CN1562000A - 4-hydroxy-2-oxo-1-pyrrolidine acetamide freeze-dried preparation and its preparing method - Google Patents
4-hydroxy-2-oxo-1-pyrrolidine acetamide freeze-dried preparation and its preparing method Download PDFInfo
- Publication number
- CN1562000A CN1562000A CN 200410029667 CN200410029667A CN1562000A CN 1562000 A CN1562000 A CN 1562000A CN 200410029667 CN200410029667 CN 200410029667 CN 200410029667 A CN200410029667 A CN 200410029667A CN 1562000 A CN1562000 A CN 1562000A
- Authority
- CN
- China
- Prior art keywords
- oxo
- solution
- hydroxyl
- pyrrolidine acetamide
- pharmaceutically acceptable
- 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
Abstract
The invention relates to a 4-hydroxy-2-oxo-1-pyrrolidine acetamide freeze-dried preparation and its preparing method, which is manufactured by freezing and drying a solution containing the 4-hydroxy-2-oxo-1-pyrrolidine acetamide or the 4-hydroxy-2-oxo-1-pyrrolidine acetamide and a pharmaceutically acceptable excipient; the pH value of said solution is between 4.5-7.5, preferredly in the scope of 4.5-6.5. Said excipient may be one or more than one materials chosen from glycine, lactose, sodium chloride, glucose and sorbitol. The solution may also contain a conventionally pharmaceutically acceptable assistant including stabilizer, analgesic, and buffer; a pharmaceutically acceptable pH regulator; and/or pharmaceutically acceptable medicines that have other secondary functions. The inventive freeze-dried preparation has a steady performance, a rapid effection, and a winne roler; it is easy to use, store and transport; and it is mainly used in the first aid of cerebral anoxic, which makes some serious patients get a prompt rescue.
Description
Technical field
The present invention belongs to field of pharmaceutical preparations, specifically, relates to a kind of 4-hydroxyl-2-OXo-1-pyrrolidine acetamide lyophilized formulations and preparation method thereof.
Technical background
(claim oxiracetam again, Oxiracetam) be the cyclic derivatives of a new hydroxy-amino-butyric acid (GABOB) to 4-hydroxyl-2-OXo-1-pyrrolidine acetamide, is piracetam (Piracetam) class nootropics.Have half senile cell vigor is strengthened, significantly improve the effect of brain memory, effective to senile memory and mental deterioration.Be applicable to that clinically brain function is incomplete, memory disorder, especially senile dementia in addition, is used for neurosis, cerebral trauma, the rehabilitation of diseases such as encephalitis.In recent years, the foreign study personnel have found the anti-platelet aggregation of 4-hydroxyl-2-OXo-1-pyrrolidine acetamide ex hoc genus anne medicine again and to erythrocytic pharmacological property, and have detoxifcation and immunization.Can predict, 4-hydroxyl-2-OXo-1-pyrrolidine acetamide will have more wide prospect than present piracetam salable.This medicine social need amount is bigger at present, and dosage form is single, has only capsule, can not meet the need of market.And capsule has onset slow, and Time of Administration is long, is not suitable for the drawback of emergency rescue.
Summary of the invention
In order to overcome the deficiency of prior art, the object of the present invention is to provide a kind of 4-hydroxyl-2-OXo-1-pyrrolidine acetamide pharmaceutical preparation, its stable performance, instant effect, effect is strong, is easy to transportation and storage, and is easy to use.
Another object of the present invention is to provide a kind of method for preparing above-mentioned 4-hydroxyl-2-OXo-1-pyrrolidine acetamide injection medicine preparation, and method is simple for this, helps large-scale production.
The appropriate formulation that the inventor is rapid-action in order to seek, the effect strong, stable performance, convenient transportation store, and the stability problem of solution preparation process Chinese medicine, having done a large amount of deep researchs explores, find to adopt freeze drying process and suitable condition to prepare lyophilized formulations, can solve problems such as stability of formulation and transportation storage effectively, the injection instant effect, good drug efficacy.
