CN101069681A - Injection containing burufen - Google Patents
Injection containing burufen Download PDFInfo
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- CN101069681A CN101069681A CN 200610044134 CN200610044134A CN101069681A CN 101069681 A CN101069681 A CN 101069681A CN 200610044134 CN200610044134 CN 200610044134 CN 200610044134 A CN200610044134 A CN 200610044134A CN 101069681 A CN101069681 A CN 101069681A
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- ibuprofen
- injection
- shallower
- clarify
- yellow
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Abstract
The present invention provides an injection preparation containing ibuprofen and its preparation method. Said invention provides the concrete steps of its preparation method. Said ibuprofen injection preparation has high solubility and bioavailability, and its product quality is stable.
Description
Technical field:
The present invention relates to a kind of medicine and preparation method thereof, be specifically related to a kind of ibuprofen for injection and preparation method that is used for the treatment of diseases such as pain that a variety of causes causes, heating.
Background technology
Ibuprofen, promptly 2-(4-isobutyl phenenyl) propanoic acid is NSAID (non-steroidal anti-inflammatory drug) (NSAIDs), is that first is used for the fragrant class medicine in clinical and still widely used so far Lip river in the world, is acknowledged as one of safest medicine among the NSAIDs.Pharmacological action shows its antiinflammatory, analgesia, refrigeration function.Clinical various acute, chronic arthritiss, soft tissue rheumatism disease, tenosynovitis, motional injury and headache, myalgia, dysmenorrhea, pain and the cancerous pain etc. after getting a tooth pulled out of being used for.This medicine is recommended as the first ladder medicine in the medication of analgesia ladder, at home and abroad all record in the pharmacopeia, it is one of essential drugs of China, but (S)-ibuprofen has overcome ibuprofen some shortcomings aspect use pharmacodynamics and pharmacokinetics, the external existing trend that substitutes the raceme ibuprofen with (S)-ibuprofen.Its clinical meaning is as follows:
1. (S)-ibuprofen is an active single enantiomer of tool medicine generation, so use the (S)-ibuprofen that is lower than raceme ibuprofen dosage can produce pharmacological action equal even strong degree, also produces to a certain degree pharmacological action even be less than 1/2 dosage.
2. (S)-ibuprofen does not need conversion process, and the back obtains sufficiently high blood drug level easily rapidly in the body so enter, and shows rapid-actionly, acts on strong characteristics.
3. (S)-ibuprofen does not disturb body fat tissue biological synthetic, has got rid of the possibility of bringing out the hyperreaction reaction.
4. (S)-ibuprofen has reduced dosage, and not only reduction is brought out the probability of genotoxic potential but also is that the heavy dose of preparation of preparation is more favourable.
5. (S)-ibuprofen shows better simply pharmacodynamics and pharmacokinetics characteristics, thereby helps optimization of dosage etc.
(S)-ibuprofen (S)--2-(4-isobutyl phenenyl) propanoic acid is at first developed successfully by Austrian Gebro-BroschehGmb H company, and commodity were called Seractil through the approval listing in 1994.In June, 1997, the Pelletech company of microsphere technical point company of Switzerland Spirig also succeeded in developing, commodity Soptifen by name and Ultraprofen.The said firm registers its product in the world by its affiliate.Just seeking at present to enter other country, comprising Spain, Hungary etc.In addition, also there is this medicine listing in Denmark Nycomed company, and commodity are called Nyfen.All there are this medicine listing in U.S. Alemarle Corp, France etc.
Ibuprofen and (S)-ibuprofen have only ordinary preparations such as tablet, capsule, dispersible tablet, oral administration mixed suspension clinically at present, (NSAIDs) is the same with other NSAID (non-steroidal anti-inflammatory drug), exist dissolubility little, absorb slow, bioavailability is low, onset is relatively slow, the patient of child, old people and the solid preparation of can not swallowing is made troubles; The United States Patent (USP) 5463117 of nineteen ninety-five once disclosed the manufacture method of ibuprofen salt, but the ibuprofen injection, particularly ibuprofen for injection launch of energy suitability for industrialized production are not arranged so far.
Summary of the invention
Purpose of the present invention is exactly not have the deficiency of injection type for solving existing ibuprofen, and a kind of injection and preparation method that contains ibuprofen is provided, and said preparation has solved product dissolubility and route of administration problem.
