CN104337775A - Naproxen injection - Google Patents
Naproxen injection Download PDFInfo
- Publication number
- CN104337775A CN104337775A CN201410627837.9A CN201410627837A CN104337775A CN 104337775 A CN104337775 A CN 104337775A CN 201410627837 A CN201410627837 A CN 201410627837A CN 104337775 A CN104337775 A CN 104337775A
- Authority
- CN
- China
- Prior art keywords
- injection
- naproxen
- fatty acid
- smooth
- polysorbate
- 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
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 title claims abstract description 32
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 title claims abstract description 31
- 229960002009 naproxen Drugs 0.000 title claims abstract description 31
- 238000002347 injection Methods 0.000 title claims abstract description 28
- 239000007924 injection Substances 0.000 title claims abstract description 28
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 17
- 229930195729 fatty acid Natural products 0.000 claims abstract description 17
- 239000000194 fatty acid Substances 0.000 claims abstract description 17
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims abstract description 11
- 239000000787 lecithin Substances 0.000 claims abstract description 11
- 235000010445 lecithin Nutrition 0.000 claims abstract description 11
- 229940067606 lecithin Drugs 0.000 claims abstract description 11
- 229920000136 polysorbate Polymers 0.000 claims abstract description 9
- 229950008882 polysorbate Drugs 0.000 claims abstract description 9
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
- 235000011572 Pyrus ussuriensis Nutrition 0.000 claims description 16
- 244000173166 Pyrus ussuriensis Species 0.000 claims description 16
- 150000004665 fatty acids Chemical class 0.000 claims description 16
- 239000008215 water for injection Substances 0.000 claims description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- 238000003756 stirring Methods 0.000 claims description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 10
- 239000008346 aqueous phase Substances 0.000 claims description 10
- 210000003022 colostrum Anatomy 0.000 claims description 10
- 235000021277 colostrum Nutrition 0.000 claims description 10
- 239000000839 emulsion Substances 0.000 claims description 10
- 239000012071 phase Substances 0.000 claims description 10
- 239000004005 microsphere Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 6
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 5
- 238000013019 agitation Methods 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 238000004108 freeze drying Methods 0.000 claims description 5
- 239000012982 microporous membrane Substances 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 239000011780 sodium chloride Substances 0.000 claims description 5
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 239000003995 emulsifying agent Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 239000002202 Polyethylene glycol Substances 0.000 abstract 2
- 239000004372 Polyvinyl alcohol Substances 0.000 abstract 2
- 229920002451 polyvinyl alcohol Polymers 0.000 abstract 2
- -1 sorbitan fatty acid Chemical class 0.000 abstract 1
- 229920001219 Polysorbate 40 Polymers 0.000 description 5
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 5
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 5
- 229940101027 polysorbate 40 Drugs 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 208000006820 Arthralgia Diseases 0.000 description 1
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 206010013935 Dysmenorrhoea Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 208000004371 toothache Diseases 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a preparation method for naproxen injection. The naproxen injection comprises the following components in parts by weight: 2 to 5 parts of naproxen, 1 to 5 parts of PVA (polyvinyl alcohol), 1 to 2 parts of lecithin , 0.5 to 1 part of sorbitan fatty acid, 0.5 to 1 part of polysorbate and 1 to 3 parts of PEG (polyethylene glycol). The naproxen injection is high in stability and solubility, and the preparation process is simple.
Description
Technical field
The present invention relates to a kind of preparation method of naproxen injection.
Background technology
Naproxen has another name called (+)-Alpha-Methyl-6-methoxyl-2-naphthylacetic acid, is a kind of NSAID (non-steroidal anti-inflammatory drug), has the effect of antipyretic-antalgic antiinflammatory, can suppress the synthesis of prostaglandin and play anti-inflammatory and analgesic effect.For alleviating mild to moderate pain, as arthralgia, neuralgia, myalgia, migraine, headache, dysmenorrhea, toothache.This product is dissolved in methanol/ethanol, does not dissolve in water.
Summary of the invention
The invention provides a kind of preparation method of naproxen injection; This injection has the features such as solubility is good, good stability, and drug loading is high, safety of clinical trials is good, overcomes the deficiencies in the prior art part.
In injection, the ratio of each component is naproxen 1-5 part; PVA1-5 part; PVP1-2 part; Lecithin 1-3 part; The smooth 0.5-1 part of fatty acid Pyrusussuriensis; Polysorbate 0.5-1 part; PEG1-3 part.Described PVA molecular weight is between 5000-20000.
As preferably, emulsifying agent is the mixture of the smooth and Polysorbate of fatty acid Pyrusussuriensis, and its ratio is than being 0.5:1-1:2.
As preferably, PVA is 3-5 part.
As preferably, fatty acid Pyrusussuriensis is smooth is fatty acid Pyrusussuriensis smooth 80,40,20; Polysorbate is polyoxyethylene sorbitan monoleate, 40,20.
As preferably, PVP is selected from PVP-4000 or PVP-6000.
The preparation method of above-mentioned injection naproxen, comprises the steps:
(1) each component is taken by formula proportion;
(2) naproxen and PVP, lecithin add in water for injection successively, and stirring and dissolving obtains interior aqueous phase W1;
(3) PVA, fatty acid Pyrusussuriensis is smooth and Polysorbate is dissolved in volume ratio is in the dichloromethane/acetone of 3: 1, obtains oil phase;
(4) PEG adds in water for injection to be stirred to and dissolves completely, obtains outer aqueous phase W2;
(5) under agitation slowly added in oil phase by W1, under ice bath, supersound process 20s obtains colostrum; Slowly added in W2 by colostrum and stir 10min and obtain emulsion, poured into by emulsion in the aqueous solution for injection of sodium chloride, ice bath stirs 4h volatile residue organic solvent, and collect microsphere by 0.45 μm of filtering with microporous membrane, water for injection washs 3 times, vacuum lyophilization.
Detailed description of the invention
Embodiment 1: a kind of injection naproxen
Naproxen 500g;
PVA400g；
PVP100g；
Lecithin 100g;
The smooth 2050g of fatty acid Pyrusussuriensis;
Polysorbate 40 50g;
PEG100g；
Naproxen, PVP and lecithin are added successively in 1000mL water for injection, stirring and dissolving obtains interior aqueous phase W1; It is in the 1000mL dichloromethane/acetone of 3: 1 that smooth for fatty acid Pyrusussuriensis 20, polysorbate 40 are dissolved in volume ratio, obtains oil phase;
PEG is added in water for injection to be stirred to and dissolve completely, obtain outer aqueous phase W2;
Under agitation slowly added in oil phase by W1, under ice bath, supersound process 20s obtains colostrum; Colostrum is slowly added in W2 and stirs 10min and obtain emulsion, poured into by emulsion in the aqueous solution for injection of 1000mL sodium chloride, ice bath stirs 4h volatile residue organic solvent, collects microsphere by 0.45 μm of filtering with microporous membrane, water for injection washs 3 times, vacuum lyophilization.
Embodiment 2: a kind of injection naproxen
Naproxen 300g;
PVA200g；
PVP300g；
Lecithin 200g
The smooth 8050g of fatty acid Pyrusussuriensis;
Polysorbate 40 50g;
PEG50g。
Naproxen, PVP and lecithin are added successively in 1000mL water for injection, stirring and dissolving obtains interior aqueous phase W1; It is in the 1000mL dichloromethane/acetone of 3: 1 that smooth for fatty acid Pyrusussuriensis 20, polysorbate 40 are dissolved in volume ratio, obtains oil phase;
PEG is added in water for injection to be stirred to and dissolve completely, obtain outer aqueous phase W2;
Under agitation slowly added in oil phase by W1, under ice bath, supersound process 20s obtains colostrum; Colostrum is slowly added in W2 and stirs 10min and obtain emulsion, poured into by emulsion in the aqueous solution for injection of 1000mL sodium chloride, ice bath stirs 4h volatile residue organic solvent, collects microsphere by 0.45 μm of filtering with microporous membrane, water for injection washs 3 times, vacuum lyophilization.
Embodiment 3: a kind of note injection naproxen
Naproxen 400g;
PVA100g；
PVP100g；
Lecithin 100g
The smooth 2050g of fatty acid Pyrusussuriensis;
Polyoxyethylene sorbitan monoleate 50g;
Glycerol 100g;
Naproxen, PVP and lecithin are added successively in 1000mL water for injection, stirring and dissolving obtains interior aqueous phase W1; It is in the 1000mL dichloromethane/acetone of 3: 1 that smooth for fatty acid Pyrusussuriensis 20, polysorbate 40 are dissolved in volume ratio, obtains oil phase;
PEG is added in water for injection to be stirred to and dissolve completely, obtain outer aqueous phase W2;
Under agitation slowly added in oil phase by W1, under ice bath, supersound process 20s obtains colostrum; Colostrum is slowly added in W2 and stirs 10min and obtain emulsion, poured into by emulsion in the aqueous solution for injection of 1000mL sodium chloride, ice bath stirs 4h volatile residue organic solvent, collects microsphere by 0.45 μm of filtering with microporous membrane, water for injection washs 3 times, vacuum lyophilization.
Embodiment 4: droplet measurement
The injection of Example 1-3, is dissolved in water into the solution of every 1mL containing 1mg naproxen, measures with laser diffraction particle size instrument.The naproxen injection that acetonideexample 1-3 prepares is spherical shape, and even particle size distribution, whole particle diameter is between 300-550nm.
Embodiment 5: envelop rate detects
The injection of naproxen is dissolved in water into the solution of every 1mL containing naproxen 1mg, with the centrifugation 15min of 6000r/min, gets supernatant 1mL, with dissolve with ethanol, measure the content of naproxen.
Dose in envelop rate=microsphere/(dose in the dose+medium in microsphere) × 100%
The envelop rate of injection prepared by embodiment 1-3, between 80%-90%.
Embodiment 6: dissolution velocity is investigated
Each two bottles of injection in random selecting embodiment 1-3, numbering 1-6, sample number into spectrum 7 after physical mixed, the naproxen freeze-dried powder numbering 8 of having gone on the market, by the dissolving method of clinical application, inject 10mL water for injection respectively, eddy mixer jolts, completely clear and bright for index to dissolve, calculate dissolution velocity.
Experimental result shows that the dissolution velocity of injection of the present invention is obviously better than the injection of direct packaging.
Embodiment 7: study on the stability
The injection that the sample prepared by embodiment 1-3 and raw material directly mix subpackage is placed in high temperature 40 DEG C, lower 6 months of relative humidity 75% ± 5% condition respectively, carries out acceleration and investigates.
Claims (6)
1. a naproxen injection, is characterized in that the parts by weight of component are:
Naproxen 1-5 part;
PVA1-5 part
PVP1-2 part;
Lecithin 1-3 part;
The smooth 0.5-1 part of fatty acid Pyrusussuriensis;
Polysorbate 0.5-1 part;
PEG1-3 part;
Described PVA molecular weight is between 5000-20000.
2. pharmaceutical composition as claimed in claim 1, it is characterized in that described emulsifying agent is the mixture of the smooth and Polysorbate of fatty acid Pyrusussuriensis, its ratio is than being 0.5:1-1:2.
3. pharmaceutical composition as claimed in claim 1, is characterized in that PVA is 3-5 part.
4. pharmaceutical composition as claimed in claim 1, it is characterized in that fatty acid Pyrusussuriensis used smooth be fatty acid Pyrusussuriensis smooth 80,40,20; Polysorbate is polyoxyethylene sorbitan monoleate, 40,20.
5. pharmaceutical composition as claimed in claim 1, is characterized in that described PVP is selected from PVP-4000 or PVP-6000.
6. the preparation method of injection naproxen as described in claim arbitrary in claim 1-5, comprises the steps:
(1) each component is taken by formula proportion;
(2) naproxen and PVP, lecithin add in water for injection successively, and stirring and dissolving obtains interior aqueous phase W1;
(3) PVA, fatty acid Pyrusussuriensis is smooth and Polysorbate is dissolved in volume ratio is in the dichloromethane/acetone of 3: 1, obtains oil phase;
(4) PEG adds in water for injection to be stirred to and dissolves completely, obtains outer aqueous phase W2;
(5) under agitation slowly added in oil phase by W1, under ice bath, supersound process 20s obtains colostrum; Slowly added in W2 by colostrum and stir 10min and obtain emulsion, poured into by emulsion in the aqueous solution for injection of sodium chloride, ice bath stirs 4h volatile residue organic solvent, and collect microsphere by 0.45 μm of filtering with microporous membrane, water for injection washs 3 times, vacuum lyophilization.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410627837.9A CN104337775A (en) | 2014-11-10 | 2014-11-10 | Naproxen injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410627837.9A CN104337775A (en) | 2014-11-10 | 2014-11-10 | Naproxen injection |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104337775A true CN104337775A (en) | 2015-02-11 |
Family
ID=52494771
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410627837.9A Pending CN104337775A (en) | 2014-11-10 | 2014-11-10 | Naproxen injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104337775A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104784125A (en) * | 2015-04-14 | 2015-07-22 | 海南皇隆制药股份有限公司 | Quality-controllable naproxen sodium freeze-dried powder injection with good solubility and stability |
| CN108743525A (en) * | 2018-07-17 | 2018-11-06 | 安徽天安生物科技股份有限公司 | A kind of anti-oxidant naproxen injection and preparation method thereof |
| CN113730344A (en) * | 2021-09-13 | 2021-12-03 | 艾迈华创(武汉)科技有限公司 | Injectable naproxen preparation and application thereof |
-
2014
- 2014-11-10 CN CN201410627837.9A patent/CN104337775A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104784125A (en) * | 2015-04-14 | 2015-07-22 | 海南皇隆制药股份有限公司 | Quality-controllable naproxen sodium freeze-dried powder injection with good solubility and stability |
| CN104784125B (en) * | 2015-04-14 | 2017-10-03 | 海南皇隆制药股份有限公司 | A kind of naproxen sodium for injection freeze-dried powder and preparation method thereof |
| CN108743525A (en) * | 2018-07-17 | 2018-11-06 | 安徽天安生物科技股份有限公司 | A kind of anti-oxidant naproxen injection and preparation method thereof |
| CN113730344A (en) * | 2021-09-13 | 2021-12-03 | 艾迈华创(武汉)科技有限公司 | Injectable naproxen preparation and application thereof |
| CN113730344B (en) * | 2021-09-13 | 2023-10-20 | 艾迈华创(武汉)科技有限公司 | Naproxen preparation for injection and application thereof |
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|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20150211 |