CN105362236B - A kind of mensiso freeze-dried powder and preparation method thereof - Google Patents
A kind of mensiso freeze-dried powder and preparation method thereof Download PDFInfo
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- CN105362236B CN105362236B CN201510776798.3A CN201510776798A CN105362236B CN 105362236 B CN105362236 B CN 105362236B CN 201510776798 A CN201510776798 A CN 201510776798A CN 105362236 B CN105362236 B CN 105362236B
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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
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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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
- A61K47/08—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
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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
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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
- A61K9/0012—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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Abstract
The invention discloses a kind of mensiso freeze-dried powder and preparation method thereof, which is made of mensiso, mannitol, polyethylene glycol, pH adjusting agent；The pH value of system is controlled between 6.0~6.5 by pH adjusting agent, the mensiso appearance is full, uniform color, and moisture content is relatively low, and drug content is high and related substance is few, and it is unexpected obtain product draw it is moist small, it is low to envionmental humidity requirement.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, and in particular to a kind of mensiso freeze-dried powder and preparation method thereof.
Background technology
Mensiso is the aminoglycoside antibiotics of a new generation, and utilization clinically is extensive, because it is not only
The deficiency of traditional aminoglycoside antibiotics is compensated for, and compared with traditional aminoglycoside antibiotics, its antimicrobial spectrum is more
Extensively.Suitable for the following infection caused by gram-negative bacteria (including pseudomonas aeruginosa), staphylococcus and other sensitive bacterias：It exhales
Desorption system infection, urogenital infections, infection of biliary tract, Skin and soft tissue infection, infectious diarrhea and septicemia etc..
The Chinese patent application of 104546699 A of Publication No. CN discloses sisomicin sulfate injection composition
Preparation method includes the following steps：Recipe quantity mensiso and natrium adetate is taken to be dissolved in the 60- of water for injection total amount
80%, add sodium hydrogensulfite and L-cysteine stirring and dissolving；Acid for adjusting pH phosphorate to 5.2-5.5,0.2% activated carbon is added to inhale
Attached 30 minutes, decarburization injected water to formula full dose；It is filtered by 0.45um filtering with microporous membrane, then by 0.22um micropores
Film aseptic filtration, is dispensed into ampoule bottle, rushes nitrogen, seals ampoule bottle, 100 DEG C of flowing steam sterilizations 30 minutes to get.The sulphur
Sour sisomicin is used in the form of injection, and preparation method is relatively simple, however impurity content is more, and is stablized
Property it is insufficient.
Invention content
The present invention provides a kind of mensiso freeze-dried powder and preparation method thereof, the mensiso freeze-dried powders
Needle appearance is full, uniform color, and moisture content is relatively low, and drug content is high and related substance is few, and accident obtain product draw it is wet
Property it is small, to envionmental humidity require it is low；The preparation method process is simple, quality controllable and be suitable for industrialized production.
A kind of mensiso freeze-dried powder, by mensiso, mannitol, polyethylene glycol and pH adjusting agent system
At；
The pH value of the pH adjusting agent control system is 6.0~6.5.
Pass through and specific auxiliary material be added, so as to get mensiso appearance is full, uniform color, it is not easy to collapse
Fall into and spray bottle phenomenon, have higher drug content and it is lower draw moist, and solution rate is fast, insoluble in solution
Particle is seldom；Meanwhile by stringent control ph, being effectively improved the stability of product.
Preferably, the pH adjusting agent is sodium hydroxide solution, a concentration of 1mol/L, sodium hydroxide is cheap,
Human body will not be had adverse effect on when for adjusting pH value.
The ratio regular meeting of mensiso, mannitol and polyethylene glycol is to the appearance of product and draws and moist generates larger shadow
It rings, preferably, the weight ratio of mensiso, mannitol and polyethylene glycol is 1：1~2：2~3.
As most preferably, the composition of every 1000 bottles of freeze-dried powders is：
The present invention also provides a kind of preparation methods of the mensiso freeze-dried powder, include the following steps：
(1) mensiso, mannitol, polyethylene glycol are dissolved in water for injection, stirred to dissolve, then use hydrogen-oxygen
Change sodium solution and adjust pH value to 5.5~6.5, obtains mixed solution；
(2) activated carbon is added in the mixed solution that step (1) is prepared, stirs, filtering decarbonization obtains filtrate；
(3) filtrate that step (2) obtains is freeze-dried, and obtains the mensiso freeze-dried powder.
