CN101732255A - Flurbiprofen liposome and preparation method thereof - Google Patents
Flurbiprofen liposome and preparation method thereof Download PDFInfo
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- CN101732255A CN101732255A CN201010022493A CN201010022493A CN101732255A CN 101732255 A CN101732255 A CN 101732255A CN 201010022493 A CN201010022493 A CN 201010022493A CN 201010022493 A CN201010022493 A CN 201010022493A CN 101732255 A CN101732255 A CN 101732255A
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Abstract
The invention relates to a flurbiprofen liposome and a preparation method thereof. The flurbiprofen liposome is prepared by weighting the following materials in part by weight: 1 to 10 parts of cholesterol, 5 to 40 parts of yolk lecithin, 2 to 50 parts of flurbiprofen and 1 to 10 parts of vitamin C; dissolving the materials with chloroform and methanol in a mass ratio of 4:1; uniformly mixing the materials to obtain mixed solution; putting the solution into a rotary evaporator; distilling the solution under reduced pressure for removing the chloroform and the methanol to obtain a lipid membrane; adding phosphate buffer with pH between 6 and 8 into the lipid membrane; rotating for 1 to 4 h in warm bath at the temperature of between 20 and 60 DEG C on the rotary evaporator; and carrying out water bath ultrasound for 5 to 30 min, and then filtering the mixture with a 0.22 to 0.45 mu m filter membrane to obtain the flurbiprofen liposome. The flurbiprofen liposome prepared by the invention has good stability, targeting property and slow-releasing property, can reduce administration dosage and reduce toxic and side effect of medicaments, is suitable for percutaneous administration and oral administration, and can be widely used for preparing oral liquid, aerosol, spray, and ophthalmic and external liposome administration formulations.
Description
Technical field
The present invention relates to a kind of flurbiprofen liposome and preparation method thereof.Belong to technical field of medicine.
Background technology
Flurbiprofen is one of outstanding kind in the non-steroidal anti-inflammatory analgesic, is mainly used in treatment rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, wound pain and other pain.Thereby flurbiprofen is the effect of playing anti-inflammatory analgesic by the activity that suppresses the prostaglandin synthetase epoxidase.This medicine is oral effectively, better tolerance, and life-time service neither promotes also not suppress self metabolism.Although flurbiprofen has unique anti-inflammatory analgesic effect clinically, flurbiprofen is a lipophilic drugs, and dissolubility is lower in the water, causes oral administration biaavailability lower, and has more serious gastrointestinal tract and central nervous system's untoward reaction.At present, the report great majority of relevant flurbiprofen dosage form all are confined to the percutaneous dosing method of flurbiprofen, as " flurbiprofen cataplasma and preparation thereof " (Chinese invention patent application number: 03116441.2, publication number: CN144353A) and " external use plaster that contains flurbiprofen " (the Chinese invention patent application number: 200580048135.4, publication number: CN101119716A).Liposome is the vesicle that phospholipid is dispersed in a near-spherical that forms in the water.The material that constitutes lipid bilayer (carrier) mainly is phospholipid (lecithin, cephalin, fabaceous lecithin) and cholesterol etc., but every layer of equal entrapped drug wherein, and because existing hydrophilic group has hydrophobic group again in its molecular structure, water soluble drug is encapsulated in the vesicle hydrophilic group interlayer, and fat-soluble medicine then is scattered in the interlayer of hydrophobic group of vesicle.Liposome both had been fit to the percutaneous dosing method as pharmaceutical carrier, was fit to the oral administration method again.And liposome is nontoxic or toxic and side effects is little to body, and its liposome bilayer and biomembrane have bigger similarity and tissue intersolubility, thereby are easy to be organized absorption, have improved drug bioavailability.
Summary of the invention
The object of the present invention is to provide a kind of composition of flurbiprofen liposome, further aim of the present invention is the preparation method that discloses this flurbiprofen liposome.The flurbiprofen liposome of the present invention's preparation both had been fit to percutaneous dosing, be fit to oral administration again, nontoxic or toxic and side effects is little to body, its liposome bilayer and biomembrane have bigger similarity and tissue intersolubility, thereby be easy to be organized absorption, improved drug bioavailability.
