sodium benzoate, or methyl or ethyl or propyl or butyl or a mixture of sodium benzoate and methyl or a mixture of sodium benzoate and ethyl or a mixture of sodium benzoate and propyl or a mixture of sodium benzoate and butyl or a mixture of sodium benzoate, methyl or ethyl or a mixture of sodium benzoate, methyl or ethyl or sodium benzoate, methyl or ethyl or methyl or ethyl and mixtures of propyl paraben, or sodium benzoate, methyl paraben, and butyl paraben, or mixtures of methyl paraben, ethyl paraben, and propyl paraben, or mixtures of methyl paraben, ethyl paraben, and butyl paraben, or mixtures of ethyl paraben, propyl paraben, and butyl paraben, or mixtures of sodium benzoate, methyl paraben, ethyl paraben, propyl paraben, and butyl paraben.
In one embodiment, the sweetener is selected from one or more of sucralose, sucrose, acesulfame potassium, mannitol and aspartame, which significantly improves the palatability of the medicament and improves the sensory experience.
In one embodiment, the pH regulator is selected from one or more of sodium hydroxide, potassium hydroxide, ammonia solution, triethanolamine, potassium citrate, sodium bicarbonate and sodium citrate, and the pH is regulated.
In one embodiment, the aromatic is selected from one or more of sweet orange essence, strawberry essence, orange essence, vanilla essence and miscellaneous fruit essence, which can significantly improve the smell of the medicine and enhance the sensory experience.
In one embodiment, the antioxidant is one or more selected from sodium metabisulfite and vitamin C, so that the oxidation resistance of the medicine is remarkably improved and the medicine is more stable.
In one embodiment, the pharmaceutical liquid composition has a pH of 3.0 to 8.0, including but not limited to 3.0, 3.5, 4.0, 4.2, 4.4, 4.5, 4.9, 5.0, 5.2, 5.4, 5.5, 5.9, 6.0, 6.2, 6.4, 6.5, 6.9, 7.0, and 8.0. Further, the pH of the pharmaceutical liquid composition is 4.5 to 6.0.
The invention also provides a preparation method of the pharmaceutical liquid composition, which comprises the following steps:
mixing the water, sodium picosulfate, magnesium oxide, citric acid and amino acid compound.
In one embodiment, the mixing comprises:
mixing the magnesium oxide and citric acid in water to prepare a first mixture S1;
mixing the mixture S1 with an amino acid compound to prepare a mixture S2;
the mixture S2 was mixed with sodium picosulfate.
Further, the preparation method of the pharmaceutical liquid composition also containing pharmaceutically acceptable auxiliary materials comprises the following steps:
mixing the magnesium oxide and citric acid in water to prepare a first mixture S1;
mixing the mixture S1 with an amino acid compound to prepare a mixture S2;
mixing the mixture S2 with pharmaceutically acceptable auxiliary materials to prepare a mixture S3;
the mixture S3 was mixed with sodium picosulfate.
The invention also provides the use of a pharmaceutical liquid composition as described above for the preparation of a laxative.
The invention also provides application of the pharmaceutical liquid composition in preparing colon cleansing agents.
The invention is further illustrated below with reference to specific examples.
Examples 1 to 14 and comparative examples 1 to 7
The following examples provide liquid compositions containing sodium picosulfate and methods for preparing the same, as follows:
(1) The prescriptions of examples 1 to 14 are shown in the following tables 1 to 2, and the prescriptions of comparative examples 1 to 7 are shown in the following table 3.
(2) The preparation method comprises the following steps: dissolving magnesium oxide and citric acid in the amount shown in Table 1-3, adding glycine, adding other adjuvants, adding sodium picosulfate, dissolving, and adjusting pH to 4.9 with 3mol/L sodium hydroxide solution.
TABLE 1
TABLE 2
TABLE 3 Table 3
And (3) testing:
1. the contents of sodium picosulfate, magnesium oxide, and citric acid in examples 1 to 14 and comparative examples 1 to 7 were measured by liquid chromatography, respectively, and the results are shown in table 4 below.
TABLE 4 Table 4
As can be seen from table 4, there was no significant difference between the contents of the main components in examples 1 to 14 and comparative examples 2 to comparative example, compared to comparative example 1. Thus, it can be considered that the liquid compositions of examples 1 to 14 of the present invention and the products (CLENPIQ) obtained in the U.S. market TM ) As a colon cleanser with the same or similar effect.
2. The pharmaceutical liquid compositions prepared in examples 1 to 14 and comparative examples 1 to 7 were allowed to stand at a high temperature (60 ℃) to examine the changes of comparative sodium picosulfate impurity A (sodium 4- [ (pyridin-2-yl) (4-hydroxyphenyl) methyl ] phenylsulfate) for 30 days, and the results are shown in Table 5 below.
