CN107432860A - A kind of preparation method of levo-oxiracetam freeze-dried powder - Google Patents
A kind of preparation method of levo-oxiracetam freeze-dried powder Download PDFInfo
- Publication number
- CN107432860A CN107432860A CN201610356638.8A CN201610356638A CN107432860A CN 107432860 A CN107432860 A CN 107432860A CN 201610356638 A CN201610356638 A CN 201610356638A CN 107432860 A CN107432860 A CN 107432860A
- Authority
- CN
- China
- Prior art keywords
- levo
- oxiracetam
- freeze
- dried powder
- minutes
- 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.)
- Granted
Links
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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- 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
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—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
- A61K47/16—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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a kind of preparation method of levo-oxiracetam freeze-dried powder；The levo-oxiracetam freeze-dried powder contains the supplementary material of following percentage by weight：Levo-oxiracetam 50% ~ 59%, L serines 20% ~ 25%, mannitol 10% ~ 17%, sodium glutamate 5% ~ 7%, sodium hydrogensulfite 5% ~ 10%, phenol 0.1% ~ 0.5%；The levo-oxiracetam freeze-dried powder by concentrated compounding, dilute match somebody with somebody, be freeze-dried and roll lid step and be made.The present invention utilizes specific excipient composition, coordinate specific Freeze Drying Technique again, so that the levo-oxiracetam freeze-dried powder prepared has solid shape, without spray bottle phenomenon in freeze-drying process, product homogeneity is good, and levels character is consistent, antibiotic property is strong, steriling test is qualified, and product stability is good, and particulate matter substantially reduces reduction.
Description
Technical field
The invention belongs to pharmaceutical field, and in particular to a kind of preparation method of levo-oxiracetam freeze-dried powder.
Background technology
Oxiracetam (oxiracetam) is a kind of hydroxy-amino-butyric acid of synthesis (BABOB) cyclic derivatives, in being only used for
Pivot nervous system, cerebral cortex, hippocampus are mainly distributed on, there is activation, protection or the functional rehabilitation for promoting nerve cell, improved
The mnemonic learning function of disturbance of intelligence patient, and medicine also acts in itself without direct vasoactive without central excitation, it is right
The influence of ability of learning and memory is a kind of lasting facilitation.
The medicine listed in 1987 in Italy, and the formulation of listing is tablet, 800mg；Capsule, 800mg；Parenteral solution, 1g/5ml.
It is domestic at present there was only oxiracetam capsule and parenteral solution listing, and main active used is racemic modification.Ye Lei etc. is in public affairs
The number of opening is obvious to the promoting wakening gone into a coma caused by alcoholism to mention levo-oxiracetam in the A patents of CN 103735545, and right
Rotation Oxiracetam does not act on substantially, and the awake effect of above-mentioned rush of levo-oxiracetam is 2 times of racemization Oxiracetam；Left-handed Aura
The western smooth promoting wakening to stupor caused by wound, anesthesia is notable.Peak etc. is opened in the A of Publication No. CN 103599101 patent
Disclose levo-oxiracetam has substantially to traumatic brain injury learning and memory in rats cognition dysfunction caused by hydraulic pressure and freely falling body
Improvement result, its drug effect is far above dextrorotation Oxiracetam, and 200mg/kg levo-oxiracetams and 400mg/kg Oxiracetams
Effect it is suitable.Pharmacokinetic study results are shown：Levo-oxiracetam and dextrorotation Oxiracetam nothing in beasle dog body are obvious
Chiral inversion, beasle dog single intravenous injection give after left-handed and 2 multiple doses racemization Oxiracetams levo-oxiracetam in blood plasma
The equal no significant difference of main pharmacokinetic parameters.The result of the tests such as safe pharmacology, anxious malicious, long poison show, in isodose level
Under, levo-oxiracetam is with Oxiracetam to animal subject or the toxicity no significant difference of cell.Above-mentioned preclinical result of study
Show, levo-oxiracetam is the main active that drug effect is played in Oxiracetam body, and exclusive use this product, which can reduce clinic, to be made
With dosage, potential toxicity is reduced.