The invention provides a kind of 4-hydroxyl-2-OXo-1-pyrrolidine acetamide lyophilized formulations, it is made after lyophilization by the solution that contains 4-hydroxyl-2-OXo-1-pyrrolidine acetamide.Described solution is preferably controlled pH value 4.5～7.5, more preferably between 4.5～6.5.
Also can contain pharmaceutically acceptable excipient in the described solution.Described pharmaceutically acceptable excipient is to be generally used for preparing lyophilized formulations, get the filling bracket effect, make exsiccant medicine can keep the material of certain volume, for example: glycine, lactose, sodium chloride, glucose, sorbitol or other pharmaceutically acceptable excipient or their mixture, preferred glycine.The consumption of described excipient is to prepare the used conventional amount used of lyophilized formulations usually.
Described solution can be to be the solution of solvent with water, can be to be the solution of solvent with the organic solvent, can be the solution of solvent with water and organic solvent also.Described organic solvent can be pharmaceutically acceptable organic solvent.
Described solution can comprise pharmaceutically acceptable pH regulator agent, to regulate the pH value of described solution.Described pH regulator agent can be at least a pharmaceutically acceptable material that is used to regulate pH value, it can be one or more the material in alkali compounds, buffer system and the acid, for example: phosphate buffer, sodium hydroxide, phosphoric acid, acetic acid etc., preferably phosphoric acid salt buffer.
The material that also can further comprise one or more in the acceptable adjuvant on the conventional pharmaceutical such as stabilizing agent, analgesics and buffer agent in 4-hydroxyl of the present invention-2-OXo-1-pyrrolidine acetamide pharmaceutical preparation.
A kind of 4-hydroxyl provided by the invention-2-OXo-1-pyrrolidine acetamide lyophilized formulations, can after lyophilization, make by one or more the solution of excipient that contains in 4-hydroxyl-2-OXo-1-pyrrolidine acetamide or 4-hydroxyl-2-OXo-1-pyrrolidine acetamide and glycine, lactose, sodium chloride, glucose, sorbitol and other the pharmaceutically acceptable excipient; The pH value of described solution is 4.5～7.5, more preferably 4.5～6.5; The consumption of described excipient is the conventional amount used for preparing the used excipient of lyophilized formulations usually; Described solution is solvent with water and/or pharmaceutically acceptable organic solvent.Can contain 10 to 60% in the described solution, preferred 10 to 35% (percentage by weight) 4-hydroxyl-2-OXo-1-pyrrolidine acetamide, 0 to 50%, preferred 10 to 40% (percentage by weight) excipient, and the solvent of surplus.The preferred glycine of described excipient.
The invention provides the method for a kind of 4-of preparation hydroxyl-2-OXo-1-pyrrolidine acetamide medicament freeze-drying preparation, comprise: (1) preparation contains the solution of 4-hydroxyl-2-OXo-1-pyrrolidine acetamide, described solution is preferably controlled pH value 4.5～7.5, more preferably between 4.5～6.5; And (1) step of (2) lyophilization gained solution.
Solution described in described (1) step can be to be the solution of solvent with water and/or organic solvent.Described organic solvent can be pharmaceutically acceptable organic solvent.Described solution also can contain pharmaceutically acceptable excipient, can be that described 4-hydroxyl-2-OXo-1-pyrrolidine acetamide and excipient can be dissolved in water for injection and/or other solvents separately or together, or described 4-hydroxyl-2-OXo-1-pyrrolidine acetamide adding contains in the solution of described excipient, or the adding of described excipient contains in the solution of described 4-hydroxyl-2-OXo-1-pyrrolidine acetamide.
In described (1) step, acceptable adjuvant on the conventional pharmaceutical can be added, for example: stabilizing agent, analgesics and/or buffer agent etc. in gained solution.
Before the lyophilization step in described (2) step, the solution of the described 4-of containing hydroxyl-2-OXo-1-pyrrolidine acetamide or 4-hydroxyl-2-OXo-1-pyrrolidine acetamide and excipient can be removed impurity according to conventional method, removes pyrogen, decolouring, filtration sterilization.
