CN106714799A - Method for producing freeze-dried preparation - Google Patents
Method for producing freeze-dried preparation Download PDFInfo
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- CN106714799A CN106714799A CN201580052376.XA CN201580052376A CN106714799A CN 106714799 A CN106714799 A CN 106714799A CN 201580052376 A CN201580052376 A CN 201580052376A CN 106714799 A CN106714799 A CN 106714799A
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- Prior art keywords
- tazobactam
- piperacillin
- freeze
- sodium
- aqueous solution
- Prior art date
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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
- A61K9/14—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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
- A61K31/431—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems containing further heterocyclic rings, e.g. ticarcillin, azlocillin, oxacillin
-
- 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
- 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)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention addresses the main problem of providing a novel method for producing a freeze-dried preparation (combination drug) for injection that comprises tazobactam sodium and piperacillin sodium. An example of the production method according to the present invention is as follows. A method for producing a freeze-dried preparation for injection, said method being characterized by comprising: (a) a step for blowing carbon dioxide gas into an aqueous sodium hydroxide solution; and (b) a step for dissolving tazobactam and piperacillin in the solution obtained in step (a). According to the present invention, a freeze-dried preparation showing good defoaming performance after redissolution can be obtained.
Description
Technical field
Contain tazobactam sodium (Tazobactam Sodium) and avocin the present invention relates to one kind
The new manufacture method of the injection freeze-dried preparation of (Piperacillin Sodium).
Background technology
The compounding ingredient of Tazobactam and Piperacillin is with trade name " Zosyn " (registration mark), with freezing used for intravenous injection
The form of drying agent is widely used in the whole world.
The injection freeze-dried preparation of the Tazobactam and Piperacillin is combined with to manufacture, it is necessary in freeze-drying
The Tazobactam of free form and Piperacillin is set to be reacted with sodium ion in preceding solution, generation Tazobactam and Piperacillin are each
From sodium salt.But, the stability of both Tazobactam and Piperacillin in aqueous slkali is all low, it is impossible to using in injection
It is used for the highly basic such as the sodium hydroxide solution of pH adjustment or sodium etc. in manufacture.
In order to solve above-mentioned problem, it is known to by Tazobactam free acid and Piperacillin hydrate dissolution in sodium acid carbonate
The aqueous solution, will add the solution of buffer (citrate etc.) and aminocarboxylic chelants (EDTA etc.) carry out freeze-drying and
The method (with reference to patent document 1) of manufacture.In addition, similarly, it is known to by Tazobactam free acid and Piperacillin hydrate
Be dissolved in sodium bicarbonate aqueous solution, the carbon dioxide content of dissolving has been degassed to a certain amount of solution carry out freeze-drying and
The method (with reference to patent document 2) of manufacture.In the method, instead of buffer or aminocarboxylic chelants, entered using Piperacillin
Row pH is adjusted, it is thus impossible to make final active constituent content accurate.
Prior art literature
Patent document
Patent document 1:International Publication No. 2004/091666
Patent document 2:International Publication No. 2007/065862
The content of the invention
Invent problem to be solved
Major subjects of the present invention are, there is provided a kind of injection freeze-drying containing tazobactam sodium and avocin
The new manufacture method of preparation (compounding ingredient).
Technical scheme for solving problem
In the manufacture of freeze-dried preparation, the liquid measure for drying object is certainly more few more favourable.Therefore, for a small amount of
When sodium hydroxide solution is to carry out pH adjustment with sodium, because NaOH is highly basic, therefore, during using sodium hydroxide solution,
Active ingredient is possible to be decomposed.
In addition, it is necessary to be redissolved freeze-dried preparation with water etc. before intravenous administration freeze-dried preparation.
When the injection freeze-dried preparation that Tazobactam and Piperacillin will be combined with is dissolved in water etc., because solubility is low, therefore
Need the operation such as stirring.Generally, in the case of producing bubble in solution after agitation, at medical scene, the preferably bubble promptly
Disappear.