But existing injection levo-oxiracetam freeze-dried powder exists without solid shape, is not easy to form skeleton, in freeze-drying process
Easily there is the problems such as spray bottle phenomenon, product homogeneity are bad, levels character is inconsistent, and asking for product stability difference be present
Inscribe, it is necessary to dissolve in 5% glucose injection or 0.9% 100~250ml of sodium chloride injection, preparation turns into before Clinical practice
Drip-feed solution use, levo-oxiracetam freeze-dried powder prepare turn into drip-feed solution after, with standing time extension its
Particulate matter increases, and this just brings very big potential safety hazard to clinical use.In addition, existing left-handed Austria of injection
La Xitan freeze-dried powder antibiotic properties are also poor, easily cause steriling test unqualified.
The content of the invention
In view of this, it is an object of the invention to provide a kind of preparation method of levo-oxiracetam freeze-dried powder, left-handed Austria of preparation
La Xitan freeze-dried powders have solid shape, in freeze-drying process without spray bottle phenomenon, product homogeneity is good, and antibiotic property is strong, sterile inspection
It is qualified to test, and product stability is good, prepares after turning into drip-feed solution, and particulate matter is reduced.
To reach above-mentioned purpose, the present invention provides following technical scheme：
A kind of preparation method of levo-oxiracetam freeze-dried powder, the levo-oxiracetam freeze-dried powder contain following percentage by weight
Supplementary material：Levo-oxiracetam 50%~59%, Serine 20%~25%, mannitol 10%~17%, sodium glutamate 5%~7%,
Sodium hydrogensulfite 5%~10%, phenol 0.1%~0.5%；The levo-oxiracetam freeze-dried powder by concentrated compounding, it is dilute match somebody with somebody, freeze it is dry
It is dry and roll lid step and be made, wherein the step of freeze-drying is：Temperature is quickly refrigerated to -40 DEG C, keeps constant temperature 60 minutes,
- 10 DEG C are warming up to 5 DEG C/h, keeps constant temperature 80 minutes, then extremely -40 DEG C of snap frozen, cryostat 120 minutes；Then
Drying is vacuumized, -10 DEG C are warming up to 10 DEG C/h, -10 DEG C of constant temperature 150 minutes；0 DEG C is warming up to 4 DEG C/h, 0 DEG C of perseverance
Temperature 300 minutes；10 DEG C are warming up to 5 DEG C/h, 10 DEG C of constant temperature 240 minutes；30 DEG C, 30 DEG C are warming up to 10 DEG C/h
Constant temperature 60 minutes, while preceding case vacuum drop reaches 10Pa/10 timesharing, freezes and terminates.
Further, the levo-oxiracetam freeze-dried powder contains the supplementary material of following percentage by weight：Levo-oxiracetam 53%,
Serine 22%, mannitol 12%, sodium glutamate 5.7%, sodium hydrogensulfite 7%, phenol 0.3%.
Further, the step of concentrated compounding is：The supplementary material of recipe quantity is placed in container, adds 10 times of weights of levo-oxiracetam
The sterilized water for injection stirring of part is measured, after dissolving, adds the needle-use activated carbon of mass fraction 0.1%, 30min is stirred, then uses
0.45 micron of miillpore filter filtration, collects filtrate.
Further, it is described it is dilute with the step of be：Sterilized water for injection is added into filtrate to 1000 times of filtrate volume, is used
0.1mol/L hydrochloric acid or 0.1mol/L sodium hydroxide adjust pH value to 3.2~3.6, are then removed with 0.22 micron of miillpore filter
Bacterium is filtered, filling after taking filtrate qualified to be sub-packed in sterile glass vials.
The beneficial effects of the present invention are：
The present invention utilizes specific excipient composition, then coordinates specific Freeze Drying Technique so that the levo-oxiracetam of preparation
Freeze-dried powder has solid shape, and without spray bottle phenomenon in freeze-drying process, product homogeneity is good, and levels character is consistent, antibiotic property
By force, steriling test is qualified, and product stability is good, dissolves in glucose injection or sodium chloride injection is prepared and dripped as vein
After noting solution, particulate matter substantially reduces reduction, is advantageous to improve the security that medicine uses, reduces adverse drug reaction.
