CN107303266B - Levo-oxiracetam injection and preparation method thereof - Google Patents
Levo-oxiracetam injection and preparation method thereof Download PDFInfo
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- CN107303266B CN107303266B CN201610238973.8A CN201610238973A CN107303266B CN 107303266 B CN107303266 B CN 107303266B CN 201610238973 A CN201610238973 A CN 201610238973A CN 107303266 B CN107303266 B CN 107303266B
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- 229960001227 oxiracetam Drugs 0.000 title claims abstract description 38
- 238000002347 injection Methods 0.000 title claims abstract description 37
- 239000007924 injection Substances 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000003814 drug Substances 0.000 claims abstract description 19
- 239000007788 liquid Substances 0.000 claims abstract description 19
- 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
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims abstract description 13
- 229960003194 meglumine Drugs 0.000 claims abstract description 13
- 238000011049 filling Methods 0.000 claims abstract description 12
- 230000001954 sterilising effect Effects 0.000 claims abstract description 11
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims abstract description 10
- 238000004659 sterilization and disinfection Methods 0.000 claims abstract description 10
- 229940124274 edetate disodium Drugs 0.000 claims abstract description 8
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- 239000000463 material Substances 0.000 claims abstract description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- 239000000243 solution Substances 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000008215 water for injection Substances 0.000 claims description 9
- 238000005429 filling process Methods 0.000 claims description 8
- 239000003708 ampul Substances 0.000 claims description 6
- 238000007865 diluting Methods 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 238000003860 storage Methods 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 239000000706 filtrate Substances 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 238000007689 inspection Methods 0.000 claims description 3
- 239000012528 membrane Substances 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000011265 semifinished product Substances 0.000 claims description 3
- 238000005303 weighing Methods 0.000 claims description 3
- 239000006260 foam Substances 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 4
- 239000012535 impurity Substances 0.000 abstract description 3
- 230000000087 stabilizing effect Effects 0.000 abstract description 2
- 238000010790 dilution Methods 0.000 abstract 1
- 239000012895 dilution Substances 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- IHLAQQPQKRMGSS-UHFFFAOYSA-N oxiracetam Chemical compound NC(=O)CN1CC(O)CC1=O IHLAQQPQKRMGSS-UHFFFAOYSA-N 0.000 description 7
- 230000007774 longterm Effects 0.000 description 5
- 238000011835 investigation Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- SUHOOTKUPISOBE-UHFFFAOYSA-N O-phosphoethanolamine Chemical compound NCCOP(O)(O)=O SUHOOTKUPISOBE-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 239000002664 nootropic agent Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010028400 Mutagenic effect Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 206010074268 Reproductive toxicity Diseases 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 201000004559 cerebral degeneration Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- -1 cyclic GABOB derivative Chemical class 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 231100000243 mutagenic effect Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 210000000956 olfactory bulb Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 description 1
- 229950004354 phosphorylcholine Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000007696 reproductive toxicity Effects 0.000 description 1
- 231100000372 reproductive toxicity Toxicity 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
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- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
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- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract
The invention discloses a levo-oxiracetam injection and a preparation method thereof; each mL of injection contains the following raw and auxiliary materials: 180-220mg of levo-oxiracetam, 0.01-0.1mg of edetate disodium, 4-5mg of methylparaben and 10-16mg of meglumine; the preparation method of the injection comprises the steps of concentration, dilution, filling, sterilization and the like. The prepared levo-oxiracetam injection does not foam, does not have the problem of liquid medicine adhesion, has high product yield, good product stability, long validity period and few product impurities by utilizing the defoaming effect of methyl hydroxybenzoate and the dissolving-assisting stabilizing effect of disodium edetate and meglumine, and all indexes meet the production requirements.
Description
Technical Field
The invention belongs to the field of pharmacy, and particularly relates to a levo-oxiracetam injection and a preparation method thereof.
