CN115569146A - Pharmaceutical composition and preparation method and application thereof - Google Patents
Pharmaceutical composition and preparation method and application thereof Download PDFInfo
- Publication number
- CN115569146A CN115569146A CN202211530673.9A CN202211530673A CN115569146A CN 115569146 A CN115569146 A CN 115569146A CN 202211530673 A CN202211530673 A CN 202211530673A CN 115569146 A CN115569146 A CN 115569146A
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- Prior art keywords
- omeprazole
- simethicone
- hydrotalcite
- composition
- parts
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- 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.)
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- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 5
- 239000000203 mixture Substances 0.000 claims abstract description 50
- 229960000381 omeprazole Drugs 0.000 claims abstract description 46
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 claims abstract description 43
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 claims abstract description 36
- 229960001545 hydrotalcite Drugs 0.000 claims abstract description 36
- 229910001701 hydrotalcite Inorganic materials 0.000 claims abstract description 36
- 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 35
- 229940083037 simethicone Drugs 0.000 claims abstract description 34
- 210000004211 gastric acid Anatomy 0.000 claims abstract description 23
- 239000003814 drug Substances 0.000 claims abstract description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 13
- 238000003756 stirring Methods 0.000 claims description 13
- 239000002994 raw material Substances 0.000 claims description 11
- 239000002562 thickening agent Substances 0.000 claims description 10
- 238000000227 grinding Methods 0.000 claims description 9
- 239000000084 colloidal system Substances 0.000 claims description 8
- 239000002245 particle Substances 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 7
- 239000008213 purified water Substances 0.000 claims description 6
- UJOHNXQDVUADCG-UHFFFAOYSA-L aluminum;magnesium;carbonate Chemical compound [Mg+2].[Al+3].[O-]C([O-])=O UJOHNXQDVUADCG-UHFFFAOYSA-L 0.000 claims description 5
- 206010016766 flatulence Diseases 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 230000008961 swelling Effects 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229940100692 oral suspension Drugs 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 14
- 230000000694 effects Effects 0.000 abstract description 13
- 239000011777 magnesium Substances 0.000 abstract description 6
- 229910052749 magnesium Inorganic materials 0.000 abstract description 6
- 239000002253 acid Substances 0.000 abstract description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 abstract description 4
- 238000006386 neutralization reaction Methods 0.000 abstract description 2
- 239000000725 suspension Substances 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 230000002496 gastric effect Effects 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 6
- 238000005538 encapsulation Methods 0.000 description 6
- 239000007789 gas Substances 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- MQEUGMWHWPYFDD-UHFFFAOYSA-N magnesium;6-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-1h-benzimidazole Chemical compound [Mg].N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C MQEUGMWHWPYFDD-UHFFFAOYSA-N 0.000 description 5
- 229960003117 omeprazole magnesium Drugs 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 4
- 239000002131 composite material Substances 0.000 description 4
- -1 compound omeprazole sodium bicarbonate Chemical class 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 208000007107 Stomach Ulcer Diseases 0.000 description 3
- 230000003187 abdominal effect Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 210000001156 gastric mucosa Anatomy 0.000 description 3
- 201000005917 gastric ulcer Diseases 0.000 description 3
- 239000007902 hard capsule Substances 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 239000011859 microparticle Substances 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 230000035699 permeability Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000004062 sedimentation Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 102000057297 Pepsin A Human genes 0.000 description 2
- 108090000284 Pepsin A Proteins 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 229940069428 antacid Drugs 0.000 description 2
- 239000003159 antacid agent Substances 0.000 description 2
- 229960001631 carbomer Drugs 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 229940126534 drug product Drugs 0.000 description 2
- 208000000718 duodenal ulcer Diseases 0.000 description 2
- 201000006549 dyspepsia Diseases 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 238000009505 enteric coating Methods 0.000 description 2
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 229940111202 pepsin Drugs 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 238000003825 pressing Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000013049 sediment Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- 206010000060 Abdominal distension Diseases 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 206010063655 Erosive oesophagitis Diseases 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 208000031361 Hiccup 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