Embodiment
In order that the purpose of the present invention, technical scheme and beneficial effect are clearer, the preferred embodiments of the present invention will be entered below
The detailed description of row.
Embodiment 1
The prescription of the levo-oxiracetam freeze-dried powder of embodiment 1 is as shown in the table：
| Prescription | Percentage by weight |
| Levo-oxiracetam | 50% |
| Serine | 25% |
| Mannitol | 14.9% |
| Sodium glutamate | 5% |
| Sodium hydrogensulfite | 5% |
| Phenol | 0.1% |
The preparation method of the levo-oxiracetam freeze-dried powder of embodiment 1, comprises the following steps：
(1) concentrated compounding：The supplementary material of recipe quantity is placed in container, the sterile injection for adding 10 times of parts by weight of levo-oxiracetam is used
Water stirs, and after dissolving, adds the needle-use activated carbon of mass fraction 0.1%, stirs 30min, is then filtered with 0.45 micron of micropore
Membrane filtration mistake, filtrate is collected, it is standby；
(2) it is dilute to match somebody with somebody：Sterilized water for injection is added into filtrate to 1000 times of filtrate volume, with 0.1mol/L hydrochloric acid or
0.1mol/L sodium hydroxide adjusts pH value to 3.2~3.6, then with 0.22 micron of miillpore filter aseptic filtration, takes filtrate to close
It is filling after lattice to be sub-packed in sterile glass vials, it is standby；
(3) it is freeze-dried：The above-mentioned decoction being sub-packed in sterile glass vials is put in freeze drier, is quickly refrigerated to temperature
- 40 DEG C, keep constant temperature 60 minutes, be warming up to -10 DEG C with 5 DEG C/h, keep constant temperature 80 minutes, then extremely -40 DEG C of snap frozen,
Cryostat 120 minutes；Then drying is vacuumized, -10 DEG C are warming up to 10 DEG C/h, -10 DEG C of constant temperature 150 minutes；With 4 DEG C
/ hour is warming up to 0 DEG C, 0 DEG C of constant temperature 300 minutes；10 DEG C are warming up to 5 DEG C/h, 10 DEG C of constant temperature 240 minutes；With 10 DEG C/
Hour is warming up to 30 DEG C, 30 DEG C of constant temperature 60 minutes, while preceding case vacuum drop reaches 10Pa/10 timesharing, freezes and terminates；
(4) lid is rolled：Aluminium-plastic combined cover needs once purged sterilizing, drying, then carries out rolling lid, produces.
Embodiment 2
The prescription of the levo-oxiracetam freeze-dried powder of embodiment 2 is as shown in the table：
| Prescription | Percentage by weight |
| Levo-oxiracetam | 53% |
| Serine | 22% |
| Mannitol | 12% |
| Sodium glutamate | 5.7% |
| Sodium hydrogensulfite | 7% |
| Phenol | 0.3% |
The preparation method of the levo-oxiracetam freeze-dried powder of embodiment 2 is same as Example 1.
Embodiment 3
The prescription of the levo-oxiracetam freeze-dried powder of embodiment 3 is as shown in the table：
| Prescription | Percentage by weight |
| Levo-oxiracetam | 54% |
| Serine | 20% |
| Mannitol | 10% |
| Sodium glutamate | 6% |
| Sodium hydrogensulfite | 9.5% |
| Phenol | 0.5% |
The preparation method of the levo-oxiracetam freeze-dried powder of embodiment 3 is same as Example 1.
Comparative example 1
The levo-oxiracetam freeze-dried powder of comparative example 1 does not add sodium hydrogensulfite, remaining component and preparation method and embodiment 2
It is identical.
Comparative example 2
The levo-oxiracetam freeze-dried powder of comparative example 2 does not add phenol, and remaining component and preparation method are same as Example 2.
First, character observation：
Levo-oxiracetam freeze-dried powder made from embodiment 1-3 is sampled, investigation project is tested, investigates project：Character,
Visible foreign matters, pH, relevant material, content, sterility test.
From character observation result, levo-oxiracetam freeze-dried powder has solid shape made from embodiment 1-3, is freezing
Without spray bottle phenomenon in journey, product homogeneity is good, and levels character is consistent, and product impurity is few, and indices meet production requirement.
2nd, particulate matter is investigated：
By levo-oxiracetam freeze-dried powder made from embodiment 2 and comparative example 1 respectively with 250ml 0.9% sodium chloride injection and
5% glucose injection dilutes, and preparation turns into drip-feed solution, with reference to Chinese Pharmacopoeia the 4th particulate matter of version in 2015
The method of inspection technique first (light blockage method), its particulate matter was determined respectively at 0,4,8,12 hour, calculated in each sign loading amount
The number of capacitive particulate, result of the test not see the table below：
Result is investigated from particulate matter, the product stability of embodiment 2 is substantially better than comparative example 1, dissolves in glucose note
To penetrate liquid or sodium chloride injection is prepared after turning into drip-feed solution, the particulate matter of embodiment 2 is considerably less than comparative example 1,
With the extension of standing time, the particulate matter of embodiment 2 does not almost increase, and the particulate matter of comparative example 1 is notable
Increase increases.
3rd, antibacterial ability is tested：
Each 20 bottles of levo-oxiracetam freeze-dried powder made from Example 2 and comparative example 2, is placed under natural conditions after open bottle cover
(25 DEG C ± 5 DEG C of temperature, relative humidity 70% ± 10%) is placed 15 days, is sampled respectively at 0 day, 5 days, 10 days, 15 days,
Each time point takes 5 bottles, carries out Sterility testing according to version Chinese Pharmacopoeia in 2010, result of the test see the table below：
From Sterility testing result, the product antibacterial ability of embodiment 2 is substantially better than comparative example 2.
Finally illustrate, preferred embodiment above is merely illustrative of the technical solution of the present invention and unrestricted, although by above-mentioned
The present invention is described in detail for preferred embodiment, it is to be understood by those skilled in the art that can in form and
Various changes are made in details to it, without departing from claims of the present invention limited range.
Claims (4)
- A kind of 1. preparation method of levo-oxiracetam freeze-dried powder, it is characterised in that：The levo-oxiracetam freeze-dried powder contains the supplementary material of following percentage by weight：Levo-oxiracetam 50% ~ 59%, Serine 20% ~ 25%, mannitol 10% ~ 17%, sodium glutamate 5% ~ 7%, sodium hydrogensulfite 5% ~ 10%, phenol 0.1% ~ 0.5%；The levo-oxiracetam freeze-dried powder by concentrated compounding, it is dilute match somebody with somebody, be freeze-dried and roll lid step and be made, wherein the step of freeze-drying is：Temperature is quickly refrigerated to -40 DEG C, keeps constant temperature 60 minutes, -10 DEG C is warming up to 5 DEG C/h, keeps constant temperature 80 minutes, then extremely -40 DEG C of snap frozen, cryostat 120 minutes；Then drying is vacuumized, -10 DEG C are warming up to 10 DEG C/h, -10 DEG C of constant temperature 150 minutes；0 DEG C is warming up to 4 DEG C/h, 0 DEG C of constant temperature 300 minutes；10 DEG C are warming up to 5 DEG C/h, 10 DEG C of constant temperature 240 minutes；30 DEG C are warming up to 10 DEG C/h, 30 DEG C of constant temperature 60 minutes, while preceding case vacuum drop reaches 10Pa/10 timesharing, freezes and terminates.
- 2. levo-oxiracetam freeze-dried powder according to claim 1, it is characterised in that：The levo-oxiracetam freeze-dried powder contains the supplementary material of following percentage by weight：Levo-oxiracetam 53%, Serine 22%, mannitol 12%, sodium glutamate 5.7%, sodium hydrogensulfite 7%, phenol 0.3%.
- 3. the preparation method of levo-oxiracetam freeze-dried powder according to claim 1 or 2, it is characterised in that：The step of concentrated compounding is：The supplementary material of recipe quantity is placed in container, the sterilized water for injection stirring of 10 times of parts by weight of levo-oxiracetam is added, after dissolving, adds the needle-use activated carbon of mass fraction 0.1%, stir 30min, then filtered with 0.45 micron of miillpore filter, collect filtrate.
