CN101032497A - Polyenylphosphatidylcholine freeze - dried powder injection for injecting and the preparing method thereof - Google Patents
Polyenylphosphatidylcholine freeze - dried powder injection for injecting and the preparing method thereof Download PDFInfo
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- CN101032497A CN101032497A CN 200610009780 CN200610009780A CN101032497A CN 101032497 A CN101032497 A CN 101032497A CN 200610009780 CN200610009780 CN 200610009780 CN 200610009780 A CN200610009780 A CN 200610009780A CN 101032497 A CN101032497 A CN 101032497A
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Abstract
The present invention is freeze dried Essentiale phospholipids powder for injection and its preparation process. The freeze dried Essentiale phospholipids powder for injection consists of Essentiale phospholipids in 0.1-0.5 weight portions, alkaline material in such amount of regulating the pH value to 5.0-9.0, and excipient in 0.002-0.7 weight portions. The medicine of the present invention is used in treating acute and chronic liver diseases, psoriasis, radiation syndrome and other diseases.
Description
Technical field:
The present invention relates to a kind of polyenylphosphatidylfreezee freezee-dried powder injection for injecting and preparation method thereof.
Background technology:
The Polyene Phosphatidylcholine injection liquid that uses clinically at present is hydro-acupuncture preparation, in moisture more liquid environment, its Main Ingredients and Appearance is rich in unsaturated fatty acid, easy oxidized generation color change, content descends, and related substance increases and lessens the curative effect and increase toxic and side effects.The present invention can solve above problem effectively, and the present invention makes lyophilized injectable powder, moisture less than 5% situation under, its stability increases greatly, has guaranteed the quality of preparation, has reduced toxic and side effects.
Summary of the invention:
The purpose of this invention is to provide a kind ofly can increase preparation stability, pharmaceutical preparation polyenylphosphatidylfreezee freezee-dried powder injection for injecting of treatment acute and chronic hepatitis, psoriasis, radiation syndrome and preparation method thereof.
Above-mentioned purpose realizes by following technical scheme:
A kind of polyenylphosphatidylfreezee freezee-dried powder injection for injecting, its composition comprises: alkaline matter, excipient that polyene phosphatidylcholine, pharmacology allow, the parts by weight of described polyene phosphatidylcholine are 0.1～0.5, the parts by weight of described alkaline matter are 5.0～9.0 o'clock needed amounts for adjusting to pH value, and the parts by weight of described excipient are 0.002～0.7.
Above-mentioned polyenylphosphatidylfreezee freezee-dried powder injection for injecting, its composition also comprises: cosolvent, described cosolvent be its parts by weight of ethanol be 5～40 or its parts by weight of propylene glycol be 2～40 or its parts by weight of benzyl alcohol be 0.1～10.
Above-mentioned polyenylphosphatidylfreezee freezee-dried powder injection for injecting, described alkaline matter are inorganic base or basic amino acid.
Above-mentioned polyenylphosphatidylfreezee freezee-dried powder injection for injecting, described alkaline matter are sodium hydroxide or potassium hydroxide or sodium carbonate or potassium carbonate or sodium bicarbonate or potassium bicarbonate.
Above-mentioned polyenylphosphatidylfreezee freezee-dried powder injection for injecting, described basic amino acid are lysine or arginine or thin propylhomoserin or valine or the different leucin of L-.
Above-mentioned polyenylphosphatidylfreezee freezee-dried powder injection for injecting, described excipient are lactose or mannitol or dextran.
The preparation method of above-mentioned polyenylphosphatidylfreezee freezee-dried powder injection for injecting, get cosolvent 50-280ml and add polyene phosphatidylcholine 0.1-23.25 stirring, and adding alkaline matter 0.5-5, and then stir, transfer PH to 5.0-9.0 with alkaline matter, adding excipient 5-70 again is dissolved in water, adding 0.1%-5% injection activated carbon again stirred 20 minutes for 60 ℃, filter afterwards, supply water for injection to the film that 200-500ml also crosses 0.22mm again and make 100, fill is pressed the freeze-dry process lyophilizing and is got final product in cillin bottle.
This technical scheme has following beneficial effect:
1. preparation technology of the present invention was both dissolved principal agent with a small amount of solvent, can not influence the lyophilizing effect again, so the proper proportion of cosolvent and alkaline matter is crucial.
2. polyene phosphatidylcholine is because of mainly containing multiple unsaturated fatty acid among the present invention, and insoluble in water, meeting increases its dissolubility under alkali condition, so added an amount of cosolvent in the composition of the present invention.
3. the Polyene Phosphatidylcholine injection liquid that uses clinically at present is hydro-acupuncture preparation, in moisture more liquid environment, its Main Ingredients and Appearance is rich in unsaturated fatty acid, easy oxidized generation color change, content descends, and related substance increases and lessens the curative effect and increase toxic and side effects.The present invention makes lyophilized injectable powder, moisture less than 5% situation under, its stability increases greatly, has guaranteed the quality of preparation, has reduced toxic and side effects.
4. freeze dried polyene lecithin powder of the present invention is low because of its water content, good stability, and quality can be guaranteed, and the storage transportation is all very convenient, can guarantee data for clinical drug use.
5. polyenylphosphatidylfreezee freezee-dried powder injection for injecting of the present invention usability methods clinically is used for the treatment of all types of acute and chronic hepatopathys for freeze dried polyene lecithin powder being dissolved in dark osmometer solution iv drip such as glucose or sodium chloride.
6. this product is the lyophilized injectable powder of polyenic phosphatidylcholine, and because of this product dissolving back viscosity is bigger, freeze drying technology requires high, has made lyophilized injectable powder through experiment repeatedly after breaking through technological difficulties.
7. lyophilized injectable powder of the present invention compares with having aqueous injection both at home and abroad now, because of its water content low (being lower than 5%), has slowed down possible hydrolysis to greatest extent, and its stability is improved.More because of it rolls the certain vacuum of maintenance in the lid bottle under vacuum condition, reduced contacting of medicine and oxygen, slowed down oxidation reaction again to greatest extent, make this product aspect stable, more be better than liquid drugs injection, quality gets better protection.
8. injectable powder of the present invention is easy to storage and transportation, under equal conditions, its good stability is in liquid drugs injection (effect duration of liquid drugs injection is 2 years), following 3 years of normal storage requirement, the content of this product, pH value, related substance and other test ratings and relatively do not have significant change in 0 month, the convenient clinical and patient that can effectively extend the expiration date uses.
9. polyenylphosphatidylfreezee freezee-dried powder injection for injecting of the present invention was stored 3 years at ambient temperature, and each detects index and has no significant change.Quality meets the regulation of quality standard.And Polyene Phosphatidylcholine injection liquid is stored 2 years qualified (every index descends to some extent) at ambient temperature, stores after 3 years, and every index (except that PH) does not all meet the regulation of quality standard.This product effect duration can reach 3 years, and liquid drugs injection effect duration has only 2 years, and concrete comparative result sees the following form:
The stable comparison sheet of injection polyenic phosphatidylcholine and Polyene Phosphatidylcholine injection liquid
| Kind | The stability testing index | |||||||||||
| PH value | Clarity | Content (%) | Related substance (%) | |||||||||
| 0 day | Room temperature 2 years | Room temperature 3 years | 0 day | Room temperature 2 years | Room temperature 3 years | 0 day | Room temperature 2 years | Room temperature 3 years | 0 day | Room temperature 2 years | Room temperature 3 years | |
| The injection polyene phosphatidylcholine | 8.15 | 8.20 | 8.19 | Qualified | Qualified | Qualified | 99.4 | 98.7 | 97.2 | 0.29 | 0.31 | 0.39 |
| Polyene phosphatidylcholine freezes injection (commercially available) | 7.92 | 7.81 | 7.74 | Qualified | Qualified | Qualified | 98.6 | 94.1 | 88.3 | 0.34 | 0.87 | 2.56 |
10. injection polyene phosphatidylcholine safety testing:
The present invention divides the generic new drug 5 classes by the registration of national new drug, tests by the safety testing method of national Bureau of Drugs Supervision 5 kind new medicines, and the result confirms that this product Sanguis Leporis seu oryctolagi pipe irritation test shows that this product do not have the blood vessel zest; The haemolysis agglutination test shows that this product do not have haemolysis, blood coagulation, and the Cavia porcellus sensitivity test shows; This product does not have anaphylaxis, and above evidence this product is clinical safe and reliable, and this product was placed 2 years in shady and cool dry place, carries out the detection of every index, and the result there is no obvious change, and this product has good stability under these process conditions.