Preferably, the addition of step (2) described activated carbon is the 0.05~0.5% of liquor capacity, further preferably
It is 0.02~0.15%, mixing time is 30 minutes.Activated carbon there's almost no absorption to main ingredient mensiso and make at this time
With solution colour is colorless and clear liquid after filtering, and the mensiso after activated carbon adsorption carries out the inspection in relation to substance
It surveys, total impurities are 5.0% hereinafter, bacterial endotoxin meets regulation.
Preferably, the freeze-drying process described in step (3) is：Cool the filtrate to -40~-45 DEG C, pre-freeze 1~2 hour,
It vacuumizes, 25~30 DEG C is warming up to the speed of 5.4~6.0 DEG C/h, then keep the temperature 1~2 hour, obtain mensiso freeze-drying
Powder needle.This method is simple for process, it is only necessary to after being freezed, with the heating rate of 5.4~6.0 DEG C/h, 25~30 DEG C are warming up to,
Two sections of temperature-rise periods need not be separately set again, and obtained mensiso shape is loose, full.
Compared with the prior art, it is simple not only to prepare survival processes, easy to operate, is greatly saved so existing by the present invention
The production cost of technology；And the product prepared there has been qualitative leap in stability side, be conducive to produce in enormous quantities, convenient for storage
It deposits and market sale.
Specific implementation mode
Embodiment 1
Composition (specification：7.5 ten thousand units /) 1000 bottles：
Preparation method：
(1) mensiso of recipe quantity, mannitol, polyethylene glycol are first dissolved in water for injection, stirred to dissolve,
PH value is adjusted to 6.0~6.5 with 1mol/L sodium hydroxide solutions；
(2) activated carbon of preparating liquid total amount 0.1% is added in the solution that above-mentioned steps (1) are prepared, stirs 30 minutes,
Coarse filtration and 0.22 μm of miillpore filter aseptic filtration processing, gained filtrate is semi-finished product stoste.
(3) the semi-finished product stoste that step (2) obtains is cooled to -42 DEG C, and pre-freeze 2 hours vacuumizes, with the speed of 5.5 DEG C/h
Degree is warming up to 30 DEG C, then keeps the temperature 1 hour to get to mensiso freeze-dried powder.
Embodiment 2
Composition (specification：7.5 ten thousand units /) 1000 bottles：
Preparation method：
(1) mensiso of recipe quantity, mannitol, polyethylene glycol are first dissolved in water for injection, stirred to dissolve,
PH value is adjusted to 6.0~6.5 with 1mol/L sodium hydroxide solutions；
(2) activated carbon of preparating liquid total amount 0.1% is added in the solution that above-mentioned steps (1) are prepared, stirs 30 minutes,
Coarse filtration and 0.22 μm of miillpore filter aseptic filtration processing, gained filtrate is semi-finished product stoste.
(3) the semi-finished product stoste that step (2) obtains is cooled to -42 DEG C, and pre-freeze 2 hours vacuumizes, with the speed of 5.5 DEG C/h
Degree is warming up to 25 DEG C, then keeps the temperature 2 hours to get to mensiso freeze-dried powder.
Comparative example 1
In addition to being added without mannitol, remaining step is the same as embodiment 1.
Comparative example 2
In addition to being added without polyethylene glycol, remaining step is the same as embodiment 1.
Comparative example 3
In addition to being added without mannitol and polyethylene glycol, remaining step is the same as embodiment 1.
Comparative example 4
In addition to freeze-drying carries out according to the following steps, remaining step is the same as embodiment 1.
Dividing the semi-finished product stoste filled to be put into freeze drying box, temperature control is kept for 2 hours at -40 DEG C；It is evacuated to
Start to distil less than 14Pa, products temperature is warming up to 0 DEG C~-10 DEG C and keeps, is kept again 3 hours after ice crystal disappearance；
After lyophilization, carries out being warming up to 25 DEG C and be kept for 3 hours in the temperature range, sealing, packaging and storage after finished product qualification.
Comparative example 5
Other steps are same as Example 1, and the operation of step (1) is as follows：
(1) mensiso of recipe quantity, mannitol, polyethylene glycol are first dissolved in water for injection, stirred to dissolve,
PH value is adjusted to 5.2~5.5 with 1mol/L sodium hydroxide solutions.
