CN101077336A - Injection containing ketoprofen and preparation method thereof - Google Patents
Injection containing ketoprofen and preparation method thereof Download PDFInfo
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- CN101077336A CN101077336A CN 200610044528 CN200610044528A CN101077336A CN 101077336 A CN101077336 A CN 101077336A CN 200610044528 CN200610044528 CN 200610044528 CN 200610044528 A CN200610044528 A CN 200610044528A CN 101077336 A CN101077336 A CN 101077336A
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- ketone ibuprofen
- injection
- ibuprofen
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- ketone
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Abstract
The present invention provides one kind of injection containing ketoproten and its preparation process, and features that the injection contains ketoproten, alkaline assistant and stuffing in the molar ratio between ketoproten and alkaline assistant of 1 to 1, and the weight ratio between ketoproten and stuffing of 1 to 0-10. The injection containing ketoproten is superior to traditional orally taken ketoproten preparation, and has new administration way, high product quality, high bioavailability and fast acting.
Description
Technical field:
The present invention relates to a kind of medicine and preparation method thereof, be specifically related to a kind of injection ketone ibuprofen and preparation method that is used for the treatment of diseases such as pain that a variety of causes causes, heating.
Background technology
Ketone ibuprofen is 3-benzoyl-Alpha-Methyl phenylacetic 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, particularly the dextrorotation ketone ibuprofen has overcome ketone ibuprofen some shortcomings aspect use pharmacodynamics and pharmacokinetics, the external existing trend that substitutes the raceme ketone ibuprofen with the dextrorotation ketone ibuprofen.Its clinical meaning is as follows:
1. the dextrorotation ketone ibuprofen is a tool medicine active single enantiomer of generation, so use the dextrorotation ketone ibuprofen be lower than raceme ketone ibuprofen dosage can produce pharmacological action equal even strong degree, also produce to a certain degree pharmacological action even be less than 1/2 dosage.
2. the dextrorotation ketone 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. the dextrorotation ketone ibuprofen does not disturb body fat tissue biological synthetic, has got rid of the possibility of bringing out the hyperreaction reaction.
4. the dextrorotation ketone 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. the dextrorotation ketone ibuprofen shows better simply pharmacodynamics and pharmacokinetics characteristics, thereby helps optimization of dosage etc.
Dextrorotation ketone ibuprofen (S)-2-(4-isobutyl phenenyl) propanoic acid is at first developed successfully by Austrian Gebro-Broscheh Gmb 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.
Ketone ibuprofen and dextrorotation ketone 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; United States Patent (USP) 4845281 in 1989 once disclosed the manufacture method of ketone ibuprofen salt, but the ketone ibuprofen injection, particularly injection ketone ibuprofen 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 ketone ibuprofen, and a kind of injection and preparation method that contains ketone 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 injection that contains ketone ibuprofen contains principal agent ketone ibuprofen, alkaline auxiliary solvent, filler in the described injection.The mole proportioning of ketone ibuprofen and alkaline auxiliary solvent is 1: 1; The weight ratio of ketone ibuprofen and filler is 1: 0-10.Described alkaline auxiliary solvent is any among arginine, D-arginine, DL-arginine or lysine, D-lysine, DL-lysine, the trometamol; Described filler is any in lactose, mannitol, sorbitol, the low molecular dextran.Wherein the weight proportion of each component is:
Ketone ibuprofen or dextrorotation ketone ibuprofen 200
Arginine or lysine or trometamol 137 or 115 or 96
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 ketone 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.
Injection ketone ibuprofen of the present invention and preparation method adopt following prepared:
The ketone 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 ketone 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: ketone 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: ketone 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: ketone 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: dextrorotation ketone 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: dextrorotation ketone ibuprofen 200g
Trometamol 96g
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.
The product stability result tests as follows:
One, 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 | |||||||
| 0505103 | 0 | Off-white powder | 1.16 | 7.1 | Clarify, be shallower than yellow No. 7 | 0.17 | 0.77 | 98.58 |
| 1 | Off-white powder | 1.12 | 7.1 | Clarify, be shallower than yellow No. 7 | 0.24 | 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 | 1.24 | 7.1 | Clarify, be shallower than yellow No. 7 | 0.23 | 1.02 | 98.88 | |
| 6 | Off-white powder | 1.10 | 7.1 | Clarify, be shallower than yellow No. 7 | 0.36 | 1.40 | 98.71 | |
| 0505113 | 0 | Off-white powder | 1.30 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.13 | 0.84 | 98.81 |
| 1 | Off-white powder | 1.27 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.15 | 0.61 | 98.28 | |
| 2 | Off-white powder | 1.24 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.22 | 0.77 | 98.71 | |
| 3 | Off-white powder | 1.33 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.22 | 1.21 | 98.83 | |
| 6 | Off-white powder | 1.22 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.33 | 1.32 | 98.95 | |
| 0505123 | 0 | Off-white powder | 1.11 | 7.2 | Clarify, be shallower than yellow No. 7 | 0.18 | 0.86 | 99.21 |
| 1 | Off-white powder | 1.23 | 7.2 | Clarify, be shallower than yellow No. 7 | 0.21 | 0.77 | 98.61 | |
| 2 | Off-white powder | 1.10 | 7.2 | Clarify, be shallower than yellow No. 7 | 0.18 | 0.66 | 99.13 | |
| 3 | Off-white powder | 1.23 | 7.2 | Clarify, be shallower than yellow No. 7 | 0.11 | 1.10 | 98.12 | |
| 6 | Off-white powder | 1.31 | 7.2 | Clarify, be shallower than yellow No. 7 | 0.33 | 1.16 | 98.33 |
Two, 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 | |||||||
| 0505102 | 0 | Off-white powder | 1.14 | 7.2 | Clarify, be shallower than yellow No. 7 | 0.19 | 0.82 | 99.18 |
| 3 | Off-white powder | 1.16 | 7.2 | Clarify, be shallower than yellow No. 7 | 0.24 | 1.22 | 98.52 | |
| 6 | Off-white powder | 1.14 | 7.2 | Clarify, be shallower than yellow No. 7 | 0.15 | 0.76 | 99.03 | |
| 0505112 | 0 | Off-white powder | 1.29 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.16 | 0.72 | 98.99 |
| 3 | Off-white powder | 1.31 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.20 | 1.19 | 98.61 | |
| 6 | Off-white powder | 1.23 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.19 | 0.69 | 99.25 | |
| 0505122 | 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 | 0.15 | 0.77 | 98.54 | |
| 6 | Off-white powder | 1.18 | 7.3 | Clarify, be shallower than yellow No. 7 | 0.15 | 0.89 | 99.08 |
Claims (7)
1, a kind of injection that contains ketone ibuprofen is characterized in that wherein containing principal agent ketone ibuprofen, alkaline auxiliary solvent and filler, and the mole proportioning of ketone ibuprofen and alkaline auxiliary solvent is 1: 1; The weight ratio of ketone ibuprofen and filler is 1: 0-10.
2,, it is characterized in that described ketone ibuprofen is the racemic modification ketone ibuprofen according to the described injection of claim 1.
3,, it is characterized in that described ketone ibuprofen is the d-isomer ketone ibuprofen according to the described injection of claim 1.
4,, 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.
5,, 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.
6, a kind of preparation method that contains the ketone ibuprofen injection, it is characterized in that the described raw material of claim 1 is dissolved in respectively in water and the organic solvent, ketone ibuprofen is 1 with the volume of organic solvent ratio: 0.05-50, fully mixing, decolouring, filtration, packing, lyophilizing.
7,, it is characterized in that described organic solvent can be any in ethanol, acetone, isopropyl alcohol, the methanol according to the described preparation method that contains the ketone ibuprofen injection of claim 6.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610044528 CN101077336A (en) | 2006-06-02 | 2006-06-02 | Injection containing ketoprofen and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610044528 CN101077336A (en) | 2006-06-02 | 2006-06-02 | Injection containing ketoprofen and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101077336A true CN101077336A (en) | 2007-11-28 |
Family
ID=38905108
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610044528 Pending CN101077336A (en) | 2006-06-02 | 2006-06-02 | Injection containing ketoprofen and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101077336A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101467997B (en) * | 2007-12-26 | 2010-12-15 | 北京大北农动物保健科技有限责任公司 | Compound medicament composition for animals and uses thereof |
| CN101935293A (en) * | 2010-09-03 | 2011-01-05 | 蚌埠丰原涂山制药有限公司 | Method for preparing arginine ketoprofenate |
| 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 |
| CN103230373A (en) * | 2013-04-12 | 2013-08-07 | 沈阳双鼎制药有限公司 | Dexlansoprazole freeze-drying powder for injection and preparation method thereof |
| 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 |
| CN107854429A (en) * | 2017-12-25 | 2018-03-30 | 南京正科医药股份有限公司 | A kind of dexketoprofen trometamol parenteral solution and its preparation technology |
| CN108478524A (en) * | 2018-06-29 | 2018-09-04 | 佛山市南海东方澳龙制药有限公司 | Ketoprofen injection and its preparation method and application |
-
2006
- 2006-06-02 CN CN 200610044528 patent/CN101077336A/en active Pending
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101467997B (en) * | 2007-12-26 | 2010-12-15 | 北京大北农动物保健科技有限责任公司 | Compound medicament composition for animals and uses thereof |
| CN101935293A (en) * | 2010-09-03 | 2011-01-05 | 蚌埠丰原涂山制药有限公司 | Method for preparing arginine ketoprofenate |
| CN101935293B (en) * | 2010-09-03 | 2013-12-11 | 蚌埠丰原涂山制药有限公司 | Method for preparing arginine ketoprofenate |
| 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 |
| 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 |
| CN103230373A (en) * | 2013-04-12 | 2013-08-07 | 沈阳双鼎制药有限公司 | Dexlansoprazole freeze-drying powder for injection and preparation method thereof |
| 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 |
| 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 |
| 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 |
| CN107854429A (en) * | 2017-12-25 | 2018-03-30 | 南京正科医药股份有限公司 | A kind of dexketoprofen trometamol parenteral solution and its preparation technology |
| CN108478524A (en) * | 2018-06-29 | 2018-09-04 | 佛山市南海东方澳龙制药有限公司 | Ketoprofen injection and its preparation method and application |
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Open date: 20071128 |