CN115177585A - Nimodipine oral solution and preparation method thereof - Google Patents
Nimodipine oral solution and preparation method thereof Download PDFInfo
- Publication number
- CN115177585A CN115177585A CN202210907464.5A CN202210907464A CN115177585A CN 115177585 A CN115177585 A CN 115177585A CN 202210907464 A CN202210907464 A CN 202210907464A CN 115177585 A CN115177585 A CN 115177585A
- Authority
- CN
- China
- Prior art keywords
- nimodipine
- oral solution
- solution
- weight percentage
- glycerol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229940069214 nimodipine oral solution Drugs 0.000 title claims abstract description 47
- 238000002360 preparation method Methods 0.000 title claims abstract description 37
- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 claims abstract description 35
- 229960000715 nimodipine Drugs 0.000 claims abstract description 35
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims abstract description 32
- KPQJOKRSYYJJEL-VLQRKCJKSA-K [Na+].[Na+].CC1(C)[C@H](CC[C@@]2(C)[C@H]1CC[C@]1(C)[C@@H]2C(=O)C=C2[C@@H]3C[C@](C)(CC[C@]3(C)CC[C@@]12C)C([O-])=O)O[C@H]1O[C@@H]([C@@H](O)[C@H](O)[C@H]1O[C@@H]1O[C@@H]([C@@H](O)[C@H](O)[C@H]1O)C([O-])=O)C([O-])=O Chemical compound [Na+].[Na+].CC1(C)[C@H](CC[C@@]2(C)[C@H]1CC[C@]1(C)[C@@H]2C(=O)C=C2[C@@H]3C[C@](C)(CC[C@]3(C)CC[C@@]12C)C([O-])=O)O[C@H]1O[C@@H]([C@@H](O)[C@H](O)[C@H]1O[C@@H]1O[C@@H]([C@@H](O)[C@H](O)[C@H]1O)C([O-])=O)C([O-])=O KPQJOKRSYYJJEL-VLQRKCJKSA-K 0.000 claims abstract description 23
- 239000003814 drug Substances 0.000 claims abstract description 16
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims abstract description 14
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 claims abstract description 14
- 229960002216 methylparaben Drugs 0.000 claims abstract description 14
- 235000003599 food sweetener Nutrition 0.000 claims abstract description 12
- 239000007788 liquid Substances 0.000 claims abstract description 12
- 239000003765 sweetening agent Substances 0.000 claims abstract description 12
- 239000003755 preservative agent Substances 0.000 claims abstract description 9
- 230000002335 preservative effect Effects 0.000 claims abstract description 9
- 239000000463 material Substances 0.000 claims abstract description 4
- 239000004480 active ingredient Substances 0.000 claims abstract description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 78
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 71
- 238000003756 stirring Methods 0.000 claims description 40
- 229960004756 ethanol Drugs 0.000 claims description 26
- 229960005150 glycerol Drugs 0.000 claims description 26
- -1 Glycyrrhizic acid disodium salt Chemical class 0.000 claims description 20
- 229940068918 polyethylene glycol 400 Drugs 0.000 claims description 20
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
- VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 claims description 10
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 claims description 10
- 229960004949 glycyrrhizic acid Drugs 0.000 claims description 10
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 claims description 10
- 239000001685 glycyrrhizic acid Substances 0.000 claims description 10
- 235000019410 glycyrrhizin Nutrition 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- 235000016623 Fragaria vesca Nutrition 0.000 claims description 8
- 240000009088 Fragaria x ananassa Species 0.000 claims description 8
- 235000011363 Fragaria x ananassa Nutrition 0.000 claims description 8
- 239000002202 Polyethylene glycol Substances 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 229920001223 polyethylene glycol Polymers 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 244000144730 Amygdalus persica Species 0.000 claims description 6
- 235000006040 Prunus persica var persica Nutrition 0.000 claims description 6
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 235000004936 Bromus mango Nutrition 0.000 claims description 5
- 235000012828 Citrullus lanatus var citroides Nutrition 0.000 claims description 5
- 235000015001 Cucumis melo var inodorus Nutrition 0.000 claims description 5
- 240000002495 Cucumis melo var. inodorus Species 0.000 claims description 5
- 240000007228 Mangifera indica Species 0.000 claims description 5
- 235000014826 Mangifera indica Nutrition 0.000 claims description 5
- 240000008790 Musa x paradisiaca Species 0.000 claims description 5
- 235000018290 Musa x paradisiaca Nutrition 0.000 claims description 5
- 235000011034 Rubus glaucus Nutrition 0.000 claims description 5
- 244000235659 Rubus idaeus Species 0.000 claims description 5
- 235000009122 Rubus idaeus Nutrition 0.000 claims description 5
- 235000009184 Spondias indica Nutrition 0.000 claims description 5
- 235000009754 Vitis X bourquina Nutrition 0.000 claims description 5
- 235000012333 Vitis X labruscana Nutrition 0.000 claims description 5
- 240000006365 Vitis vinifera Species 0.000 claims description 5
- 235000014787 Vitis vinifera Nutrition 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 241000167854 Bourreria succulenta Species 0.000 claims description 4
- 235000006679 Mentha X verticillata Nutrition 0.000 claims description 4
- 235000002899 Mentha suaveolens Nutrition 0.000 claims description 4
- 235000001636 Mentha x rotundifolia Nutrition 0.000 claims description 4
- 244000183278 Nephelium litchi Species 0.000 claims description 4
- 235000019693 cherries Nutrition 0.000 claims description 4
- 229960004063 propylene glycol Drugs 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 239000000796 flavoring agent Substances 0.000 claims description 2
- 235000013355 food flavoring agent Nutrition 0.000 claims description 2
- 244000241235 Citrullus lanatus Species 0.000 claims 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims 1
- 229960003742 phenol Drugs 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 229940100688 oral solution Drugs 0.000 abstract description 10
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 2
- 239000002699 waste material Substances 0.000 abstract description 2
- 239000000686 essence Substances 0.000 description 55
- 239000000243 solution Substances 0.000 description 37
- 238000005187 foaming Methods 0.000 description 21
- 238000011049 filling Methods 0.000 description 17
- 230000000694 effects Effects 0.000 description 11
- 238000012360 testing method Methods 0.000 description 8
- 238000009472 formulation Methods 0.000 description 7
- 239000006260 foam Substances 0.000 description 6
- 241000219109 Citrullus Species 0.000 description 4
- 206010019233 Headaches Diseases 0.000 description 4
- XINCECQTMHSORG-UHFFFAOYSA-N Isoamyl isovalerate Chemical compound CC(C)CCOC(=O)CC(C)C XINCECQTMHSORG-UHFFFAOYSA-N 0.000 description 4
- 239000004376 Sucralose Substances 0.000 description 4
- 231100000869 headache Toxicity 0.000 description 4
- 238000007689 inspection Methods 0.000 description 4
- 208000001286 intracranial vasospasm Diseases 0.000 description 4
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 4
- 235000019408 sucralose Nutrition 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 208000019695 Migraine disease Diseases 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 206010027599 migraine Diseases 0.000 description 3
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 208000028389 Nerve injury Diseases 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 206010061373 Sudden Hearing Loss Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000003925 brain function Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 208000003906 hydrocephalus Diseases 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000000873 masking effect Effects 0.000 description 2
- 230000008764 nerve damage Effects 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- VRNMTDDYCXDILN-UHFFFAOYSA-N 1-(2-methoxyethyl)-2,6-dimethyl-4-(3-nitrophenyl)-5-propan-2-yloxycarbonyl-4h-pyridine-3-carboxylic acid Chemical compound CC(C)OC(=O)C1=C(C)N(CCOC)C(C)=C(C(O)=O)C1C1=CC=CC([N+]([O-])=O)=C1 VRNMTDDYCXDILN-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 206010013911 Dysgeusia Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940127292 dihydropyridine calcium channel blocker Drugs 0.000 description 1
- 239000002866 dihydropyridine calcium channel blocker Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 238000005429 filling process Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 235000021395 porridge Nutrition 0.000 description 1
- 208000018316 severe headache Diseases 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—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
- 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
- A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
-
- 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
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Abstract
The invention discloses a nimodipine oral solution and a preparation method thereof, which consists of a medicament active ingredient nimodipine, a sweetening agent disodium glycyrrhizinate, a preservative methylparaben and other pharmaceutically acceptable auxiliary materials. The oral solution provided by the invention has good taste and smell, high comprehensive acceptance and good medicine taking compliance of children and old patients; the preparation method of the oral liquid provided by the invention is simple to operate, has high industrial operation feasibility, less three-waste discharge, is green, environment-friendly and sustainable, is beneficial to large-scale industrial production, and is more suitable for industrialization.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a nimodipine oral solution and a preparation method thereof.
Background
Subarachnoid hemorrhage is a very serious common disease, mainly caused by rupture of blood vessels on the brain base or brain surface and blood flowing into subarachnoid cavity, and complications mainly comprise cerebral vasospasm, hydrocephalus, re-hemorrhage and the like. The world health organization survey shows that the Chinese incidence is about 2.0/10 ten thousand per year, and the Chinese incidence is also reported to be 6-20/10 ten thousand per year. Migraine is the most common type of primary headache in clinic, and clinically, the headache is mainly manifested by paroxysmal moderate and severe headache and pulsatory headache, and the headache mostly occurs in children and adolescence, and the peak of the disease occurs in middle and young age.
Nimodipine is a dihydropyridine calcium channel blocker, is mainly used for preventing and treating cerebral vasospasm after subarachnoid hemorrhage, ischemic nerve injury caused by the cerebral vasospasm, senile brain function injury, migraine, sudden deafness, light and moderate hypertension and the like clinically, and has the trade name of NYMILIZE and the chemical name of NYMILIZE: 2-methoxyethyl-1,4-dihydro-2,6-dimethyl-4- (m-nitrophenyl) -3,5-pyridinedicarboxylic acid isopropyl ester with molecular formula C 21 H 26 N 2 O 7 The structural formula is as follows:
currently, the formulations on the market containing nimodipine are tablets, capsules and injections. For children and elderly patients, especially children and elderly patients with nervous system diseases, common tablets and capsules have the problems of dysphagia, poor oral compliance, difficult water solubility of the medicine, slow dissolution speed, slow effect, short action time, strong toxicity after being taken for many times, and low bioavailability; the commercial nimodipine injection has no exact research data for children patients, and the effectiveness and safety are not clear. The nimodipine can be prepared into a solution agent due to certain solubility in an organic solvent, but the oral solution prepared by the common method has poor taste, certain afterbitterness and bad peculiar smell, and poor drug compliance of children and old patients, particularly children and old patients suffering from nervous system diseases.
In addition, an investigation shows that 90.8 percent of acute pediatric patients and 83.9 percent of chronic pediatric patients have the main obstacle of medicine taking, namely, the bad taste of the medicine, and the southern medical and economic institute of China, the '2016 research report on the medicine taking safety of children, the white paper book' indicates that 19.8 percent of parents can dissolve the medicine in milk, sugar water, beverage, porridge soup and the like to be taken by children, and the treatment effect of the medicine can be influenced by the measures.
Therefore, it is necessary to develop an oral nimodipine solution with good taste and high comprehensive acceptance.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to solve the problems in the existing nimodipine oral solution by providing the nimodipine oral solution with good taste and high comprehensive acceptance.
The technical scheme of the invention is as follows:
the invention provides a nimodipine oral solution, which consists of a medicament active ingredient nimodipine, a sweetening agent disodium glycyrrhizinate, a preservative methylparaben and other pharmaceutically acceptable auxiliary materials;
according to the above nimodipine oral solution, the other pharmaceutically acceptable excipients are preferably a solvent or a solvent and an aromatic;
according to the above nimodipine oral solution, the solvent is preferably 1 to 4 of polyethylene glycol, glycerol, ethanol and propylene glycol, more preferably 1 to 3 of polyethylene glycol, glycerol, ethanol and propylene glycol, more preferably 3 of polyethylene glycol, glycerol, ethanol and propylene glycol, and most preferably polyethylene glycol, glycerol and ethanol;
according to the above nimodipine oral solution, the oral solution may be composed of nimodipine, disodium glycyrrhizinate, methylparaben, polyethylene glycol 400, glycerol and ethanol;
according to the above nimodipine oral solution, the oral solution may be composed of nimodipine, disodium glycyrrhizinate, methylparaben, polyethylene glycol 400, glycerol, ethanol and aromatics;
according to the nimodipine oral solution, the weight percentage of the disodium glycyrrhizinate in the formula is preferably 0.01-1.0%, more preferably 0.015-0.5%, more preferably 0.05-0.5%, especially preferably 0.05-0.2%, and most preferably 0.2%;
according to the nimodipine oral solution, the weight percentage of the methyl hydroxybenzoate in the prescription is preferably 0.015-0.5%, more preferably 0.02-0.5%, even more preferably 0.05-0.2%, and most preferably 0.2%;
according to the nimodipine oral solution, the weight ratio of the disodium glycyrrhizinate to the methylparaben is preferably 1 (0.3-3), more preferably 1 (1-3), and most preferably 1:1;
according to the nimodipine oral solution, the weight percentage of the polyethylene glycol in the formula is preferably 30-60%, more preferably 37-50% or 50-60%, and most preferably 50%;
according to the nimodipine oral solution, the weight percentage of the glycerol in the formula is preferably 33.4-66.7%, more preferably 33.4-60%, more preferably 34.4-60%, particularly preferably 36.7-60%, particularly preferably 38.8-60%, particularly preferably 39.3-60%, and most preferably 47%;
according to the nimodipine oral solution, the weight percentage of the ethanol in the prescription is preferably 0.5-5%, and most preferably 2%;
according to the nimodipine oral solution, the weight percentage of the essence in the formula is preferably 0.5-2%, more preferably 0.5-1.2%, and most preferably 1%;
according to the above nimodipine oral solution, the above polyethylene glycol is preferably polyethylene glycol 400;
further, according to the nimodipine oral solution, the weight percentage content of each component is preferably as follows:
components | The weight percentage content |
Nimodipine | 0.1%-5% |
Glycyrrhizic acid disodium salt | 0.05%-0.5% |
Hydroxy phenyl methyl ester | 0.05%-0.5% |
Polyethylene glycol 400 | 30%-60% |
Glycerol | 33.4%-66.7% |
Ethanol | 0.5%-5% |
Aromatic agent | 0.5%-2% |
Total of | 100% |
Or the like, or, alternatively,
components | The weight percentage content |
Nimodipine | 0.1%-5% |
Glycyrrhizic acid disodium salt | 0.05%-0.5% |
Hydroxy phenyl methyl ester | 0.05%-0.5% |
Polyethylene glycol 400 | 30%-60% |
Glycerol | 45%-66.7% |
Ethanol | 0.5%-5% |
Total of | 100% |
Further, according to the nimodipine oral solution, the weight percentage of each component is preferably as follows:
components | The weight percentage content |
Nimodipine | 0.1-5.0% |
Glycyrrhizic acid disodium salt | 0.2%-0.5% |
Hydroxy phenyl methyl ester | 0.2%-0.5% |
Polyethylene glycol 400 | 37%-50% |
Glycerol | 47%-60% |
Ethanol | 0.5%-5% |
Aromatic agent | 0.5-1.2% |
Total of | 100% |
Or the like, or, alternatively,
components | The weight percentage content |
Nimodipine | 0.1-5.0% |
Glycyrrhizic acid disodium salt | 0.2%-0.5% |
Hydroxy phenyl methyl ester | 0.2%-0.5% |
Polyethylene glycol 400 | 37%-50% |
Glycerol | 47%-60% |
Ethanol | 0.5%-5% |
Total of | 100% |
Further, according to the nimodipine oral solution, the weight percentage of each component is more preferably as follows:
components | The weight percentage content |
Nimodipine | 0.6% |
Glycyrrhizic acid disodium salt | 0.2%-0.5% |
Hydroxy phenyl methyl ester | 0.2%-0.5% |
Polyethylene glycol 400 | 37%-50% |
Glycerol | 47%-60% |
Ethanol | 2% |
Aromatic agent | 0.5-1.2% |
Total of | 100% |
Or the like, or, alternatively,
components | The weight percentage content |
Nimodipine | 0.6% |
Glycyrrhizic acid disodium salt | 0.2%-0.5% |
Hydroxy phenyl methyl ester | 0.2%-0.5% |
Polyethylene glycol 400 | 37%-50% |
Glycerol | 47%-60% |
Ethanol | 2% |
Total of | 100% |
Further, according to the nimodipine oral solution, the weight percentage content of each component is most preferably as follows:
or the like, or, alternatively,
components | The weight percentage content |
Nimodipine | 0.6% |
Glycyrrhizic acid disodium salt | 0.2% |
Hydroxy phenyl methyl ester | 0.2% |
Polyethylene glycol 400 | 37%-50% |
Glycerol | 47%-60% |
Ethanol | 2% |
Total of | 100% |
According to the nimodipine oral solution, the aromatic is preferably one or more of cherry type essence, raspberry type essence, strawberry type essence, mint type essence, honeydew melon type essence, juicy peach type essence, mango type essence, apple type essence, banana type essence, watermelon type essence, orange type essence, grape type essence and litchi type essence, more preferably one or more of cherry type essence, raspberry type essence, strawberry type essence, orange type essence, mint type essence, honeydew melon essence, juicy peach type essence, mango type essence, apple type essence, banana type essence, watermelon type essence, grape type essence and litchi type essence, more preferably cherry essence, raspberry essence, strawberry essence, mint essence, honeydew melon essence, juicy peach essence, mango essence, apple essence, banana essence, watermelon essence, orange essence, litchi essence, or grape essence, especially preferably raspberry essence, strawberry essence, orange essence, honeydew melon essence, juicy peach essence, mango essence, banana essence, watermelon essence, apple essence, or grape essence, especially preferably strawberry essence, orange essence, juicy peach essence, apple essence, or apple essence, most preferably strawberry essence, or orange essence;
the second aspect of the present invention provides a preparation method of the nimodipine oral solution, which specifically comprises the following steps:
(1) Adding polyethylene glycol 400 of a prescription amount into a preparation tank 1, adding nimodipine of the prescription amount into the preparation tank, stirring and dissolving, wherein the stirring speed is 1000-2000rpm, and the stirring time is 30-60min, so as to obtain a solution 1;
(2) Adding the glycerol with the prescription amount into a preparation tank 2, adding the sweetening agent with the prescription amount, and stirring until the sweetening agent is dissolved to obtain a solution 2;
(3) Pouring the solution 2 into the solution 1, and stirring for 30-60min to obtain a solution 3;
(4) Adding a prescription amount of preservative into a preparation tank 3, adding a prescription amount of 95% ethanol, and stirring until the preservative is dissolved to obtain a solution 4;
(5) And pouring the solution 4 into the solution 3, starting stirring at the stirring speed of 1000-2000rpm for 60-120 min, and uniformly mixing to obtain the nimodipine oral solution.