The lyophilization step in described (2) step can be conventional or known freeze drying process step.Described freeze drying process carries out under aseptic condition, can adjust lyophilization cycle according to conventional or known method according to the demand of clinical preparation and concrete production equipment.
The invention provides the method for a kind of 4-of preparation hydroxyl-2-OXo-1-pyrrolidine acetamide medicament freeze-drying preparation, also can may further comprise the steps:
(1) prepare the solution that contains 4-hydroxyl-2-OXo-1-pyrrolidine acetamide or contain 4-hydroxyl-2-OXo-1-pyrrolidine acetamide and pharmaceutically acceptable excipient, described solution pH value is preferably 4.5～7.5, more preferably between 4.5～6.5;
(2) in (1) step gains, use activated carbon decolorizing, remove pyrogen, filtration sterilization; And
(3) (2) step of lyophilization gained solution.
In described (2) step, described activated carbon dosage can be 0.05%～5%, preferred 0.1%～2%.After adding active carbon, can stir filtering decarbonization 10～30 minutes down at 25 ℃～60 ℃.Described filtration sterilization can be with 0.22 μ m filtering with microporous membrane.
The lyophilization of described (3) step can be carried out in accordance with the following methods:
(1) pre-freeze: respectively the temperature in the freeze drying box is reduced in advance about 0 ℃～-60 ℃, lyophilizing solution is put into carries out pre-freeze on the freeze drying box internal partition treating of installing of branch;
(2) sublimation drying: vacuum in the freeze drying box is risen to below the 13.33Pa (0.1mmHg post), close fridge, slowly heating, condenser temperature drops to-30 ℃, carries out sublimation drying 12～15 hours; And
(3) dry again: as baking temperature to be controlled at 10 ℃～30 ℃, until treating that the freeze-dried products temperature is near the plate temperature.Condenser temperature drops to below-30 ℃, dry 10～15 hours again.
Should avoid the contact such as metal ions such as ferrum in the process of preparation preparation of the present invention, it might influence the color of preparation, and medicament contg is descended.
4-hydroxyl of the present invention-2-OXo-1-pyrrolidine acetamide freeze-dried powder preparation can be dissolved in water for injection or other injection to lyophilized formulations before using.Described injection can be conventional injection, as is used for the isotonic water medium of venoclysis, for example 5% glucose injection or 0.9% sodium chloride injection.According to therapeutic process and patient's situation, use 4-hydroxyl of the present invention-2-OXo-1-pyrrolidine acetamide freeze-dried powder preparation general every day of consumption so that the amount of 4-hydroxyl-2-OXo-1-pyrrolidine acetamide be advisable at about 0.8～1.0g.
Injection 4-hydroxyl provided by the invention-2-OXo-1-pyrrolidine acetamide pharmaceutical preparation, stable performance, dissolving is rapidly fully used easily in use.Said preparation has satisfied the demand of people to different dosage form, its instant effect, and effect is strong, is mainly used in the cerebral anoxia first aid, some severe cases is in time rescued, for the patient removes slight illness.Overcome the shortcoming of present single capsule preparation.Preparation of the present invention only needs airtight preservation to get final product, and this provides convenience for the transportation of preparation and storage.And preparation method of the present invention is simple and easy to do, helps large-scale production.
The specific embodiment
Below will the invention will be further described by embodiment, these descriptions are not that content of the present invention is done further to limit.One skilled in the art will understand that to be equal to replacement to what technical characterictic of the present invention was done, or corresponding the improvement, still belong within protection scope of the present invention.