Background
An intelligence promoting medicine is also called as brain activating element, and is a novel central nervous system medicine for promoting learning and enhancing memory. Nootropic agents require selective action on the cerebral cortex and have the characteristics of selective activation, protection and promotion of functional recovery of damaged nerve cells. One difference with other nerve drugs is that their above-mentioned action does not go through the reticular system or olfactory bulb, but directly acts on the cortex. Neither behavior nor sedation and excitement is affected, so that the medicines have attracted extensive attention and interest, and the demand for the medicines is increasing.
Oxiracetam (oxiracetam, CAS No.: 62613-82-5) has the chemical name of 4-hydroxy-2-oxo-1-pyrrolidine acetamide, is an anti-hypoxia nootropic drug (the compound is disclosed in US4118396) which is synthesized for the first time in 1974 by ISFS. P.A. company of Italy, is a cyclic GABOB derivative, can promote the synthesis of phosphorylcholine and phosphorylethanolamine, promote brain metabolism, penetrate blood brain barrier, has stimulation effect on specific central nervous pathways, can improve intelligence and memory, has better curative effect on cerebrovascular diseases, brain trauma, brain tumor, intracranial infection, brain degeneration diseases and the like, and has extremely low toxicity, no mutagenic effect, carcinogenic effect and reproductive toxicity. The chemical structure and preparation of oxiracetam is disclosed in US4118396 by Giorgio et al, and the pharmaceutical efficacy of oxiracetam in the S configuration (levo) is shown in the clinical results in WO9306826A by Chiodini et al, which is stronger than that in the R configuration (dextro), with oxiracetam and levooxiracetam structures shown below.
The existing levo-oxiracetam injection is easy to generate foam in the filling process, an ampoule bottle is adopted for filling, the liquid medicine is adhered to the bottle opening, the liquid medicine is carbonized in the ampoule bottle sealing process, so that visible foreign matters of a product are unqualified, the product yield is reduced, and the unknown safety of the patient in medicine use is increased; the penicillin bottle is adopted for filling, the solution is adhered to the bottle mouth, the plug is easy to jump, and the product yield is also reduced.
Disclosure of Invention
In view of the above, the invention aims to provide a levo-oxiracetam injection and a preparation method thereof, wherein the injection does not foam, does not have the problem of adhesion of the injection, and improves the product yield.
In order to achieve the purpose, the invention provides the following technical scheme:
a levo-oxiracetam injection contains the following raw and auxiliary materials in each mL of injection: 180-220mg of levo-oxiracetam, 0.01-0.1mg of edetate disodium, 4-5mg of methylparaben and 10-16mg of meglumine.
Furthermore, each mL of the injection contains the following raw and auxiliary materials: 200mg of levo-oxiracetam, 0.05mg of edetate disodium, 4.5mg of methylparaben and 13mg of meglumine.
The preparation method of the levo-oxiracetam injection comprises the following steps:
(1) concentration and preparation: weighing methylparaben and meglumine according to the prescription amount, adding the methylparaben and the meglumine into water for injection, stirring and dissolving, adjusting the pH value to 6.0 by using 0.1mol/L hydrochloric acid solution, adding edetate disodium and levooxiracetam according to the prescription amount, stirring and dissolving, and adjusting the pH value to 5.0 by using 0.1mol/L hydrochloric acid solution to obtain concentrated solution;
(2) diluting and preparing: taking the concentrated solution, diluting to constant volume with water for injection, filtering with 0.45 μm filter membrane, and collecting filtrate;
(3) filling: after the inspection is qualified, filling the liquid medicine in a production line, wherein the horizontal height of the position of the buffer liquid storage tank is 10-15 cm higher than that of the position of the liquid medicine nozzle during filling;
(4) and (3) sterilization: and (3) feeding the filled semi-finished product of the anzaiton into a steam sterilization pot for sterilization to obtain the levo-oxiracetam injection.
Further, nitrogen is required to be introduced for treatment in the concentration process in the step (1), and the nitrogen flow is 0.03-0.08L/min; and (3) in the filling process of the step (3), the buffer liquid storage tank needs to be filled with nitrogen, and the filling process needs to be filled with nitrogen with the purity of 99.99% so that the oxygen content in the water for injection in the tank does not exceed 0.01%.