The present inventor etc. is repeated further investigation, as a result finds, can be water-soluble by the NaOH to strong basicity
The so easy method of carbon dioxide is blasted in liquid and above-mentioned problem is solved, the present invention is completed.
As the present invention, example can be enumerated and invented described as follows.
[1] a kind of manufacture method of injection freeze-dried preparation, it is characterised in that the method includes following (a) and (b)
In described operation (hereinafter referred to as " preparation method of the present invention ").
A () is to the operation that carbon dioxide is blasted in sodium hydrate aqueous solution；
B () Tazobactam and Piperacillin are dissolved in the operation of resulting solution in above-mentioned (a) operation.
[2] manufacture method of freeze-dried preparation as described above described in [1], the method includes：By in (a) operation
In blast carbon dioxide, sodium hydrate aqueous solution is adjusted in the range of pH7.0~9.2.
[3] manufacture method of freeze-dried preparation as described above described in [1] or [2], it also includes：Triazole bar will have been dissolved
Smooth and Piperacillin and the work that the sodium hydrate aqueous solution acid of carbon dioxide is adjusted in the range of pH5.5~6.8 is blasted
Sequence.
[4] manufacture method of freeze-dried preparation as described above described in [3], wherein, the acid is hydrochloric acid, citric acid, phosphorus
Acid.
[5] manufacture method of freeze-dried preparation as described above any one of [1]~[4], it also includes following (c)
In described operation：
C () blasts the operation of non-active gas.
[6] manufacture method of freeze-dried preparation as described above described in [5], wherein, the non-active gas are nitrogen.
It is a feature of the present invention that in the system containing tazobactam sodium and the injection freeze-dried preparation of avocin
In making, Tazobactam and Piperacillin are dissolved in the sodium hydrate aqueous solution for blasting carbon dioxide.Thus, even if using
The sodium hydrate aqueous solution of highly basic, it is also possible to strongly suppress the decomposition of Tazobactam and Piperacillin, and without special problem
The carrying out active ingredient sodium.
The effect of invention
According to preparation method of the present invention, even if using the sodium hydrate aqueous solution of strong basicity, it is also possible to by being blasted in solution
Carbon dioxide and prevent the pH of solution too high, therefore, it can suppress the decomposition of Tazobactam and Piperacillin, and manufacture this to match somebody with somebody
Mixture (injection freeze-dried preparation).In addition, adding water for injection in the freeze-dried preparation obtained with preparation method of the present invention
And when being redissolved, so-called froth breaking is good.
Brief description of the drawings
Fig. 1 shows the photo of the state before and after being redissolved.The left-hand container of each photo represents commercially available product sample, right side
Container represents the freeze-dried preparation sample obtained with preparation method of the present invention.Upper left photo represents the state before being redissolved, and upper right is shone
State of the piece expression after water for injection redissolution, left photo represents the state after standing 30 seconds, and photo represents quiet in the right side
The state after 1 minute is put, lower-left photo represents the state after standing 2 minutes, and bottom right photo represents the state after standing 6 minutes.
Specific embodiment
Hereinafter, the present invention is described in detail in detail.
I. on preparation method of the present invention
A () is to the operation that carbon dioxide is blasted in sodium hydrate aqueous solution
This operation is to the operation that carbon dioxide is blasted in sodium hydrate aqueous solution.
Sodium hydrate aqueous solution can be prepared by the addition NaOH in water and dissolving.As hydrogen in the aqueous solution
The concentration of sodium oxide molybdena, such as 1~20 mass % are suitable, preferably 2~10 mass %, more preferably 3~5 mass %.As
Water for preparing the aqueous solution, can enumerate such as water for injection, Purified Water, distilled water, normal saline solution, but preferably injection
Water.
Alternatively, it is also possible to by commercially available sodium hydrate aqueous solution directly or suitably dilute with water and use.
Then, to carbon dioxide is blasted in sodium hydrate aqueous solution, preparation is dissolved with the sodium hydrate aqueous solution of carbonic acid.Make
Method to blast carbon dioxide, can enumerate for example common gas and blast method.Specifically, can enumerate for example while with stirring
The stirring sodium hydrate aqueous solution such as machine is mixed, while the ascending pipe of insertion carbon dioxide, two are blasted with the pressure of the degree of not bumping
The method of carbonoxide.Used as the pressure of the carbon dioxide for blasting, 0.5~2.0bar is suitable, preferably 0.5~1.0bar.
In the present invention, the aqueous solution is adjusted to pH7.0 by carbon dioxide is blasted in sodium hydrate aqueous solution
In the range of~9.2 (preferably pH7.5~8.0).As needed, used after carbon dioxide being blasted in the aqueous solution suitable
The aqueous solution micro-adjustment is in the range of the pH by suitable acid, or blasts carbon dioxide while using suitable sour by the aqueous solution
Micro-adjustment is in the range of the pH.As the acid for micro-adjustment pH, such as hydrochloric acid, citric acid, phosphoric acid can be enumerated.Wherein,
Hydrochloric acid is particularly suitable.
B () Tazobactam and Piperacillin are dissolved in the operation of the solution obtained in above-mentioned (a) operation
This operation is that Tazobactam and Piperacillin are dissolved in the sodium hydrate aqueous solution for having blasted carbon dioxide
Operation.To obtain the operation of the aqueous solution for being dissolved with Tazobactam and Piperacillin.
As the concentration of the Tazobactam in the aqueous solution, it is not particularly limited, such as 1~20 mass % can be enumerated, it is excellent
Elect 3~7 mass % as.When it is less than 1 mass %, it is not easy to obtain the freeze-dried preparation of given potency.When it is more than 20
During quality %, stirring during dissolving is difficult.As the concentration of Piperacillin in the aqueous solution, it is not particularly limited, example can be enumerated
Such as 10~50 mass %, preferably 20~30 mass %.When it is less than 10 mass %, it is not easy to obtain the freezing of given potency
Drying agent.When it is more than 50 mass %, dissolving is difficult.In addition, in the aqueous solution Tazobactam and Piperacillin potency
Than being preferably 1:8 (Tazobactams:Piperacillin).
The Tazobactam and Piperacillin of dissolving can be hydrate.On Piperacillin, usually using hydrate.
To the order that Tazobactam and Piperacillin are dissolved in the aqueous solution is not particularly limited.Can first dissolve and appoint
One kind, alternatively, it is also possible to both are dissolved simultaneously.
This dissolving can be carried out using conventional method.Specifically, for example, the hydroxide of carbon dioxide can blasted
Tazobactam and Piperacillin hydrate are added in sodium water solution, while being stirred with mixer etc. while dissolving.As dissolving temperature
Degree, can enumerate such as 3~15 DEG C.More preferably 4~10 DEG C.When it is less than 3 DEG C, dissolving needs the time, when it is higher than 15 DEG C
When, it is possible to promote the decomposition of Tazobactam and Piperacillin.
In preparation method of the present invention, following operations are preferably included：Tazobactam and Piperacillin will have been dissolved and two have been blasted
The sodium hydrate aqueous solution acid of carbonoxide is adjusted to the operation in the range of pH5.5~6.8 (preferably pH5.7~6.6).As with
In the acid for adjusting the pH, acid same as described above can be enumerated.Wherein, hydrochloric acid is particularly suitable.
Tazobactam and Piperacillin are dissolved, is according to circumstances adjusted after pH, liquid measure can be carried out with water as needed
Adjustment.As the water adjusted for liquid measure, such as water for injection, Purified Water, distilled water, normal saline solution can be enumerated, but preferably
Water for injection.
C () blasts the operation of non-active gas
This operation is in being dissolved with Tazobactam and Piperacillin and having blasted the sodium hydrate aqueous solution of carbon dioxide
Blast the operation of non-active gas.
As above-mentioned non-active gas, such as nitrogen, argon gas can be enumerated.As long as in general, it is used as non-active gas
Gas, be just not particularly limited, it is easy to operation and cheap nitrogen is suitable.
Can be carried out non-after Tazobactam and Piperacillin are dissolved in through the solution obtained by (a) operation
Active gases is blasted, in addition it is also possible to while Tazobactam and Piperacillin are dissolved in through obtained by (a) operation
Solution can also be dissolved in through (a) operation by Tazobactam and Piperacillin while carry out blasting for non-active gas
PH adjusting stages or liquid measure adjusting stage after resulting solution carry out blasting for non-active gas.
For the amount of the non-active gas for blasting the time of non-active gas and blasting, no matter which kind of non-active gas,
All it is not particularly limited, for example, blasting non-active gas until the amount of carbon dioxide is in the solution obtained in described (a) operation
Below 200mg/L (preferably below 75mg/L), oxygen amount for below 10ppm (preferably below 1ppm) be suitable.
By the way that two in the aqueous solution to non-active gas are blasted in the solution obtained in (b) operation, can be removed
Carbonoxide or oxygen.If residual carbon dioxide in the aqueous solution, the variation of pH can be produced in freeze-drying.In addition, if
Oxygen is remained in the aqueous solution, then can promote the decomposition of Tazobactam and Piperacillin.
The solution obtained in (b) operation after non-active gas has been blasted to be filtered preferably by conventional method
Sterilizing.Used as the method for filtration sterilization, can enumerate for example carries out filtration sterilization using 0.22 μm of molecular filter.
D () carries out the operation of freeze-drying
The solution dispensing obtained in (c) operation by described in carries out freeze-drying in sterile chamber using conventional method.And
And, it is however generally that, with nitrogen displacement and will can be jumped a queue (beat bolt) inside the vial after freeze-drying, obtain note of the invention
Penetrate with freeze-dried preparation (hereinafter referred to as " invention formulation ").
In invention formulation, it is believed that Tazobactam and Piperacillin exist in the form of sodium salt.
In invention formulation, tazobactam sodium preferably comprises 0.25g (potency) or 0.5g (potency), and avocin is preferred
Containing 2.0g (potency) or 4.0g (potency), (potency ratio is 1：8).
II. on invention formulation
Invention formulation generally can be redissolved and be used by adding arbitrary Suitable solutions (redissolution liquid).
As this redissolution liquid, water for injection, physiological saline, 5% (w/v) glucose injection, other common transfusions can be enumerated.Should
The liquid measure for being redissolved liquid is different because of purposes etc., is not particularly limited, but to be filled in 0.5 of liquid measure in vial before freeze-drying
~5 times of amounts or below 500mL are suitable.
The invention formulation being redissolved for example can carry out intravenous administration as injection or point drops etc..
As the dosage of invention formulation, the nature and extent of state, disease according to patients such as age or body weight etc.
And it is different, used as tazobactam sodium avocin, every 1 4.5g (potency) of being grown up is suitable.Can be according to age or body
State or disease etc. of patient is waited again, with 1 day 1 time~5 times, preferably 1 day 1 time~4 times suitable doses at intervals amounts.
Embodiment
Hereinafter, embodiment is enumerated, illustrates the present invention, but the present invention not by any of these embodiments in further detail
Limit.