Embodiment 1-4
Get an amount of 4-hydroxyl-2-OXo-1-pyrrolidine acetamide (Tianjin money good fortune medicine) and an amount of glycine (Beijing Jianli Pharmaceutical Co., Ltd), add an amount of injection water, stirring makes dissolving fully, be 4,5.7,5.7,7.5 with phosphoric acid-sodium dihydrogen phosphate buffer, NaOH solution control pH value respectively, add water for injection to full dose, obtain every milliliter and contain 4-hydroxyl-2-OXo-1-pyrrolidine acetamide 333mg, the solution of glycine 70mg.Add active carbon according to the consumption of 0.05,0.5,1,2% (g/ml) respectively, stirred 50,30,20,15 minutes down at 20,25,30,40 ℃ respectively, decarbonization filtering, gained filtrate is with 0.22 μ m microporous filter membrane fine straining degerming.Under aseptic condition, gained solution is put in the aseptic cillin bottle, put in the freezer dryer according to the method lyophilization of embodiment 8 after about respectively 22,25,28,30 hours, sterile sealing promptly gets 4-hydroxyl of the present invention-2-OXo-1-pyrrolidine acetamide freeze-dried powder preparation A, B, C, D
Embodiment 5
Get an amount of 4-hydroxyl-2-OXo-1-pyrrolidine acetamide, add an amount of water for injection, stir it is dissolved fully, the solution pH value is about about 7.0, obtains every milliliter of solution that contains 4-hydroxyl-2-OXo-1-pyrrolidine acetamide 150mg, 900mg.Add active carbon according to the consumption of 1% (g/ml), 30 ℃ were stirred 30 minutes down, decarbonization filtering, and gained filtrate is with 0.22 μ m microporous filter membrane fine straining degerming.Under aseptic condition gained solution is put in the aseptic cillin bottle, put the interior lyophilization of freezer dryer after about respectively 25 hours, sterile sealing promptly gets 4-hydroxyl of the present invention-2-OXo-1-pyrrolidine acetamide freeze-dried powder preparation E, F.
Embodiment 6
Get an amount of 4-hydroxyl-2-OXo-1-pyrrolidine acetamide and sorbitol, add an amount of water for injection, stirring is dissolved it fully.Add NaH
2PO
4Solution is transferred about solution pH value to 6.5, obtains every milliliter of solution that contains 4-hydroxyl-2-OXo-1-pyrrolidine acetamide 333mg and sorbitol 80mg.Add active carbon according to the consumption of 2% (g/ml), 25 ℃ were stirred 30 minutes down, decarbonization filtering, and gained filtrate is with 0.22 μ m microporous filter membrane fine straining degerming.Under aseptic condition gained solution is put in the aseptic cillin bottle, put the interior lyophilization of freezer dryer after 28 hours, sterile sealing promptly gets 4-hydroxyl of the present invention-2-OXo-1-pyrrolidine acetamide freeze-dried powder preparation G.
Embodiment 7
Get an amount of 4-hydroxyl-2-OXo-1-pyrrolidine acetamide and glycine or lactose (import), add an amount of water for injection, stirring is dissolved it fully, obtains every milliliter and contains the solution of 4-hydroxyl-2-OXo-1-pyrrolidine acetamide 200mg and glycine 500mg and the solution of 4-hydroxyl-2-OXo-1-pyrrolidine acetamide 333mg and lactose 60mg.Add active carbon according to the consumption of 1% (g/ml), 30 ℃ were stirred 30 minutes down, decarbonization filtering, and gained filtrate is with 0.22 μ m microporous filter membrane fine straining degerming.Under aseptic condition gained solution is put in the aseptic cillin bottle, put the interior lyophilization of freezer dryer after about respectively 25 hours, sterile sealing promptly gets 4-hydroxyl of the present invention-2-OXo-1-pyrrolidine acetamide freeze-dried powder preparation H, I.
Embodiment 8
With embodiment 1 to 4 gained solution lyophilization in accordance with the following methods, prepare 4-hydroxyl of the present invention-2-OXo-1-pyrrolidine acetamide freeze-dried powder preparation:
Pre-freeze: respectively the temperature in the freeze drying box is reduced in advance about-20 ℃ ,-25 ℃ ,-30 ℃ ,-40 ℃, lyophilizing solution is put into carries out pre-freeze on the freeze drying box internal partition treating of installing of branch.