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 201000008629 Zollinger-Ellison syndrome Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 239000012792 core layer Substances 0.000 description 1
- PGZIKUPSQINGKT-UHFFFAOYSA-N dialuminum;dioxido(oxo)silane Chemical compound [Al+3].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O.[O-][Si]([O-])=O PGZIKUPSQINGKT-UHFFFAOYSA-N 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- 229960002986 dinoprostone Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000012055 enteric layer Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000027119 gastric acid secretion Effects 0.000 description 1
- 230000030136 gastric emptying Effects 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 201000000052 gastrinoma Diseases 0.000 description 1
- 239000003485 histamine H2 receptor antagonist Substances 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000002370 magnesium bicarbonate Substances 0.000 description 1
- 229910000022 magnesium bicarbonate Inorganic materials 0.000 description 1
- 235000014824 magnesium bicarbonate Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 208000000689 peptic esophagitis Diseases 0.000 description 1
- 230000008855 peristalsis Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 208000018556 stomach disease Diseases 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 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
- A61K31/33—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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K31/695—Silicon compounds
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
Abstract
The invention relates to the technical field of medicines, in particular to a pharmaceutical composition, and also relates to a preparation method and application thereof. A composition for the treatment of gastric acid comprising simethicone, hydrotalcite and omeprazole. Omeprazole is wrapped in simethicone to achieve a slow release effect, magnesium aluminocarbonate firstly reaches an acid environment, and after neutralization, omeprazole is released, so that the stability of omeprazole can be improved, the respective functions of the omeprazole and the simethicone are fully and coordinately exerted, and an excellent effect is achieved.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a pharmaceutical composition, and also relates to a preparation method and application thereof.
Background
The hydrotalcite is an antacid and has the following functions of 1 neutralizing gastric acid. Can be used for treating stomach inflammation or ulcer caused by excessive gastric acid secretion; 2. maintain gastric pH. Maintaining the pH of the stomach between 3 and 5; 3. adsorption and binding. The hydrotalcite can directly inhibit the activity of the protease through adsorption and combination with the pepsin, and is beneficial to repairing the ulcer surface; 4. the hydrotalcite can stimulate gastric mucosa, increase prostaglandin E2 synthesis, and enhance gastric mucosa protection.
Omeprazole, a proton pump inhibitor that is effective in inhibiting the secretion of gastric acid. It also has inhibitory effect on pepsin secretion, does not change blood flow of gastric mucosa obviously, and does not affect body temperature, gastric cavity temperature, arterial blood pressure, venous hemoglobin, arterial oxygen partial pressure, carbon dioxide partial pressure and arterial blood pH. Can be used for treating gastric and duodenal ulcer, reflux or erosive esophagitis, zollinger-Ellison syndrome, etc., and also for treating gastric and duodenal ulcer with H2 receptor antagonist.
In the prior art, omeprazole and antacids such as hydrotalcite and sodium bicarbonate are used in a combined mode to treat gastric acid, hydrotalcite quickly reduces the concentration of gastric acid and pain of a patient, and omeprazole reduces the capability of gastric cells to release gastric acid, so that symptoms are treated firstly, and the root cause is also treated secondly.
CN202110709042.2 an omeprazole aluminum magnesium carbonate composite tablet and a preparation process thereof the omeprazole aluminum magnesium carbonate composite tablet is a three-layer composite structure of an omeprazole tablet core layer, an enteric coating and an aluminum magnesium carbonate layer which are sequentially tableted from inside to outside, and omeprazole and auxiliary materials are firstly pressed into a tablet core; then hydroxypropyl methylcellulose phthalate and the tablet core are directly tabletted for the second time, and an enteric-coated layer is pressed; and finally, carrying out third tabletting on the hydrotalcite and the auxiliary materials and the tablet core subjected to the secondary pressing, and pressing into a pressed tablet of omeprazole → an enteric coating → a hydrotalcite quick-acting layer. After a patient takes the composite tablet, the hydrotalcite layer in the medicine is rapidly disintegrated, the gastric acid concentration is rapidly reduced, the pain of the patient is reduced, and then the omeprazole coated with the enteric layer enters the intestinal tract to be released, so that the gastric acid releasing capacity of gastric cells is reduced, and the traditional Chinese medicine compound tablet treats the symptoms and then costs the root.
CN201510051650.3 an oral solid pharmaceutical composition containing omeprazole, aiming at the problems that part of omeprazole raw material medicines existing after disintegration of a compound omeprazole sodium bicarbonate capsule are degraded when exposed to an aqueous environment without the dissolution of sodium bicarbonate to improve the pH value and the compound capsule has poor long-term storage stability, designs a compound omeprazole magnesium sodium bicarbonate composition, provides a prescription and a process to further prepare the compound omeprazole magnesium bicarbonate sodium composition into a hard capsule, and the hard capsule can release omeprazole magnesium after the sodium bicarbonate is completely dissolved, so that the risk of exposure of the omeprazole magnesium to a low pH environment is avoided, and the stability of the compound omeprazole sodium bicarbonate capsule after taking is improved. Meanwhile, the omeprazole magnesium is selected as the raw material drug, so that the stability of the raw material drug is enhanced, and the long-term storage stability of the preparation is improved. The compound hard capsule has simple preparation method, can be produced by adopting the conventional preparation method, does not need special equipment, has the remarkable advantages of easy industrialization, high production efficiency, good stability, controllable quality and the like, and has prominent substantive characteristics and remarkable progress.
The prior art is all solid dosage forms, and the drug effect exerting time and the administration are limited.
Simethicone, simethicone-silica mixture, CAS No. 8050-81-5, is a surfactant for gastrointestinal administration that is not absorbed after administration, but which alters the surface tension of air bubbles present in the alimentary tract, either in the food or in the mucus, and causes the air bubbles to break down. The released gas can be absorbed by the intestinal wall and the stomach wall and is gradually discharged out of the body through peristalsis. In clinic, the traditional Chinese medicine is mainly used for patients who are in bed after abdominal operation or abdominal distension caused by excessive gas production in intestinal tracts. It can also be used as additive of contrast agent for gastroscope, X-ray, and ultrasonic examination, and can be used for eliminating gas in gastrointestinal tract to make examination more clear. In addition, the detergent also has a treatment effect on poisoning caused by a detergent with surface activity. Since simethicone is not absorbed by oral administration, almost no side effects occur.
Lichunwei et al (37, 4 th, 2022, modern Drugs and clinical Drugs & clinical Vol. 37 No. 4 April 2022) use simethicone in combination with omeprazole to treat functional dyspepsia in children, and as a result, can significantly improve gastric emptying function, rapidly relieve clinical symptoms, and maintain sustained relief, and has good safety and tolerance. But at present, no compound preparation of simethicone and omeprazole exists.
TABLETS and SUSPENSIONs containing magnesium aluminocarbonate and simethicone are commercially available (Talsil @ Forte TABLETS and Talsil @ Forte SUSPENSION) and are used for treating dyspepsia, gastroesophageal reflux disease, acid digestive disease, pain pressure, hiccup, abdominal flatulence and other diseases. There is no record in the prior art of liquid dosage forms using omeprazole in combination with magnesium aluminocarbonate and simethicone.
Disclosure of Invention
The invention provides a liquid preparation formulation for combined use of omeprazole, hydrotalcite and simethicone, which is orally taken to treat gastric acid, abdominal flatulence and other stomach diseases.
Simethicone is a surfactant of a viscous liquid, and is almost insoluble in water; the hydrotalcite is a solid which is not dissolved in water; omeprazole is a white solid which is insoluble in water and easy to be damaged in an acid environment, the stability is poor, and the influence of gastric acid on the omeprazole needs to be eliminated after oral administration.
The invention aims to achieve the following effects: after the three medicinal compositions are orally taken, simethicone firstly plays a role in eliminating gas in gastrointestinal tracts, and is beneficial to contact of hydrotalcite and gastric juice while eliminating flatulence symptoms, so that the hydrotalcite can more quickly and effectively reduce the concentration of gastric acid. Meanwhile, bubbles are generated after the hydrotalcite reacts with the gastric acid, and simethicone can be eliminated in time. The slow-release omeprazole can better play a role after gastric acid and air bubbles are eliminated.