Further, the preparation method of the nimodipine oral solution preferably comprises the following steps:
(1) Adding polyethylene glycol 400 of a prescription amount into a preparation tank 1, adding nimodipine of the prescription amount into the preparation tank, stirring and dissolving, wherein the stirring speed is 1000-2000rpm, and the stirring time is 30-60min, so as to obtain a solution 1;
(2) Adding the glycerol with the prescription amount into a preparation tank 2, adding the disodium glycyrrhizinate with the prescription amount, and stirring until the disodium glycyrrhizinate is dissolved to obtain a solution 2;
(3) Pouring the solution 2 into the solution 1, and stirring for 30-60min to obtain a solution 3;
(4) Adding a prescribed amount of methylparaben and an aromatic agent into a preparation tank 3, adding a prescribed amount of 95% ethanol, and stirring until the mixture is dissolved to obtain a solution 4;
(5) And pouring the solution 4 into the solution 3, starting stirring at the stirring speed of 1000-2000rpm for 60-120 min, and uniformly mixing to obtain the nimodipine oral solution.
The third aspect of the invention provides a use of the nimodipine oral solution or the nimodipine oral solution prepared by the method in preparing a medicament for treating and/or preventing complications of subarachnoid hemorrhage patients; the complications of the subarachnoid hemorrhage are preferably cerebral vasospasm, hydrocephalus, re-bleeding, ischemic nerve injury, senile brain function injury, migraine, mild, moderate hypertension, and/or sudden deafness. Different dosages are used depending on the administration method, age, weight and condition of the patient. Typically in the case of oral administration, about 10ml of oral solution is administered every 4 hours per adult.
The nimodipine oral solution and the preparation method thereof provided by the invention have the following beneficial effects:
1. the oral solution provided by the invention has good taste and smell, high comprehensive acceptance and good medicine taking compliance of children and old patients;
2. the disodium glycyrrhizinate and methylparaben in the oral solution provided by the invention have a synergistic effect, so that the problems that nimodipine oral solution is too viscous to generate a large amount of foam in the production and filling processes, the foam is serious and cannot be removed in a short time are solved, on one hand, the operation steps are simplified, the step of sucking away the generated foam when the oral solution is prepared is avoided, and the extra material loss generated when the foam is sucked away is also avoided, and on the other hand, the problems that the liquid in a packaging bottle generates foam and the foam often overflows the bottle opening due to the impact force when the filling needle injects the liquid into the packaging bottle when the oral solution is filled are solved, so that the product filling quantity is not uniform and is not qualified;
3. the oral solution provided by the invention has good smell even if only the sweetening agent disodium glycyrrhizinate is used and no aromatic is added, and the medicine taking compliance of children and old patients is good;
4. the preparation method of the oral liquid provided by the invention is simple to operate, has high industrial operation feasibility, less three-waste discharge, is green, environment-friendly and sustainable, is beneficial to large-scale industrial production, and is more suitable for industrialization.
Detailed Description
For better understanding of the technical solutions of the present invention, the technical solutions of the present invention are further described below with reference to specific examples, which are only used for assisting understanding of the present invention and should not be construed as specifically limiting the present invention.
In the following examples, nimodipine drug substance and various excipients were all commercially available.
In the following examples, the percentages referred to are by weight unless otherwise indicated.
The formulations of the nimodipine oral liquids of examples 1-11 and the amounts (i.e., unit amounts) and ratios (i.e., weight percent amounts) of the components in the formulations are as follows:
the preparation method of nimodipine oral liquid in examples 1 to 11:
(1) Adding polyethylene glycol 400 of a prescription amount into a preparation tank 1, adding nimodipine of the prescription amount into the preparation tank, stirring and dissolving, wherein the stirring speed is 1000-2000rpm, and the stirring time is 30-60min, so as to obtain a solution 1;
(2) Adding the glycerol with the prescription amount into a preparation tank 2, adding the sweetening agent with the prescription amount, and stirring until the sweetening agent is dissolved to obtain a solution 2;
(3) Pouring the solution 2 into the solution 1, and stirring for 30-60min to obtain a solution 3;
(4) Adding a prescription amount of preservative into a preparation tank 3, adding a prescription amount of 95% ethanol, and stirring until the preservative is dissolved to obtain a solution 4;
(5) And pouring the solution 4 into the solution 3, starting stirring at the stirring speed of 1000-2000rpm for 60-120 min, and uniformly mixing to obtain the nimodipine oral solution.