[embodiment 1]
NaOH 2.4kg is dissolved in water for injection 56.25L, carbon dioxide is blasted, is for about 7.7 by pH adjustment.To drum
The sodium hydrate aqueous solution of carbon dioxide is entered, by pH micro-adjustments has been after 7.7, while blasting nitrogen with the aqueous hydrochloric acid solution of 0.5M
Gas, while adding Tazobactam 2.976kg, Piperacillin hydrate 23.81kg, then, further adds the hydrochloric acid water of 0.1M
Solution and water for injection, obtain the aqueous solution 125L of pH6.5.Solution after preparation is carried out into filtration sterilization, dispensing is in aseptic appearance
After device, conventionally implement freeze-drying, obtain being drawn containing tazobactam sodium 0.25g (potency), piperazine in each container
XiLin sodium 2.0g (potency) or tazobactam sodium 0.5g (potency), the invention formulation of avocin 4.0g (potency).
Hereinafter, the invention formulation containing tazobactam sodium 0.25g (potency), avocin 2.0g (potency) is referred to as
Invention formulation 2.25, the invention formulation containing tazobactam sodium 0.5g (potency), avocin 4.0g (potency) is claimed
It is invention formulation 4.5.
The rheological parameters' change with time of [test example 1] pH
The rheological parameters' change with time of the pH of the invention formulation that will be obtained in embodiment 1 and commercially available product (Zosyn (registration mark) vein
Injection 2.25, used for intravenous injection 4.5) compare and observe.The results are shown in table 1.It should be noted that in table,
The numerical value write in parantheses represents that the pH described in the census schedule (interview form) by Zosyn (registration mark) is determined
The result that method is obtained, the numerical value without parantheses represents the injection recorded in being augmented by the 16th Japanese Pharmacopoeia second of modification
The result obtained with pH assay methods described in Tazobactam, Piperacillin.
[table 1]
Learn：It can be seen that through when reduce tendency, but the pH rheological parameters' change with time of invention formulation and the pH of commercially available product through when
Change turns to peer-level.
The purity test of [test example 2] Tazobactam and Piperacillin
The purity test of Tazobactam and Piperacillin in the invention formulation that will be obtained in embodiment 1 40 DEG C/
It is (Zosyn (registration mark) used for intravenous injection 2.25, used for intravenous injection with commercially available product under conditions of 75%RH or 60 DEG C/75%RH
4.5) carried out using conventional method together.The results are shown in table 2 and table 3.It should be noted that Tazobactam and Piperacillin
Content augmented by the 16th Japanese Pharmacopoeia second of modification in institute in the injection Tazobactam Piperacillin that records
The purity test method of record and carry out.
[table 2]
Tazobactam content (%)
[table 3]
Piperacillin content (%)
Learn：By using preparation method of the present invention, the preparation with commercially available product peer-level in terms of quality can be obtained.
[test example 3] froth breaking is tested
Invention formulation 4.5 and commercially available product (Zosyn (registration mark) 4.5) used for intravenous injection for obtaining in embodiment 1
In be separately added into water for injection 20mL, dissolve and stand by reverse mixing, until freeze-drying thing disappears.By now
Froth breaking state is shown in Fig. 1.
After standing 1 minute, commercially available product can be seen on top clearly steeps, but invention formulation is not readily apparent top
Bubble, tiny bubble is observed on middle part~top.After standing 2 minutes, the bubble of invention formulation all disappears, but commercially available product exists
Bubble is observed on liquid level.After 30 seconds 7 minutes, the bubble of commercially available product also disappears final standing.
Therefore, learn：For invention formulation, the froth breaking after being redissolved with water for injection is excellent.
Industrial applicibility
Preparation method of the present invention is peer-level with the Zosyn (registration mark) as commercially available product in terms of quality, is disappeared in manufacture
The good freeze-dried preparation aspect of bubble is useful.
Claims (2)
1. a kind of manufacture method of injection freeze-dried preparation, the method includes the operation described in following (a) and (b)：
A () is to the operation that carbon dioxide is blasted in sodium hydrate aqueous solution；
B be dissolved in through the operation in the solution obtained by above-mentioned (a) operation for Tazobactam and Piperacillin by ().
2. the manufacture method of injection freeze-dried preparation as claimed in claim 1, it includes：By in (a) operation
In blast carbon dioxide, sodium hydrate aqueous solution is adjusted in the range of pH7.0~9.2.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2014206834 | 2014-10-08 | ||
| JP2014-206834 | 2014-10-08 | ||
| PCT/JP2015/078269 WO2016056527A1 (en) | 2014-10-08 | 2015-10-06 | Method for producing freeze-dried preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106714799A true CN106714799A (en) | 2017-05-24 |
Family
ID=55653138
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201580052376.XA Pending CN106714799A (en) | 2014-10-08 | 2015-10-06 | Method for producing freeze-dried preparation |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JPWO2016056527A1 (en) |
| KR (1) | KR20170067709A (en) |
| CN (1) | CN106714799A (en) |
| TW (1) | TW201626987A (en) |
| WO (1) | WO2016056527A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113209030B (en) * | 2021-04-27 | 2023-04-25 | 海南通用康力制药有限公司 | Preparation method of piperacillin sodium and tazobactam sodium sterile powder injection |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1802179A (en) * | 2003-04-14 | 2006-07-12 | 惠氏控股公司 | Compositions containing piperacillin and tazobactam useful for injection |
| CN1927201A (en) * | 2006-08-25 | 2007-03-14 | 天津和美生物技术有限公司 | Antibiotic compound recipe comprising piperacillin |
| CN101269072A (en) * | 2008-05-09 | 2008-09-24 | 郑飞雄 | Pharmaceutical composition containing beta-lactamase restrainer and piperacillin sodium with steady content and preparation method thereof |
| CN101299995A (en) * | 2005-12-05 | 2008-11-05 | 桑多斯股份公司 | Process for the preparation of lyophilized piperacilline sodium with improved stability after reconstitution |
| CN103239454A (en) * | 2013-05-06 | 2013-08-14 | 齐鲁天和惠世制药有限公司 | Production method of piperacillin sodium tazobactam sodium freeze-drying preparation for injection |
-
2015
- 2015-10-06 TW TW104132837A patent/TW201626987A/en unknown
- 2015-10-06 JP JP2016553104A patent/JPWO2016056527A1/en active Pending
- 2015-10-06 KR KR1020177002794A patent/KR20170067709A/en unknown
- 2015-10-06 WO PCT/JP2015/078269 patent/WO2016056527A1/en active Application Filing
- 2015-10-06 CN CN201580052376.XA patent/CN106714799A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1802179A (en) * | 2003-04-14 | 2006-07-12 | 惠氏控股公司 | Compositions containing piperacillin and tazobactam useful for injection |
| CN101299995A (en) * | 2005-12-05 | 2008-11-05 | 桑多斯股份公司 | Process for the preparation of lyophilized piperacilline sodium with improved stability after reconstitution |
| CN1927201A (en) * | 2006-08-25 | 2007-03-14 | 天津和美生物技术有限公司 | Antibiotic compound recipe comprising piperacillin |
| CN101269072A (en) * | 2008-05-09 | 2008-09-24 | 郑飞雄 | Pharmaceutical composition containing beta-lactamase restrainer and piperacillin sodium with steady content and preparation method thereof |
| CN103239454A (en) * | 2013-05-06 | 2013-08-14 | 齐鲁天和惠世制药有限公司 | Production method of piperacillin sodium tazobactam sodium freeze-drying preparation for injection |
Non-Patent Citations (1)
| Title |
|---|
| NARENDRA R DESAI等: "Zosyn(piperacillin/tazobactam) reformulation: Expanded compatibility and coadministration with lactated Ringer’s solutions and selected aminoglycosides", 《THERAPEUTICS AND CLINICAL RISK MANAGEMENT》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JPWO2016056527A1 (en) | 2017-07-20 |
| TW201626987A (en) | 2016-08-01 |
| WO2016056527A1 (en) | 2016-04-14 |
| KR20170067709A (en) | 2017-06-16 |
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