CN1621035A - Injection of flurbiprofen and its preparing method - Google Patents
Injection of flurbiprofen and its preparing method Download PDFInfo
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- CN1621035A CN1621035A CN 200310109673 CN200310109673A CN1621035A CN 1621035 A CN1621035 A CN 1621035A CN 200310109673 CN200310109673 CN 200310109673 CN 200310109673 A CN200310109673 A CN 200310109673A CN 1621035 A CN1621035 A CN 1621035A
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- flurbiprofen axetil
- flurbiprofen
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Abstract
The present invention is flurbiprofen ester injection as antiphlogistic and analgetic medicine and its preparation process. Main medicine and supplementary material including solvent, emulsifier, isotonic agent, buffering agent and pH regulator are mixed to compound the injection. Compared with available oral flurbiprofen preparation, the flurbiprofen ester injection has even high curative effect, even fast action, long lasting effect and less stomach mucous membrane damage and other negative effect. The present invention is used in treating chronic rheumarthritis, etc and is especially suitable for relieve post-operational pain and pain caused by cancer, and it has high effect and no addiction.
Description
Technical field
The present invention is a kind of Flurbiprofen axetil injecting medicine-feeding form and preparation method thereof.
Background technology
Flurbiprofen axetil (Flurbrofene axetil) is the acetoxyl group ethyl ester of flurbiprofen, and hydrolysis generates flurbiprofen under the effect of Carboxylesterase in vivo, and the latter is to the inhibitory action of having synthesized of prostaglandin.Flurbiprofen is a clinical widely used NSAID (non-steroidal anti-inflammatory drug) (NSAID), has antiinflammatory, pain relieving and refrigeration function, the clinical treatment that is used for pain or inflammation disease.China is in the flurbiprofen crude drug and the tablet listing of approval Shanghai Sunve Pharmaceutical Co., Ltd. in 1998, its crude drug is criticized piece number: the accurate word of traditional Chinese medicines (1998) X-362 number, be used for the treatment of rheumatoid arthritis, after ratified slow releasing tablet and eye drop (contracted pupil and postoperative antiinflammatory thereof when being used to suppress intraocular surgery) again successively.The existing market preparation mostly is oral agents, owing to have been found that untoward reaction such as easily causing gastrointestinal disturbance behind the oral flurbiprofen, and when treatment postoperative pain or the pain that causes because of cancer, most of patients can't oral drugs, influence clinical use, therefore be necessary to develop other form of administration of flurbiprofen, as the intravenously administrable dosage form.
Summary of the invention
Purpose of the present invention just provides a kind of Flurbiprofen axetil injecting medicine-feeding form and preparation method thereof, Flurbiprofen axetil injection drug of the present invention, by principal agent Flurbiprofen axetil and adjuvant solvent refining soybean oil, emulsifying agent is made with extra care lecithin, and isotonic agent glycerol, buffer agent sodium hydrogen phosphate, the pH regulator agent citric acid aqueous injection that is mixed and forms.Because flurbiprofen is insoluble in water, so flurbiprofen is made the prodrug Flurbiprofen axetil.This prodrug has certain close ester, dissolves in and makes the injection emulsion agent in the soybean oil, is used for intravenous injection.The injection emulsion agent can optionally be accumulated in inflammation tissue and vascular injury site, changed interior distribution of body of medicine, made drug selectivity arrive diseased region, subsequently by prostaglandin (PG) synthetic cell, as macrophage and neutrophilic granulocyte picked-up, suppress the biosynthesis of PG.The preparation technology of Flurbiprofen axetil injection drug is, principal agent Flurbiprofen axetil and adjuvant solvent and emulsifying agent are gone in the emulsion tank, 50-60 ℃ of insulation, stirred rotating speed 2500-3000rpm, mixed dissolution 10 minutes, the water for injection and the concentrated glycerin that add amount of calculation then, 50-60 ℃ of insulation stirred 20 minutes, made thick emulsion.Pour thick emulsion into homogenizer again, high pressure homogenize keeps 700-750kg/cm
3High pressure.Then buffer is added medicinal liquid, adding pH value is 6.5.After again medicinal liquid being the filter membrane pressure filtration of 0.65 μ m by the aperture, filling the 5ml peace and cut open.115 ℃ of sterilizations of high steam 20 minutes, leak detection, lamp inspection, labeling, packing.