Sublimation drying: vacuum in the freeze drying box is risen to below the 13.33Pa (0.1mmHg post), close fridge.Slowly heat by the heating system under the dividing plate, dividing plate suitably is heated to about 10 ℃, to supply with the required heat of distillation of ice, condenser temperature drops to below-30 ℃, carries out sublimation drying 15,11,13,12 hours.
Dry again: baking temperature is controlled at 15 ℃, 20 ℃, 30 ℃, 10 ℃ respectively, and the plate temperature control overlaps with the plate temperature until products temperature below 30 ℃, promptly reaches exsiccant terminal point.Condenser temperature drops to-33 ℃, dry 11,10,13,15 hours again.
Embodiment 9
The solubility property of the preparation of the present invention that embodiment 1-7 is made is investigated.Preparation A of the present invention, B, C, D, E, F, G, H, I all can dissolve after adding water for injection well, and the clarity of gained solution is all qualified.
Embodiment 10
The content limit of the preparation of the present invention that embodiment 1～7 is made, character, acidity, moisture, related substance, pyrogen, aseptic, content uniformity, clarity, assay etc. are investigated.
(1) content limit: the three batch sample content of preparation B after measured, labelled amount is 90.0%～110.0%, so determine that preparation B contains 4-hydroxyl-2-OXo-1-pyrrolidine acetamide (C as a result
6H
10N
2O
3) should be 90.0%～110.0% of labelled amount.
(2) character:, be white or off-white powder or loose block according to preparation A to I sample appearance actual measurement situation.
(3) acidity, the pH value of preparation B of the present invention, C is 4.5～6.5.The pH value of its three batch sample after measured is all in this scope.
(4) clarity of solution and color, preparation of the present invention are white or loose block, and the color of its aqueous solution is not deeper than yellow No. 5, the aqueous solution clarification.
(5) adopt two appendix aquametries of Chinese Pharmacopoeia version in 2000, first method-Ka Shi aquametry to measure the moisture of this product, the moisture of preparation of the present invention does not all surpass 2.0% after measured.
(6) related substance: adopt high effective liquid chromatography for measuring, system suitability test and acid, alkali, oxidation destructive testing show that this system can make impurity separate with principal agent effectively, and adjuvant is noiseless to measuring, adopt Self-control method quantitative to impurity, need testing solution is as showing assorted peak, and the peak area at maximum contaminant peak is not more than 1.5 times of contrast solution main peak peak area.
(7) pyrogen:, up to specification according to the method inspection under two appendix XID of Chinese Pharmacopoeia version in 2000 item.
(8) aseptic: according to the method inspection under the aseptic item of two appendix of Chinese Pharmacopoeia version in 2000, preparation of the present invention is all up to specification.
(9) clarity: according to the regulation under two appendix injections of Chinese Pharmacopoeia version in 2000 item, tackle preparation of the present invention and carry out the inspection of clarity, with reference to the method inspection under two second clarity test items of Ministry of Public Health ministry standard, all up to specification.
Embodiment 11
Can investigate the stability of formulation of the present invention that embodiment 1～7 makes.
Carried out influence factor's test (strong illumination 4800Lx, 60 ℃ of high temperature and high humidity RH92.5%), accelerated test (40 ℃ ± 2 ℃ of temperature, humidity RH75% ± 5%), and long term test (25 ℃ ± 2 ℃ of temperature, humidity RH60% ± 10%), specifically investigated appearance color, acidity, the clarity of solution and color, related substance, assay.
Result of the test is as follows: (1) preparation of the present invention is tested 10 days results of investigation through the influence factor and shown: under each influence factor's condition, every index is all stable.(2) preparation of the present invention shows through 6 months result of accelerated test investigation: every index is all stable, with preparation shading of the present invention, sealing, in shady and cool dry place placement, can preserve 2 years.(3) preparation of the present invention is investigated 9 months through long term test, and every quality standard all meets declares the quality standard draft.