This product through 1,5,24,72 hour and 5～7 days, is observed zest and hemolytic such as table 1, table 2 for animal intramuscular injection 1ml.
0.9% sodium chloride solution of table 1 this product (1ml) was once a day observed stimulation after 24 hours.
Illustrate: one, non-stimulated
37 ℃ of table 2 this product hemolytics, 100% hemolysis time comparison sheet
| Cosolvent concentration | 10％ | 20％ | 30％ | 40％ |
| This product | 24 hours no haemolysis | 24 hours no haemolysis | 24 hours no haemolysis | 6～20 hours |
Conclusion: this product is safe and reliable, and is clinical easy to use, is better than the liquid drugs injection dosage form of equal composition.
11. because of this product raw material indissoluble, adding cosolvent, excipient can be made lyophilized injectable powder under the bigger situation of this product viscosity, has carried out a large amount of practical explorations on freeze-dry process, the formation of this cover freeze-dry process is technology point.
Can add 60 ℃ of depyrogenations of active carbon 12. open among the preparation technology of the present invention, because of active carbon has adsorption to polyene phosphatidylcholine, if the temperature height, activated carbon dosage is big, will the content of this product be impacted.We take activated carbon processing in advance, and 20 minutes processing methods of 60 ℃ of insulations are compared with active carbon pyrogen method in the past; Temperature reduces, and the time shortens, and activated carbon dosage reduces, and the content loss of polyene phosphatidylcholine is controlled in 1%, has promptly guaranteed the apyrogeneity of medicine, has guaranteed product quality again.
The specific embodiment of the invention:
Embodiment 1:
Polyenylphosphatidylfreezee freezee-dried powder injection for injecting is got benzyl alcohol 25ml, adds polyene phosphatidylcholine 23.25g and stirs, and add sodium bicarbonate 0.5g, mixes, and stirs; The reuse sodium bicarbonate solution is transferred PH to 5.0, adds mannitol 5g again and is dissolved in water; Adding 0.01% injection activated carbon again stirred 20 minutes for 60 ℃; Filter afterwards, supply water for injection again and make 100 to the film that 200ml also crosses 0.22mm, fill is pressed the freeze-dry process lyophilizing and is got final product in cillin bottle.
Embodiment 2:
Embodiment 1 described polyenylphosphatidylfreezee freezee-dried powder injection for injecting is got propylene glycol 75ml, adds polyene phosphatidylcholine 23.25g and stirs, and adding potassium bicarbonate 0.5g is an amount of, mix and stir, the reuse potassium bicarbonate solution is transferred PH to 6.0, adds dextran 5g again and is dissolved in water; Adding 1% injection activated carbon again stirred 20 minutes for 60 ℃; Filter afterwards, supply water for injection again and make 100 to the film that 500ml also crosses 0.22mm, fill is pressed the freeze-dry process lyophilizing and is got final product in cillin bottle.
Embodiment 3:
Embodiment 1 described polyenylphosphatidylfreezee freezee-dried powder injection for injecting is got ethanol 75ml, adds polyene phosphatidylcholine 23.25g stirring and adds water, and add sodium carbonate 4g, mixes and stirs, and the reuse sodium carbonate liquor is transferred PH to 7.0, adds lactose 5g again and dissolves; Adding 2% injection activated carbon again stirred 20 minutes for 60 ℃; Filter afterwards, supply water for injection again and make 100 to the film that 300ml also crosses 0.22mm, fill is pressed the freeze-dry process lyophilizing and is got final product in cillin bottle.
Embodiment 4:
Embodiment 1 described polyenylphosphatidylfreezee freezee-dried powder injection for injecting is got benzyl alcohol 50ml, adds polyene phosphatidylcholine 23.25g and stirs, and add sodium hydroxide 2g, mixes; The reuse sodium hydroxide solution is transferred about PH to 8.0, adds mannitol 7g again and is dissolved in water; Adding 0.3% injection activated carbon again stirred 20 minutes for 60 ℃; Filter afterwards, supply water for injection again and make 100 to the film that 400ml also crosses 0.22mm, fill is pressed the freeze-dry process lyophilizing and is got final product in cillin bottle.
Embodiment 5:
Embodiment 1 described polyenylphosphatidylfreezee freezee-dried powder injection for injecting is got propylene glycol 100ml and is added polyene phosphatidylcholine 23.25g and stir, and adds potassium carbonate 3g and mix in right amount, and the reuse solution of potassium carbonate is transferred PH to 9.0, adds dextran 7g again and is dissolved in water; Adding 2% injection activated carbon again stirred 20 minutes for 60 ℃; Filter afterwards, supply water for injection again and make 100 to the film that 500ml also crosses 0.22mm, fill is pressed the freeze-dry process lyophilizing and is got final product in cillin bottle.
Embodiment 6:
Embodiment 1 described polyenylphosphatidylfreezee freezee-dried powder injection for injecting is got ethanol 100ml and is added polyene phosphatidylcholine 23.25g stirring, and adds sodium hydroxide 3g, mixes and stirs, and the reuse sodium hydroxide solution is transferred PH to 6.0 to add lactose 7g again and is dissolved in water; Add 0.5% injection activated carbon again and stirred 20 minutes for 60 ℃, filter afterwards, supply water for injection again and make 100 to the film that 500ml also crosses 0.22mm, fill is pressed the freeze-dry process lyophilizing and is got final product in cillin bottle.
Embodiment 7:
Embodiment 1 described polyenylphosphatidylfreezee freezee-dried powder injection for injecting is got propylene glycol 280ml and is added polyene phosphatidylcholine 0.1g stirring, and adding mannitol 20g is dissolved in water; Add 0.01% injection activated carbon again and stirred 20 minutes for 60 ℃, filter afterwards, supply water for injection again and make 100 to the film that 500ml also crosses 0.22mm, fill is pressed the freeze-dry process lyophilizing and is got final product in cillin bottle.
Embodiment 8:
Embodiment 1 described polyenylphosphatidylfreezee freezee-dried powder injection for injecting; get benzyl alcohol 70ml and add polyene phosphatidylcholine 0.5g stirring, and adding sodium bicarbonate 3g is an amount of, mixing is stirred; the reuse sodium bicarbonate solution is transferred PH to 5.0; add dextran 35g again and be dissolved in water adds 60 ℃ of stirrings of 0.5% injection activated carbon 20 minutes, filtration afterwards again; supply water for injection to the film that 500ml also crosses 0.22mm again and make 100;, fill is pressed the freeze-dry process lyophilizing and is got final product in cillin bottle.
Embodiment 9:
Embodiment 11 described polyenylphosphatidylfreezee freezee-dried powder injection for injecting, described alkaline matter are the mixture of inorganic base or basic amino acid or two kinds of alkaline matters.
Embodiment 10:
Embodiment 1 described polyenylphosphatidylfreezee freezee-dried powder injection for injecting, its composition also comprises: cosolvent, described cosolvent be its parts by weight of ethanol be 5 the gram or 20 the gram 40 the gram or its parts by weight of propylene glycol be 2 the gram 30 the gram or 40 the gram its parts by weight of benzyl alcohol be 0.1 the gram or 5 the gram or 10 the gram.
Embodiment 11:
Embodiment 1 or 2 described polyenylphosphatidylfreezee freezee-dried powder injection for injecting, described alkaline matter are sodium hydroxide or potassium hydroxide or sodium carbonate or potassium carbonate or sodium bicarbonate or potassium bicarbonate.
Embodiment 12:
Embodiment 1 or 2 described polyenylphosphatidylfreezee freezee-dried powder injection for injecting, described basic amino acid are lysine or arginine or thin propylhomoserin or valine or the different leucin of L-.
Embodiment 13:
Embodiment 1 or 2 described polyenylphosphatidylfreezee freezee-dried powder injection for injecting, described excipient are lactose or mannitol or dextran.
Claims (7)
1. polyenylphosphatidylfreezee freezee-dried powder injection for injecting, its composition comprises: alkaline matter, excipient that polyene phosphatidylcholine, pharmacology allow, it is characterized in that: the parts by weight of described polyene phosphatidylcholine are 0.1～0.5, the parts by weight of described alkaline matter are 5.0～9.0 o'clock needed amounts for adjusting to pH value, and the parts by weight of described excipient are 0.002～0.7.
2. polyenylphosphatidylfreezee freezee-dried powder injection for injecting according to claim 1, it is characterized in that: its composition also comprises: cosolvent, described cosolvent be its parts by weight of ethanol be 5～40 or its parts by weight of propylene glycol be 2～40 or its parts by weight of benzyl alcohol be 0.1～10.
3. polyenylphosphatidylfreezee freezee-dried powder injection for injecting according to claim 1 and 2 is characterized in that: described alkaline matter is inorganic base or basic amino acid.
4. polyenylphosphatidylfreezee freezee-dried powder injection for injecting according to claim 1 and 2 is characterized in that: described alkaline matter is sodium hydroxide or potassium hydroxide or sodium carbonate or potassium carbonate or sodium bicarbonate or potassium bicarbonate.
5. polyenylphosphatidylfreezee freezee-dried powder injection for injecting according to claim 3 is characterized in that: described basic amino acid is lysine or arginine or valine or L-isoleucine.
6. polyenylphosphatidylfreezee freezee-dried powder injection for injecting according to claim 1 is characterized in that: described excipient is lactose or mannitol or dextran.
7. the preparation method of the described polyenylphosphatidylfreezee freezee-dried powder injection for injecting of claim 1, it is characterized in that: get cosolvent 50-280ml and add polyene phosphatidylcholine 0.1-23.25 stirring, and adding alkaline matter 0.5-5, and then stir, transfer PH to 5.0-9.0 with alkaline matter, adding excipient 5-70 again is dissolved in water, adding 0.1%-5% injection activated carbon again stirred 20 minutes for 60 ℃, filter afterwards, supply water for injection to the film that 200-500ml also crosses 0.22mm again and make 100, fill is pressed the freeze-dry process lyophilizing and is got final product in cillin bottle.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610009780 CN101032497A (en) | 2006-03-08 | 2006-03-08 | Polyenylphosphatidylcholine freeze - dried powder injection for injecting and the preparing method thereof |
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|---|---|---|---|
| CN 200610009780 CN101032497A (en) | 2006-03-08 | 2006-03-08 | Polyenylphosphatidylcholine freeze - dried powder injection for injecting and the preparing method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106509869A (en) * | 2016-11-07 | 2017-03-22 | 北京国仁堂医药科技发展有限公司 | Application of phosphatidylcholine combined with sodium bicarbonate in preparations of liver protecting food, health-care products or drugs |
| CN112870337A (en) * | 2021-01-26 | 2021-06-01 | 浙江科瑞特生物科技有限公司 | Freeze-dried powder of composite hormone of somatotropin and chorionic gonadotropin and preparation method thereof |
-
2006
- 2006-03-08 CN CN 200610009780 patent/CN101032497A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106509869A (en) * | 2016-11-07 | 2017-03-22 | 北京国仁堂医药科技发展有限公司 | Application of phosphatidylcholine combined with sodium bicarbonate in preparations of liver protecting food, health-care products or drugs |
| CN112870337A (en) * | 2021-01-26 | 2021-06-01 | 浙江科瑞特生物科技有限公司 | Freeze-dried powder of composite hormone of somatotropin and chorionic gonadotropin and preparation method thereof |
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Open date: 20070912 |