The formulations of the nimodipine oral liquids of examples 12-20 and the amounts (i.e., unit amounts) and ratios (i.e., weight percent amounts) of the components in the formulations are shown in the following table:
the preparation method of nimodipine oral liquid in examples 12 to 20:
(1) Adding polyethylene glycol 400 of a prescription amount into a preparation tank 1, adding nimodipine of the prescription amount into the preparation tank, stirring and dissolving, wherein the stirring speed is 1000-2000rpm, and the stirring time is 30-60min, so as to obtain a solution 1;
(2) Adding the glycerol with the prescription amount into a preparation tank 2, adding the disodium glycyrrhizinate with the prescription amount, and stirring until the disodium glycyrrhizinate is dissolved to obtain a solution 2;
(3) Pouring the solution 2 into the solution 1, and stirring for 30-60min to obtain a solution 3;
(4) Adding a prescribed amount of methylparaben and an aromatic agent into a preparation tank 3, adding a prescribed amount of 95% ethanol, and stirring until the mixture is dissolved to obtain a solution 4;
(5) And pouring the solution 4 into the solution 3, starting stirring at the stirring speed of 1000-2000rpm for 60-120 min, and uniformly mixing to obtain the nimodipine oral solution.
Test example 1 taste test
10 subjects were selected and the oral solutions prepared in examples 1-20 were randomly subjected to mouth feel and overall acceptability determination. The measurement results were rated according to the rating scale shown in table 1 below. The highest value and the lowest value of the evaluation values of each grade of each nimodipine oral solution of 10 subjects are respectively removed, then the average value is calculated, and the determination results are shown in the following table:
TABLE 1
Grade | 0-1 | 1.1-2 | 2.1-3 | 3.1-4 | 4.1-5 | 5.1-6 |
Sweet/bitter mouthfeel | Neglect to count | Light and slight | Middle lower level | Medium and high grade | Middle-high class | High, etc |
TABLE 2
Referring to tables 1-2, based on an analysis of the data measured in examples 1-20, the technical effect of examples 15-20 in mouthfeel and overall acceptability is better in the 18 groups of examples, and particularly the technical effect of examples 12-17 and example 19 in mouthfeel and overall acceptability is better in the 18 groups of examples, with the technical effect of example 12 in mouthfeel and overall acceptability being the best in the 18 groups of examples. The nimodipine oral solution prepared by the technical scheme of the invention has obvious improvement on the aspects of taste and comprehensive acceptability, and has obvious effects of improving the medicine taking compliance and the clinical medicine taking rationality of children and old people, thereby having better treatment effect on complications of subarachnoid hemorrhage patients and effectively solving the technical problems in the prior art.
Test example 2 odor test
TABLE 3 evaluation of the Effect of sweetening and flavoring Agents on the odor masking of methylparaben
The results are shown in table 3, and the masking effect on the bad smell is weak by simply increasing the dosage of the sucralose; when disodium glycyrrhizinate is adopted to replace sucralose as a sweetening agent, a better covering effect is achieved on unpleasant odor; when disodium glycyrrhizinate is adopted to replace sucralose and various essences are compounded, the covering effect on bad smell is better; when 1% of strawberry essence is adopted to compound 0.2% of disodium glycyrrhizinate, the covering effect on the bad smell is the best.
Test example 3 foaming test
Nimodipine oral liquid capable of being filled into 20 bottles (100 ml per bottle) is prepared according to the examples 1-20, and is filled by an oral liquid filling machine, and the foaming condition during filling is recorded; after filling, the contents were checked according to the minimum filling inspection method (general rule 0942) in the "chinese pharmacopoeia" (2020 edition), and the labeled and average filling amounts of the nimodipine oral liquids of examples 1 to 20 were recorded, respectively.
Examples | Foaming behaviour | Indicating the amount of filling | Minimum loading | Average loading | Result of load check |
Example 1 | Foaming | 100ml | 97ml | 97.2ml | Relatively uniform and qualified |
Example 2 | Foaming | 100ml | 97ml | 97.5ml | Relatively uniform and qualified |
Example 3 | Foaming | 100ml | 97ml | 97.4ml | Relatively uniform and qualified |
Example 4 | Foaming | 100ml | 97ml | 97.8ml | Relatively uniform and qualified |
Example 5 | Slight foaming | 100ml | 97ml | 99.5ml | Uniform and qualified |
Example 6 | Slight foaming | 100ml | 97ml | 98.9ml | Uniform and qualified |
Example 7 | Slight foaming | 100ml | 97ml | 99.1ml | Uniform and qualified |
Example 8 | Slight blistering | 100ml | 97ml | 98.9ml | Uniform and qualified |
Example 9 | Slight foaming | 100ml | 97ml | 99.3ml | Is uniform and qualified |
Example 10 | Severe blistering | 100ml | 97ml | 96.4ml | Non-uniformity and fail |
Example 11 | Severe blistering | 100ml | 97ml | 95.5ml | Non-uniformity and fail |
Example 12 | Slight foaming | 100ml | 97ml | 99.1ml | Uniform and qualified |
Example 13 | Slight foaming | 100ml | 97ml | 99.0ml | Uniform and qualified |
Example 14 | Slight foaming | 100ml | 97ml | 99.1ml | Uniform and qualified |
Example 15 | Slight blistering | 100ml | 97ml | 99.2ml | Is uniform and qualified |
Example 16 | Slight foaming | 100ml | 97ml | 99.0ml | Uniform and qualified |
Example 17 | Slight foaming | 100ml | 97ml | 99.3ml | Is uniform and qualified |
Example 18 | Slight foaming | 100ml | 97ml | 98.9ml | Is uniform and qualified |
Example 19 | Slight foaming | 100ml | 97ml | 99.4ml | Uniform and qualified |
Example 20 | Slight foaming | 100ml | 97ml | 99.0ml | Is uniform and qualified |
According to the experimental investigation result, the following results are obtained: the formulas of the embodiments 1 to 9 and the embodiments 12 to 20 of the invention simultaneously contain the disodium glycyrrhizinate and the methylparaben, so that the prepared preparation has less foaming during filling, the filling amount is uniform, and the filling amount inspection is qualified; in the embodiment 10, disodium glycyrrhizinate exists in the prescription, but benzoic acid is used for replacing methyl hydroxybenzoate, and the prepared preparation has serious foaming during filling, uneven filling amount and unqualified filling amount inspection; in example 11, in the formulation, methyl hydroxybenzoate was present but benzene sucralose was used instead of disodium glycyrrhizinate, and the prepared preparation was very foamy during filling, the filling amount was not uniform, and the filling amount inspection was not qualified.
Test example 4 stability test
The preparations obtained in examples 1 to 20 were placed in a constant temperature and humidity chamber at 25 ℃ and RH60%, sampled at 0, 6 and 12 months, and the appearance was examined, and the change of foreign matter, pH, related substances and contents was observed, and the results are shown in Table 5.
Table 5 long term test results for formulations 1-20
According to the experimental investigation result, the following results are obtained: all indexes of the preparation prepared by the embodiments 1-20 of the invention meet the regulations; comprehensively considered, the method has high yield, good safety and stable quality, and is worthy of popularization in production.
Claims (10)
1. A nimodipine oral solution is characterized by comprising a nimodipine active ingredient, a sweetening agent disodium glycyrrhizinate, a preservative methylparaben and other pharmaceutically acceptable auxiliary materials.
2. Nimodipine oral solution according to claim 1, wherein the other pharmaceutically acceptable excipients are solvents or solvents and aromatics.
3. The nimodipine oral solution according to claim 2, wherein the solvent is 1-4 of polyethylene glycol, glycerol, ethanol, propylene glycol.
4. The nimodipine oral solution according to claim 1, which is composed of nimodipine, disodium glycyrrhizinate, methylparaben, polyethylene glycol 400, glycerol and ethanol; or, the composition comprises nimodipine, disodium glycyrrhizinate, methylparaben, polyethylene glycol 400, glycerol, ethanol and aromatic.
5. The nimodipine oral solution according to any one of claims 1 to 4, wherein the weight percentage of the disodium glycyrrhizinate in the prescription is 0.01-1.0%; and/or the weight percentage of the methyl hydroxybenzoate in the prescription is 0.015-0.5%; and/or the weight ratio of the disodium glycyrrhizinate to the methylparaben is 1 (0.3-3); and/or, the weight percentage of the polyethylene glycol in the prescription is 30-60%; and/or, the weight percentage of the glycerol in the prescription is 33.4-66.7%; the weight percentage of the ethanol in the prescription is 0.5-5%; and/or the essence accounts for 0.5 to 2 percent of the weight of the formula.
6. The nimodipine oral solution according to claim 1, wherein the weight percentage of each component is:
Or the like, or, alternatively,
7. the nimodipine oral solution according to claim 1, wherein the weight percentage of each component is:
Or the like, or, alternatively,
。
8. Nimodipine oral solution according to any of claims 1 to 7, wherein the flavoring agent is one or more of cherry-based, raspberry-based, strawberry-based, mint-based, honeydew melon-based, juicy peach-based, mango-based, apple-based, banana-based, watermelon-based, orange-based, grape-based, litchi-based.
9. A method for preparing nimodipine oral solution according to any one of claims 1 to 7, which comprises the following steps:
(1) Adding polyethylene glycol 400 of a prescription amount into a preparation tank 1, adding nimodipine of the prescription amount into the preparation tank, stirring and dissolving, wherein the stirring speed is 1000-2000rpm, and the stirring time is 30-60min, so as to obtain a solution 1;
(2) Adding the glycerol with the prescription amount into a preparation tank 2, adding the sweetening agent with the prescription amount, and stirring until the sweetening agent is dissolved to obtain a solution 2;
(3) Pouring the solution 2 into the solution 1, and stirring for 30-60min to obtain a solution 3;
(4) Adding a prescription amount of preservative into a preparation tank 3, adding a prescription amount of 95% ethanol, and stirring until the preservative is dissolved to obtain a solution 4;
(5) And pouring the solution 4 into the solution 3, starting stirring at the stirring speed of 1000-2000rpm for 60-120 min, and uniformly mixing to obtain the nimodipine oral solution.
10. Use of the nimodipine oral solution according to any one of claims 1 to 7 or the nimodipine oral liquid prepared by the method according to claim 8 for the preparation of a medicament for the treatment and/or prevention of complications in subarachnoid hemorrhage patients.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210907464.5A CN115177585A (en) | 2022-07-29 | 2022-07-29 | Nimodipine oral solution and preparation method thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210907464.5A CN115177585A (en) | 2022-07-29 | 2022-07-29 | Nimodipine oral solution and preparation method thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
CN115177585A true CN115177585A (en) | 2022-10-14 |
Family
ID=83520715
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210907464.5A Pending CN115177585A (en) | 2022-07-29 | 2022-07-29 | Nimodipine oral solution and preparation method thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115177585A (en) |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106074366A (en) * | 2016-06-16 | 2016-11-09 | 邢涛 | Injection of disturbance of consciousness and preparation method thereof after treatment cerebral trauma and brain surgery |
US10342787B1 (en) * | 2018-01-25 | 2019-07-09 | Arbor Pharmaceuticals, Llc | Non-aqueous liquid nimodipine compositions |
CN113509434A (en) * | 2021-04-26 | 2021-10-19 | 广东金城金素制药有限公司 | Nimodipine oral solution, preparation method and application thereof |
US20220218684A1 (en) * | 2018-01-25 | 2022-07-14 | Arbor Pharmaceuticals, Llc | Liquid nimodipine compositions |
-
2022
- 2022-07-29 CN CN202210907464.5A patent/CN115177585A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106074366A (en) * | 2016-06-16 | 2016-11-09 | 邢涛 | Injection of disturbance of consciousness and preparation method thereof after treatment cerebral trauma and brain surgery |
US10342787B1 (en) * | 2018-01-25 | 2019-07-09 | Arbor Pharmaceuticals, Llc | Non-aqueous liquid nimodipine compositions |
US20220218684A1 (en) * | 2018-01-25 | 2022-07-14 | Arbor Pharmaceuticals, Llc | Liquid nimodipine compositions |
CN113509434A (en) * | 2021-04-26 | 2021-10-19 | 广东金城金素制药有限公司 | Nimodipine oral solution, preparation method and application thereof |
Non-Patent Citations (1)
Title |
---|
师海波等: "《最新临床药物手册 第3版》", vol. 3, 军事医学科学出版社, pages: 832 - 350 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6939550B2 (en) | Stabilized antihistamine syrup | |
EP1025858A1 (en) | Medicinal compositions with relieved bitterness, etc. | |
JPH11514013A (en) | A novel stable liquid formulation of paracetamol and its production method | |
KR20130099140A (en) | Bepotastine compositions | |
US10959985B1 (en) | Pharmaceutical compositions including carvedilol and methods of using the same | |
JP4959335B2 (en) | Methylphenidate solution and related administration and manufacturing methods | |
US9855228B1 (en) | Oral solution comprising atomoxetine hydrochloride and methods thereof | |
CN115177585A (en) | Nimodipine oral solution and preparation method thereof | |
WO2020239052A1 (en) | Chloral hydrate-containing medicinal kit and uses thereof | |
US11779567B2 (en) | Method for optimizing 5-hydroxytryptamine function in the brain for therapeutic purposes | |
GB2564444A (en) | Liquid pharmaceutical composition of flecainide | |
HU179989B (en) | Process for preparing pharmacological compositions containing r-/+/-1-/1-phenyl-ethyl/-1h-imidazol-5-carboxylic acid ethyl ester for intravenous administration | |
CN113509434A (en) | Nimodipine oral solution, preparation method and application thereof | |
NL2024160B1 (en) | Pharmaceutical liquid composition, kit of parts comprising the pharmaceutical liquid composition, and method for preparing the pharmaceutical liquid composition | |
CN114159387B (en) | Dextromethorphan hydrobromide oral solution | |
CN115645357A (en) | Lacosamide oral solution prescription and preparation process thereof | |
WO2023101252A1 (en) | Ophthalmic nanoemulsion composition for treating macular degeneration and method for preparing same | |
CN116172948A (en) | Cetirizine hydrochloride oral solution and preparation method thereof | |
CN115590813A (en) | Loratadine oral solution and preparation method thereof | |
EP4279062A1 (en) | Liquid composition and its use, treatment method and kit | |
GB2617419A (en) | Stable composition of chloral hydrate | |
CA3233691A1 (en) | Compositions and methods for treating sialorrhea | |
KR20240006523A (en) | Tizanidine liquid preparation and uses thereof | |
CN117180186A (en) | Ebastine oral solution and preparation method thereof | |
WO2024062443A1 (en) | Pharmaceutical compositions |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |