CN107616965A - A kind of paracetamol high-capacity injection and preparation method thereof - Google Patents
A kind of paracetamol high-capacity injection and preparation method thereof Download PDFInfo
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- CN107616965A CN107616965A CN201710917124.XA CN201710917124A CN107616965A CN 107616965 A CN107616965 A CN 107616965A CN 201710917124 A CN201710917124 A CN 201710917124A CN 107616965 A CN107616965 A CN 107616965A
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- paracetamol
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Abstract
The invention discloses a kind of paracetamol high-capacity injection, and it is made up of paracetamol, isotonic agent mannitol and water for injection；The concentration of paracetamol in the injection is 100ml/g, and the isotonic agent mannitol is used to adjust the osmotic pressure molar density of injection to consistent with blood of human body.The application by using hot water dissolving in process, liquid intermediate pH scopes are prepared in strict control in process of production, ensure that paracetamol in most suitable pH scopes solution, controls dissolved oxygen and residual oxygen in process in addition, avoid paracetamol from aoxidizing, ensure qualified product.Paracetamol high-capacity injection supplementary product consumption prepared by the present invention is small, and risk is low, avoids the increase about material.
Description
Technical field
The present invention relates to a kind of liquid injection agent field, and in particular to a kind of paracetamol high-capacity injection and its
Preparation method.
Background technology
Paracetamol, molecular formula C8H9NO2, usually white crystalline powder, it can be dissolved in ethanol, acetone and heat
Water, water is insoluble in, insoluble in petroleum ether and benzene；Odorlessness, bitter.Paracetamol is widely used OTC anodyne
And alexipyretic.It is generally used for alleviating heating, headache and other slight pain and pain and controlled for most flu and influenza
Treat the main component in wanting.Paracetamol injection determined, indication are for generating heat, it can also be used to alleviate light moderate pain,
Such as headache, courbature, arthralgia and neuralgia, dysmenorrhoea, carcinomas pain and postoperative analgesia.Paracetamol injection determined can
For to aspirin-sensitive or intolerable patient.Paracetamol injection determined twists to various severe pain and visceral smooth muscle
It is bitterly invalid.
Product is protected using different types of buffer, antioxidant to product on the market now, has been avoided
The increase of material is closed, but so operation adds the detection of auxiliary material and controlled risk.
The content of the invention
[technical problems to be solved]
Present invention aim to address above-mentioned problem of the prior art, there is provided a kind of paracetamol high-capacity injection
And preparation method thereof, the present invention uses paracetamol and isotonic agent mannitol, and product is eliminated by technologic protection
In auxiliary material addition, and ensure the quality level of product.
[technical scheme]
In order to reach above-mentioned technique effect, the present invention takes following technical scheme：
A kind of paracetamol high-capacity injection, it is by paracetamol, isotonic agent mannitol and injection
Water forms；The concentration of paracetamol in the injection is 100ml/g, and the isotonic agent mannitol is used for injection
Osmotic pressure molar density is adjusted to consistent with blood of human body.
The further technical scheme of the present invention, the pH value of the paracetamol injection is 5.2~5.7；It is described
PH adjusting agent is watery hydrochloric acid or sodium hydroxide.
A kind of preparation method of above-mentioned paracetamol high-capacity injection, it comprises the following steps：
Step A, the preparation of concentrated solution
Appropriate water for injection is added into dense preparing tank, puts into the mannitol weighed up, then stirring adds total dosage to dissolving
1/2 activated carbon, stirs, standing adsorption；The temperature for controlling the concentrated solution is 60~70 DEG C；
Step B, the dilute of concentrated solution match somebody with somebody
The concentrated solution that step A is prepared filters through stud while hot, is sent into the dilute preparing tank that volume is 1000mL；Then match somebody with somebody to dilute
Water for injection is added in tank to the 80% of dilute preparing tank cumulative volume, control oxyty is less than 3%, is subsequently added into acetparaminosalol
Phenol, it is 60~80 DEG C to control solution temperature, stirring to dissolving；Water for injection is added to dilute preparing tank cumulative volume；Add remaining
Activated carbon, 10min is stood after stirring, filtered, filtrate is weak solution；
Step C, the post processing of paracetamol injection
It is 5.2~5.6 by the weak solution watery hydrochloric acid or sodium hydroxide that have stood regulation pH value, sampling detection pH value, sweet
Reveal alcohol content and whether Determination Paracetamol in Paracetamol is qualified；After qualified, canned, welding cap, packaged injection is protected at 121 DEG C
Warm 12h is sterilized, then cooling, lamp inspection, packaging, product inspection.
The further technical scheme of the present invention, the oxyty of the water for injection are less than 0.5%.
The further technical scheme of the present invention, the activated carbon are 0.01% using gross mass and the volume ratio of injection
~0.02%.
The further technical scheme of the present invention, in stepb, adds remaining activated carbon, after being stood after stirring,
Filtered with stud.
The present invention is will be described in detail below.
Because the injection of the present invention is high-capacity injection, it is therefore desirable to paracetamol is carried out substantial amounts of molten
Solution.Found by the research to product critical component attribute, paracetamol is insoluble in water, can be dissolved in hot water, easily oxidation
Degraded, therefore, for the application by using hot water dissolving in process, liquid intermediate pH models are prepared in strict control in process of production
Enclose, ensure that paracetamol in most suitable pH scopes solution, controls dissolved oxygen and residual oxygen, avoided to second in process in addition
Acylamino- phenol aoxidizes, and ensures qualified product.Present invention employs supplementary product consumption minimum principle --- and supplementary product consumption is smaller, wind
Dangerous lower and bold employs 121 DEG C, 12min transition killing terminal sterilization.
In the present invention, paracetamol content most temperature when pH value is in the range of 5.2~5.7, relevant material minimum.
Initiation material, intermediate, condensate, the side reaction product mainly brought into process of production about material, and stored
Catabolite in journey etc..Because mannitol not readily dissolves, in preparation process, the concentrated solution of mannitol need to be first prepared, is ensured
The perfect solution of mannitol, so as to reduce paracetamol heated time, protect paracetamol.It is and such as right in just love
During Paracetamol, it is 70~80 DEG C to control solution temperature, can increase the solubility of paracetamol, ensure to acetyl ammonia
A large amount of dissolvings of base phenol.If too high temperature will be to have an impact to paracetamol, its drug effect is further influenceed.The present invention exists
Also strict control dissolved oxygen, avoids dissolved oxygen from excessively causing the oxidation of paracetamol in step B.The dilute preparing tank can be used and taken out very
Empty nitrogen filled protection, so as to control the concentration of dissolved oxygen to be less than 3%.In the preparation process in accordance with the present invention, the effect of activated carbon is to be used for
The decolouring of injection, refine and remove thermal source；Activated carbon is removed filtering and filtered using stud, and time of repose is defined to 10min, long
Time cause principal component to be adsorbed, the too short time can not ensure the removal of product thermal source, pigment and heavy metal.
[beneficial effect]
The present invention compared with prior art, has following beneficial effect：
Paracetamol high-capacity injection supplementary product consumption prepared by the present invention is small, and risk is low, avoids relevant material
Increase.The preparation technology of the present invention is easy and effective, ensure that the quality level of product.
Embodiment
With reference to embodiments of the invention, the invention will be further elaborated.
Embodiment 1：
A kind of paracetamol high-capacity injection, it is by paracetamol, isotonic agent mannitol and injection
Water forms；The concentration of paracetamol in the injection is 100ml/g, and the isotonic agent mannitol is used for injection
Osmotic pressure molar density is adjusted to consistent with blood of human body.The pH value of the paracetamol injection is 5.2~5.7；Institute
It is watery hydrochloric acid or sodium hydroxide to state pH adjusting agent.
The preparation method of above-mentioned paracetamol high-capacity injection, comprises the following steps：
Step A, the preparation of concentrated solution
Appropriate water for injection is added into dense preparing tank, puts into the mannitol weighed up, then stirring adds total dosage to dissolving
1/2 activated carbon, stirs, standing adsorption；The temperature for controlling the concentrated solution is 60~70 DEG C；
Step B, the dilute of concentrated solution match somebody with somebody
The concentrated solution that step A is prepared filters through stud while hot, is sent into the dilute preparing tank that volume is 1000mL；Then match somebody with somebody to dilute
Water for injection is added in tank to the 80% of dilute preparing tank cumulative volume, control oxyty is less than 3%, is subsequently added into acetparaminosalol
Phenol, it is 60~80 DEG C to control solution temperature, stirring to dissolving；Water for injection is added to dilute preparing tank cumulative volume；Add remaining
Activated carbon, 10min is stood after stirring, filtered, filtrate is weak solution；
Step C, the post processing of paracetamol injection
It is 5.2~5.6 by the weak solution watery hydrochloric acid or sodium hydroxide that have stood regulation pH value, sampling detection pH value, sweet
Reveal alcohol content and whether Determination Paracetamol in Paracetamol is qualified；After qualified, canned, welding cap, packaged injection is protected at 121 DEG C
Warm 12h is sterilized, then cooling, lamp inspection, packaging, product inspection.
Embodiment 2
More parts of paracetamol 1g for being ground into fine powder is weighed, respectively at 25 DEG C ± 2 DEG C；40℃±2℃；50℃±2℃；
60℃±2℃；70℃±2℃；In 80 DEG C ± 2 DEG C of 30mL water, every strength shaking in 5 minutes 30 seconds；In observation 30 minutes
Dissolving situation, such as without visual visible particles of solute or during drop, that is, be considered as and be completely dissolved.As a result it is as shown in table 1.
Table 1 is the dissolving situation under paracetamol different temperatures
| Temperature | Experimental result |
| 25℃ | There is visual visible particles of solute |
| 41℃ | There is visual visible particles of solute |
| 52℃ | There is visual visible particles of solute |
| 60℃ | Without visual visible particles of solute |
| 70℃ | Without visual visible particles of solute |
| 82℃ | Without visual visible particles of solute |
From table 1 it follows that paracetamol can be dissolved in 60~80 DEG C of water, therefore the application is being prepared to second
During amino phenols injection, in order to increase the solubility to ethylamino phenol, the solubility for preparing solution is controlled in said temperature scope
It is interior.
Embodiment 3
According to the dissolubility result of embodiment 2 design the dilute feed temperature matched somebody with somebody of concentrated solution, take respectively 30~40 DEG C, 40~50
DEG C, 50~60 DEG C, 60~70 DEG C, 70~80 DEG C, influence of the different temperatures to product quality is investigated, to determine the optimal temperature that feeds intake
Degree.As a result it is as shown in table 2.
Table 2 is the dilute impurity content matched somebody with somebody of concentrated solution under different temperatures scope
From table 2 it can be seen that relevant material influence of the feed temperature on product in the embodiment 3 is smaller, 30~60
The dissolving of DEG C paracetamol is incomplete, and content heterogeneity, paracetamol is more soluble in higher temperatures, 60~80
DEG C when, paracetamol is soluble, and relevant content of material is minimum.The medicine of first paracetamol can be answered if temperature is too high
Effect.Therefore the selected feed temperature of the present invention is 60~80 DEG C.
Embodiment 4
That reasonability to activated carbon dosage in prescription of the present invention is tested.Paracetamol great Rong of the present invention
The concentrated compounding for measuring injection is matched somebody with somebody in technique with dilute, and thermal source is decolourized, refined and gone using activated carbon；Therefore, the present embodiment exists
During concentrated compounding, respectively according to mass volume ratio by dose volume 0.00%, 0.005%, 0.01%, 0.02%,
0.05% addition activated carbon is investigated；During dilute match somebody with somebody, respectively according to mass volume ratio by dose volume 0.00%,
0.005%th, 0.01%, 0.02%, 0.05% addition activated carbon is investigated.Then to the character of sample, pH, relevant material,
Mannitol content, Determination Paracetamol in Paracetamol are investigated.As a result it is as shown in table 3.
Table 3 is the testing result of activated carbon dosage
From table 3 it is observed that different activities charcoal dosage to sample pH value, relevant material and mannitol content without obvious poor
It is different, according to as the few as possible principle of supplementary product consumption, determine activated carbon prescription dosage be preferably dose volume 0.01%~
0.02%.
Embodiment 4
Because paracetamol is more sensitive to oxygen, in the presence of oxygen, meeting oxidation Decomposition, therefore, to entirely matching somebody with somebody
Influence of the dissolved oxygen amount of solution to product quality is studied during system.Under the conditions of not nitrogen charging, oxygen in water is about
7mg/L.Therefore, the present embodiment is respectively 1.0mg/L, 3.0mg/L, 5.0mg/L, 7.0mg/L to design dissolved oxygen concentration parameter,
Influence degree of the dissolved oxygen amount in solution to product quality is investigated, it is determined that rational technical process control parameter.
The character of sample, pH, relevant material, Determination Paracetamol in Paracetamol are investigated respectively.As a result it is as shown in table 4.
Table 4 is influence of the different dissolved oxygen amounts to injection quality
As can be seen from Table 4, from the point of view of the content with reference to pH, about material, dissolved oxygen amount difference influences bright on product quality
It is aobvious, it is relatively low in the relevant material of below 3.1mg/L products, therefore need to control dissolved oxygen in below 3mg/L in production technology.
In summary it can be seen, the present invention is had found by the research to product critical component attribute, though paracetamol is difficult
Water is dissolved in, but hot water can be dissolved in；And easy oxidative degradation；Therefore, the application by using hot water dissolving in process, in life
Liquid intermediate pH scopes are prepared in strict control during production, ensure paracetamol in most suitable pH scopes solution, separately
Control dissolved oxygen and residual oxygen in process outside, avoid paracetamol from aoxidizing, ensure qualified product.Pair prepared by the present invention
Paracetamol high-capacity injection supplementary product consumption is small, and risk is low, avoids the increase about material.
Although reference be made herein to invention has been described for explanatory embodiment of the invention, and above-described embodiment is only this hair
Bright preferable embodiment, embodiments of the present invention are simultaneously not restricted to the described embodiments, it should be appreciated that people in the art
Member can be designed that a lot of other modifications and embodiment, and these modifications and embodiment will fall in principle disclosed in the present application
Within scope and spirit.
Claims (6)
1. a kind of paracetamol high-capacity injection, it is characterised in that it is by paracetamol, isotonic agent mannitol
Formed with water for injection；The concentration of paracetamol in the injection is 100ml/g, and the isotonic agent mannitol is used for will
The osmotic pressure molar density of injection is adjusted to consistent with blood of human body.
2. paracetamol high-capacity injection according to claim 1, it is characterised in that the paracetamol
The pH value of injection is 5.2~5.7；The pH adjusting agent is watery hydrochloric acid or sodium hydroxide.
3. a kind of preparation method of the paracetamol high-capacity injection of claim 1 or 2, it is characterised in that it includes
Following steps：
Step A, the preparation of concentrated solution
Appropriate water for injection is added into dense preparing tank, puts into the mannitol weighed up, then stirring adds total dosage 1/2 to dissolving
Activated carbon, stir, standing adsorption；The temperature for controlling the concentrated solution is 60~70 DEG C；
Step B, the dilute of concentrated solution match somebody with somebody
The concentrated solution that step A is prepared filters through stud while hot, is sent into the dilute preparing tank that volume is 1000mL；Then into dilute preparing tank
Water for injection is added to the 80% of dilute preparing tank cumulative volume, control oxyty is less than 3%, is subsequently added into paracetamol, controls
Solution temperature processed is 60~80 DEG C, stirring to dissolving；Water for injection is added to dilute preparing tank cumulative volume；Add remaining activity
Charcoal, 10min is stood after stirring, filtered, filtrate is weak solution；
Step C, the post processing of paracetamol injection
It is 5.2~5.6 by the weak solution watery hydrochloric acid or sodium hydroxide that have stood regulation pH value, sampling detection pH value, mannitol
Whether content and Determination Paracetamol in Paracetamol are qualified；After qualified, canned, welding cap, packaged injection is incubated at 121 DEG C
12h is sterilized, then cooling, lamp inspection, packaging, product inspection.
4. the preparation method of paracetamol high-capacity injection according to claim 3, it is characterised in that the injection
It is less than 0.5% with the oxyty of water.
5. the preparation method of paracetamol high-capacity injection according to claim 3, it is characterised in that the activity
Charcoal is 0.01%~0.02% using gross mass and the volume ratio of injection.
6. the preparation method of paracetamol high-capacity injection according to claim 3, it is characterised in that in step B
In, remaining activated carbon is added, after being stood after stirring, is filtered with stud.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201710917124.XA CN107616965A (en) | 2017-09-27 | 2017-09-27 | A kind of paracetamol high-capacity injection and preparation method thereof |
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| CN201710917124.XA CN107616965A (en) | 2017-09-27 | 2017-09-27 | A kind of paracetamol high-capacity injection and preparation method thereof |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102258485A (en) * | 2011-01-11 | 2011-11-30 | 北京润德康医药技术有限公司 | Acetaminophen-contained preparation for injection and applications thereof |
| CN104586758A (en) * | 2015-01-20 | 2015-05-06 | 石家庄四药有限公司 | Paracetamol injection and preparation method thereof |
-
2017
- 2017-09-27 CN CN201710917124.XA patent/CN107616965A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102258485A (en) * | 2011-01-11 | 2011-11-30 | 北京润德康医药技术有限公司 | Acetaminophen-contained preparation for injection and applications thereof |
| CN104586758A (en) * | 2015-01-20 | 2015-05-06 | 石家庄四药有限公司 | Paracetamol injection and preparation method thereof |
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