The present invention solves the technical scheme that the prior art problem adopted:
A kind of ibuprofen injection that contains contains principal agent ibuprofen, alkaline auxiliary solvent, filler in the described injection.The mole proportioning of ibuprofen and alkaline auxiliary solvent is 1: 1; The weight ratio of ibuprofen and filler is 1: 0-6.Described alkaline auxiliary solvent is arginine or lysine or trometamol, and described filler is lactose, mannitol, sorbitol, low molecular dextran etc.Wherein the weight proportion of each component is:
Ibuprofen or (S)-ibuprofen 200
Arginine or lysine or trometamol 169 or 142 or 121
Filler 0-1200
Organic solvent 10---10000
Water is an amount of
Hydrochloric acid is an amount of
Add among the present invention an amount of lactose, mannitol, sorbitol, low molecular dextran one or more, helps pharmaceutical drying, improves product yield, and the raising of the outward appearance of product, dissolubility quality, and it is different to reduce to adorn the method for double differences.
The preparation method that contains the ibuprofen injection of the present invention is that raw material is dissolved in respectively in an amount of water and organic solvent, and fully mixing, decolouring, filtration, packing, lyophilizing form.
Ibuprofen for injection of the present invention and preparation method adopt following prepared:
The ibuprofen of recipe quantity is dissolved in ethanol organic solvents such as (or acetone or isopropyl alcohol or methanol), arginine (or lysine, DL-lysine, D-lysine, D-arginine, DL-arginine, trometamol) and mannitol are dissolved in the water for injection, mix the back, add hydrochloric acid adjusting PH to 6-8, adopt micropore aseptic filtration, filtrate is packing according to dosage, quick-freezing then, per minute reduces the 10-15 degree, cool to-30 to-50 degree until solution, kept 2-3 hour, to-20 to-35 degree of heating again carry out sublimation drying, seal, gland gets.
The invention has the advantages that: said preparation overcomes ordinary preparations such as traditional oral ibuprofen preparation such as tablet, capsule, dispersible tablet, oral administration mixed suspension, the dissolubility that exists is little, absorb the deficiency slow, that bioavailability is low, onset is relatively slow, and the patient of child, old people and the solid preparation of can not swallowing is made troubles; Said preparation has solved product dissolubility and route of administration problem, and the constant product quality of gained, bioavailability height, onset be advantage rapidly.
The specific embodiment
Embodiment 1:
Prescription: ibuprofen 200g
Arginine 169g
Mannitol 150g
Ethanol 500ML
Water 4500ML
Hydrochloric acid is an amount of
Cumulative volume 5000ML
Technology: with above-mentioned supplementary material dissolving, mixing, decolouring, filtration, packing, lyophilizing.
Embodiment 2:
Prescription: ibuprofen 200g
Lysine 142g
Mannitol 200g
Ethanol 100ML
Water 9900ML
Hydrochloric acid is an amount of
Cumulative volume 10000ML
Technology: with above-mentioned supplementary material dissolving, mixing, decolouring, filtration, packing, lyophilizing
Embodiment 3:
Prescription: ibuprofen 200g
DL-lysine 142g
Mannitol 200g
Ethanol 500ML
Water 5500ML
Hydrochloric acid is an amount of
Cumulative volume 6000ML
Technology: with above-mentioned supplementary material dissolving, mixing, decolouring, filtration, packing, lyophilizing.
Embodiment 4:
Prescription: (S)-ibuprofen 200g
DL-lysine 142g
Mannitol 200g
Acetone 500ML
Water 5500ML
Hydrochloric acid is an amount of
Cumulative volume 6000ML
Technology: with above-mentioned supplementary material dissolving, mixing, decolouring, filtration, packing, lyophilizing
Embodiment 5:
Prescription: (S)-ibuprofen 200g
Trometamol 121g
Mannitol 200g
Acetone 500ML
Water 4500ML
Hydrochloric acid is an amount of
Cumulative volume 5000ML
Technology: with above-mentioned supplementary material dissolving, mixing, decolouring, filtration, packing, lyophilizing.
4, product stability result
Accelerated test result
(specification 3.0g; 40 ℃ ± 2 ℃ of conditions, RH75%)
| Lot number | Time (moon) | The investigation project | ||||||
| Outward appearance | Moisture (%) | Acidity | Clarity of solution and color | Related substance (%) | Content (%) | |||
| Single impurity | Total impurities | |||||||
| 0406203 | 0 | Off-white powder | 1.19 | 7.1 | Clarify, be shallower than yellow No. 7 | 0.17 | 0.77 | 98.58 |
| 1 | Off-white powder | 1.22 | 7.1 | Clarify, be shallower than yellow No. 7 | 0.22 | 0.69 | 98.56 | |
| 2 | Off-white powder | 1.20 | 7.1 | Clarify, be shallower than yellow No. 7 | 0.18 | 0.69 | 98.92 | |
| 3 | Off-white powder | 1.21 | 7.1 | Clarify, be shallower than yellow No. 7 | 0.24 | 1.02 | 98.88 | |
| 6 | Off-white powder | 1.20 | 7.1 | Clarify, be shallower than yellow No. 7 | 0.36 | 1.40 | 98.71 | |
| 0406213 | 0 | Off-white powder | 1.20 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.19 | 0.94 | 98.81 |
| 1 | Off-white powder | 1.27 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.12 | 0.51 | 98.08 | |
| 2 | Off-white powder | 1.24 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.20 | 0.77 | 98.71 | |
| 3 | Off-white powder | 1.23 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.26 | 1.11 | 98.73 | |
| 6 | Off-white powder | 1.22 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.32 | 1.32 | 98.95 | |
| 0406223 | 0 | Off-white powder | 1.21 | 7.2 | Clarify, be shallower than yellow No. 7 | 0.18 | 0.76 | 99.01 |
| 1 | Off-white powder | 1.23 | 7.2 | Clarify, be shallower than yellow No. 7 | 0.26 | 0.77 | 98.61 | |
| 2 | Off-white powder | 1.20 | 7.2 | Clarify, be shallower than yellow No. 7 | 0.18 | 0.76 | 99.03 | |
| 3 | Off-white powder | 1.23 | 7.2 | Clarify, be shallower than yellow No. 7 | 0.24 | 1.10 | 98.12 | |
| 6 | Off-white powder | 1.21 | 7.2 | Clarify, be shallower than yellow No. 7 | 0.33 | 1.36 | 98.63 | |
Long-term test results
(specification 0.75g; 25 ℃ ± 2 ℃ of conditions, RH60%)
| Lot number | Time (moon) | The investigation project | ||||||
| Outward appearance | Moisture (%) | Acidity | Clarity of solution and color | Related substance (%) | Content (%) | |||
| Single impurity | Total impurities | |||||||
| 0406202 | 0 | Off-white powder | 1.14 | 7.2 | Clarify, be shallower than yellow No. 7 | 0.19 | 0.82 | 99.08 |
| 3 | Off-white powder | 1.16 | 7.2 | Clarify, be shallower than yellow No. 7 | 0.21 | 1.12 | 98.52 | |
| 6 | Off-white powder | 1.14 | 7.2 | Clarify, be shallower than yellow No. 7 | 0.15 | 0.76 | 99.13 | |
| 0406212 | 0 | Off-white powder | 1.29 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.19 | 0.82 | 98.99 |
| 3 | Off-white powder | 1.31 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.20 | 1.19 | 98.51 | |
| 6 | Off-white powder | 1.23 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.14 | 0.79 | 99.15 | |
| 0406222 | 0 | Off-white powder | 1.12 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.19 | 0.83 | 98.20 |
| 3 | Off-white powder | 1.16 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.13 | 0.67 | 98.84 | |
| 6 | Off-white powder | 1.18 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.15 | 0.89 | 99.08 | |
Claims (6)
1, a kind of injection that contains ibuprofen is characterized in that wherein containing principal agent ibuprofen, alkaline auxiliary solvent, filler, and the mole proportioning of ibuprofen and alkaline auxiliary solvent is 1: 1; The weight ratio of ibuprofen and filler is 1: 0-6.
2,, it is characterized in that described ibuprofen is racemic modification ibuprofen or d-isomer ibuprofen according to the described injection of claim 1.
3,, it is characterized in that described alkaline auxiliary solvent is any among arginine, D-arginine, DL-arginine or lysine, D-lysine, DL-lysine, the trometamol according to the described injection of claim 1.
4,, it is characterized in that described filler is any among lactose, mannitol, sorbitol, the low molecular dextran according to the described injection of claim 1.
5, a kind of preparation method that contains the ibuprofen injection is characterized in that raw material is dissolved in respectively in an amount of water and organic solvent, and the volume ratio of ibuprofen and machine solvent is 1: 0.05-50, fully mixing, decolouring, filtration, packing, lyophilizing.
6,, it is characterized in that described organic solvent can be any in ethanol, acetone, isopropyl alcohol, the methanol according to the described injection of claim 5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610044134 CN101069681A (en) | 2006-05-10 | 2006-05-10 | Injection containing burufen |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610044134 CN101069681A (en) | 2006-05-10 | 2006-05-10 | Injection containing burufen |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101069681A true CN101069681A (en) | 2007-11-14 |
Family
ID=38897200
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610044134 Pending CN101069681A (en) | 2006-05-10 | 2006-05-10 | Injection containing burufen |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101069681A (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101978945A (en) * | 2010-10-25 | 2011-02-23 | 北京世纪博康医药科技有限公司 | Ibuprofen medicinal composition |
| CN102085179A (en) * | 2011-01-20 | 2011-06-08 | 罗军 | Ibuprofen injection and preparation method thereof |
| CN102335114A (en) * | 2010-07-23 | 2012-02-01 | 重庆医药工业研究院有限责任公司 | Stable ibuprofen arginine injection and preparation method thereof |
| CN102552117A (en) * | 2010-12-27 | 2012-07-11 | 成都国为医药科技有限公司 | Injection containing ibuprofen and preparation method of injection |
| CN102791268A (en) * | 2009-12-23 | 2012-11-21 | 坎伯兰医药品股份有限公司 | Treating critically ill patients with intravenous ibuprofen |
| CN104323988A (en) * | 2014-11-27 | 2015-02-04 | 北京蓝丹医药科技有限公司 | Dexibuprofen pharmaceutical composition for injection |
| CN105055389A (en) * | 2015-08-03 | 2015-11-18 | 北京蓝丹医药科技有限公司 | Ibuprofen pharmaceutical composition for treating congenital heart disease in premature infants |
| CN105997901A (en) * | 2016-07-27 | 2016-10-12 | 济南东方开元医药新技术有限公司 | Ibuprofen tromethamine freeze-dried powder injection composition for infantile injection and preparation method |
| WO2018025128A1 (en) * | 2016-08-02 | 2018-02-08 | Jamil Irfan | Stable ibuprofen injectable composition |
| CN110123769A (en) * | 2019-05-24 | 2019-08-16 | 北京悦康科创医药科技股份有限公司 | A kind of ibuprofen slow-release piller and preparation method thereof |
-
2006
- 2006-05-10 CN CN 200610044134 patent/CN101069681A/en active Pending
Cited By (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102791268A (en) * | 2009-12-23 | 2012-11-21 | 坎伯兰医药品股份有限公司 | Treating critically ill patients with intravenous ibuprofen |
| CN102335114A (en) * | 2010-07-23 | 2012-02-01 | 重庆医药工业研究院有限责任公司 | Stable ibuprofen arginine injection and preparation method thereof |
| CN102335114B (en) * | 2010-07-23 | 2015-07-15 | 重庆医药工业研究院有限责任公司 | Stable ibuprofen arginine injection and preparation method thereof |
| CN101978945B (en) * | 2010-10-25 | 2016-03-30 | 北京世纪博康医药科技有限公司 | A kind of ibuprofen medicinal composition |
| CN101978945A (en) * | 2010-10-25 | 2011-02-23 | 北京世纪博康医药科技有限公司 | Ibuprofen medicinal composition |
| CN102552117A (en) * | 2010-12-27 | 2012-07-11 | 成都国为医药科技有限公司 | Injection containing ibuprofen and preparation method of injection |
| CN102085179A (en) * | 2011-01-20 | 2011-06-08 | 罗军 | Ibuprofen injection and preparation method thereof |
| CN102085179B (en) * | 2011-01-20 | 2012-08-29 | 罗军 | Ibuprofen injection and preparation method thereof |
| CN104323988A (en) * | 2014-11-27 | 2015-02-04 | 北京蓝丹医药科技有限公司 | Dexibuprofen pharmaceutical composition for injection |
| CN105055389B (en) * | 2015-08-03 | 2018-08-10 | 北京蓝丹医药科技有限公司 | A kind of ibuprofen medicinal composition for premature's congenital heart disease |
| CN105055389A (en) * | 2015-08-03 | 2015-11-18 | 北京蓝丹医药科技有限公司 | Ibuprofen pharmaceutical composition for treating congenital heart disease in premature infants |
| CN105997901A (en) * | 2016-07-27 | 2016-10-12 | 济南东方开元医药新技术有限公司 | Ibuprofen tromethamine freeze-dried powder injection composition for infantile injection and preparation method |
| WO2018025128A1 (en) * | 2016-08-02 | 2018-02-08 | Jamil Irfan | Stable ibuprofen injectable composition |
| CN109843266A (en) * | 2016-08-02 | 2019-06-04 | 安巴知识产权有限公司 | Stable brufen injectable composition |
| US20190183823A1 (en) * | 2016-08-02 | 2019-06-20 | Ambah Ip Limited | Stable ibuprofen injectable composition |
| JP2019523292A (en) * | 2016-08-02 | 2019-08-22 | アンバー アイピー リミテッド | Stable composition for ibuprofen injection formulation |
| AU2017307313B2 (en) * | 2016-08-02 | 2021-09-09 | Ambah Ip Limited | Stable ibuprofen injectable composition |
| US11541024B2 (en) * | 2016-08-02 | 2023-01-03 | Ambah Ip Limited | Stable ibuprofen injectable composition |
| CN109843266B (en) * | 2016-08-02 | 2023-08-11 | 安巴知识产权有限公司 | Stable ibuprofen injection composition |
| JP7386080B2 (en) | 2016-08-02 | 2023-11-24 | アンバー アイピー リミテッド | Stable ibuprofen injection composition |
| CN110123769A (en) * | 2019-05-24 | 2019-08-16 | 北京悦康科创医药科技股份有限公司 | A kind of ibuprofen slow-release piller and preparation method thereof |
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Open date: 20071114 |