CN104352458A - Acyclovir lyophilized formulation for injection and preparation method acyclovir lyophilized formulation - Google Patents
Acyclovir lyophilized formulation for injection and preparation method acyclovir lyophilized formulation Download PDFInfo
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- CN104352458A CN104352458A CN201410720719.2A CN201410720719A CN104352458A CN 104352458 A CN104352458 A CN 104352458A CN 201410720719 A CN201410720719 A CN 201410720719A CN 104352458 A CN104352458 A CN 104352458A
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Abstract
The invention relates to an acyclovir lyophilized formulation for injection and a preparation method of the acyclovir lyophilized formulation. The acyclovir lyophilized formulation for injection comprises acyclovir, sodium hydroxide, mannitol and a pH value stabilizing agent, wherein the weight ratio of the acyclovir to the mannitol is 1;(1-10). The acyclovir lyophilized formulation is advanced in prescription and good in product formability; the solution before being frozen is clear in appearance; the lyophilized product is good in solubility; and the re-dissolved solution is good in clarity, low in impurity content, good in stability and controllable in quality.
Description
Technical field
The invention belongs to field of medicine preparations, specifically, the present invention relates to a kind of lyophilized acyclovir preparation for injection and preparation method thereof.
Background technology
Aciclovir for injection main component is acyclovir (chemical name: 9-(2-hydroxyl ethoxymethyl) guanine, compound shown in formula 1).It is purines nucleoside analog, is a kind of antiviral agents of high-efficiency broad spectrum, the huge market demand.Be mainly used in the various infection caused by herpes simplex virus (HSV), can be used for onset or recurring skin, mucosa, the HSV that external genitalia infects and immunodeficiency person occurs infects.For the choice drug for the treatment of HSV encephalitis, minimizing sickness rate and reduction mortality rate are all better than vidarabine.Also can be used for herpes zoster, ebb virus's (Epstein-Barr virus), and the infection such as the concurrent chickenpox of immunodeficiency person.
Acyclovir is soluble,very slightly in water, can add sodium hydroxide as cosolvent in its prescription.But lyophilized formulations prepared by conventional method is amorphous dried powder, and be need to take a long time the slightly solubility lyophilized cake that could dissolve.That is, when adding lysate in lyophilized formulations, lyophilized cake becomes the block of slightly solubility, needs repeatedly jolting with strength and cost to dissolve for a long time.On the other hand, the moisture of lyophilized formulations is lower, more can ensure product quality and stability.The product that common process obtains is difficult to ensure long-time stability.
Therefore, current lyophilized acyclovir preparation for injection still haves much room for improvement.
Summary of the invention
The present invention is intended to solve one of technical problem in correlation technique at least to a certain extent.For this reason, one object of the present invention is to propose a kind of lyophilized acyclovir preparation for injection, and prescription is advanced, and formed product is good, and freeze the clarification of front solution appearance, dried frozen aquatic products solubility is good, and the clarity after redissolution is good, and impurity content is low, and good stability is quality controllable.
Another object of the present invention is the preparation method providing a kind of stable lyophilized acyclovir preparation for injection.
In one aspect of the invention, the present invention proposes a kind of lyophilized acyclovir preparation for injection.According to embodiments of the invention; described lyophilized formulations comprises acyclovir, sodium hydroxide, mannitol and pH value stabilizing agent; wherein mannitol based has higher disintegrate temperature in it; can be used as cryoprotective agent and excipient; before and after lyophilizing, be crystalline solid and no hygroscopicity, contribute to product and preserve.According to a particular embodiment of the invention, applicant screens through prescribed study, in lyophilized acyclovir preparation for injection, the weight ratio of described acyclovir and described mannitol is 1:1-10, the product appearance obtained thus is loose block, and impurity content is low, and solubility is good.According to a particular embodiment of the invention, the weight ratio of preferred acyclovir and mannitol is 1:2-5.The lyophilizing finished product moisture of gained is very low thus, and at room temperature store 24 months, its impurity content is not all higher than 0.8%, the color of lyophilized injectable powder is unchanged, after redissolving, clarity is good, and indices has no significant change, and embodies beat all product stability.