By above-mentioned experimental result as can be known, preparation process of the present invention is rationally feasible, and steady quality is reliable.
Claims (10)
1, a kind of 4-hydroxyl-2-OXo-1-pyrrolidine acetamide lyophilized formulations, the solution by containing 4-hydroxyl-2-OXo-1-pyrrolidine acetamide makes after lyophilization; The pH value of described solution is in 4.5～7.5 scopes; Described solution is solvent with water and/or pharmaceutically acceptable organic solvent.
2, preparation according to claim 1, the pH value that it is characterized in that described solution is in 4.5～6.5 scopes.
3, preparation according to claim 1 is characterized in that described solution also contains pharmaceutically acceptable excipient.
4, preparation according to claim 1 is characterized in that described solution also contains one or more the material in acceptable adjuvant on the conventional pharmaceutical that comprises stabilizing agent, analgesics and buffer agent, pharmaceutically acceptable pH regulator agent and the pharmaceutically acceptable medicine with other miscellaneous functions.
5, a kind of 4-hydroxyl-2-OXo-1-pyrrolidine acetamide lyophilized formulations by the solution of 4-hydroxyl-2-OXo-1-pyrrolidine acetamide or the solution of 4-hydroxyl-2-OXo-1-pyrrolidine acetamide and pharmaceutically acceptable excipient, makes after lyophilization; The pH value of described solution is 4.5～7.5; Described solution is solvent with water and/or pharmaceutically acceptable organic solvent.
6,, it is characterized in that described excipient is one or more the material that is selected from glycine, lactose, sodium chloride, glucose, sorbitol and other the pharmaceutically acceptable excipient according to claim 3 or 5 described preparations.
7, preparation according to claim 5 is characterized in that containing in the described solution the described 4-hydroxyl-2-OXo-1-pyrrolidine acetamide of 10 to 60% (percentage by weights), the described excipient of 0 to 50% (percentage by weight) and the described solvent of surplus; The pH value of described solution is 4.5～6.5.
8, preparation according to claim 6 is characterized in that described excipient is a glycine.
9, a kind of method for preparing 4-hydroxyl-2-OXo-1-pyrrolidine acetamide lyophilized formulations comprises:
(1) preparation contain 4-hydroxyl-2-OXo-1-pyrrolidine acetamide or contain 4-hydroxyl-2-OXo-1-pyrrolidine acetamide and pharmaceutically acceptable excipient, its pH value is 4.5～7.5 solution; And
(2) (1) step of lyophilization gained solution.
10, according to the method for claim 9, it is characterized in that before described (2) step, also comprise the step of (1) step gained solution being removed pyrogen, filtration sterilization according to conventional method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410029667 CN1562000A (en) | 2004-03-23 | 2004-03-30 | 4-hydroxy-2-oxo-1-pyrrolidine acetamide freeze-dried preparation and its preparing method |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200410006286 | 2004-03-23 | ||
| CN200410006286.0 | 2004-03-23 | ||
| CN 200410029667 CN1562000A (en) | 2004-03-23 | 2004-03-30 | 4-hydroxy-2-oxo-1-pyrrolidine acetamide freeze-dried preparation and its preparing method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1562000A true CN1562000A (en) | 2005-01-12 |
Family
ID=34523723
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410029667 Pending CN1562000A (en) | 2004-03-23 | 2004-03-30 | 4-hydroxy-2-oxo-1-pyrrolidine acetamide freeze-dried preparation and its preparing method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1562000A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102274195A (en) * | 2011-07-18 | 2011-12-14 | 石药集团欧意药业有限公司 | Oxiracetam freeze-dried powder preparation and preparation method thereof |
| 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 |