Due to the nature of the three main drugs and the different mechanisms and occasions for the respective actions, great challenges are brought to the preparation. Researchers can prepare three medicines with treatment effects into oral liquid through a large number of tests by creative formulas and processes, the process is simple, and other auxiliary materials are less. Is characterized in that no additional sustained-release auxiliary materials are needed, the self characteristics of the three main medicine components are utilized, the aims of quick effect taking of simethicone and hydrotalcite and sustained-release protection effect on omeprazole are achieved, and the effects are unexpected compared with single use or combined use of the simethicone and the hydrotalcite.
In order to achieve the purpose, the invention adopts the following technical scheme:
adding appropriate amount of dichloromethane into simethicone, stirring, adding omeprazole, stirring for dissolving, volatilizing dichloromethane, adding appropriate amount of magnesium aluminate while volatilizing dichloromethane to obtain solid, pulverizing the solid, adding appropriate amount of excipient and the rest magnesium aluminate to obtain suspension.
The composition for treating gastric acid comprises the following raw materials in parts by weight:
2-5 parts of simethicone; 5-20 parts of hydrotalcite; 0.5-1 part of omeprazole.
The composition preferably comprises the following raw materials in parts by weight:
4 parts of simethicone; 15 parts of hydrotalcite; and 1 part of omeprazole.
The composition preferably further comprises 0.5-2 parts of a thickening agent.
The composition is preferably an oral suspension.
A composition for treating gastric acid, preferably comprises the following raw materials in weight volume content:
simethicone, the weight volume content is 2% -5%;
the aluminum magnesium carbonate, the weight volume content is 5% -20%;
omeprazole with the weight volume ratio content of 0.5-1 percent.
The weight volume content, abbreviated as w/v, is given in g/100ml.1% solution, i.e. 100ml, contains 1g.
The composition preferably comprises the following raw materials in weight volume content:
simethicone, the weight volume content is 4 percent;
the hydrotalcite is 15 percent by weight volume;
omeprazole with the weight volume ratio content of 1 percent.
The composition preferably further comprises 0.5-2% of a thickening agent.
The thickening agent of the composition is hydroxypropyl methylcellulose or carbomer preferably.
The preparation method of the composition for treating gastric acid preferably comprises the following steps:
(1) Dissolving omeprazole in dichloromethane, adding simethicone, stirring uniformly, adding one third of hydrotalcite, grinding by a colloid mill, and volatilizing dichloromethane to obtain a premix;
(2) Dissolving a thickening agent in water, and obtaining a solution I after complete swelling;
(3) Adding the premix obtained in the step (1) into water, and uniformly stirring to obtain a solution II;
(4) Adding the rest two thirds of the hydrotalcite into the solution I, grinding by a colloid mill, adding the solution II, adjusting the pH to 8.5, adding purified water to a preset concentration, and stirring and uniformly mixing to obtain the magnesium aluminate-silicate solution.
The composition is applied to the preparation of oral medicines for treating gastric acid and flatulence.
The particle size of the hydrotalcite is less than or equal to 3000 nanometers; preferably, the particle size of the hydrotalcite is less than or equal to 2000 nm.
The invention has the beneficial effects that:
the composition comprises simethicone, hydrotalcite and omeprazole, the omeprazole and part of hydrotalcite are wrapped in the simethicone through a creative formula and a creative process to achieve a slow release effect, the uncoated hydrotalcite firstly reaches an acid environment in one step, and after acid neutralization, the omeprazole is released, so that the stability of the omeprazole can be improved; simethicone has the effects of emulsifying, coating and promoting gas discharge, the respective functions of the simethicone and the simethicone are fully coordinated and exerted, and an excellent treatment effect is achieved.
Detailed Description
The invention is further illustrated with reference to the following specific examples:
the following examples are provided to further illustrate the compositions of the present invention. The following examples are illustrative of the preferred embodiments of the present invention, but the present invention is not limited thereto, and any other changes, modifications, combinations, substitutions and simplifications which do not depart from the spirit and principles of the present invention should be construed as equivalents thereof, and they are included in the scope of the present invention.
Example 1: composition and preparation method thereof
TABLE 1 composition recipe
| Prescription | Remarks to note | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 | Prescription 5 | Prescription 6 | Prescription 7 | Prescription 8 | Prescription 9 | Prescription 10 |
| Simethicone | -- | 2% | 2% | 3% | 3% | 4% | 5% | 5% | 4% | 4% | -- |
| Omeprazole | Particle size less than 2000 nm | 1% | 1% | 1% | 1% | 1% | 1% | 1% | 1% | 0.5% | 1% |
| Hydrotalcite | Particle size less than 2000 nm | 10% | 15% | 10% | 15% | 15% | 10% | 15% | 20% | 5% | 15% |
| Hydroxypropyl methylcellulose sodium | -- | 1% | 1% | 1% | 1% | 1% | -- | -- | -- | 1% | 1% |
| Carbomer | -- | -- | -- | -- | -- | -- | 1% | 1% | 1% | -- | -- |
| Purified water | -- | Proper amount of | Proper amount of | Proper amount of | Proper amount of | Proper amount of | Proper amount of | Proper amount of | Proper amount of | Proper amount of | Proper amount of |
A method for preparing a composition for the treatment of gastric acid having a formula 1-9, comprising the steps of:
(1) Dissolving omeprazole in dichloromethane of 10 times, adding simethicone, stirring uniformly, adding one third of hydrotalcite, grinding with a colloid mill to below 30 microns, and volatilizing dichloromethane to obtain a premix;
(2) Dissolving a thickening agent in 5 times of water, and completely swelling to obtain a solution I;
(3) Adding the premix obtained in the step (1) into 5 times of water, and uniformly stirring to obtain a solution II;
(4) Adding the rest two-thirds of the hydrotalcite into the solution I, grinding by a colloid mill to be below 30 microns, adding the solution II, adjusting the pH to 8.5, adding purified water to a preset concentration, and stirring and uniformly mixing to obtain the compositions 1-9 respectively.
The preparation method of the formula 10 comprises the following steps:
(1) Dissolving a thickening agent in 5 times of water, and completely swelling to obtain a solution I;
(2) Adding omeprazole and hydrotalcite into the solution I, grinding by a colloid mill to be below 30 microns, adjusting the pH to 8.5, adding purified water to reach a preset concentration, and stirring and uniformly mixing to obtain the composition 10.
The composition for treating gastric acid in the formulas 1 to 9 is prepared according to the following preparation method:
(1) Dissolving a thickening agent in 5 times of water, and completely swelling to obtain a solution I;
(2) Adding omeprazole, hydrotalcite and simethicone into the solution I, grinding by a colloid mill to be below 30 microns, adjusting the pH to 8.5, adding purified water to reach a preset concentration, and stirring and uniformly mixing to obtain the composition 11-19.
The appearance of the resulting suspension and the relevant parameters were as follows:
1. appearance character
The method comprises the following steps: a small amount of the suspension was taken and visually observed in a bright place.
As a result: compositions 1-19 were all milky white suspensions.
2. Particle size
The method comprises the following steps: according to Chinese pharmacopoeia, the particle size of the sample is measured by using a laser particle size analyzer
As a result: less than or equal to 30 microns.
Example 2: stability test
Volume ratio of sedimentation
The determination method comprises the following steps: 50ml of the suspension prepared according to the formula 1, 4, 5, 8 and 10 of the above example 1 is weighed out by a measuring cylinder with a plug, the plug is sealed, the mixture is vigorously shaken for 1 minute, the starting height H0 of the suspension is recorded, the mixture is kept still for 3 hours, the final height H of the suspension is recorded, and the calculation is carried out according to the following formula: the sedimentation volume ratio = H/H0,
the sedimentation volume ratios of compositions 1 to 19 are 0.91, 0.94, 0.96, 0.94, 0.99, 0.95, 0.99, 0.85, 0.86, 0.90, 0.91, 0.89, 0.90, 0.87, 0.91, respectively.
(II) Re-Dispersion test
Compositions 1-19 were placed in a 100mL graduated cylinder and rotated at 20 revolutions per minute for a period of time to observe whether the sediment at the bottom of the cylinder was re-dispersed uniformly.
