CN102552291A - Vein medication preparation for fospropofol disodium, as well as preparation method and application of vein medication preparation - Google Patents
Vein medication preparation for fospropofol disodium, as well as preparation method and application of vein medication preparation Download PDFInfo
- Publication number
- CN102552291A CN102552291A CN2012100004323A CN201210000432A CN102552291A CN 102552291 A CN102552291 A CN 102552291A CN 2012100004323 A CN2012100004323 A CN 2012100004323A CN 201210000432 A CN201210000432 A CN 201210000432A CN 102552291 A CN102552291 A CN 102552291A
- Authority
- CN
- China
- Prior art keywords
- sodium
- preparation
- phosphorus propofol
- intravenous administration
- adds
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention provides a vein medication preparation for fospropofol disodium, as well as the preparation method and the application of the vein medication preparation. The vein medication preparation comprises fospropofol disodium, pH buffer regulator, osmotic pressure regulator and antioxidant; and the preparation is mainly used for anesthetic in surgery. The invention has the advantages that suitable pH buffer regulator is used, the fospropofol disodium has the least degradation products at 121 DEG C through the buffered pH range, and the preparation is kept steady at room temperature.
Description
Technical field:
The present invention relates to a kind of phosphorus propofol sodium intravenous administration formulation.
Technical background:
Propofol is colorless oil, and is water insoluble, because its low water solublity, then this medicine uses cosolvent to prepare as carrier usually, but has document to show that cosolvent can cause serious adverse in vivo.Clinical drug safety can't ensure.
Phosphorus propofol sodium (Fospropofol disodium), chemical name 2,6-diisopropyl benzene oxygen methyl acid phosphate disodium, phosphorus propofol sodium is the water-soluble prodrug of propofol, is a kind of sedative hypnotic that is applied to diagnose with treatment stage.The phosphorus propofol sodium good water solubility, thus in the process of preparation directly water make solvent, avoid the use of cosolvent and surfactant has improved drug safety.Phosphorus propofol sodium is the precursor medicine of propofol, and itself does not have pharmaceutically active, but this medicine good water solubility, the back is the propofol active component through the effect metabolism of alkali phosphatase in the entering body, thus the performance pharmaceutically active.
Summary of the invention
The present invention provides a kind of phosphorus propofol sodium intravenous administration formulation, and said preparation comprises the phosphorus propofol sodium of effective dose, the agent of pH dash adjustment, antioxidant, osmotic pressure regulator.In the process of preparation, use suitable pH dash adjustment agent, the pH of injection be buffered to suitable pH, make medicine under 121 ℃ of conditions of high temperature with long term store during catabolite be reduced to minimum.
Of the present invention specifying
Preparation of the present invention comprises that the phosphorus propofol sodium structural formula is following:
The object of the present invention is to provide a kind of pharmaceutical dosage phosphorus propofol sodium intravenous administration formulation that contains.
Also comprise antioxidant, the agent of pH dash adjustment, osmotic pressure regulator in the phosphorus propofol sodium intravenous administration formulation.
The amount ranges of phosphorus propofol sodium in the preparation process is 1-20% (w/v).
The pH of preparation can control what of catabolite of phosphorus propofol sodium among the present invention, so select suitable pH, could let phosphorus propofol sodium stable during long term store, and it is minimum that catabolite is reduced.Pass through test of many times; PH is in the 8-10 scope; Can effectively suppress the generation of catabolite; Wherein use the agent of pH dash adjustment that in sodium carbonate, sodium bicarbonate, sodium phosphate, dibastic sodium phosphate, sodium dihydrogen phosphate, arginine, glycine, the tromethane one or more are arranged, wherein amount ranges is 0-0.5mol/L.
The osmotic pressure regulator that uses among the present invention has one or more in sodium chloride, glucose, potassium chloride, sodium citrate, calcium chloride, the lactic acid.Wherein the scope of use amount is 0-6%.Can use sodium chloride to process corresponding phosphorus propofol sodium sodium chloride injection separately; Also can use glucose to process corresponding phosphorus propofol sodium glucose injection, can also use lactose, sodium chloride, potassium chloride, calcium chloride to process the phosphorus propofol sodium ringer's injection.
The antioxidant that uses among the present invention has citric acid, ascorbic acid, monothioglycerol, sodium sulfite, EDTA, cysteine, sodium metabisulfite.Wherein the scope of use amount is 0-1%.
Another object of the present invention is to provide the method for preparing of phosphorus propofol sodium intravenous administration formulation.