In order to achieve the above object, the present invention adopts following technical scheme:
Flurbiprofen liposome of the present invention is made up of following parts by weight:
1～10 part in cholesterol
2～50 parts of flurbiprofens
5～40 parts of Ovum Gallus domesticus Flavus lecithins
1～10 part of vitamin C
The preparation method of flurbiprofen liposome provided by the invention is as follows:
Take by weighing earlier 1～10 part in cholesterol by weight, 5～40 parts of Ovum Gallus domesticus Flavus lecithins, 1～10 part of 2～50 parts of flurbiprofens and vitamin C, the reuse chloroform/methanol makes their dissolvings, and mix homogeneously obtains mixed solution, the consumption of chloroform/methanol is 2000～20000 times of cholesterol consumption, then above-mentioned mixed solution is placed Rotary Evaporators, chloroform and methanol are removed in distilling under reduced pressure, making lipid film, then is that 6～8 phosphate buffer joins in the lipid film with pH, is rotating 1～4h on the Rotary Evaporators in 20～60 ℃ of temperature are bathed, behind the last ultrasonic 5～30min of water-bath, the filter membrane of crossing 0.22～0.45 μ m makes flurbiprofen liposome;
Above-mentioned chloroform/methanol is a chloroform: methanol=4: 1 mass ratioes.
The present invention has the following advantages:
1. preparation method of the present invention is simple to operation, and preparation process Chinese medicine loss amount is few, and the crude drug Ovum Gallus domesticus Flavus lecithin has good biocompatibility, biodegradable.
2. add antioxidant vitamin C in the medicine of the present invention, improve the stability of liposome, avoided phospholipid in vivo and in vitro peroxidating and produce toxic and side effects.
3. flurbiprofen is a kind of hydrophobic drug, it is positioned the hydrophobic region of liposome BLM, flurbiprofen adds Ovum Gallus domesticus Flavus lecithin has increased the degree of order that lecithin molecules is arranged, thereby has reduced the flowability of BLM, improves the stability of flurbiprofen liposome.
The flurbiprofen liposome of 4 the present invention preparation both had been fit to percutaneous dosing, be fit to oral administration again, nontoxic or toxic and side effects is little to body, its liposome bilayer and biomembrane have bigger similarity and tissue intersolubility, thereby be easy to be organized absorption, improved drug bioavailability.
5. flurbiprofen liposome of the present invention is of many uses, can be used for oral liquid, aerosol, spray, eye usefulness or external-use liposome form of administration.
The specific embodiment
Embodiment 1
Take by weighing 6.0mg flurbiprofen, 15.0mg Ovum Gallus domesticus Flavus lecithin, 3.0mg cholesterol, 3.0mg vitamin C, make their dissolvings with the chloroform/methanol (mass ratio 4: 1) of 6.0g, and mix homogeneously obtains solution.Above-mentioned solution is placed Rotary Evaporators, and chloroform and methanol are removed in distilling under reduced pressure, make lipid film.With pH is that 6 phosphate buffer joins in the lipid film, is rotating 4h on the Rotary Evaporators in 20 ℃ of temperature are bathed, and behind the ultrasonic 5min of water-bath, the filter membrane of crossing 0.22 μ m makes flurbiprofen liposome.Above-mentioned raw materials is commercially available.
Embodiment 2
Take by weighing 6.0mg flurbiprofen, 15.0mg Ovum Gallus domesticus Flavus lecithin, 30.0mg cholesterol, 3.0mg vitamin C, make its dissolving, mix homogeneously with the chloroform/methanol (mass ratio 4: 1) of 60g.Above-mentioned solution is placed Rotary Evaporators, and chloroform and methanol are removed in distilling under reduced pressure, make lipid film.With pH is that 7 phosphate buffer joins in the lipid film flask, is rotating 1h on the Rotary Evaporators in 60 ℃ of temperature are bathed, and behind the ultrasonic 30min of water-bath, the filter membrane of crossing 0.45 μ m makes flurbiprofen liposome.
Embodiment 3
Take by weighing 30.0mg flurbiprofen, 50.8mg Ovum Gallus domesticus Flavus lecithin, 6.0mg cholesterol, 6.0mg vitamin C, make its dissolving, mix homogeneously with the chloroform/methanol (mass ratio 4: 1) of 6.0g.Above-mentioned solution is placed Rotary Evaporators, and chloroform and methanol are removed in distilling under reduced pressure, make lipid film.With pH is that 7 phosphate buffer joins in the lipid film flask, is rotating 3h on the Rotary Evaporators in 30 ℃ of temperature are bathed, and behind the ultrasonic 15min of water-bath, the filter membrane of crossing 0.45 μ m makes flurbiprofen liposome.
Embodiment 4
Take by weighing 64.0mg flurbiprofen, 25.4mg Ovum Gallus domesticus Flavus lecithin, 15.0mg cholesterol, 15.0mg vitamin C, make its dissolving, mix homogeneously with 30g chloroform/methanol (mass ratio 4: 1).Above-mentioned solution is placed Rotary Evaporators, and chloroform and methanol are removed in distilling under reduced pressure, make lipid film.With pH is that 8 phosphate buffer joins in the lipid film flask, is rotating 2h on the Rotary Evaporators in 50 ℃ of temperature are bathed, and behind the ultrasonic 25min of water-bath, the filter membrane of crossing 0.22 μ m makes flurbiprofen liposome.