According to a particular embodiment of the invention, the specification of described lyophilized acyclovir preparation for injection is 0.25g or 0.5g.The specification that the present invention mentions all refers to the quality of main component in preparation, the quality namely containing acyclovir in lyophilized formulations.
According to embodiments of the invention, described pH value stabilizing agent is phosphate and or sodium acetate.Thus can stabilising system pH value further, avoid producing hydrolysis and produce impurity, and contribute to product lyophilizing molding.
According to a particular embodiment of the invention, described phosphate is be selected from least one in sodium hydrogen phosphate, sodium dihydrogen phosphate and sodium phosphate, is preferably at least one in sodium hydrogen phosphate and sodium dihydrogen phosphate.Thus can stabilising system pH value further, avoid producing hydrolysis and produce impurity, and contribute to product lyophilizing molding.
In another aspect of this invention, the present invention also proposes the method preparing lyophilized acyclovir preparation for injection, comprising: by acyclovir and mannitol mixing, drop into sodium hydroxide, be stirred to whole dissolving after adding water for injection; Ethanol is added in lysate, and by pH value stabilizing agent adjust ph; In the lysate after adjust ph, add needle-use activated carbon, stir, filtering decarbonization, by the degerming microporous filter membrane fine straining of medicinal liquid with 0.22 micron, obtain acyclovir sterile liquid medicine, then subpackage, partly jump a queue, lyophilization, tamponade, rolls lid, obtains described lyophilized acyclovir preparation for injection.
According to concrete example of the present invention, the scope of adjust ph is 11.0-11.5, preferred 11.2-11.4.Progressively adding thus according to sodium hydroxide, regulation system pH value is to obtain consoluet acyclovir.Add pH value stabilizing agent and contribute to the pH value that solution remains stable, avoid product impurity to produce.
According to embodiments of the invention, in acyclovir solution, add ethanol, can beat all further lifting pre-freeze effect, shorten lyophilization cycle, and contribute to solute and freeze with crystal form, and non-amorphous, can effectively avoid Freeze concentration layer to occur; On the other hand, ethanol can suppress acyclovir product to be hydrolyzed generation impurity, reduces its related substances, strengthens product stability.According to a particular embodiment of the invention, the addition of described ethanol is the 1.0-3.0 volume % of described lysate.According to a particular embodiment of the invention, the addition of described ethanol is preferably 1.5-2.0 volume %, most preferably is 1.8 volume %.Amount of alcohol is too small, and do not reach the effect shortening lyophilization cycle, amount of alcohol is excessive, can affect acyclovir dissolving in the solution.After freezing dry process terminates, ethanol can be completely removed, and does not produce any impact to product quality.
According to a particular embodiment of the invention, the consumption of described needle-use activated carbon is the 0.01-0.03g/100ml of the lysate volume after adjust ph, preferred 0.02g/100ml.Activated carbon dosage is excessive, and active component in solution can be caused by adsorbing to be made product yield reduce; Activated carbon dosage is too small, completely by solution decolouring, source of reducing phlegm and internal heat, the removal of impurity, and then can not affect the purity, quality etc. of product.Solution after activated carbon adsorption is colorless cleared solution, carries out the detection of related substance, and its total impurities is below 0.8%, and bacterial endotoxin conforms with the regulations.
According to a particular embodiment of the invention, after adding needle-use activated carbon, stir 10-20 minute, to adsorb further, decolorizing effect.
In a third aspect of the present invention, present invention further proposes the process of frozen drying.The preparation technology obtained thus is easy and simple to handle, energy-and time-economizing, and obtained freeze-drying prods form is good.According to embodiments of the invention, described frozen drying comprises the following steps:
(1) pre-freeze: casing is evacuated to 10-15 handkerchief, makes described acyclovir sterile liquid medicine be cooled to-15--20 degree Celsius under vacuum, freezing 10-15 minute; Be cooled to-35--40 degrees Celsius again, freezing 40-60 minute;
(2) sublimation drying: casing is evacuated to 12-30 handkerchief, is filled with nitrogen, be warming up to-20--25 degree Celsius, dry 12-20 hour;
(3) adsorption stripping and dry: be warming up to 25-40 degree Celsius, vacuum drying 3-5 hour.
Discovery is tested according to applicant, adopt in pre-freeze process and carry out quick-freezing in short-term under vacuum, contribute to solution surface to freeze, form ice crystal thin layer, remove vacuum again, be cooled to below crystallization temperature and freeze, the pre-freeze of overall solution can be completed fast, substantially increase pre-freeze efficiency, save time; On the other hand, quick-freezing in short-term under vacuum condition, can make sub-fraction solution freeze under supercooled state, can obtain further thus without the homogeneous sample of Freeze concentration, structure.
According to embodiments of the invention, the nitrogen in sublimation drying process, as noble gas, can play a protective role.
Compared with prior art, tool has the following advantages in the present invention:
(1) product appearance form is good, redissolves rapidly
By adding appropriate mannitol in prescription, realize the product of simple and easy prescription and good moldability, gained Aciclovir for injection freezes the clarification of front solution appearance, and dried frozen aquatic products solubility is good, and the clarity after redissolution is good, and impurity content is low, and good stability is quality controllable.
Lyophilization can be avoided medicine Yin Gaore and decompose rotten, and dried material is loose porous, in spongy, dissolve rapidly and completely, almost recover original character immediately after adding water.
(2) good product quality, steady in a long-term
Products obtained therefrom moisture is very low, and at room temperature store 24 months, its impurity content is not higher than 0.8%, and the color of lyophilized injectable powder is unchanged, and after redissolving, clarity is good, and indices has no significant change, and embodies beat all product stability.
The present invention, by pH value stabilizing agent adjust ph, avoids product impurity to produce; Solution after activated carbon adsorption is colorless cleared solution, carries out the detection of related substance, and its total impurities is below 0.8%, and bacterial endotoxin conforms with the regulations.
(3) lyophilization cycle is short, and production cost is low
By adding ethanol in proper amount in acyclovir medicinal liquid, and carry out quick-freezing in short-term under vacuum, contribute to solution surface to freeze, form ice crystal thin layer, remove vacuum again, be cooled to below crystallization temperature and freeze, the pre-freeze of overall solution can be completed fast, substantially increase pre-freeze efficiency, save time; On the other hand, quick-freezing in short-term under vacuum condition, can make sub-fraction solution freeze under supercooled state, can obtain further thus without the homogeneous sample of Freeze concentration, structure.
The present invention, by shortening lyophilization cycle greatly, saves production cost, and reduces energy consumption.
Additional aspect of the present invention and advantage will part provide in the following description, and part will become obvious from the following description, or be recognized by practice of the present invention.
Detailed description of the invention
Embodiments of the invention are described below in detail.Embodiment described below is exemplary, only for explaining the present invention, and can not be interpreted as limitation of the present invention.Unreceipted concrete technology or condition in embodiment, according to the technology described by the document in this area or condition or carry out according to product description.Agents useful for same or the unreceipted production firm person of instrument, being can by the conventional products of commercial acquisition.
Embodiment 1 prepares lyophilized acyclovir preparation for injection
By acyclovir and mannitol mixing, drop into sodium hydroxide after adding water for injection, be stirred to whole dissolving, add 1.5 volume % ethanol, and by sodium acetate adjust ph to 11.0, add needle-use activated carbon 0.01g/100ml, stir, filtering decarbonization, by the degerming microporous filter membrane fine straining of medicinal liquid with 0.22 micron, obtain acyclovir sterile liquid medicine, then subpackage, partly jump a queue, lyophilization, tamponade, rolls lid, obtains lyophilized formulations finished product.
Wherein, lyophilization step be:
(1) pre-freeze: casing is evacuated to 15 handkerchiefs, makes acyclovir sterile liquid medicine be cooled to-15 degrees Celsius under vacuum, freezing 15 minutes; Remove vacuum, then be cooled to-40 degrees Celsius, freezing 40 minutes;
(2) sublimation drying: casing is evacuated to 12 handkerchiefs, is filled with nitrogen, be warming up to-25 degrees Celsius, dry 20 hours;
(3) adsorption stripping and dry: be warming up to 30 degrees Celsius, vacuum drying 5 hours.
Embodiment 2 prepares lyophilized acyclovir preparation for injection
By acyclovir and mannitol mixing, drop into sodium hydroxide after adding water for injection, be stirred to whole dissolving, add 2.0 volume % ethanol, and by sodium phosphate adjust ph to 11.2, add needle-use activated carbon 0.02g/100ml, stir, filtering decarbonization, by the degerming microporous filter membrane fine straining of medicinal liquid with 0.22 micron, obtain acyclovir sterile liquid medicine, then subpackage, partly jump a queue, lyophilization, tamponade, rolls lid, obtains lyophilized formulations finished product.
Wherein, lyophilization step be:
(1) pre-freeze: casing is evacuated to 10 handkerchiefs, makes acyclovir sterile liquid medicine be cooled to-20 degrees Celsius under vacuum, freezing 15 minutes; Remove vacuum, then be cooled to-40 degrees Celsius, freezing 60 minutes;
(2) sublimation drying: casing is evacuated to 15 handkerchiefs, is filled with nitrogen, be warming up to-20 degrees Celsius, dry 18 hours;
(3) adsorption stripping and dry: be warming up to 40 degrees Celsius, vacuum drying 3 hours.
Embodiment 3 prepares lyophilized acyclovir preparation for injection
By acyclovir and mannitol mixing, drop into sodium hydroxide after adding water for injection, be stirred to whole dissolving, add 1.5 volume % ethanol, and by sodium dihydrogen phosphate adjust ph to 11.5, add needle-use activated carbon 0.02g/100ml, stir, filtering decarbonization, by the degerming microporous filter membrane fine straining of medicinal liquid with 0.22 micron, obtain acyclovir sterile liquid medicine, then subpackage, partly jump a queue, lyophilization, tamponade, rolls lid, obtains lyophilized formulations finished product.
Wherein, lyophilization step be:
(1) pre-freeze: casing is evacuated to 15 handkerchiefs, makes acyclovir sterile liquid medicine be cooled to-18 degrees Celsius under vacuum, freezing 12 minutes; Remove vacuum, then be cooled to-40 degrees Celsius, freezing 40 minutes;
(2) sublimation drying: casing is evacuated to 20 handkerchiefs, is filled with nitrogen, be warming up to-25 degrees Celsius, dry 12 hours;
(3) adsorption stripping and dry: be warming up to 30 degrees Celsius, vacuum drying 4 hours.
Embodiment 4 prepares lyophilized acyclovir preparation for injection
By acyclovir and mannitol mixing, drop into sodium hydroxide after adding water for injection, be stirred to whole dissolving, add 1.8 volume % ethanol, and by sodium hydrogen phosphate adjust ph to 11.4, add needle-use activated carbon 0.03g/100ml, stir, filtering decarbonization, by the degerming microporous filter membrane fine straining of medicinal liquid with 0.22 micron, obtain acyclovir sterile liquid medicine, then subpackage, partly jump a queue, lyophilization, tamponade, rolls lid, obtains lyophilized formulations finished product.
Wherein, lyophilization step be:
(1) pre-freeze: casing is evacuated to 15 handkerchiefs, makes acyclovir sterile liquid medicine be cooled to-20 degrees Celsius under vacuum, freezing 15 minutes; Remove vacuum, then be cooled to-40 degrees Celsius, freezing 50 minutes;
(2) sublimation drying: casing is evacuated to 30 handkerchiefs, is filled with nitrogen, be warming up to-20 degrees Celsius, dry 12 hours;
(3) adsorption stripping and dry: be warming up to 25 degrees Celsius, vacuum drying 3 hours.
Embodiment 5 prepares lyophilized acyclovir preparation for injection
By acyclovir and mannitol mixing, drop into sodium hydroxide after adding water for injection, be stirred to whole dissolving, add 3.0 volume % ethanol, and add sodium hydrogen phosphate adjust ph to 11.4, add needle-use activated carbon 0.03g/100ml, stir, filtering decarbonization, by the degerming microporous filter membrane fine straining of medicinal liquid with 0.22 micron, obtain acyclovir sterile liquid medicine, then subpackage, partly jump a queue, lyophilization, tamponade, rolls lid, obtains lyophilized formulations finished product.
Wherein, lyophilization step be:
(1) pre-freeze: casing is evacuated to 15 handkerchiefs, makes acyclovir sterile liquid medicine be cooled to-20 degrees Celsius under vacuum, freezing 15 minutes; Remove vacuum, then be cooled to-40 degrees Celsius, freezing 50 minutes;
(2) sublimation drying: casing is evacuated to 30 handkerchiefs, is filled with nitrogen, be warming up to-20 degrees Celsius, dry 12 hours;
(3) adsorption stripping and dry: be warming up to 25 degrees Celsius, vacuum drying 3 hours.
Embodiment 6 prepares lyophilized acyclovir preparation for injection
By acyclovir and mannitol mixing, drop into sodium hydroxide after adding water for injection, be stirred to whole dissolving, add 1.0 volume % ethanol, and add sodium phosphate adjust ph to 11.4, add needle-use activated carbon 0.02g/100ml, stir, filtering decarbonization, by the degerming microporous filter membrane fine straining of medicinal liquid with 0.22 micron, obtain acyclovir sterile liquid medicine, then subpackage, partly jump a queue, lyophilization, tamponade, rolls lid, obtains lyophilized formulations finished product.
Wherein, lyophilization step be:
(1) pre-freeze: casing is evacuated to 10 handkerchiefs, makes acyclovir sterile liquid medicine be cooled to-20 degrees Celsius under vacuum, freezing 10 minutes; Remove vacuum, then be cooled to-40 degrees Celsius, freezing 40 minutes;
(2) sublimation drying: casing is evacuated to 15 handkerchiefs, is filled with nitrogen, be warming up to-20 degrees Celsius, dry 12 hours;
(3) adsorption stripping and dry: be warming up to 25 degrees Celsius, vacuum drying 3 hours.
Embodiment 7 prepares lyophilized acyclovir preparation for injection
By acyclovir and mannitol mixing, drop into sodium hydroxide after adding water for injection, be stirred to whole dissolving, add 1.5 volume % ethanol, and add sodium acetate adjust ph to 11.2, add needle-use activated carbon 0.01g/100ml, stir, filtering decarbonization, by the degerming microporous filter membrane fine straining of medicinal liquid with 0.22 micron, obtain acyclovir sterile liquid medicine, then subpackage, partly jump a queue, lyophilization, tamponade, rolls lid, obtains lyophilized formulations finished product.
Wherein, lyophilization step be:
(1) pre-freeze: casing is evacuated to 15 handkerchiefs, makes acyclovir sterile liquid medicine be cooled to-15 degrees Celsius under vacuum, freezing 15 minutes; Remove vacuum, then be cooled to-40 degrees Celsius, freezing 40 minutes;
(2) sublimation drying: casing is evacuated to 12 handkerchiefs, is filled with nitrogen, be warming up to-25 degrees Celsius, dry 20 hours;
(3) adsorption stripping and dry: be warming up to 30 degrees Celsius, vacuum drying 4 hours.
Comparative example 1 prepares lyophilized acyclovir preparation for injection
Acyclovir 0.5g
Sodium hydroxide 10g
By acyclovir and mannitol mixing, drop into sodium hydroxide after adding water for injection, be stirred to whole dissolving, add needle-use activated carbon 0.03g/100ml, stir, filtering decarbonization, by the degerming microporous filter membrane fine straining of medicinal liquid with 0.22 micron, obtain acyclovir sterile liquid medicine, then subpackage, partly jump a queue, lyophilization, tamponade, rolls lid, obtains lyophilized formulations finished product.
Wherein, lyophilization step be:
(1) pre-freeze: be cooled to-40 degrees Celsius, freezing 2 hours;
(2) sublimation drying: casing is evacuated to 20 handkerchiefs, is filled with nitrogen, be warming up to-30 degrees Celsius, dry 48 hours;
(3) adsorption stripping and dry: be warming up to 38 degrees Celsius, vacuum drying 8 hours.