The present invention realizes through following measure:
A kind of method for preparing of phosphorus propofol sodium intravenous administration formulation, its preparation process is: main constituent phosphorus propofol sodium and an amount of agent of pH dash adjustment and antioxidant are dissolved in the water for injection, and regulating pH is 8.5～10.5; Add the activated carbon adsorption pyrogen again, filter, fill nitrogen, packing; Zha Gai, sterilization.
Method for preparing of the present invention comprises following a few step, in liquid dispensing container, adds 10%～95% water for injection, adds phosphorus propofol sodium, 0～0.5% (W/V) sodium chloride, 0～0.3% (W/V) sodium metabisulfite of recipe quantity 90%～115%, stirs and makes dissolving; Add (0.01～1%) Na2CO3/NaHCO3, regulate pH to 8.5～10.5, mend and add water to full dose; The medicinal charcoal that adds 0.01%～1% (W/V) then,, stirred 10～60 minutes; It is qualified to filter to clarity with the filter membrane of 0.45 μ m, fills nitrogen, after mensuration intermediate content is qualified; Decide loading amount and be sub-packed in the vial, roll lid, 121 ℃ of sterilization 8min both.
The product pH regulator is 8.5～10.5 in the method for preparing according to the invention, finds in the test, under this pH, can effectively be controlled at the generation of catabolite under the hot conditions.
Another object of the present invention is to provide a kind of preparation that is used for tranquilizing soporific, is mainly used in the anesthetis in the operation.Its dosage be initial intravenous injection 6.5mg/kg when needing then through replenishing dosage 1.6mg/kg, predose must not be crossed 577.5mg, boost must not be crossed 140mg.Can be used for anesthesia in the operation.
Phosphorus propofol sodium is through being metabolized to propofol.Propofol that from phosphorus propofol sodium, discharges and propofol difference to some extent in good time pharmacological effect.Give these article of the quick intravenous injection of health volunteer 10mg/kg, sedation effect is with the result of improvement observer's awakening/calmness scoring (MOAA/S) and comprehensive PK and PD.Propofol blood drug level peak value (2.1 ± 0.6) the μ g/mL that from phosphorus propofol sodium, discharges, on average about 8min.The time of the effect that regains one's nerve fully behind these article of study subject application is 20min to 45min.
The specific embodiment
Below in conjunction with embodiment the present invention is done further explain, but should understand the non-scope that only limits to these embodiment of scope of the present invention.
Embodiment 1: the preparation of phosphorus propofol sodium intravenous administration formulation
Prescription
The water for injection that in liquid dispensing container, adds 24000ml adds the recipe quantity phosphorus propofol sodium, stirs and makes dissolving, mends and adds water to full dose; The medicinal charcoal that adds 0.05% (W/V) then stirred 60 minutes, and it is qualified to filter to clarity with the filter membrane of 0.45 μ m; Measure intermediate content qualified after, fill nitrogen, decide loading amount and be sub-packed in the vial; Roll lid, 121 ℃ of sterilization 8min promptly get.
Embodiment 2: the preparation of phosphorus propofol sodium intravenous administration formulation
Prescription
The water for injection that in liquid dispensing container, adds 24000ml adds recipe quantity phosphorus propofol sodium, citric acid, stirs and makes dissolving, mends and adds water to full dose; The medicinal charcoal that adds 0.05% (W/V) then stirred 60 minutes, and it is qualified to filter to clarity with the filter membrane of 0.45 μ m; Measure intermediate content qualified after, fill nitrogen, decide loading amount and be sub-packed in the vial; Roll lid, 121 ℃ of sterilization 8min, both.
Embodiment 3: the preparation of phosphorus propofol sodium intravenous administration formulation
Prescription
The water for injection that in liquid dispensing container, adds 25000ml adds recipe quantity phosphorus propofol sodium, sodium chloride, citric acid, stirs and makes dissolving, mends and adds water to full dose; The medicinal charcoal that adds 0.02% (W/V) then stirred 45 minutes, and it is qualified to filter to clarity with the filter membrane of 0.45 μ m; Measure intermediate content qualified after, fill nitrogen, decide loading amount and be sub-packed in the vial; Roll lid, 121 ℃ of sterilization 8min, both.
Embodiment 4: the preparation of phosphorus propofol sodium intravenous administration formulation
Prescription
The water for injection that in liquid dispensing container, adds 20000ml adds recipe quantity phosphorus propofol sodium, citric acid, stirs and makes dissolving, adds the sodium carbonate and the manganese hydrogen sodium regulating solution pH to 9.0 of recipe quantity; The medicinal charcoal that adds 0.02% (W/V) then stirred 30 minutes, and it is qualified to filter to clarity with the filter membrane of 0.45 μ m; Measure intermediate content qualified after, fill nitrogen, decide loading amount and be sub-packed in the vial; Roll lid, 121 ℃ of sterilization 8min, both.
Embodiment 5: the preparation of phosphorus propofol sodium intravenous administration formulation
Prescription
The water for injection that in liquid dispensing container, adds 24000ml adds recipe quantity phosphorus propofol sodium, citric acid, stirs and makes dissolving, adds the sodium carbonate and the sodium dihydrogen phosphate regulator solution pH to 9.5 of recipe quantity; Benefit adds water to full dose, adds the medicinal charcoal of 1% (W/V) then, stirs 10 minutes, and it is qualified to filter to clarity with the filter membrane of 0.45 μ m; Measure intermediate content qualified after, towards nitrogen, decide loading amount and be sub-packed in the vial; Roll lid, 121 ℃ of sterilization 8min, both.
Embodiment 6: the preparation of phosphorus propofol sodium intravenous administration formulation
Prescription
The water for injection that in liquid dispensing container, adds 15000ml adds recipe quantity phosphorus propofol sodium, ascorbic acid and potassium chloride, stirs and makes dissolving, adds the tromethane regulator solution pH to 10.5 of recipe quantity; Benefit adds water to full dose, adds the medicinal charcoal of 0.5% (W/V) then, stirs 10 minutes, and it is qualified to filter to clarity with the filter membrane of 0.45 μ m; Measure intermediate content qualified after, fill nitrogen, decide loading amount and be sub-packed in the vial; Roll lid, 121 ℃ of sterilization 8min, both.
Embodiment 7: the preparation of phosphorus propofol sodium intravenous administration formulation
The water for injection that in liquid dispensing container, adds 24000ml adds recipe quantity phosphorus propofol sodium hydrate, stirs and makes dissolving, mends and adds water to full dose; The medicinal charcoal that adds 0.05% (W/V) then stirred 60 minutes, and it is qualified to filter to clarity with the filter membrane of 0.45 μ m; Measure intermediate content qualified after, fill nitrogen, decide loading amount and be sub-packed in the vial; Roll lid, 121 ℃ of sterilization 8min, both.
Embodiment 8: the preparation of phosphorus propofol sodium intravenous administration formulation
The water for injection that in liquid dispensing container, adds 24000ml adds recipe quantity phosphorus propofol sodium solvated compounds, stirs and makes dissolving; Benefit adds water to full dose, adds the medicinal charcoal of 0.05% (W/V) then, stirs 60 minutes; It is qualified to filter to clarity with the filter membrane of 0.45 μ m, measure intermediate content qualified after, fill nitrogen and decide loading amount and be sub-packed in the vial; Roll lid, 121 ℃ of sterilization 8min, both.
Embodiment 9: phosphorus propofol sodium intravenous administration formulation study on the stability
Get the phosphorus propofol sodium injection for intravenous injection of embodiment 4 gained, be positioned over relative humidity 75%, in 40 ℃ of biochemical incubators of temperature,, investigate outward appearance, particulate matter, visible foreign matters, related substance, content respectively at 1,2,3,6 sampling at the end of month.The result sees table 1
Table 1 phosphorus propofol sodium intravenous administration formulation study on the stability
Through investigating, to quicken to place 6 months, this quality does not have significant change.
Embodiment 10: the effect experiment of phosphorus propofol sodium injection in the experimental dog surgical operation
13 experimental dogs are all done out laparoscopic surgery.24h fasting water before the art.Skin clean is handled, the abdominal part preserved skin.Intravenous injection phosphorus propofol sodium injection 20mg/Kg.Breathe after the anesthesia onset and slow down, limb activity reduces gradually and even disappears, and eyeball is fixing blunt in fading away with corneal reflex.Carry out tracheal intubation rapidly.
The anaesthetic effect evaluation index: animal limb action, nociceptive reflex and eye situation etc. are observed in the injection back; Understand depth of anesthesia, record anesthesia onset time, single dose anesthesia are held time, repeated doses is held time, the evaluation index of number of repetition and the anaesthetic effects such as death condition of animal in experiment.