- 4. the preparation method of levo-oxiracetam freeze-dried powder according to claim 3, it is characterised in that：It is described it is dilute with the step of be：Sterilized water for injection is added into filtrate to 1000 times of filtrate volume, pH value is adjusted to 3.2 ~ 3.6 with 0.1mol/L hydrochloric acid or 0.1mol/L sodium hydroxide, it is filling after taking filtrate qualified to be sub-packed in sterile glass vials then with 0.22 micron of miillpore filter aseptic filtration.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610356638.8A CN107432860B (en) | 2016-05-26 | 2016-05-26 | Preparation method of levo-oxiracetam freeze-dried powder |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610356638.8A CN107432860B (en) | 2016-05-26 | 2016-05-26 | Preparation method of levo-oxiracetam freeze-dried powder |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107432860A true CN107432860A (en) | 2017-12-05 |
| CN107432860B CN107432860B (en) | 2020-09-08 |
Family
ID=60453464
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610356638.8A Active CN107432860B (en) | 2016-05-26 | 2016-05-26 | Preparation method of levo-oxiracetam freeze-dried powder |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107432860B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
-
2016
- 2016-05-26 CN CN201610356638.8A patent/CN107432860B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107432860B (en) | 2020-09-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103446067A (en) | Oxiracetam freeze-drying preparation for injection and preparation method thereof | |
| CN102160852A (en) | Ibuprofen injection and preparation method thereof | |
| CN103304471A (en) | Ropivacaine mesylate compound, preparation process thereof and pharmaceutical composition thereof | |
| CN105596302A (en) | Ulinastatin freeze-dried powder preparation and preparation method thereof | |
| CN107432860A (en) | A kind of preparation method of levo-oxiracetam freeze-dried powder | |
| CN107397727A (en) | A kind of preparation method of levo-oxiracetam freeze-dried powder | |
| CN107281118A (en) | Good levo-oxiracetam freeze-dried powder of a kind of stability and preparation method thereof | |
| CN107432863A (en) | The preparation method of injection levo-oxiracetam freeze drying powder injection | |
| CN107397724A (en) | The preparation method of injection levo-oxiracetam freeze drying powder injection | |
| CN107281135A (en) | A kind of injection levo-oxiracetam freeze-dried powder and preparation method thereof | |
| CN102166200A (en) | Freeze-drying composition containing cerebroprotein hydrolysates and preparation method of freeze-drying composition | |
| CN107397726A (en) | A kind of (S)-Esomeprazole aseptic powdery and preparation method thereof | |
| CN107432864A (en) | A kind of (S)-Esomeprazole aseptic powdery and preparation method thereof | |
| CN107397722A (en) | Injection (S)-Esomeprazole freeze-dried powder and preparation method thereof | |
| CN107432862A (en) | Injection (S)-Esomeprazole freeze-dried powder and preparation method thereof | |
| CN107281120A (en) | A kind of levo-oxiracetam freeze-dried powder and preparation method thereof | |
| CN107281137A (en) | Oxo-1-pyrrolidine ethanamide freeze-dried powder of one kind (S) -4- hydroxyls -2 and preparation method thereof | |
| CN107281123A (en) | It is a kind of（S）Oxo-1-pyrrolidine ethanamide freeze-dried powder of -4- hydroxyls -2 and preparation method thereof | |
| CN107281131A (en) | A kind of stability is good（S）Oxo-1-pyrrolidine ethanamide freeze-dried powder of -4- hydroxyls -2 and preparation method thereof | |
| CN107281139A (en) | Good levo-oxiracetam freeze-dried powder of a kind of stability and preparation method thereof | |
| CN107281132A (en) | A kind of impurity is few（S）Oxo-1-pyrrolidine ethanamide aseptic powdery of -4- hydroxyls -2 and preparation method thereof | |
| CN107281119A (en) | Few levo-oxiracetam aseptic powdery of a kind of impurity and preparation method thereof | |
| CN107281122A (en) | A kind of levo-oxiracetam freeze-dried powder and preparation method thereof | |
| CN107281114A (en) | A kind of injection levo-oxiracetam freeze-dried powder and preparation method thereof | |
| CN107281128A (en) | Few levo-oxiracetam aseptic powdery of a kind of impurity and preparation method thereof |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |