CN110721151B - Simethicone compound liquid composition and preparation method and application thereof - Google Patents
Simethicone compound liquid composition and preparation method and application thereof Download PDFInfo
- Publication number
- CN110721151B CN110721151B CN201911201842.2A CN201911201842A CN110721151B CN 110721151 B CN110721151 B CN 110721151B CN 201911201842 A CN201911201842 A CN 201911201842A CN 110721151 B CN110721151 B CN 110721151B
- Authority
- CN
- China
- Prior art keywords
- simethicone
- gastric motility
- mass
- motility promoting
- liquid composition
- Prior art date
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- 229940083037 simethicone Drugs 0.000 claims abstract description 79
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 claims abstract description 62
- 239000000203 mixture Substances 0.000 claims abstract description 56
- 239000007788 liquid Substances 0.000 claims abstract description 48
- 239000003814 drug Substances 0.000 claims abstract description 45
- 230000001737 promoting effect Effects 0.000 claims abstract description 36
- 230000030135 gastric motility Effects 0.000 claims abstract description 34
- -1 simethicone compound Chemical class 0.000 claims abstract description 34
- 238000002360 preparation method Methods 0.000 claims abstract description 26
- 229960005302 itopride Drugs 0.000 claims abstract description 21
- QQQIECGTIMUVDS-UHFFFAOYSA-N N-[[4-[2-(dimethylamino)ethoxy]phenyl]methyl]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NCC1=CC=C(OCCN(C)C)C=C1 QQQIECGTIMUVDS-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229960005132 cisapride Drugs 0.000 claims abstract description 13
- DCSUBABJRXZOMT-UHFFFAOYSA-N cisapride Natural products C1CC(NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)C(OC)CN1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229960004085 mosapride Drugs 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- YPELFRMCRYSPKZ-UHFFFAOYSA-N 4-amino-5-chloro-2-ethoxy-N-({4-[(4-fluorophenyl)methyl]morpholin-2-yl}methyl)benzamide Chemical compound CCOC1=CC(N)=C(Cl)C=C1C(=O)NCC1OCCN(CC=2C=CC(F)=CC=2)C1 YPELFRMCRYSPKZ-UHFFFAOYSA-N 0.000 claims abstract description 10
- DCSUBABJRXZOMT-IRLDBZIGSA-N cisapride Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)OC)N1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-IRLDBZIGSA-N 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 45
- 238000003756 stirring Methods 0.000 claims description 28
- 239000008213 purified water Substances 0.000 claims description 25
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 21
- 239000000839 emulsion Substances 0.000 claims description 20
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 18
- 229920002125 Sokalan® Polymers 0.000 claims description 18
- 229960001631 carbomer Drugs 0.000 claims description 18
- 239000003995 emulsifying agent Substances 0.000 claims description 17
- 239000000796 flavoring agent Substances 0.000 claims description 15
- 239000002562 thickening agent Substances 0.000 claims description 15
- 238000002156 mixing Methods 0.000 claims description 14
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 claims description 12
- 235000010358 acesulfame potassium Nutrition 0.000 claims description 12
- 229960004998 acesulfame potassium Drugs 0.000 claims description 12
- 239000000619 acesulfame-K Substances 0.000 claims description 12
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 claims description 11
- 239000002202 Polyethylene glycol Substances 0.000 claims description 11
- 235000013355 food flavoring agent Nutrition 0.000 claims description 11
- 229920001223 polyethylene glycol Polymers 0.000 claims description 11
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 10
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 10
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims description 9
- 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 claims description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 8
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 8
- 238000011049 filling Methods 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 230000001105 regulatory effect Effects 0.000 claims description 8
- 235000010199 sorbic acid Nutrition 0.000 claims description 8
- 239000004334 sorbic acid Substances 0.000 claims description 8
- 229940075582 sorbic acid Drugs 0.000 claims description 8
- 239000000600 sorbitol Substances 0.000 claims description 8
- 238000010008 shearing Methods 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 229920000136 polysorbate Polymers 0.000 claims description 5
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 claims description 4
- 239000005711 Benzoic acid Substances 0.000 claims description 4
- 235000010233 benzoic acid Nutrition 0.000 claims description 4
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 4
- 239000000194 fatty acid Substances 0.000 claims description 4
- 229930195729 fatty acid Natural products 0.000 claims description 4
- 229920001519 homopolymer Polymers 0.000 claims description 4
- 235000010241 potassium sorbate Nutrition 0.000 claims description 4
- 239000004302 potassium sorbate Substances 0.000 claims description 4
- 229940069338 potassium sorbate Drugs 0.000 claims description 4
- 206010000059 abdominal discomfort Diseases 0.000 claims description 3
- 239000000022 bacteriostatic agent Substances 0.000 claims description 3
- 230000002496 gastric effect Effects 0.000 claims description 3
- 229950008882 polysorbate Drugs 0.000 claims description 3
- 229940085605 saccharin sodium Drugs 0.000 claims description 3
- 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 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- 229960004365 benzoic acid Drugs 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 2
- 235000010234 sodium benzoate Nutrition 0.000 claims description 2
- 239000004299 sodium benzoate Substances 0.000 claims description 2
- 229960003885 sodium benzoate Drugs 0.000 claims description 2
- 229940100515 sorbitan Drugs 0.000 claims description 2
- 229960002920 sorbitol Drugs 0.000 claims description 2
- 235000010356 sorbitol Nutrition 0.000 claims description 2
- 230000009429 distress Effects 0.000 claims 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims 1
- 229960005420 etoposide Drugs 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 239000003921 oil Substances 0.000 description 17
- 230000000052 comparative effect Effects 0.000 description 16
- 238000009472 formulation Methods 0.000 description 11
- 241000234295 Musa Species 0.000 description 8
- 235000018290 Musa x paradisiaca Nutrition 0.000 description 8
- 230000000968 intestinal effect Effects 0.000 description 8
- 206010000060 Abdominal distension Diseases 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000011521 glass Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 201000006549 dyspepsia Diseases 0.000 description 4
- 235000019634 flavors Nutrition 0.000 description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 239000007968 orange flavor Substances 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000013329 compounding Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 2
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 2
- 102000014630 G protein-coupled serotonin receptor activity proteins Human genes 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 208000028659 discharge Diseases 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000004945 emulsification Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 238000005187 foaming Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000010355 oscillation Effects 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000008855 peristalsis Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 208000036649 Dysbacteriosis Diseases 0.000 description 1
- 208000027244 Dysbiosis Diseases 0.000 description 1
- 206010015137 Eructation Diseases 0.000 description 1
- 206010061958 Food Intolerance Diseases 0.000 description 1
- 206010067715 Gastrointestinal sounds abnormal Diseases 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- XINCECQTMHSORG-UHFFFAOYSA-N Isoamyl isovalerate Chemical compound CC(C)CCOC(=O)CC(C)C XINCECQTMHSORG-UHFFFAOYSA-N 0.000 description 1
- 229920002675 Polyoxyl Polymers 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
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
- IYFATESGLOUGBX-YVNJGZBMSA-N Sorbitan monopalmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O IYFATESGLOUGBX-YVNJGZBMSA-N 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 208000019790 abdominal distention Diseases 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 210000003815 abdominal wall Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 239000012490 blank solution Substances 0.000 description 1
- 238000004061 bleaching Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000004913 chyme Anatomy 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 230000007140 dysbiosis Effects 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000003736 gastrointestinal content Anatomy 0.000 description 1
- 230000005176 gastrointestinal motility Effects 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000012088 reference solution Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000037152 sensory function Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
-
- 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4468—Non condensed piperidines, e.g. piperocaine having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- 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
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Inorganic Chemistry (AREA)
- Nutrition Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The application relates to a simethicone compound liquid composition, a preparation method and application thereof, wherein the simethicone compound liquid composition comprises the following components: the medicament comprises simethicone and a gastric motility promoting medicament or pharmaceutically acceptable salt thereof, wherein the gastric motility promoting medicament is one or two of itopride, mosapride and cisapride, and the mass ratio of the simethicone to the gastric motility promoting medicament or the pharmaceutically acceptable salt thereof is 10-40:1. The simethicone and the gastric motility promoting medicine are compounded according to a specific proportion, and are prepared into a liquid preparation form, so that the defoaming capability is enhanced, defoaming can be completed only by 3-5 seconds, meanwhile, the stability is better, and the better preparation form and defoaming capability can be maintained after the simethicone and the gastric motility promoting medicine are stored for 30 days.
Description
Technical Field
The application relates to the technical field of medicines, in particular to a simethicone compound liquid composition, a preparation method and application thereof.
Background
Functional abdominal distension is a kind of functional bowel disease, often accompanied by poor appetite, eructation, borborygmus, increased exhaust and other symptoms, is not rare clinically, mainly is a feeling of repeated abdominal distension, accompanied by or not accompanied by measurable increase of abdominal circumference, and no known effective treatment method exists at present. The etiology and pathogenesis of the disease are not completely elucidated, and recent theories comprise accumulation of intestinal gas, food intolerance, intestinal fluid retention, weak abdominal wall muscles, abnormal visceral sensory and motor functions, psychological factors and the like. Studies show that the functional abdominal distension patient has a near-end intestinal gas discharge disorder, the near-end intestinal gas accumulation phenomenon exists, and the intestinal gas is increased in the functional abdominal distension patientHas an important role in pathogenesis. The gas in the stomach and intestine comprises N 2 、O 2 、CO 2 、H 2 、CH 4 Trace gas. Dyspepsia (caused by various factors affecting absorption function such as food, digestive enzyme change, dysbacteriosis, bile secretion, etc.) can cause intestinal gas change, and cause intestinal peristalsis disorder, and further cause abdominal distention, abdominal pain, etc.
Simethicone acts as a stable surfactant to modify and break down the surface tension of air bubbles present in chyme and mucus in the digestive tract, and the released gas may be absorbed by the intestinal wall or expelled by peristalsis. The simethicone is mainly prepared by physically mixing activated simethicone and silicon dioxide, has no physiological activity, is safe and nontoxic, can be suitable for wide crowds, and has the defoaming effect of tens of times of simethicone.
Common gastrointestinal motility agents such as itopride, mosapride, cisapride, etc. for regulating and promoting gas discharge from the gastrointestinal tract are 5-hydroxytryptamine receptor agonists, which are widely used clinically for functional dyspepsia and gastrointestinal discomfort, etc. by exciting the 5-hydroxytryptamine receptor of the inter-muscular nerve plexus, stimulating acetylcholine release, enhancing gastric and duodenal motility, promoting gastrointestinal emptying, enhancing clearance of gastrointestinal contents, and the like.
Disclosure of Invention
In order to solve the problems in the prior art, the application provides a simethicone compound liquid composition, and a preparation method and application thereof.
In a first aspect, the present application provides a simethicone compound liquid composition comprising: the medicament comprises simethicone and a gastric motility promoting medicament or pharmaceutically acceptable salt thereof, wherein the gastric motility promoting medicament is one or two of itopride, mosapride and cisapride, and the mass ratio of the simethicone to the gastric motility promoting medicament or the pharmaceutically acceptable salt thereof is 10-40:1.
Further, when the gastric motility promoting medicine is itopride, the mass and volume percentage of simethicone is 2% -4%, and the mass and volume percentage of the gastric motility promoting medicine or the pharmaceutically acceptable salt thereof is 0.1% -0.2%.
The mass volume percent is the measure of the dissolution of a solid in a liquid, i.e., w (g)/v (mL), specifically, 1% of the mass volume percent is 1g of the dissolution of a solid in 100mL of liquid.
Further, when the gastric motility promoting medicine is cisapride, the mass and volume percentage of simethicone is 1% -2%, and the mass and volume percentage of the gastric motility promoting medicine or pharmaceutically acceptable salt thereof is 0.05% -0.1%.
Further, when the gastric motility promoting medicine is mosapride, the mass and volume percentage of simethicone is 0.5-1%, and the mass and volume percentage of the gastric motility promoting medicine or pharmaceutically acceptable salt thereof is 0.025-0.05%.
Further, the simethicone compound liquid composition also comprises the following components in percentage by mass and volume:
1 to 5 percent of emulsifying agent,
the emulsifier is at least two of polyethylene glycol monostearate, glyceryl monostearate, polysorbate and sorbitan fatty acid ester, preferably two emulsifiers are used in combination.
When simethicone and the gastric motility promoting medicine are prepared into liquid preparations, the simethicone and the gastric motility promoting medicine are simply dispersed in a solution with or without a thickening agent, and the preparation is easy to delaminate, so that the simethicone is separated out of the bleaching oil, and the technical problems of increasing the defoaming capability and the like cannot be achieved. Therefore, the simethicone and the gastric motility promoting medicine are prepared into emulsion forms by selecting proper emulsifying agents, so that the simethicone and the gastric motility promoting medicine can exist stably in vivo, and the effect is exerted.
Further, the composition also comprises the following components in percentage by mass and volume:
0.5 to 2 percent of thickening agent,
0.01 to 0.1 percent of bacteriostat,
5 to 20 percent of flavoring agent,
the thickener is one or two of carbomer homopolymer, carbomer copolymer and carbomer interpolymer; the bacteriostatic agent is one or two of sorbic acid, potassium sorbate, benzoic acid and sodium benzoate; the flavoring agent is one or more of sorbitol, acesulfame potassium, saccharin sodium and essence.