Statistical analysis: adopt SPSS13.0 software that data are analyzed
The result: (body weight 18.5 ± 2.2Kg) all adopts the anesthesia of phosphorus propofol sodium injection to 13 experimental dogs, carries out abdominal regulating liver-QI road and carries out the part operation.Onset time (36.2 ± 4.3) s; Initial dose (15.1 ± 4.2) min that holds time, operating time (63.4 ± 12.3) min, repeat administration 3.8 times; Repeated doses is held time, and experimental dog does not have the tractive reaction in (14.9 ± 5.8) min. operation; Degree of flaccid muscles is satisfied, and anaesthetic effect is steady, and no heart beating stops to wait the anesthesia emergency to occur.Postoperative recovery time 6-24min, the back experimental dog of reviving has no adverse reaction, and mental status is good, recovers autonomous respiration and autonomic activities, survival rate 100% at once.The experimental dog survival time after surgical operation all reaches requirement of experiment.
Claims (9)
1. phosphorus propofol sodium intravenous administration formulation and preparation method thereof is characterized in that containing phosphorus propofol sodium, osmotic pressure regulator, antioxidant, the agent of pH dash adjustment of pharmaceutical dosage.
2. the method for preparing of a phosphorus propofol sodium intravenous administration formulation, its preparation process is: phosphorus propofol sodium, tension regulator, antioxidant are dissolved in the water for injection, and adding the agent of pH dash adjustment, to regulate pH be 8.5～10.5; Add the activated carbon adsorption pyrogen again, filter, fill nitrogen; Lid is rolled in packing, sterilization.
3. like claim 1,2 said phosphorus propofol sodium intravenous administration formulations and preparation method thereof, it is characterized in that related phosphorus propofol sodium comprises its hydrate, anhydride and solvated compounds, its amount ranges is 1～20% (W/V).
4. like claim 1,2 said phosphorus propofol sodium intravenous administration formulations and preparation method thereof; It is characterized in that related osmotic pressure regulator is a kind of extremely several kinds in sodium chloride, glucose, potassium chloride, sodium citrate, calcium chloride, the lactic acid, its addition is 0～6.0%.
5. like claim 1,2 said phosphorus propofol sodium intravenous administration formulations and preparation method thereof; It is characterized in that related antioxidant is a kind of extremely several kinds in citric acid, ascorbic acid, monothioglycerol, sodium sulfite, EDTA, cysteine, the sodium metabisulfite, its addition is 0～1.0%.
6. like claim 1,2 said phosphorus propofol sodium intravenous administration formulations and preparation method thereof; It is characterized in that related pH dash adjustment agent is a kind of extremely several kinds in sodium carbonate, sodium bicarbonate, sodium phosphate, dibastic sodium phosphate, sodium dihydrogen phosphate, arginine, glycine, the tromethane, its addition is 0～0.5mol/L.
7. like the said method for preparing of claim 2, it is characterized in that: in liquid dispensing container, add 10%～100% water for injection, add phosphorus propofol sodium, 0～0.5% (W/V) sodium chloride, 0～0.3% (W/V) sodium metabisulfite of recipe quantity 90%～115%; Stirring makes dissolving, adds (0.01～1%) Na2CO3/NaHCO3, regulates pH to 8.5～10.5; Benefit adds water to full dose, adds the medicinal charcoal of 0.01%～1% (W/V) then, stirs 10～60 minutes; It is qualified to filter to clarity with the filter membrane of 0.45 μ m, fills nitrogen, after mensuration intermediate content is qualified; Decide loading amount and be sub-packed in the vial, roll lid, sterilization promptly gets.
8. like claim 2,7 said method for preparinies, it is characterized in that the pH scope is 8.5～10.5.
9. the purposes of phosphorus propofol sodium intravenous administration formulation is mainly used in the anesthetis in the operation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012100004323A CN102552291A (en) | 2012-01-04 | 2012-01-04 | Vein medication preparation for fospropofol disodium, as well as preparation method and application of vein medication preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012100004323A CN102552291A (en) | 2012-01-04 | 2012-01-04 | Vein medication preparation for fospropofol disodium, as well as preparation method and application of vein medication preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102552291A true CN102552291A (en) | 2012-07-11 |
Family
ID=46399750
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012100004323A Pending CN102552291A (en) | 2012-01-04 | 2012-01-04 | Vein medication preparation for fospropofol disodium, as well as preparation method and application of vein medication preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102552291A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102784099A (en) * | 2012-06-11 | 2012-11-21 | 陕西合成药业有限公司 | Combined preparation containing fospropofol disodium, and preparation method and application thereof |
| CN104918646A (en) * | 2012-11-08 | 2015-09-16 | 昂法玛公司 | Method and apparatus for adding buffers and other substances to medical cartridges |
| CN113416121A (en) * | 2021-07-29 | 2021-09-21 | 天津瑞普生物技术股份有限公司 | Synthesis method and application of fospropofol disodium and intermediate thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1649597A (en) * | 2002-04-08 | 2005-08-03 | 吉尔福德药物有限公司 | Pharmaceutical composition containing propofol water-soluble prodrug and administration method thereof |
| CN101756913A (en) * | 2010-01-05 | 2010-06-30 | 陕西合成药业有限公司 | Preparation method for injection phosphorus propofol sodium |
-
2012
- 2012-01-04 CN CN2012100004323A patent/CN102552291A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1649597A (en) * | 2002-04-08 | 2005-08-03 | 吉尔福德药物有限公司 | Pharmaceutical composition containing propofol water-soluble prodrug and administration method thereof |
| CN101756913A (en) * | 2010-01-05 | 2010-06-30 | 陕西合成药业有限公司 | Preparation method for injection phosphorus propofol sodium |
Non-Patent Citations (1)
| Title |
|---|
| 王会还，等: "新型镇静催眠药-磷丙泊福钠", 《医药导报》, vol. 29, no. 10, 31 October 2010 (2010-10-31), pages 1291 - 1294 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102784099A (en) * | 2012-06-11 | 2012-11-21 | 陕西合成药业有限公司 | Combined preparation containing fospropofol disodium, and preparation method and application thereof |
| CN104918646A (en) * | 2012-11-08 | 2015-09-16 | 昂法玛公司 | Method and apparatus for adding buffers and other substances to medical cartridges |
| CN113416121A (en) * | 2021-07-29 | 2021-09-21 | 天津瑞普生物技术股份有限公司 | Synthesis method and application of fospropofol disodium and intermediate thereof |
| CN113416121B (en) * | 2021-07-29 | 2022-08-05 | 天津瑞普生物技术股份有限公司 | Synthesis method and application of fospropofol disodium and intermediate thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8835508B2 (en) | Stable aqueous solution containing sodium pyruvate, and the preparation and use thereof | |
| US20090131338A1 (en) | Anesthesia arousal composition | |
| CN104224829A (en) | Injection containing sodium, potassium, magnesium, calcium and glucose injection and preparation method of injection | |
| KR20190035927A (en) | Epinephrine-based ophthalmic compositions for intraocular administration and methods for their manufacture | |
| US8597691B2 (en) | Anti-hypothermia composition | |
| US20140128355A1 (en) | Baclofen solution for low-volume therapeutic delivery | |
| CN102552291A (en) | Vein medication preparation for fospropofol disodium, as well as preparation method and application of vein medication preparation | |
| CN101455631A (en) | Meglumine cyclic adenosine injection and preparation technique thereof | |
| CN102397246A (en) | Fospropofol sodium for injection and preparation method and application thereof | |
| JPH08509712A (en) | Analgesic anesthetic composition | |
| Henneman et al. | Effects of general anesthesia on peripheral blood levels of carbohydrate and fat metabolites and serum inorganic phosphorus | |
| Natalini et al. | Intravenous 15% isoflurane lipid nanoemulsion for general anesthesia in dogs | |
| CN108354899A (en) | A kind of compound injection and preparation method thereof treating or preventing anesthesia low blood pressure | |
| CN102784099A (en) | Combined preparation containing fospropofol disodium, and preparation method and application thereof | |
| CN115919858A (en) | Analgesic pharmaceutical composition, preparation method and application thereof | |
| US20210346318A1 (en) | Epinephrine-based ophthalmic compositions for intraocular administration and methods for fabricating thereof | |
| CN102824307A (en) | Propofol medicinal composition for injection | |
| CN102558224A (en) | Phosphorus propofol sodium hydrate and preparation method and purpose thereof | |
| CN101781329A (en) | Propofol derivative for therapy | |
| EP3880168B1 (en) | Aqueous paediatric retinol formulations | |
| CN102008461A (en) | Ibuprofen drug composite for injection | |
| CN1870974B (en) | Method for producing injectable gabapentin compositions | |
| US20220280558A1 (en) | Molecular hydrogen-containing composition for preventing or improving osteoporosis | |
| CN108158989B (en) | Ambroxol hydrochloride injection composition | |
| CN102462695B (en) | Application of sodium sulfite |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120711 |