The present invention prepares the Flurbiprofen axetil injection drug, and preparation method is simple, general, and the product that makes meets every requirement of injection.Flurbiprofen axetil injection drug of the present invention, instant effect, toxicity are little.Flurbiprofen ester injection of the present invention is except that being used for easing pain and diminishing inflammations such as chronic rheumatic arthritis, osteoarthrisis deformans knee, lumbago, scapulohumeral periarthritis, and in being particularly useful for, severe pain, analgesic effect is very remarkable, and does not have addiction.Flurbiprofen axetil injection drug of the present invention is compared with the flurbiprofen peroral dosage form, and drug effect is stronger, and onset is rapider, and the persistent period is longer, and is difficult for causing untoward reaction such as gastric mucosa injury.The pharmacokinetics test shows that behind the quiet notes Flurbiprofen axetil of the health volunteer injection emulsion agent 5ml, 5-10min blood drug level is peaking, and drug eliminated half life is 5.8h.The accumulation of urine Chinese medicine is drained and is about 85% of dosage in the 48h.Behind every interval 12h successive administration 5 times, urine Chinese medicine accumulation excretion rate is nearly 85% in the 48h, does not find that medicine accumulates in vivo.Clinical trial shows, the moderate that 7.1% postoperative pain patient and 69.9% arranged to severe cancerous pain patient's pain symptom significantly improves, get final product pain relieving after the administration in the 15-30min, and long (the postoperative analgesia time is greater than 3h than oral formulations for analgesic time, carcinous analgesic time can reach more than the 9h), extremely low central nervous system's untoward reaction and the dependency of there is no of adverse reaction rate.Flurbiprofen LM preparation is safe in utilization, convenient, is expected to be widely used in clinical.
The specific embodiment
The present embodiment optimizing prescriptions is as follows:
1. prescription is formed:
Flurbiprofen axetil 50g principal agent
Exquisite soybean oil 600g solvent
Refining lecithin 70g emulsifying agent
Glycerol 112g isotonic agent
Sodium hydrogen phosphate 4.2g buffer agent
An amount of pH regulator agent of citric acid
Water for injection adds to the 50000ml medium
To pour in the thick emulsion tank by the load weighted Flurbiprofen axetil of prescription, refined soybean oil and refining lecithin and (feed intake) by 105% of recipe quantity, 50-60 ℃ of insulation, stirred 10 minutes, rotating speed 2500-3000rpm, mixed dissolution adds the water for injection and the concentrated glycerin of amount of calculation, 50-60 ℃ of insulation then, stirred 20 minutes, and made thick emulsion.Pour thick emulsion into homogenizer, high pressure homogenize keeps 700-750kg/cm
3High pressure.The buffer sodium hydrogen phosphate is added medicinal liquid, with citron acid for adjusting pH value to 6.5.After medicinal liquid is the filter membrane pressure filtration of 0.65 μ m by the aperture, fill the 50ml infusion bottle.115 ℃ of sterilizations of high steam 20 minutes, leak detection, lamp inspection, labeling is packed, and promptly gets the Flurbiprofen axetil primary infusion Emulsion of 50ml.
2. prescription is formed:
Flurbiprofen axetil 100g principal agent
Exquisite soybean oil 1000g solvent
Refining lecithin 120g emulsifying agent
Glycerol 152g isotonic agent
Sodium hydrogen phosphate 5.1g buffer agent
An amount of pH regulator agent of citric acid
Water for injection adds to the 100000ml medium
To pour in the thick emulsion tank by the load weighted Flurbiprofen axetil of prescription, refined soybean oil and refining lecithin and (feed intake) by 105% of recipe quantity, 50-60 ℃ of insulation, stirred 10 minutes, rotating speed 2500-3000rpm, mixed dissolution adds the water for injection and the concentrated glycerin of amount of calculation, 50-60 ℃ of insulation then, stirred 20 minutes, and made thick emulsion.Pour thick emulsion into homogenizer, high pressure homogenize keeps 700-750kg/cm
3High pressure.The buffer sodium hydrogen phosphate is added medicinal liquid, with citron acid for adjusting pH value to 6.5.After medicinal liquid is the filter membrane pressure filtration of 0.65 μ m by the aperture, fill the 100ml infusion bottle.115 ℃ of sterilizations of high steam 20 minutes, leak detection, lamp inspection, labeling is packed, and promptly gets the Flurbiprofen axetil transfusion Emulsion of 100ml.
3. prescription is formed:
Flurbiprofen axetil 50g principal agent
Exquisite soybean oil 500g solvent
Refining lecithin 60g emulsifying agent
Glycerol 110.5g isotonic agent
Sodium hydrogen phosphate 3.4g buffer agent
An amount of pH regulator agent of citric acid
Water for injection adds to the 5000ml medium
To pour in the thick emulsion tank by the load weighted Flurbiprofen axetil of prescription, refined soybean oil and refining lecithin and (feed intake) by 105% of recipe quantity, 50-60 ℃ of insulation, stirred 10 minutes, rotating speed 2500-3000rpm, mixed dissolution adds the water for injection and the concentrated glycerin of amount of calculation, 50-60 ℃ of insulation then, stirred 20 minutes, and made thick emulsion.Pour thick emulsion into homogenizer, high pressure homogenize keeps 700-750kg/cm
3High pressure.The buffer sodium hydrogen phosphate is added medicinal liquid, with citron acid for adjusting pH value to 6.5.After medicinal liquid is the filter membrane pressure filtration of 0.65 μ m by the aperture, fills the 5ml peace and cut open.115 ℃ of sterilizations of high steam 20 minutes, leak detection, lamp inspection, labeling is packed, and promptly gets the Flurbiprofen axetil injection of 5ml.
4. prescription is formed:
Flurbiprofen axetil 25g principal agent
Exquisite soybean oil 250g solvent
Refining lecithin 30g emulsifying agent
Glycerol 55.5g isotonic agent
Sodium hydrogen phosphate 2.4g buffer agent
An amount of pH regulator agent of citric acid
Water for injection adds to the 2000ml medium
To pour in the thick emulsion tank by the load weighted Flurbiprofen axetil of prescription, refined soybean oil and refining lecithin and (feed intake) by 105% of recipe quantity, 50-60 ℃ of insulation, stirred 10 minutes, rotating speed 2500-3000rpm, mixed dissolution adds the water for injection and the concentrated glycerin of amount of calculation, 50-60 ℃ of insulation then, stirred 20 minutes, and made thick emulsion.Pour thick emulsion into homogenizer, high pressure homogenize keeps 700-750kg/cm
3High pressure.The buffer sodium hydrogen phosphate is added medicinal liquid, with citron acid for adjusting pH value to 6.5.After medicinal liquid is the filter membrane pressure filtration of 0.65 μ m by the aperture, fills the 2ml peace and cut open.115 ℃ of sterilizations of high steam 20 minutes, leak detection, lamp inspection, labeling is packed, and promptly gets the Flurbiprofen axetil injection of 2ml.
Claims (5)
1, Flurbiprofen axetil injection drug, its feature is in the injection emulsion that is mixed and is formed by principal agent Flurbiprofen axetil and adjuvant solvent refining soybean oil, emulsifying agent refined lecithin and isotonic agent glycerol, buffer agent sodium hydrogen phosphate, pH regulator agent citric acid, product specification is: every contains 1～500ml liquid, wherein contains principal agent Flurbiprofen axetil 5～150mg.
2, the preparation method of the described Flurbiprofen axetil injection drug of claim 1 is characterized in that with the Flurbiprofen axetil being crude drug, adds adjuvant refined soybean oil and refined lecithin, insulation, mixed dissolution adds the water for injection and the concentrated glycerin of amount of calculation then, thick emulsion is made in insulation; High pressure homogenize adds buffer, the pH regulator agent, regulating pH value is 6.5, filtering with microporous membrane is filled, autoclaving, leak detection, lamp inspection, labeling, pack finished product.
3, the preparation method of Flurbiprofen axetil injection drug according to claim 2, it is characterized in that the principal agent Flurbiprofen axetil is mixed with adjuvant refined soybean oil and refined lecithin, 50-60 ℃ of insulation, stirred 10 minutes, the water for injection and the concentrated glycerin that add amount of calculation then, 50-60 ℃ of insulation stirred 20 minutes, made thick emulsion.
4, according to the preparation method of claim 2 or 3 described Flurbiprofen axetil injection drugs, it is characterized in that pouring thick emulsion into homogenizer, high pressure homogenize keeps 700-750kg/cm
3High pressure.
5, the preparation method of Flurbiprofen axetil injection drug according to claim 4 is characterized in that the buffer sodium hydrogen phosphate is added medicinal liquid, is 6.5 with the citron acid for adjusting pH value.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200310109673 CN1621035A (en) | 2003-11-26 | 2003-11-26 | Injection of flurbiprofen and its preparing method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200310109673 CN1621035A (en) | 2003-11-26 | 2003-11-26 | Injection of flurbiprofen and its preparing method |
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| CN1621035A true CN1621035A (en) | 2005-06-01 |
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| CN 200310109673 Pending CN1621035A (en) | 2003-11-26 | 2003-11-26 | Injection of flurbiprofen and its preparing method |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101940549A (en) * | 2010-08-27 | 2011-01-12 | 北京中海康医药科技发展有限公司 | Flurbiprofen axetil medium-chain and long-chain fat emulsion and preparation method thereof |
| CN102381970A (en) * | 2011-12-08 | 2012-03-21 | 南京优科生物医药有限公司 | Method for preparing flurbiprofen axetil compound |
| CN102552133A (en) * | 2010-12-15 | 2012-07-11 | 清远嘉博制药有限公司 | Middle/long chain triglyceride flurbiprofen axetil injection and preparation method thereof |
| CN102670502A (en) * | 2012-05-17 | 2012-09-19 | 北京阜康仁生物制药科技有限公司 | S(+)-flurbiprofen axetil injection emulsion |
| CN103301063A (en) * | 2013-06-14 | 2013-09-18 | 北京阜康仁生物制药科技有限公司 | S (+) -flurbiprofen axetil emulsion for injection |
| CN104173279A (en) * | 2014-08-28 | 2014-12-03 | 河北一品制药有限公司 | Flurbiprofen axetil injection and preparation method thereof |
| CN104490779A (en) * | 2014-12-26 | 2015-04-08 | 北京蓝丹医药科技有限公司 | Flurbiprofen axetil fat emulsion injection |
| CN104784115A (en) * | 2014-01-20 | 2015-07-22 | 华东理工大学 | Flurbiprofen axetil microsphere injection and preparation method thereof |
| WO2021057694A1 (en) * | 2019-09-25 | 2021-04-01 | 北京普德康利医药科技发展有限公司 | Low-content flurbiprofen axetil pharmaceutical composition, and application thereof |
-
2003
- 2003-11-26 CN CN 200310109673 patent/CN1621035A/en active Pending
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101940549A (en) * | 2010-08-27 | 2011-01-12 | 北京中海康医药科技发展有限公司 | Flurbiprofen axetil medium-chain and long-chain fat emulsion and preparation method thereof |
| CN101940549B (en) * | 2010-08-27 | 2012-04-25 | 北京中海康医药科技发展有限公司 | Flurbiprofen axetil medium-chain and long-chain fat emulsion and preparation method thereof |
| CN102552133A (en) * | 2010-12-15 | 2012-07-11 | 清远嘉博制药有限公司 | Middle/long chain triglyceride flurbiprofen axetil injection and preparation method thereof |
| CN102381970A (en) * | 2011-12-08 | 2012-03-21 | 南京优科生物医药有限公司 | Method for preparing flurbiprofen axetil compound |
| CN102670502A (en) * | 2012-05-17 | 2012-09-19 | 北京阜康仁生物制药科技有限公司 | S(+)-flurbiprofen axetil injection emulsion |
| CN103301063A (en) * | 2013-06-14 | 2013-09-18 | 北京阜康仁生物制药科技有限公司 | S (+) -flurbiprofen axetil emulsion for injection |
| CN104784115A (en) * | 2014-01-20 | 2015-07-22 | 华东理工大学 | Flurbiprofen axetil microsphere injection and preparation method thereof |
| CN104173279A (en) * | 2014-08-28 | 2014-12-03 | 河北一品制药有限公司 | Flurbiprofen axetil injection and preparation method thereof |
| CN104173279B (en) * | 2014-08-28 | 2016-08-24 | 河北一品制药有限公司 | A kind of florfenicol residues and preparation method thereof |
| CN104490779A (en) * | 2014-12-26 | 2015-04-08 | 北京蓝丹医药科技有限公司 | Flurbiprofen axetil fat emulsion injection |
| WO2021057694A1 (en) * | 2019-09-25 | 2021-04-01 | 北京普德康利医药科技发展有限公司 | Low-content flurbiprofen axetil pharmaceutical composition, and application thereof |
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