The invention has the beneficial effects that:
the prepared levo-oxiracetam injection does not foam, does not have the problem of liquid medicine adhesion, has high product yield, good product stability, long validity period and few product impurities by utilizing the defoaming effect of methyl hydroxybenzoate and the dissolving-assisting stabilizing effect of disodium edetate and meglumine, and all indexes meet the production requirements.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, preferred embodiments of the present invention will be described in detail below.
Example 1
The formula of the levo-oxiracetam injection of example 1 is shown in the following table:
the preparation method of the levo-oxiracetam injection of embodiment 1 comprises the following steps:
(1) concentration and preparation: weighing methylparaben and meglumine according to the prescription amount, adding the methylparaben and the meglumine into water for injection, stirring and dissolving, adjusting the pH value to 6.0 by using 0.1mol/L hydrochloric acid solution, adding edetate disodium and levooxiracetam according to the prescription amount, stirring and dissolving, and adjusting the pH value to 5.0 by using 0.1mol/L hydrochloric acid solution to obtain concentrated solution; nitrogen is introduced for treatment in the concentration process, and the flow rate of the nitrogen is 0.03-0.08L/min;
(2) diluting and preparing: taking the concentrated solution, diluting to 1000mL with water for injection, filtering with 0.45 μm filter membrane, and collecting filtrate;
(3) filling: after the inspection is qualified, filling the liquid medicine in a production line, wherein the horizontal height of the position of the buffer liquid storage tank is 10-15 cm higher than that of the position of the liquid medicine nozzle during filling; in the filling process, the buffer liquid storage tank needs to be filled with nitrogen, and the filling process needs to be filled with nitrogen with the purity of 99.99 percent so that the oxygen content in the water for injection in the tank does not exceed 0.01 percent;
(4) and (3) sterilization: and (3) feeding the filled Ancui semi-finished product into a steam sterilization pot for sterilization, and sterilizing at 121 ℃ for 15min to obtain the levo-oxiracetam injection.
Comparative example 1
The levo-oxiracetam injection of comparative example 1 was prepared without adding methylparaben, and the remaining components and preparation method were the same as those of example 1.
Example 2
The formula of the levo-oxiracetam injection of example 2 is shown in the following table:
the preparation method of the levo-oxiracetam injection of the embodiment 2 is the same as that of the embodiment 1.
Comparative example 2
The levo-oxiracetam injection of comparative example 2 was prepared without adding methylparaben, and the remaining components and preparation method were the same as in example 2.
Example 3
The formula of the levo-oxiracetam injection of example 3 is shown in the following table:
the preparation method of the levo-oxiracetam injection of the embodiment 3 is the same as that of the embodiment 1.
Comparative example 3
The levo-oxiracetam injection of comparative example 3 was prepared without adding methylparaben, and the remaining components and preparation method were the same as those of example 3.
Firstly, long-term test investigation:
the levo-oxiracetam injection prepared in the embodiment 1-3 is packaged on the market, placed in a long-term sample-holding box, sampled for a certain time and inspected on an investigation item.
Long-term test temperature: 20 ± 2 ℃, humidity: RH 60% ± 10%, investigation time: 0. 12 and 24 months, and the indexes are considered: appearance, visible foreign matter, pH, related substances, and content.
Long-term test stability recording:
according to the long-term test investigation results, the levo-oxiracetam injection prepared in the embodiment 1-3 has the advantages of good product stability, long validity period and few product impurities, and all indexes meet the production requirements.