Comparative example 2 prepares lyophilized acyclovir preparation for injection
Acyclovir 0.5g
Sodium hydroxide 10g
Sodium hydrogen phosphate 5g
Drop into sodium hydroxide after acyclovir being added water for injection, be stirred to whole dissolving, and add sodium hydrogen phosphate adjust ph to 11.5, add needle-use activated carbon 0.04g/100ml, stir, filtering decarbonization, by the degerming microporous filter membrane fine straining of medicinal liquid with 0.22 micron, obtain acyclovir sterile liquid medicine, then subpackage, partly jump a queue, lyophilization, tamponade, rolls lid, obtains lyophilized formulations finished product.
Wherein, lyophilization step be:
(1) pre-freeze: casing is evacuated to 15 handkerchiefs, makes acyclovir sterile liquid medicine be cooled to-20 degrees Celsius under vacuum, freezing 15 minutes; Remove vacuum, then be cooled to-40 degrees Celsius, freezing 50 minutes;
(2) sublimation drying: casing is evacuated to 30 handkerchiefs, is filled with nitrogen, be warming up to-20 degrees Celsius, dry 12 hours;
(3) adsorption stripping and dry: be warming up to 25 degrees Celsius, vacuum drying 3 hours.
Comparative example 3 prepares lyophilized acyclovir preparation for injection
By acyclovir and mannitol mixing, drop into sodium hydroxide after adding water for injection, be stirred to whole dissolving, and add sodium phosphate adjust ph to 11.5, add needle-use activated carbon 0.02g/100ml, stir, filtering decarbonization, by the degerming microporous filter membrane fine straining of medicinal liquid with 0.22 micron, obtains acyclovir sterile liquid medicine, subpackage again, partly jump a queue, lyophilization, tamponade, roll lid, obtain lyophilized formulations finished product.
Wherein, lyophilization step be:
(1) pre-freeze: casing is evacuated to 15 handkerchiefs, makes acyclovir sterile liquid medicine be cooled to-20 degrees Celsius under vacuum, freezing 15 minutes; Remove vacuum, then be cooled to-40 degrees Celsius, freezing 50 minutes;
(2) sublimation drying: casing is evacuated to 30 handkerchiefs, is filled with nitrogen, be warming up to-20 degrees Celsius, dry 12 hours;
(3) adsorption stripping and dry: be warming up to 25 degrees Celsius, vacuum drying 3 hours.
To prepare lyophilized acyclovir preparation by prescription of the present invention, preparation technology and conventional acyclovir product quality compares, result is as shown in the table:
Result shows, adds appropriate mannitol in prescription, realizes the product of simple and easy prescription and good moldability, and gained Aciclovir for injection freezes the clarification of front solution appearance, and dried frozen aquatic products solubility is good, and the clarity after redissolution is good, and impurity content is low, and good stability is quality controllable.
By pH value stabilizing agent adjust ph, product impurity is avoided to produce; Solution after activated carbon adsorption is colorless cleared solution, carries out the detection of related substance, and its total impurities is below 0.8%, and bacterial endotoxin conforms with the regulations.
By adding ethanol in proper amount in acyclovir medicinal liquid, and carry out quick-freezing in short-term under vacuum, contribute to solution surface to freeze, form ice crystal thin layer, remove vacuum again, be cooled to below crystallization temperature and freeze, the pre-freeze of overall solution can be completed fast, substantially increase pre-freeze efficiency, save time; On the other hand, quick-freezing in short-term under vacuum condition, can make sub-fraction solution freeze under supercooled state, can obtain further thus without the homogeneous sample of Freeze concentration, structure.
The present invention, by shortening lyophilization cycle greatly, saves production cost, and reduces energy consumption.
In describing the invention, it is to be appreciated that term " first ", " second " only for describing object, and can not be interpreted as instruction or hint relative importance or the implicit quantity indicating indicated technical characteristic.Thus, be limited with " first ", the feature of " second " can express or impliedly comprise one or more these features.In describing the invention, the implication of " multiple " is two or more, unless otherwise expressly limited specifically.