Preferably, the polyethylene glycol monostearate has a degree of polymerization of typically 10 to 40, which may also be referred to as polyoxyl stearate. The monoglyceride content of the glyceryl monostearate is more than 90%. The content of monoglyceride in the glyceryl monostearate is 40% -55%, and the type I or type II is preferred according to the fatty acid composition type. Polysorbate is commonly known as Tween, preferably model 40, 60, 80. The sorbitan fatty acid ester is preferably model 40, 60 or 80.
Preferably, the carbomer model is 974 or 971.
Preferably, sorbitol is selected from solid sorbitol and liquid sorbitol, the mass and volume percentages of which are based on the mass of the solid. The essence is preferably liquid essence, and the taste is one or two of banana essence, apple essence, orange essence and grape essence.
In a second aspect, the present application provides a method for preparing the simethicone compound liquid composition, which comprises the following steps: (1) Uniformly stirring and mixing simethicone and an emulsifier at 60-80 ℃ to obtain an oil phase;
(2) Stirring and dissolving gastric motility promoting medicine, correctant, antibacterial agent and appropriate amount of purified water to obtain water phase;
(3) Slowly adding the oil phase into the water phase, shearing and homogenizing to obtain emulsion;
(4) Adding the thickener into the purified water, stirring uniformly, adding the thickener into the emulsion obtained in the step (3), stirring uniformly, regulating the pH to 4.5-5.5, filtering and filling.
Preferably, in the step (1), the mixture is stirred and mixed uniformly at 65-75 ℃.
Preferably, the pH in step (4) is adjusted to 4.8-5.2.
The simethicone and the emulsifier are respectively stirred and mixed at 60-80 ℃ to obtain an oil phase, the gastric motility promoting medicine, the flavoring agent and the bacteriostat are prepared into a water phase, and the water phase, the flavoring agent and the bacteriostat are mixed uniformly and then added with the thickening agent to prepare the emulsion-form pharmaceutical preparation.
The application further provides application of the simethicone compound liquid composition or the preparation method in preparing medicines for preventing and treating gastrointestinal tract discomfort, wherein the gastrointestinal tract discomfort is preferably one or two of functional abdominal distension and dyspepsia.
The application further provides a pharmaceutical preparation for preventing and treating gastrointestinal discomfort, which comprises the simethicone compound liquid composition.
As a preferred embodiment, the application provides a simethicone compound liquid composition, which comprises the following components in percentage by mass and volume:
the application provides a simethicone compound liquid composition, a preparation method and application thereof, and the simethicone compound liquid composition has the following beneficial effects:
the simethicone and the gastric motility promoting medicine are compounded according to a specific proportion, and are prepared into a liquid emulsion form, so that the defoaming capability of the obtained preparation is obviously enhanced, defoaming can be finished only by 3-5 seconds, the stability is better, and the preparation still has better form and function after being stored for 30 days. The pharmaceutical preparation provided by the application is expected to improve clinical curative effect and reduce adverse reaction and patient compliance for patients inconvenient to take the solid preparation orally, such as postoperative abdominal distension, old people, children abdominal distension or dyspepsia.
Detailed Description
The following examples are illustrative of the application and are not intended to limit the scope of the application.
EXAMPLE 1 Simethicone and Itopride Compound liquid composition
TABLE 1 formulation of Simethicone and Itopride Compound liquid composition
| Composition of components | Dosage of | Mass volume percent |
| Itopride hydrochloride | 1g | 0.1％ |
| Simethicone | 40g | 4％ |
| Polyethylene glycol monostearate | 30g | 3％ |
| Glyceryl monostearate | 20g | 2％ |
| Carbomer 971 | 20g | 2％ |
| Sorbic acid | 0.5g | 0.05％ |
| Saccharin sodium salt | 50g | 5％ |
| Acesulfame potassium | 0.1g | 0.01％ |
| Banana flavor essence | 0.1g | 0.01％ |
| Sodium hydroxide | Proper amount of | Proper amount of |
| Purified water | About 830ml | 83％ |
In this example, using table 1 as a formulation, a pharmaceutical formulation was prepared by:
(1) Uniformly stirring and mixing simethicone and an emulsifier at 60-80 ℃ to obtain an oil phase;
(2) Stirring and dissolving itopride hydrochloride, a flavoring agent, a bacteriostat and 60% of purified water with the prescription amount to obtain a water phase;
(3) Slowly adding the oil phase into the water phase, shearing at 6000rpm for 30min, homogenizing for 1-4 times by a high pressure homogenizer at 0-300bar to obtain emulsion;
(4) Adding the thickener into purified water with the prescription amount of 40%, stirring uniformly, adding into the emulsion obtained in the step (3), stirring uniformly, regulating the pH to 5.0, adding banana essence, and filling into a glass molded medicine bottle with the volume of 50ml to obtain the finished product.
EXAMPLE 2 Simethicone and Itopride Compound liquid composition
Table 2 compounding ratio of Simethicone and Itopride
| Composition of components | Dosage of | Mass volume percent |
| Itopride hydrochloride | 2g | 0.2％ |
| Simethicone | 20g | 2％ |
| Tween 40 | 14g | 1.4％ |
| Span 40 | 16g | 1.6％ |
| Carbomer 974 | 10g | 1％ |
| Benzoic acid | 0.5g | 0.02％ |
| Liquid sorbitol | 100g | 10％ |
| Acesulfame potassium | 0.2g | 0.02％ |
| Orange flavor essence | 0.2g | 0.02％ |
| Sodium hydroxide | Proper amount of | Proper amount of |
| Purified water | About 840ml | 84％ |
The preparation method of this example is the same as that of example 1.
EXAMPLE 3 Simethicone and Mosapride Compound liquid composition
TABLE 3 formulation of Simethicone and Mosapride Compound liquid composition
| Composition of components | Dosage of | Mass volume percent |
| Mosapride hydrochloride | 0.5g | 0.05％ |
| Simethicone | 5g | 0.5％ |
| Polyethylene glycol monostearate | 6g | 0.6％ |
| Glyceryl monostearate | 4g | 0.4％ |
| Carbomer copolymers | 20g | 2％ |
| Potassium sorbate | 0.5g | 0.05％ |
| Sorbitol | 80g | 8％ |
| Acesulfame potassium | 0.1g | 0.01％ |
| Orange flavor essence | 0.1g | 0.01％ |
| Sodium hydroxide | Proper amount of | Proper amount of |
| Purified water | About 880ml | 88％ |
In this example, using table 3 as a formulation, a pharmaceutical formulation was prepared by:
(1) Uniformly stirring and mixing simethicone and an emulsifier at 65-75 ℃ to obtain an oil phase;
(2) Mixing and dissolving mosapride hydrochloride, a flavoring agent, a bacteriostatic agent and 70% of purified water with the prescription amount to obtain a water phase;
(3) Slowly adding the oil phase into the water phase, shearing at 8000rpm for 30min, homogenizing for 1-4 times by a high pressure homogenizer at 0-300bar to obtain emulsion;
(4) Adding the thickener into purified water with the prescription amount of 30%, stirring uniformly, adding into the emulsion obtained in the step (3), stirring uniformly, regulating the pH to 4.8-5.2, adding the edible essence, and filling into a glass molded medicine bottle with the volume of 10ml to obtain the finished product.
EXAMPLE 4 Simethicone and Mosapride Compound liquid composition
Table 4 formulation of Simethicone and Mosapride
| Composition of components | Dosage of | Mass volume percent |
| Mosapride hydrochloride | 0.25g | 0.025％ |
| Simethicone | 10g | 1％ |
| Polyethylene glycol monostearate | 4g | 0.4％ |
| Glyceryl monostearate | 6g | 0.6％ |
| Carbomer copolymers | 10g | 1％ |
| Sorbic acid | 0.1g | 0.01％ |
| Saccharin sodium salt | 100g | 10％ |
| Acesulfame potassium | 0.1g | 0.01％ |
| Orange flavor essence | 0.1g | 0.01％ |
| Sodium hydroxide | Proper amount of | Proper amount of |
| Purified water | About 870ml | 87％ |
The preparation method of this example is the same as that of example 3.
EXAMPLE 5 Simethicone and cisapride Compound liquid composition
Table 5 compounding ratio of Simethicone and cisapride
| Composition of components | Dosage of | Mass volume percent |
| Cisapride hydrochloride | 1g | 0.1％ |
| Simethicone | 10g | 1％ |
| Polyethylene glycol monostearate | 5g | 0.5％ |
| Glyceryl monostearate | 5g | 0.5％ |
| Carbomer homopolymers | 10g | 1％ |
| Potassium sorbate | 1g | 0.1％ |
| Liquid sorbitol | 200g | 20％ |
| Acesulfame potassium | 0.1g | 0.01％ |
| Apple-flavored essence | 0.1g | 0.01％ |
| Sodium hydroxide | Proper amount of | Proper amount of |
| Purified water | About 760ml | 76％ |
In this example, using table 5 as a formulation, a pharmaceutical formulation was prepared by:
(1) Uniformly stirring and mixing simethicone and an emulsifier at 65-75 ℃ to obtain an oil phase;
(2) Stirring and dissolving cisapride hydrochloride, a flavoring agent, a bacteriostat and 80% of purified water with the prescription amount to obtain a water phase;
(3) Slowly adding the oil phase into the water phase, shearing at 10000rpm for 20min, homogenizing for 1-4 times by a high pressure homogenizer at 0-300bar to obtain emulsion;
(4) Adding the thickener into purified water with the prescription amount of 20%, stirring uniformly, adding into the emulsion obtained in the step (3), stirring uniformly, regulating the pH to 4.8-5.2, adding the edible essence, and filling into 30ml glass molded medicine bottles to obtain the finished product.
EXAMPLE 6 Simethicone and cisapride Compound liquid composition
Table 6 formulation of Simethicone and cisapride Compound liquid composition
| Composition of components | Dosage of | Mass volume percent |
| Cisapride hydrochloride | 0.5g | 0.05％ |
| Simethicone | 20g | 2％ |
| Tween 80 | 8g | 0.8％ |
| Span 80 | 12g | 1.2％ |
| Carbomer homopolymers | 5g | 0.5％ |
| Benzoic acid | 0.5g | 0.05％ |
| Saccharin sodium salt | 120g | 12％ |
| Acesulfame potassium | 0.1g | 0.01％ |
| Orange flavor essence | 0.1g | 0.01％ |
| Sodium hydroxide | Proper amount of | Proper amount of |
| Purified water | About 830ml | 83％ |
The preparation method of this example is the same as that of example 5.
Comparative example 1
Table 7 formulation of Simethicone liquid composition
| Composition of components | Dosage of | Mass volume percent |
| Simethicone | 40g | 4％ |
| Polyethylene glycol monostearate | 5g | 0.5％ |
| Glyceryl monostearate | 5g | 0.5％ |
| Carbomer (carbomer) | 5g | 0.5％ |
| Sorbic acid | 0.1g | 0.01％ |
| Saccharin sodium salt | 50g | 5％ |
| Acesulfame potassium | 0.1g | 0.01％ |
| Banana flavor essence | 0.1g | 0.01％ |
| Sodium hydroxide | Proper amount of | Proper amount of |
| Purified water | About 870ml | 87％ |
The preparation method of this comparative example is the same as in example 1, except that simethicone is used to prepare the liquid composition.
Comparative example 2
TABLE 8 formulation of Itopride liquid compositions
The preparation method of the comparative example comprises the following steps:
mixing and stirring Itopride hydrochloride, simethicone, glycerol, xanthan gum and edible essence, adding appropriate amount of sodium hydroxide solution to adjust pH to 5.0, and filling into 30ml glass molded medicine bottle to obtain the final product.
Comparative example 3
Table 9 compounding ratio of Simethicone and Itopride
| Composition of components | Dosage of | Mass volume percent |
| Itopride hydrochloride | 0.5g | 0.05％ |
| Simethicone | 45g | 4.5％ |
| Polyethylene glycol monostearate | 30g | 3％ |
| Glyceryl monostearate | 20g | 2％ |
| Carbomer 971 | 20g | 2％ |
| Sorbic acid | 0.5g | 0.05％ |
| Saccharin sodium salt | 50g | 5％ |
| Acesulfame potassium | 0.1g | 0.01％ |
| Banana flavor essence | 0.1g | 0.01％ |
| Sodium hydroxide | Proper amount of | Proper amount of |
| Purified water | About 830ml | 83％ |
The comparative example was formulated in table 9 to prepare a pharmaceutical formulation by the following method:
(1) Uniformly stirring and mixing simethicone and an emulsifier at 60-80 ℃ to obtain an oil phase;
(2) Stirring and dissolving itopride hydrochloride, a flavoring agent, a bacteriostat and 60% of purified water with the prescription amount to obtain a water phase;
(3) Slowly adding the oil phase into the water phase, shearing at 6000rpm for 30min, homogenizing for 1-4 times by a high pressure homogenizer at 0-300bar to obtain emulsion;
(4) Adding the thickener into purified water with the prescription amount of 40%, stirring uniformly, adding into the emulsion obtained in the step (3), stirring uniformly, regulating the pH to 5.0, adding banana essence, and filling into a glass molded medicine bottle with the volume of 50ml to obtain the finished product.
Comparative example 4
Table 10 formulation of Simethicone and Itopride Compound liquid composition
| Composition of components | Dosage of | Mass volume percent |
| Itopride hydrochloride | 1g | 1％ |
| Simethicone | 40g | 4％ |
| Polyethylene glycol monostearate | 50g | 5％ |
| Carbomer 971 | 20g | 2％ |
| Sorbic acid | 0.5g | 0.05％ |
| Saccharin sodium salt | 50g | 5％ |
| Acesulfame potassium | 0.1g | 0.01％ |
| Banana flavor essence | 0.1g | 0.01％ |
| Sodium hydroxide | Proper amount of | Proper amount of |
| Purified water | About 830ml | 83％ |
The comparative example was formulated in table 10 to prepare a pharmaceutical formulation by the following method:
(1) Uniformly stirring and mixing simethicone and an emulsifier at 60-80 ℃ to obtain an oil phase;
(2) Stirring and dissolving itopride hydrochloride, a flavoring agent, a bacteriostat and 60% of purified water with the prescription amount to obtain a water phase;
(3) Slowly adding the oil phase into the water phase, shearing at 6000rpm for 30min, homogenizing for 1-4 times by a high pressure homogenizer at 0-300bar to obtain emulsion;
(4) Adding the thickener into purified water with the prescription amount of 40%, stirring uniformly, adding into the emulsion obtained in the step (3), stirring uniformly, regulating the pH to 5.0, adding banana essence, and filling into a glass molded medicine bottle with the volume of 50ml to obtain the finished product.
Experimental example 1
In this experimental example, examples 1 to 6 and comparative examples 1 to 4 were measured, and the measurement items include properties, pH, centrifugal stability, defoaming ability, viscosity, particle diameter, and content.
Centrifugal stability: taking a proper amount of the product, centrifuging for 15 minutes at a rotating speed of 4000 revolutions per minute by using a centrifugal machine with the radius of 10cm, and observing whether layering exists.
Defoaming ability: based on the USP standard of simethicone emulsion, the defoaming capability of the sample was examined using a more differentiated oscillation angle of 30 instead of 10.
Preparation of foaming liquid: weighing 10g of 9-poly-octanol and dissolving in 1000ml of purified water;
preparation of defoaming liquid: weighing 7.5ml of the sample, adding purified water to dilute to 30ml, and shaking uniformly;
and (3) measuring: 100ml of foaming liquid and 0.5ml to 250ml of defoaming liquid are taken and are put into a bottle with a plug, so that the bottle with the plug is fixed on a wrist oscillator, the oscillating frequency is 250 to 300 times per minute, the oscillating angle is 300, the oscillating radius is 10cm, the oscillating time is 10s, and the time from the end of oscillation to the appearance of no foam on the surface of the first part of foam liquid is recorded.
Viscosity: the third method of the general rule 0633 of the four parts of Chinese pharmacopoeia, namely dynamic viscosity method, is adopted for measurementHAKKE rheometer with a shear rate of 170S at 20℃ -1 Viscosity of (d) is provided.
Particle size: the measurement was performed by using a Markov Mastersize 2000 laser particle sizer, 500ml of water was used as a dispersion medium, and D10, D50 and D90 were recorded.
And (3) content measurement: taking about 2g of the liquid composition to be detected, adding 5ml of methanol, mixing uniformly by ultrasonic, adding 25ml of n-hexane, mixing uniformly by ultrasonic, and standing for layering. Adding 3g of anhydrous sodium sulfate into the upper n-hexane layer, uniformly mixing, centrifuging (4000 rpm) for 5 minutes, and taking supernatant as a sample solution; mixing polydimethylsiloxane reference 40mg with water 2ml, and collecting supernatant as reference solution; 2ml of water was taken and the supernatant was taken as a blank solution. Respectively taking the three solutions, and measuring the wavelength of 1260cm by infrared spectrophotometry -1 ±4cm -1 An absorption cell of 0.5mm was selected, and the absorbance values of the test sample solution and the control sample solution were measured.
TABLE 11 example Properties and functional comparison results
Table 12 comparative example properties and functional comparative results
Analysis of test results:
1. compared with comparative example 1, examples 1-6 are not layered after centrifugation at 4000rpm for 10min, have obviously better defoaming capability and more uniform particle size distribution under the condition of more severe vibration conditions, and have better content and viscosity results, so that the defoaming effect is better and the product quality and stability are better after the gastric motility promoting medicine is added.
2. From the results of comparative example 2, after simethicone and the gastric motility promoting medicine are prepared into a liquid mixture, a direct dispersion process is adopted, centrifugal stability and defoaming capability are obviously deteriorated, the content is smaller, and more oil drops are visually observed on the surface of the solution.
3. From the results of comparative example 3, too much simethicone added results in a decrease in content, a large amount of oil droplets appear in the form of the formulation, and too little gastric motility promoting agent is added, resulting in a significant deterioration in defoaming ability.
4. From the results of comparative example 4, the selection of the emulsifier of the application is also very important, and the single emulsifier is adopted for emulsification, and the total usage amount of the emulsifier is unchanged, but the emulsion is poor in emulsification effect, a large amount of oil drops appear on the surface of the emulsion after the emulsion is prepared into a liquid preparation form, the diameter distance of particle size distribution is increased, and the centrifugal stability and defoaming capability are obviously deteriorated.
Experimental example 2
In this experimental example, the samples prepared in examples 1 to 6 were placed in a stability test box at 60℃and sampled for 10 days, 20 days, and 30 days, respectively, to examine the stability.
Table 13 results of comparison of the Properties and functions of examples and comparative examples after 10 days, 20 days and 30 days of storage at 60℃
According to the results of the table, after the preparation is stored at 60 ℃ for 30 days, the preparation of the examples 1-6 still has good state and defoaming capability, which proves that the compound preparation of the application has good stability and is less prone to cause adverse reactions.
While the application has been described in detail in the foregoing general description and with reference to specific embodiments thereof, it will be apparent to one skilled in the art that modifications and improvements can be made thereto. Accordingly, such modifications or improvements may be made without departing from the spirit of the application and are intended to be within the scope of the application as claimed.
Claims (5)
1. Simethicone compound liquid composition is characterized by comprising the following components: the medicament comprises simethicone and a gastric motility promoting medicament or pharmaceutically acceptable salt thereof, wherein the gastric motility promoting medicament is one or two of itopride, mosapride and cisapride, and the mass ratio of the simethicone to the gastric motility promoting medicament or the pharmaceutically acceptable salt thereof is 10-40:1;
further comprises: the components with the following mass and volume percentages are as follows:
1-5% of emulsifying agent, 0.5-2% of thickening agent, 0.01-0.1% of bacteriostat and 5-20% of flavoring agent;
the emulsifier is at least two of polyethylene glycol monostearate, glyceryl monostearate, polysorbate and sorbitan fatty acid ester; the thickener is one or two of carbomer homopolymer, carbomer copolymer and carbomer interpolymer; the bacteriostatic agent is one or two of sorbic acid, potassium sorbate, benzoic acid and sodium benzoate; the flavoring agent is one or more of sorbitol, acesulfame potassium, saccharin sodium and essence;
when the etoposide is adopted as the gastric motility promoting medicine, the mass and volume percentage of simethicone is 2% -4%, and the mass and volume percentage of the gastric motility promoting medicine or pharmaceutically acceptable salt thereof is 0.1% -0.2%;
when the gastric motility promoting medicine is cisapride, the mass and volume percentage of simethicone is 1% -2%, and the mass and volume percentage of the gastric motility promoting medicine or pharmaceutically acceptable salt thereof is 0.05% -0.1%;
when the gastric motility promoting medicine is mosapride, the mass and volume percentage of simethicone is 0.5-1%, and the mass and volume percentage of the gastric motility promoting medicine or pharmaceutically acceptable salt thereof is 0.025-0.05%.
2. The simethicone compound liquid composition is characterized by comprising the following components in percentage by mass and volume:
simethicone 2% -4%
Itopride hydrochloride 0.1-0.2%
Polyethylene glycol monostearate 0.5-2.5%
0.5 to 2.5 percent of glycerin monostearate
Carbomer 971.5% -2%
Sorbic acid 0.01-0.1%
Saccharin sodium 5% -20%
0.01 to 0.1 percent of acesulfame potassium
Essence 0.01-0.1%
Purifying the water balance.
3. The preparation method of the simethicone compound liquid composition of claim 1, which is characterized by comprising the following steps:
(1) Uniformly stirring and mixing simethicone and an emulsifier at 60-80 ℃ to obtain an oil phase;
(2) Stirring and dissolving gastric motility promoting medicine, correctant, antibacterial agent and appropriate amount of purified water to obtain water phase;
(3) Slowly adding the oil phase into the water phase, shearing and homogenizing to obtain emulsion;
(4) Adding the thickener into the purified water, stirring uniformly, adding the thickener into the emulsion obtained in the step (3), stirring uniformly, regulating the pH to 4.5-5.5, filtering and filling.
4. Use of a simethicone compound liquid composition as claimed in claim 1 or 2 or a method for preparing the same as claimed in claim 3 in the preparation of a medicament for preventing and treating gastrointestinal discomfort.
5. A pharmaceutical formulation for preventing and treating gastrointestinal distress, comprising simethicone compound liquid composition according to claim 1 or 2.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| Publication number | Priority date | Publication date | Assignee | Title |
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Non-Patent Citations (1)
| Title |
|---|
| 西甲硅油联合莫沙必利治疗功能性消化不良;孙光裕等;《胃肠病学和肝病学杂志》;20080531;第17卷(第5期);第375-377页 * |
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