Embodiment 5
Take by weighing 150.0mg flurbiprofen, 120.0mg Ovum Gallus domesticus Flavus lecithin, 3.0mg cholesterol, 30.0mg vitamin C, make its dissolving, mix homogeneously with 60g chloroform/methanol (mass ratio 4: 1).Above-mentioned solution is placed Rotary Evaporators, and chloroform and methanol are removed in distilling under reduced pressure, make lipid film.With pH is that 6 phosphate buffer joins in the lipid film flask, is rotating 2h on the Rotary Evaporators in 50 ℃ of temperature are bathed, and behind the ultrasonic 20min of water-bath, the filter membrane of crossing 0.22 μ m makes flurbiprofen liposome.
Embodiment 6
Take by weighing 150.0mg flurbiprofen, 120.0mg Ovum Gallus domesticus Flavus lecithin, 30.0mg cholesterol, 30.0mg vitamin C, make its dissolving, mix homogeneously with 60g chloroform/methanol (mass ratio 4: 1).Above-mentioned solution is placed Rotary Evaporators, and chloroform and methanol are removed in distilling under reduced pressure, make lipid film.With pH is that 8 phosphate buffer joins in the lipid film flask, is rotating 2h on the Rotary Evaporators in 50 ℃ of temperature are bathed, and behind the ultrasonic 20min of water-bath, the filter membrane of crossing 0.45 μ m makes flurbiprofen liposome.
Claims (2)
1. flurbiprofen liposome is characterized in that: be made up of following parts by weight:
1～10 part in cholesterol
2～50 parts of flurbiprofens
5～40 parts of Ovum Gallus domesticus Flavus lecithins
1～10 part of vitamin C.
2. the preparation method of the described a kind of flurbiprofen liposome of claim 1, it is characterized in that: take by weighing earlier 1～10 part in cholesterol by weight, 5～40 parts of Ovum Gallus domesticus Flavus lecithins, 1～10 part of 2～50 parts of flurbiprofens and vitamin C, the reuse chloroform/methanol makes their dissolvings, and mix homogeneously obtains mixed solution, then above-mentioned mixed solution is placed Rotary Evaporators, chloroform and methanol are removed in distilling under reduced pressure, make lipid film, then be that 6～8 phosphate buffer joins in the lipid film with pH, in bathing, 20～60 ℃ of temperature rotating 1～4h on the Rotary Evaporators, behind the last ultrasonic 5～30min of water-bath, the filter membrane of crossing 0.22～0.45 μ m makes flurbiprofen liposome;
Above-mentioned chloroform/methanol is a chloroform: methanol=4: 1 mass ratioes;
The consumption of above-mentioned chloroform/methanol is 2000～20000 times of cholesterol consumption.
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| CN201010022493A CN101732255A (en) | 2010-01-07 | 2010-01-07 | Flurbiprofen liposome and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017096123A1 (en) | 2015-12-04 | 2017-06-08 | The Penn State Research Foundation | Chemical reprogramming of human glial cells into neurons with small molecule cocktail |
| CN115475152A (en) * | 2022-11-09 | 2022-12-16 | 北京泰德制药股份有限公司 | External preparation of flurbiprofen and preparation method thereof |
-
2010
- 2010-01-07 CN CN201010022493A patent/CN101732255A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017096123A1 (en) | 2015-12-04 | 2017-06-08 | The Penn State Research Foundation | Chemical reprogramming of human glial cells into neurons with small molecule cocktail |
| US9885015B2 (en) | 2015-12-04 | 2018-02-06 | The Penn State Research Foundation | Chemical reprogramming of human glial cells into neurons with small molecule cocktail |
| CN108430582A (en) * | 2015-12-04 | 2018-08-21 | 宾州研究基金会 | Neuroglia cell of human chemical heavy is programmed for neuron with small-molecule mixture |
| US10253293B2 (en) | 2015-12-04 | 2019-04-09 | The Penn State Research Foundation | Chemical reprogramming of human glial cells into neurons with small molecule cocktail |
| CN108430582B (en) * | 2015-12-04 | 2020-02-21 | 宾州研究基金会 | Chemical reprogramming of human glial cells into neurons with small molecule cocktails |
| CN115475152A (en) * | 2022-11-09 | 2022-12-16 | 北京泰德制药股份有限公司 | External preparation of flurbiprofen and preparation method thereof |
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Open date: 20100616 |