TABLE 5
As is clear from Table 5, the effect of reducing the formation of impurity A was superior to that of malic acid, tartaric acid, malonic acid, succinic acid, serine and tryptophan when the liquid composition contained one or both of glycine and alanine at a higher pH under high temperature conditions.
3. The pharmaceutical liquid compositions prepared in examples 1 to 14 and comparative examples 1 to 7 were subjected to freeze thawing cycles (-20 ℃ C., 25 ℃ C. Cycles) to examine 10 cycles versus magnesium citrate precipitation changes, and the results are shown in Table 6 below.
TABLE 6
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As can be seen from Table 6, glycine and alanine have a better effect of inhibiting precipitation during the freeze-thawing cycle than acids such as malic acid, tartaric acid, malonic acid, succinic acid, serine and tryptophan.
The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.
Claims (10)
1. A pharmaceutical liquid composition comprising water, sodium picosulfate, magnesium oxide, citric acid, and an amino acid compound;
the amino acid compound is selected from one or a mixture of glycine and alanine.
2. The pharmaceutical liquid composition according to claim 1, wherein the molar ratio of sodium picosulfate, magnesium oxide, citric acid and amino acid compound is (0.001-0.1): (10-200): (10-150): (10-200);
concentration of sodium picosulfate in the pharmaceutical liquid composition: 0.01mg/ml to 0.2mg/ml.
3. The pharmaceutical liquid composition of claim 1, wherein the pH of the pharmaceutical liquid composition is from 3.0 to 8.0.
4. A pharmaceutical liquid composition according to any one of claims 1 to 3, further comprising a pharmaceutically acceptable adjuvant.
5. The pharmaceutical liquid composition according to claim 4, wherein the adjuvant is selected from one or more of a stabilizer, a preservative, a sweetener, a pH adjuster, a fragrance, and an antioxidant.
6. The pharmaceutical liquid composition of claim 5, wherein the stabilizer is selected from one or both of disodium edentate and sodium calcium edentate; and/or
The preservative is one or more selected from sodium benzoate, methyl hydroxybenzoate, ethyl hydroxybenzoate, propyl hydroxybenzoate and butyl hydroxybenzoate; and/or
The sweetener is one or more selected from sucralose, sucrose, acesulfame potassium, mannitol and aspartame; and/or
The pH regulator is one or more selected from sodium hydroxide, potassium hydroxide, ammonia solution, triethanolamine, potassium citrate, sodium bicarbonate, potassium bicarbonate and sodium citrate; and/or
The aromatic is one or more selected from sweet orange essence, strawberry essence, orange essence, vanilla essence and miscellaneous fruit essence; and/or
The antioxidant is one or more selected from sodium metabisulfite and vitamin C.
7. A process for the preparation of a pharmaceutical liquid composition according to any one of claims 1 to 6, comprising the steps of:
mixing the water, sodium picosulfate, magnesium oxide, citric acid and amino acid compound.
8. The method of preparing a pharmaceutical liquid composition according to claim 7, wherein the mixing comprises:
mixing the magnesium oxide and citric acid in water to prepare a first mixture S1;
mixing the mixture S1 with an amino acid compound to prepare a mixture S2;
the mixture S2 was mixed with sodium picosulfate.
9. Use of a pharmaceutical liquid composition according to any one of claims 1 to 6 for the preparation of a laxative.
10. Use of a pharmaceutical liquid composition according to any one of claims 1 to 6 for the preparation of a colonic cleansing agent.
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| JP2004292356A (en) * | 2003-03-27 | 2004-10-21 | Rohto Pharmaceut Co Ltd | Preparation for catharsis |
| WO2015056897A1 (en) * | 2013-10-17 | 2015-04-23 | 강윤식 | Intestine cleansing composition |
| CN105658212A (en) * | 2013-10-17 | 2016-06-08 | 姜允植 | Bowel cleansing composition |
| US20180015078A1 (en) * | 2016-07-08 | 2018-01-18 | Ferring B.V. | Stabilized liquid formulations containing picosulfate |
| CN109310774A (en) * | 2015-08-17 | 2019-02-05 | 费林股份公司 | Containing can sulfate and magnesium citrate liquid preparation |
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| JP2004292356A (en) * | 2003-03-27 | 2004-10-21 | Rohto Pharmaceut Co Ltd | Preparation for catharsis |
| WO2015056897A1 (en) * | 2013-10-17 | 2015-04-23 | 강윤식 | Intestine cleansing composition |
| CN105658212A (en) * | 2013-10-17 | 2016-06-08 | 姜允植 | Bowel cleansing composition |
| CN109310774A (en) * | 2015-08-17 | 2019-02-05 | 费林股份公司 | Containing can sulfate and magnesium citrate liquid preparation |
| US20180015078A1 (en) * | 2016-07-08 | 2018-01-18 | Ferring B.V. | Stabilized liquid formulations containing picosulfate |
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