| CN102670527A (en) * | 2012-05-28 | 2012-09-19 | 南京优科生物医药研究有限公司 | Freeze-dried powder injection of L-oxiracetam and process for preparing freeze-dried powder injection |
| WO2013020391A1 (en) | 2011-08-11 | 2013-02-14 | 重庆润泽医疗器械有限公司 | (s)-4-hydroxy-2-oxo-1-pyrrolidineacetamide racemate crystal form ii and preparation method therefor |
| WO2013020389A1 (en) | 2011-08-11 | 2013-02-14 | 重庆润泽医疗器械有限公司 | Method for purifying levo-oxiracetam |
| WO2013020388A1 (en) | 2011-08-11 | 2013-02-14 | 重庆润泽医疗器械有限公司 | Method for purifying (s)-oxiracetam |
-
2004
- 2004-03-30 CN CN 200410029667 patent/CN1562000A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102274195A (en) * | 2011-07-18 | 2011-12-14 | 石药集团欧意药业有限公司 | Oxiracetam freeze-dried powder preparation and preparation method thereof |
| WO2013020391A1 (en) | 2011-08-11 | 2013-02-14 | 重庆润泽医疗器械有限公司 | (s)-4-hydroxy-2-oxo-1-pyrrolidineacetamide racemate crystal form ii and preparation method therefor |
| WO2013020389A1 (en) | 2011-08-11 | 2013-02-14 | 重庆润泽医疗器械有限公司 | Method for purifying levo-oxiracetam |
| WO2013020388A1 (en) | 2011-08-11 | 2013-02-14 | 重庆润泽医疗器械有限公司 | Method for purifying (s)-oxiracetam |
| 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 |
| CN102670527A (en) * | 2012-05-28 | 2012-09-19 | 南京优科生物医药研究有限公司 | Freeze-dried powder injection of L-oxiracetam and process for preparing freeze-dried powder injection |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2759382C2 (en) | Drug for injection based on saponin b4 pulsatilla | |
| CN101327193A (en) | Lornoxicam freeze-dried injection and preparation method thereof | |
| CN1313086C (en) | Aarin preparation for injection and preparing process thereof | |
| CN1562000A (en) | 4-hydroxy-2-oxo-1-pyrrolidine acetamide freeze-dried preparation and its preparing method | |
| CN101062011A (en) | Calcium dobesilate injection | |
| CN101181243A (en) | Adenosine cyclophosphate freeze-dry preparations and preparation method thereof | |
| CN111346061B (en) | Chlorogenic acid composition and preparation method thereof | |
| CN1290491C (en) | Medicine for treating acute ischemic cerebral apoplexy and its preparing method | |
| CN101904862B (en) | Water-soluble vitamin composition freeze-drying preparation for injection | |
| CN1931139A (en) | Freeze dried ligustrazine hydrochloride prepn for injection and its prepn process | |
| CN1257709C (en) | Tensicor freeze-drying formulation and its making method | |
| CN1729984A (en) | Freeze dry formulation of fasudil hydrochloride and its preparation process | |
| CN1732934A (en) | Freeze dry betahistine hydrochloride injection and method for preparing the same | |
| CN1272009C (en) | Freeze dried preparation of diammonium glycyrrhizinate and its preparation | |
| CN101327191A (en) | Lactobionic acid azithromycin for injections and preparation method thereof | |
| CN1686140A (en) | Valacyclovir hydrochloride freeze dried preparation and its preparation method | |
| CN1305478C (en) | Freeze drying preparation of amifostine, and preparation method | |
| IL300341A (en) | Pharmaceutical composition of aquaporin inhibitor and preparation method thereof | |
| CN106674225B (en) | A kind of Riboflavin sodium phosphate compound and its pharmaceutical composition | |
| RU2080857C1 (en) | Method of preparing the preparation chondroitin sulfate injection form | |
| RU2471484C2 (en) | Method for preparing composition for injections containing sodium cevtriaxone and sodium tazobactam | |
| CN1820753A (en) | Freeze-dried powder injection containing leucovorin sodium and its preparing method | |
| CN103495152B (en) | Thymopentin-containing medicine composition, as well as preparation and preparation method thereof | |
| CN111420027B (en) | Composition containing polymyxin B sulfate, freeze-dried powder, preparation method and application thereof | |
| CN108218894A (en) | A kind of cefoxitin sodium crystal-form compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |