CN102727427A - Isotonic naloxone injection and preparation method thereof - Google Patents
Isotonic naloxone injection and preparation method thereof Download PDFInfo
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- CN102727427A CN102727427A CN2011100874647A CN201110087464A CN102727427A CN 102727427 A CN102727427 A CN 102727427A CN 2011100874647 A CN2011100874647 A CN 2011100874647A CN 201110087464 A CN201110087464 A CN 201110087464A CN 102727427 A CN102727427 A CN 102727427A
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- naloxone
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Abstract
An isotonic naloxone injection contains naloxone or water-soluble medicinal salt thereof, glucose, citric acid and sodium citrate. The injection has the advantages of high stability, small content change of a known impurity 2,2'-bisnaloxone, and high security.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, relate to a kind of grade and ooze injection and preparation method thereof, be specifically related to a kind of grade and ooze naloxone injection and preparation method thereof.
Background technology
Naloxone hydrochloride is antipyretic-antalgic and non_steroidal anti_inflammatory drug, and is oral invalid, must drug administration by injection.Naloxone hydrochloride injection is the widest opiate receptor antagonistic of present clinical practice, is mainly used in: (1) rescue narcosis analgesic acute poisoning, and the respiration inhibition of this type of antagonism medicine, and patient is revived; (2) residual action of antagonism narcosis analgesic, neonate are influenced by narcosis analgesic in its parent and cause respiration inhibition, available article antagonism; (3) rescue acute alcoholism: quiet notes or intramuscular injection naloxone 0.4～0.6mg can make the patient clear-headed; (4) be the narcosis analgesic addict to doubting, quiet notes 0.2～0.4mg can excite withdrawal symptom, and diagnostic value is arranged; (5) the short effect of waking up can activate physiological awakening system through the cholinergic effect and make patient clear-headed, is used for that general anesthesia wakens and shock and some coma patient.
Chinese patent CN200510080479.5 discloses a kind of naloxone hydrochloride injection and production method thereof of new packing, and this method comprises the steps: that (1) prepare article in the middle of the naloxone hydrochloride injection; (2) article in the middle of the above-mentioned naloxone hydrochloride injection are carried out aseptic filtration, obtain filtrating; (3) with above-mentioned filtrating sterile filling in cillin bottle; (4) flowing steam sterilization.This production method is through a filtration sterilization, a flowing steam sterilization process, and product is safer, and quality is more reliable; And, in filtration sterilization, can remove the particulate matter in the medicinal liquid, greatly reduce phlebitic occurrence probability.
Chinese patent CN200910016081.3 discloses a kind of preparation technology of naloxone hydrochloride injection; Through strict control pH scope aborning; Can make naloxone hydrochloride injection pH in put procedure constant, adopt the method for inert gas shielding in producing simultaneously, reduce to the oxygen content that reaches in the ampoule in the medicinal liquid minimum; Prevent the oxidation deterioration of naloxone hydrochloride injection, reduced related substance.Guaranteed product quality greatly through above two technology.
The pH value scope of above-mentioned two naloxone hydrochloride injections regulation is 3.0-4.0, wherein the known impurities in the injection 2,2 in the long term store '-two naloxone content increase, there is risk in safety.
The naloxone hydrochloride injection of domestic production at present basically all is a hypisotonic solution, and the pH value scope is 3.0-4.0, and method for using is for the instillation of dilution posterior vein, the direct intravenous injection of original solution or can not select intramuscular injection under the intravenous injection situation.In clinical practice, when finding intravenous injection or intramuscular injection, part patient produces slight IR.
In sum: solve naloxone injection long-time stability and osmotic pressure and cross the low zest that produces, the safety that improves injection is the problem that study of pharmacy presses for solution.
We are unexpected in the process of development naloxone injection to find that pH is in 4.5～5.5 scopes, is that the injection of adjuvant is more stable than external commercially available with citric acid, sodium citrate, glucose.The adjuvant that adopts in the injection prescription of the present invention is citric acid, sodium citrate, glucose.Abroad, the naloxone hydrochloride injection of Hospira company exploitation prescription is sodium chloride, hydrochloric acid or sodium hydroxide and nitrogen, injection inflated with nitrogen wherein, and equipment requirements is high, and nitrogen gas purity is wayward, operates more loaded down with trivial details.Therefore, injection prescription of the present invention is compared with the injection that goes on the market, and the pH value stabilizing agent uses organic acid (salt) to substitute strong acid and strong base, existing cushioning effect, and Wheat Protein reduces injection and fills the nitrogen operation again; Add glucose simultaneously as isoosmotic adjusting agent, improve the zest of domestic hypotonic naloxone injection.
Summary of the invention
The present invention provides a kind of grade to ooze the naloxone injection, contains naloxone or its water solublity officinal salt, glucose, citric acid, sodium citrate in the said injection.
Said naloxone water solublity officinal salt is preferably hydrochlorate, and the concentration of naloxone hydrochloride is 0.1mg/ml～2.0mg/ml.Preferred concentration is 0.4mg/ml～1.0mg/ml.
The pH scope of said injection is 4.5～5.5.
The concentration of said glucose is 45mg/ml～55mg/ml, said citric acid and sodium citrate, and concentration all is 1mg/ml～3mg/ml.
This injection good stability, known impurities 2,2 wherein '-two naloxone changes of contents are little, safe.
The present invention also provides a kind of grade to ooze the method for preparing of naloxone injection, and this method may further comprise the steps:
(1) glucose for injection, citric acid, sodium citrate are dissolved in an amount of water for injection, add activated carbon adsorption and remove thermal source, decarburization adds naloxone hydrochloride, and stirring and dissolving adds the injection water to aequum;
(2) gained solution is smart considers the back embedding in ampoule bottle, and 115 ℃ of pressure sterilizings 30 minutes promptly get injection.
The specific embodiment
Below further illustrate the present invention through embodiment, but be not limited to embodiment.
Embodiment 1
Prescription:
Technology:
Recipe quantity glucose, citric acid, sodium citrate are added an amount of water for injection dissolving, add an amount of needle-use activated carbon, heated and stirred, filtering decarbonization; In the fine straining liquid of cool to room temperature, add the naloxone hydrochloride that accurately takes by weighing, stir dissolving, add water to amount of preparation 1000ml, surveying pH is 4.5; With 0.22 μ m mixed cellulose ester microporous membrane filtration sterilization, concentration is 0.4mg/1ml, every ampoule packing 1ml or 10ml; Sealing by fusing, 115 ℃ of pressure sterilizings 30 minutes get product.
Embodiment 2
Prescription:
Technology:
Recipe quantity glucose, citric acid, sodium citrate are added an amount of water for injection dissolving, add an amount of needle-use activated carbon, heated and stirred, filtering decarbonization; In the fine straining liquid of cool to room temperature, add the naloxone hydrochloride that accurately takes by weighing, stir dissolving, add water to amount of preparation 1000ml, surveying PH is 5.5; With 0.22 μ m mixed cellulose ester microporous membrane filtration sterilization, concentration is 1mg/1ml, every ampoule packing 1ml or 2ml; Sealing by fusing, 115 ℃ of pressure sterilizings 30 minutes get product.
Test Example 1
Naloxone hydrochloride injection product chemistry stability test among the present invention
Test method:, naloxone hydrochloride injection among the present invention and external commercially available article are carried out thimble test and accelerated test with reference to the requirement of naloxone hydrochloride crude drug quality standard (Chinese Pharmacopoeia 2005 version two ones), naloxone hydrochloride injection quality standard (Chinese Pharmacopoeia 2005 version two ones) and two relevant injections of version appendix in 2005 of Chinese Pharmacopoeia.
The prepared injection liquid samples of the present invention is carried out stability test under the same conditions with external commercially available prod.
Experiment condition: naloxone hydrochloride injection sample of the present invention and external commercially available article are carried out high high-temp stability test (investigating 10 days down for 60 ℃) and accelerated test (40 ± 2 ℃ of temperature; Relative humidity is 75% ± 5%); Purpose is the stability of investigating in drug fever stability test and the accelerated test, observes the relatively variation of both outward appearance, pH value, known impurities amount and content.Concrete data are seen table 1～table 5:
Table 1 high high-temp stability is investigated the result
Table 2 self-control sample (concentration 0.4mg/ml) accelerated test is investigated the result
| The investigation time | Character | PH value | 2,2 '-two naloxones (%) | Content (%) |
| 0 month | Colourless clear liquid | 4.50 | 0.12 | 99.2 |
| January | Colourless clear liquid | 4.50 | 0.13 | 99.1 |
| February | Colourless clear liquid | 4.52 | 0.15 | 98.7 |
| March | Colourless clear liquid | 4.51 | 0.17 | 98.5 |
| June | Colourless clear liquid | 4.54 | 0.20 | 98.1 |
Table 3 self-control sample (concentration 1.0mg/ml) accelerated test is investigated the result
| The investigation time | Character | PH value | 2,2 '-two naloxones (%) | Content (%) |
| 0 month | Colourless clear liquid | 5.55 | 0.13 | 99.7 |
| January | Colourless clear liquid | 5.57 | 0.14 | 99.6 |
| February | Colourless clear liquid | 5.59 | 0.16 | 99.5 |
| March | Colourless clear liquid | 5.60 | 0.18 | 99.3 |
| June | Colourless clear liquid | 5.62 | 0.21 | 98.9 |
The external commercially available article of table 4 (concentration 0.4mg/ml) accelerated test is investigated the result
| The investigation time | Character | PH value | 2,2 '-two naloxones (%) | Content (%) |
| 0 month | Colourless clear liquid | 3.64 | 0.10 | 98.9 |
| January | Colourless clear liquid | 3.67 | 0.16 | 98.5 |
| February | Colourless clear liquid | 3.70 | 0.19 | 98.1 |
| March | Colourless clear liquid | 3.74 | 0.23 | 97.8 |
| June | Colourless clear liquid | 3.81 | 0.38 | 97.2 |
The external commercially available article of table 5 (concentration 1.0mg/ml) accelerated test is investigated the result
| The investigation time | Character | PH value | 2,2 '-two naloxones (%) | Content (%) |
| 0 month | Colourless clear liquid | 3.52 | 0.11 | 100.2 |
| January | Colourless clear liquid | 3.56 | 0.16 | 99.8 |
| February | Colourless clear liquid | 3.62 | 0.21 | 99.4 |
| March | Colourless clear liquid | 3.68 | 0.27 | 99.1 |
| June | Colourless clear liquid | 3.78 | 0.39 | 98.6 |
The result shows; Compare with external commercially available prod; Injection liquid samples of the present invention was in 60 ℃ of held 10 days and accelerated test 6 months; Its outward appearance, known impurities amount and content are all in that " in Chinese pharmacopoeia version naloxone hydrochloride injection in 2005 the quality standard span of control, its integral result is superior to external commercially available article, shows that its stability increases.
Claims (7)
1. a grade is oozed the naloxone injection, it is characterized in that: contain naloxone or its water solublity officinal salt, glucose, citric acid, sodium citrate in the said injection.
2. injection according to claim 1 is characterized in that: said naloxone water solublity officinal salt is a hydrochlorate.
3. injection according to claim 2 is characterized in that: the concentration of said naloxone hydrochloride is 0.1mg/ml～2.0mg/ml.
4. injection according to claim 3 is characterized in that: the concentration of said naloxone hydrochloride is 0.4mg/ml～1.0mg/ml.
5. injection according to claim 1 is characterized in that: the pH scope of said injection is 4.5～5.5.
6. injection according to claim 1 is characterized in that: the concentration of said glucose is 45mg/ml～55mg/ml, said citric acid and sodium citrate, and concentration all is 1mg/ml～3mg/ml.
7. method for preparing that the described grade of claim 1 is oozed the naloxone injection is characterized in that: said method comprising the steps of:
(1) glucose for injection, citric acid, sodium citrate are dissolved in an amount of water for injection, add activated carbon adsorption and remove thermal source, decarburization adds naloxone hydrochloride, and stirring and dissolving adds the injection water to aequum;
(2) gained solution is smart considers the back embedding in ampoule bottle, and 115 ℃ of pressure sterilizings 30 minutes promptly get injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100874647A CN102727427A (en) | 2011-04-08 | 2011-04-08 | Isotonic naloxone injection and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100874647A CN102727427A (en) | 2011-04-08 | 2011-04-08 | Isotonic naloxone injection and preparation method thereof |
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| CN102727427A true CN102727427A (en) | 2012-10-17 |
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| CN2011100874647A Pending CN102727427A (en) | 2011-04-08 | 2011-04-08 | Isotonic naloxone injection and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103877016A (en) * | 2014-04-11 | 2014-06-25 | 成都苑东药业有限公司 | Pharmaceutical composition of naloxone hydrochloride injection and preparation method thereof |
| CN104127380A (en) * | 2014-08-23 | 2014-11-05 | 成都天台山制药有限公司 | Pharmaceutical composition of naloxone hydrochloride injection and preparation method of pharmaceutical composition |
-
2011
- 2011-04-08 CN CN2011100874647A patent/CN102727427A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103877016A (en) * | 2014-04-11 | 2014-06-25 | 成都苑东药业有限公司 | Pharmaceutical composition of naloxone hydrochloride injection and preparation method thereof |
| CN104127380A (en) * | 2014-08-23 | 2014-11-05 | 成都天台山制药有限公司 | Pharmaceutical composition of naloxone hydrochloride injection and preparation method of pharmaceutical composition |
| CN104127380B (en) * | 2014-08-23 | 2017-01-25 | 成都天台山制药有限公司 | Pharmaceutical composition of naloxone hydrochloride injection and preparation method of pharmaceutical composition |
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Application publication date: 20121017 |