Compositions 1-9 re-dispersed uniformly and compositions 10-19 had a small amount of sediment undispersed and remained at the bottom of the cylinder.
Example 3: encapsulation efficiency
The encapsulation efficiency of solutions II in compositions 1-9, compositions 10-19, was determined according to the guidelines of the pharmacopoeia for the formulation of microparticles, and was determined after separation by a suitable method (e.g. gel column chromatography, centrifugation or dialysis) and calculated according to the following formula: encapsulation efficiency = (amount of drug encapsulated versus total drug not encapsulated in microparticle formulation) × 100% = (1-amount of drug not encapsulated in liquid medium/total amount of drug encapsulated versus not encapsulated in microparticle formulation) × 100% the compositions 1-10 encapsulation efficiencies were 60%, 45%, 100%, 70%, 100%, 80%, 100%, 0, 5%, 6%, 5%, 6%, 10%, 9%, 5%, 12%, respectively.
Example 4: rate of leakage
Compositions 3, 5, 6, 7 and 9 with 100% encapsulation efficiency were selected for permeability experiments.
Penetration = (amount of drug product penetrating into medium after storage for a certain period of time/amount of drug product encapsulated before storage) × 100%
The permeabilities of solutions II obtained during the preparation of compositions 3, 5, 6, 7, 9 were 5%, 1%, 3%, 1%, respectively.
As can be seen from the data in the above embodiments, the suspension obtained by the composition and the preparation method thereof of the present application is stable, has a high drug encapsulation rate and a low permeability, and is beneficial to the exertion of drug effects and long-term storage stability.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited by the embodiments, and any other changes, modifications, combinations, substitutions and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, combinations, substitutions and simplifications are intended to be included in the scope of the present invention.
Claims (10)
1. The composition for treating gastric acid is characterized by comprising the following raw materials in parts by weight:
2-5 parts of simethicone; 5-20 parts of hydrotalcite; 0.5-1 part of omeprazole.
2. The composition according to claim 1, characterized by comprising the following raw materials in parts by weight:
4 parts of simethicone; 15 parts of hydrotalcite; and 1 part of omeprazole.
3. The composition of claim 1, further comprising 0.5 to 2 parts of a thickener.
4. Composition according to claim 1 or 3, characterized in that it is an oral suspension.
5. A composition for treating gastric acid is characterized by comprising the following raw materials in weight volume content:
simethicone with the weight volume content of 2-5 percent;
the aluminum magnesium carbonate, the weight volume content is 5% -20%;
omeprazole, the weight volume ratio content is 0.5% -1%.
6. The composition according to claim 5, characterized by comprising the following raw materials in weight volume content:
simethicone, the weight volume content is 4 percent;
hydrotalcite, the weight volume content is 15%;
omeprazole, the weight volume ratio content is 1%.
7. A process for the preparation of a composition for the treatment of gastric acid according to any of claims 1 to 6, comprising the steps of:
(1) Dissolving omeprazole in dichloromethane, adding simethicone, stirring uniformly, adding one third of hydrotalcite, grinding by a colloid mill, and volatilizing dichloromethane to obtain a premix;
(2) Dissolving a thickening agent in water, and obtaining a solution I after complete swelling;
(3) Adding the premix obtained in the step (1) into water, and uniformly stirring to obtain a solution II;
(4) Adding the rest two thirds of the hydrotalcite into the solution I, grinding by a colloid mill, adding the solution II, adjusting the pH to 8.5, adding purified water to a predetermined concentration, and stirring and uniformly mixing to obtain the catalyst.
8. The process according to claim 7, wherein the mass of dichloromethane in step (1) is 10-20 times the mass of omeprazole, the mass of water in step (2) is 5-10 times the mass of the thickening agent, and the mass of water in step (3) is 3-5 times the mass of the premix.
9. The method according to claim 7, wherein the grinding particle size in steps (1) and (4) is 30 μm or less.
10. Use of a composition according to any one of claims 1 to 6 or a composition prepared by the process according to any one of claims 7 to 9 for the manufacture of an oral medicament for the treatment of gastric acid, flatulence.
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