In the description of this description, specific features, structure, material or feature that the description of reference term " embodiment ", " some embodiments ", " example ", " concrete example " or " some examples " etc. means to describe in conjunction with this embodiment or example are contained at least one embodiment of the present invention or example.In this manual, to the schematic representation of above-mentioned term not must for be identical embodiment or example.And the specific features of description, structure, material or feature can combine in one or more embodiment in office or example in an appropriate manner.In addition, when not conflicting, the feature of the different embodiment described in this description or example and different embodiment or example can carry out combining and combining by those skilled in the art.
Although illustrate and describe embodiments of the invention above, be understandable that, above-described embodiment is exemplary, can not be interpreted as limitation of the present invention, and those of ordinary skill in the art can change above-described embodiment within the scope of the invention, revises, replace and modification.
Claims (10)
1. a lyophilized acyclovir preparation for injection, is characterized in that, comprises acyclovir, sodium hydroxide, mannitol and pH value stabilizing agent, and wherein, the weight ratio of described acyclovir and described mannitol is 1:1-10.
2. lyophilized acyclovir preparation for injection according to claim 1, is characterized in that, the weight ratio of described acyclovir and described mannitol is 1:2-5.
3. lyophilized acyclovir preparation for injection according to claim 1, is characterized in that, the specification of described lyophilized acyclovir preparation for injection is 0.25g or 0.5g.
4. lyophilized acyclovir preparation for injection according to claim 1, it is characterized in that, described pH value stabilizing agent be phosphate and or sodium acetate, optional, described phosphate is be selected from least one in sodium hydrogen phosphate, sodium dihydrogen phosphate and sodium phosphate, is preferably at least one in sodium hydrogen phosphate and sodium dihydrogen phosphate.
5. a preparation method for lyophilized acyclovir preparation for injection described in any one of claim 1-4, is characterized in that, comprising: by acyclovir and mannitol mixing, drop into sodium hydroxide, be stirred to whole dissolving after adding water for injection;
Ethanol is added in lysate, and by pH value stabilizing agent adjust ph;
In the lysate after adjust ph, add needle-use activated carbon, stir, filtering decarbonization;
By the degerming microporous filter membrane fine straining of medicinal liquid with 0.22 micron, obtain acyclovir sterile liquid medicine;
Subpackage, partly jumps a queue, lyophilization, and lid is rolled in tamponade, obtains described lyophilized acyclovir preparation for injection.
6. preparation method according to claim 5, is characterized in that, the scope of described adjust ph is 11.0-11.5, preferred 11.2-11.4.
7. preparation method according to claim 5, is characterized in that, the addition of described ethanol is the 1.0-3.0 volume % of described lysate, is preferably 1.5-2.0 volume %.
8. preparation method according to claim 5, is characterized in that, the consumption of described needle-use activated carbon is the 0.01-0.03g/100ml of the lysate volume after adjust ph, preferred 0.02g/100ml.
9. preparation method according to claim 5, is characterized in that, stirs 10-20 minute after adding needle-use activated carbon.
10. preparation method according to claim 5, is characterized in that, described lyophilization comprises the following steps:
(1) pre-freeze: casing is evacuated to 10-15 handkerchief, makes described acyclovir sterile liquid medicine be cooled to-15--20 degree Celsius under vacuum, freezing 10-15 minute; Remove vacuum, then be cooled to-35--40 degree Celsius, freezing 40-60 minute;
(2) sublimation drying: casing is evacuated to 12-30 handkerchief, is filled with nitrogen, be warming up to-20--25 degree Celsius, dry 12-20 hour;
(3) adsorption stripping and dry: be warming up to 25-40 degree Celsius, vacuum drying 3-5 hour.
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| CN108358926A (en) * | 2018-04-28 | 2018-08-03 | 安徽海康药业有限责任公司 | A method of removal crystal's bulk pharmaceutical chemicals bacterial endotoxin |
| CN113476413A (en) * | 2021-08-09 | 2021-10-08 | 海南海灵化学制药有限公司 | Preparation method of ganciclovir sodium freeze-dried powder for injection |
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