The sulfuric acid Xi Suo meter that mensiso freeze-dried powder prepared by Examples 1 to 2 is prepared with comparative example 1~5
Star freeze-dried powder carries out long-term quality testing in 9 months respectively, specific detection method according to《Pharmacopoeia of People's Republic of China》
Version second in 2005, the results are shown in Table 1：
1 mensiso quality measurements of table
As it can be seen that the indices of injection mensiso produced by the present invention meet regulation, when being added without mannitol
When with one or two kinds of in polyethylene glycol, occur collapsing, not full and spray bottle phenomenon, and drug content and solubility are apparent
Decline；When routine change is lyophilized, drug content is decreased obviously with solubility, but to appearance without too much influence；Work as pH value
When change, starting character is preferable, but stability is poor, and after placing a period of time, drug content is decreased obviously with solubility.
Claims (6)
1. a kind of mensiso freeze-dried powder, which is characterized in that by mensiso, mannitol, polyethylene glycol and pH
Conditioning agent is made；
The pH value of the pH adjusting agent control system is 6.0~6.5；
The preparation method of the mensiso freeze-dried powder includes the following steps：
(1) mensiso, mannitol, polyethylene glycol are dissolved in water for injection, stirred to dissolve, then use sodium hydroxide
Solution adjusts pH value to 6.0~6.5, obtains mixed solution；
(2) activated carbon is added in the mixed solution that step (1) is prepared, stirs, filtering decarbonization obtains filtrate；
(3) filtrate that step (2) obtains is freeze-dried, and obtains the mensiso freeze-dried powder；
Freeze-drying process described in step (3) is：- 40~-45 DEG C are cooled the filtrate to, pre-freeze 1~2 hour vacuumizes, with 5.4
The speed of~6.0 DEG C/h is warming up to 25~30 DEG C, then keeps the temperature 1~2 hour, obtains mensiso freeze-dried powder.
2. mensiso freeze-dried powder according to claim 1, which is characterized in that the pH adjusting agent is hydrogen-oxygen
Change sodium solution.
3. mensiso freeze-dried powder according to claim 1, which is characterized in that mensiso, mannitol
Weight ratio with polyethylene glycol is 1：1~2：2~3.
4. mensiso freeze-dried powder according to claim 1, which is characterized in that the place of every 1000 bottles of freeze-dried powders
Square group becomes：
5. a kind of preparation method of such as Claims 1 to 4 any one of them mensiso freeze-dried powder, feature exist
In including the following steps：
(1) mensiso, mannitol, polyethylene glycol are dissolved in water for injection, stirred to dissolve, then use sodium hydroxide
Solution adjusts pH value to 6.0~6.5, obtains mixed solution；
(2) activated carbon is added in the mixed solution that step (1) is prepared, stirs, filtering decarbonization obtains filtrate；
(3) filtrate that step (2) obtains is freeze-dried, and obtains the mensiso freeze-dried powder；
Freeze-drying process described in step (3) is：- 40~-45 DEG C are cooled the filtrate to, pre-freeze 1~2 hour vacuumizes, with 5.4
The speed of~6.0 DEG C/h is warming up to 25~30 DEG C, then keeps the temperature 1~2 hour, obtains mensiso freeze-dried powder.
6. the preparation method of mensiso freeze-dried powder according to claim 5, which is characterized in that step (2) institute
The addition for stating activated carbon is the 0.05~0.5% of liquor capacity.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510776798.3A CN105362236B (en) | 2015-11-13 | 2015-11-13 | A kind of mensiso freeze-dried powder and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510776798.3A CN105362236B (en) | 2015-11-13 | 2015-11-13 | A kind of mensiso freeze-dried powder and preparation method thereof |
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| CN105362236A CN105362236A (en) | 2016-03-02 |
| CN105362236B true CN105362236B (en) | 2018-10-16 |
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| CN113209029A (en) * | 2021-04-26 | 2021-08-06 | 海南通用康力制药有限公司 | Preparation method of sisomicin sulfate sterile powder injection for injection |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101874789A (en) * | 2007-08-23 | 2010-11-03 | 姚俊华 | Lansoprazole-contained freeze-dried powder injection |
| CN102552179A (en) * | 2012-01-13 | 2012-07-11 | 山东罗欣药业股份有限公司 | Rabeprazole sodium composite lyophilized injectable powder and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07165586A (en) * | 1993-12-13 | 1995-06-27 | Shionogi & Co Ltd | Steroid ointment for external use |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101874789A (en) * | 2007-08-23 | 2010-11-03 | 姚俊华 | Lansoprazole-contained freeze-dried powder injection |
| CN102552179A (en) * | 2012-01-13 | 2012-07-11 | 山东罗欣药业股份有限公司 | Rabeprazole sodium composite lyophilized injectable powder and preparation method thereof |
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