Secondly, calculating the yield:
the product yields of examples 1 to 3 and comparative examples 1 to 3 were calculated as follows:
| example 1 | Example 2 | Example 3 | Comparative example 1 | Comparative example 2 | Comparative example 3 | |
| Theoretical yield (bottle) | 200 | 200 | 200 | 200 | 200 | 200 |
| Actual production (bottle) | 172 | 165 | 170 | 134 | 130 | 125 |
| Yield (%) | 86 | 82.5 | 85 | 67 | 65 | 62.5 |
According to the calculation result of the yield, the liquid medicine adhered to the bottle mouth is carbonized to cause that the visible foreign matters of the injection are unqualified when the ampoule bottle is sealed by melting at high temperature because the liquid medicine is adhered to the bottle mouth of the ampoule bottle in the filling process of the comparative example, so that the product yield is reduced; in the embodiment, the liquid medicine does not foam, so that the situation of adhering the opening of the ampoule is avoided, and the yield is greatly improved.
Finally, it is noted that the above-mentioned preferred embodiments illustrate rather than limit the invention, and that, although the invention has been described in detail with reference to the above-mentioned preferred embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the scope of the invention as defined by the appended claims.
Claims (3)
1. A levo-oxiracetam injection is characterized in that: each mL of injection contains the following raw and auxiliary materials: 220mg of levo-oxiracetam 180-containing material, 0.01-0.1mg of edetate disodium, 4-5mg of methylparaben and 10-16mg of meglumine;
the preparation method of the levo-oxiracetam injection comprises the following steps:
(1) concentration and preparation: weighing methylparaben and meglumine according to the prescription amount, adding the methylparaben and the meglumine into water for injection, stirring and dissolving, adjusting the pH value to 6.0 by using 0.1mol/L hydrochloric acid solution, adding edetate disodium and levooxiracetam according to the prescription amount, stirring and dissolving, and adjusting the pH value to 5.0 by using 0.1mol/L hydrochloric acid solution to obtain concentrated solution;
(2) diluting and preparing: taking the concentrated solution, diluting to constant volume with water for injection, filtering with 0.45 μm filter membrane, and collecting filtrate;
(3) filling: after the inspection is qualified, filling the liquid medicine in a production line, wherein the horizontal height of the position of the buffer liquid storage tank is 10-15 cm higher than that of the position of the liquid medicine nozzle during filling;
(4) and (3) sterilization: and (4) feeding the filled ampoule semi-finished product into a steam sterilization pot for sterilization to obtain the levo-oxiracetam injection.
2. The levo-oxiracetam injection according to claim 1, characterized in that: each mL of injection contains the following raw and auxiliary materials: 200mg of levo-oxiracetam, 0.05mg of edetate disodium, 4.5mg of methylparaben and 13mg of meglumine.
3. The levo-oxiracetam injection according to claim 1 or 2, characterized in that: the concentration preparation process in the step (1) needs nitrogen introduction treatment, and the nitrogen flow is 0.03-0.08L/min; and (3) in the filling process of the step (3), the buffer liquid storage tank needs to be filled with nitrogen, and the filling process needs to be filled with nitrogen with the purity of 99.99% so that the oxygen content in the water for injection in the tank does not exceed 0.01%.
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| CN102525899A (en) * | 2012-01-17 | 2012-07-04 | 山东罗欣药业股份有限公司 | Injection solution of oxiracetam composition and preparation method thereof |
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|---|---|---|---|---|
| CN101217939A (en) * | 2005-05-27 | 2008-07-09 | 灵药生物技术有限公司 | Injectable compositions and process of preparation thereof |
| KR20090098325A (en) * | 2008-03-14 | 2009-09-17 | 엔자이텍 주식회사 | New Production Process of Racemic or Optically Pure (S) -Oxyracetam |
| CN101766565A (en) * | 2008-12-31 | 2010-07-07 | 北京利乐生制药科技有限公司 | Oral liquid preparation with levo-oxiracetam as active component |
| CN101766597A (en) * | 2008-12-31 | 2010-07-07 | 北京利乐生制药科技有限公司 | Injection preparation with levo-oxiracetam as active component |
| CN102512363A (en) * | 2011-12-23 | 2012-06-27 | 重庆药友制药有限责任公司 | Oxiracetam injection and preparation method thereof |
| CN102525899A (en) * | 2012-01-17 | 2012-07-04 | 山东罗欣药业股份有限公司 | Injection solution of oxiracetam composition and preparation method thereof |
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