CN101574319A - Podophyllotoxin vesicle and preparation method thereof - Google Patents
Podophyllotoxin vesicle and preparation method thereof Download PDFInfo
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- CN101574319A CN101574319A CNA200810106183XA CN200810106183A CN101574319A CN 101574319 A CN101574319 A CN 101574319A CN A200810106183X A CNA200810106183X A CN A200810106183XA CN 200810106183 A CN200810106183 A CN 200810106183A CN 101574319 A CN101574319 A CN 101574319A
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- podophyllotoxin
- ether
- polyoxyethylene
- vesicle
- phosphate buffer
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Abstract
The invention relates to a podophyllotoxin vesicle and a preparation method thereof. The preparation method takes a non-ionic surfactant and modification lipids as vesicle materials, and adds cholesterol, dicetyl phosphate and the like as stabilizers. The vesicle having the advantage of good preparation stability is a novel preparation easy to industrialize.
Description
Technical field
The present invention relates to podophyllotoxin vesicle and preparation method thereof.
Background technology
Single chamber or multilamellar vesicles that liposome is made up of phospholipid bilayer, be study maximum target medicine carriers, be used for the antimonial of antineoplastic agent and leishmaniasis mostly, can significantly reduce drug toxicity and keep the activity of longer time.But there is shortcoming in the performance of liposome: 1. because its chemical instability, and preparation and storage difficulties, the medicine encapsulation ratio is not high and easily seepage takes place and lose targeting.2. raw materials used phospholipid is difficult to purification, and easy oxidation deterioration and reduce membrane fluidity cause the being wrapped seepage of medicine.3. the phospholipid valency height of purification.Therefore, people have studied the carrier that chemical composition is determined, character is stable, can constitute liposome sample vesicle widely.Many synthetic surfactants can both form vesicle, but wherein the toxicity of ion-type is bigger, should not be used as pharmaceutical carrier.Non-ionic surface active agent can self assembly form vesicle in solution.
Podophyllotoxin (Podophyllotoxin) is a kind of specific cytotoxic substance that extracts from plants such as Tibet Rhizoma Dysosmae Versipellis, the podophyllotoxin tincture is a line external used medicine of world health organisation recommendations treatment condyloma acuminatum, have antiviral, anti-tumor activity, with the podophyllotoxin be principal agent compound liniment in clinical practice for a long time, its therapeutical effect has obtained certainly.The major defect that exists is that the transdermal ability of medicine is not enough, and is relatively poor to the targeting of epithelial tissue.Usually only be used for the skin lesion surface, can cause the damage of normal surrounding tissue during improper use or more serious system occur to absorb toxicity.In addition, latent infection being difficult to prove effective is its major reason that high relapse rate occurs.Patent reports such as existing podophyllotoxin liposome, but traditional liposomal is owing to inherent defect, cost height, instability.
Summary of the invention
The object of the invention is to provide podophyllotoxin vesicle.
Another purpose of the present invention is to provide the podophyllotoxin vesicle preparation method.
The present invention is implemented by the following technical programs.
Podophyllotoxin vesicle of the present invention comprises following parts by weight of component: podophyllotoxin 1-10 non-ionic surface active agent 5-120 stabilizing agent 0-100 modifies lipid 0-50.
Non-ionic surface active agent can be polyglycerol alkyl ether in the podophyllotoxin vesicle of the present invention, the glucose alkyl ether, crown ether, polyoxyethylene alkyl ether, fatty alcohol-polyoxyethylene ether (AEO), polyoxyethylene carboxylate, aliphatic amine polyoxyethylene ether, alkylolamides polyoxy ethane ether, the block polyoxyethylene polyoxypropylene ether, alkyl poly glucoside, ethylene glycol monostearate or two stearate, polyethylene glycol stearate diester, propylene glycol monostearate, propylene glycol alginate, glyceryl monostearate and two stearate, the Span class, sorbitan mono-laurate (Span-20), anhydrous sorbitol monopalmitate (Span-40), sorbitan monostearate (Span-60), sorbitan monooleate (Span-80), a kind of composition or more than one any combination in the sucrose fatty acid ester, stabilizing agent can be cholesterol, di(2-ethylhexyl)phosphate spermaceti fat, the phospholipid amide one or more, modify lipid and can be polyethylene glycol-lactic acid, Polyethylene Glycol-DSPE, polyoxyethylene fatty acid ester, N-palmityl-L-homocysteine, the polyethylene glycol-caprolactone, polyethylene glycol-Acetic acid, hydroxy-, bimol. cyclic ester lactide, polyethylene glycol-cetyl cyanoacrylate, the polyoxyethylene fatty acid ester class, polyoxyethylene fatty acid ether, polyoxyethylene methyl Oleum Ricini ether one or more.
Podophyllotoxin vesicle preparation method of the present invention, can for: get non-ionic surface active agent, stabilizing agent, modification lipid, podophyllotoxin and be dissolved in an amount of organic solvent dissolution, solution for standby; Other gets phosphate buffer, at 30-70 ℃ of constant temperature and under stirring, at the uniform velocity drips above-mentioned organic solvent solution, adds the back and continues to stir, wave to the greatest extent to ether, add phosphate buffer to full dose, ultrasonic or cross high pressure dispersing emulsification machine 1-3 time, filter, lyophilization or fill, promptly.
Podophyllotoxin vesicle preparation method of the present invention also can for: get non-ionic surface active agent, stabilizing agent, modification lipid, podophyllotoxin and be dissolved in an amount of organic solvent, on Rotary Evaporators, 30-70 ℃ of vacuum evaporation is to dry film, add phosphate buffer then, supersound process, filter, promptly.
Podophyllotoxin vesicle preparation method of the present invention can also for: get non-ionic surface active agent, stabilizing agent, modification lipid, podophyllotoxin and be dissolved in an amount of organic solvent, add phosphate buffer, supersound process, again mixed liquor reduction vaporization under 30-70 ℃ of water bath with thermostatic control is removed organic solvent to gel formation, add an amount of phosphate buffer, continue reduction vaporization to forming suspension.
Phosphate buffer also can be ammonium sulfate buffer, the amino buffer of trihydroxy methyl or other buffer in the podophyllotoxin vesicle preparation method of the present invention, and organic solvent can be ether, chloroform, ethanol, dichloromethane, n-amyl alcohol, isoamyl alcohol.
The present invention adopts non-ionic surface active agent as the capsule material, and cost is low, easy suitability for industrialized production, and product has than big promotional value than liposome is stable, adopts the modification lipid can change vesicle pharmacokinetics in vivo simultaneously, can be beneficial to some treatment of diseases.
The specific embodiment:
The present invention is described further by embodiment, but is not limited to the present invention.
Instrument: RE-52A type Rotary Evaporators (Shanghai Yarong Biochemical Instrument Plant); Microjet instrument (U.S.); Ultrasonoscope (Shanghai)
Embodiment 1
Get span 20 50mg, cholesterol 50mg, podophyllotoxin 10mg is dissolved in 50ml ether dissolution, solution for standby; Other gets phosphate buffer 1 30ml, at 35 ℃ of constant temperature and under stirring, at the uniform velocity drips above-mentioned diethyl ether solution, adds the back and continues to stir, wave to the greatest extent to ether, and supersound process 10min, 0.22 μ m micro-pore-film filtration, promptly.
Embodiment 2
Get span 40 1200mg, di(2-ethylhexyl)phosphate spermaceti fat 1000mg, podophyllotoxin 100mg are dissolved in 260ml chloroform, heating for dissolving, solution for standby; Other gets ammonium sulfate buffer (350mmol/L) 800ml, at 40 ℃ of constant temperature and under stirring, at the uniform velocity drips above-mentioned chloroformic solution, adds the back and continues to stir, and waves to the greatest extent to chloroform, crosses high pressure dispersing emulsification machine 2 times, 0.22 μ m micro-pore-film filtration, promptly.
Embodiment 3
Get sorbester p18 500mg, cholesterol 600mg, podophyllotoxin 20mg is dissolved in the 200ml chloroform, on Rotary Evaporators, 40 ℃ of vacuum evaporation are to dry film, add phosphate buffer (pH7.0) 400ml then, supersound process 10min, 0.22 μ m micro-pore-film filtration, promptly.
Embodiment 4
Get span 40 400mg, phospholipid amide 30mg, podophyllotoxin 10mg are dissolved in the 50ml ether, add phosphate buffer (pH7.0) 100ml, supersound process, again mixed liquor reduction vaporization under 50 ℃ of waters bath with thermostatic control is removed ether to gel formation, add the 50ml phosphate buffer, continue reduction vaporization to ether and wave to the greatest extent, promptly.
Embodiment 5
Get sorbester p18 1000mg, cholesterol 500mg, Polyethylene Glycol-DSPE 300mg, podophyllotoxin 30mg, be dissolved in the 220ml ether, add phosphate buffer (pH7.0) 600ml, supersound process 10min, again mixed liquor reduction vaporization under 55 ℃ of waters bath with thermostatic control is removed organic solvent to gel formation, add the 100ml phosphate buffer, continue reduction vaporization to ether and wave to the greatest extent, promptly.
Embodiment 6
Get sorbester p18 800mg, di(2-ethylhexyl)phosphate spermaceti fat 300mg, polyethylene glycol-lactic acid 400mg, podophyllotoxin 70mg, be dissolved in the 180ml ether, add phosphate buffer (pH7.0) 160ml, supersound process 5min, again mixed liquor reduction vaporization under 40 ℃ of waters bath with thermostatic control is removed organic solvent to gel formation, add the 80ml phosphate buffer, continue reduction vaporization to ether and wave to the greatest extent, promptly.
Embodiment 7
Get sugar esters 600mg, di(2-ethylhexyl)phosphate spermaceti fat 400mg, podophyllotoxin 20mg, be dissolved in the 250ml ether, add phosphate buffer (pH7.0) 230ml, supersound process 10min, again mixed liquor reduction vaporization under 50 ℃ of waters bath with thermostatic control is removed organic solvent to gel formation, add the 50ml phosphate buffer, continue reduction vaporization to ether and wave to the greatest extent, promptly.
Claims (6)
1, podophyllotoxin vesicle is characterized in that comprising following parts by weight of component:
Podophyllotoxin 1-10 non-ionic surface active agent 5-120 stabilizing agent 0-100 modifies lipid 0-50.
2, podophyllotoxin vesicle as claimed in claim 1, it is characterized in that non-ionic surface active agent can be polyglycerol alkyl ether, the glucose alkyl ether, crown ether, polyoxyethylene alkyl ether, fatty alcohol-polyoxyethylene ether (AEO), polyoxyethylene carboxylate, aliphatic amine polyoxyethylene ether, alkylolamides polyoxy ethane ether, the block polyoxyethylene polyoxypropylene ether, alkyl poly glucoside, ethylene glycol monostearate or two stearate, polyethylene glycol stearate diester, propylene glycol monostearate, propylene glycol alginate, glyceryl monostearate and two stearate, the Span class, sorbitan mono-laurate (Span-20), anhydrous sorbitol monopalmitate (Span-40), sorbitan monostearate (Span-60), sorbitan monooleate (Span-80), a kind of composition or more than one any combination in the sucrose fatty acid ester, stabilizing agent can be cholesterol, di(2-ethylhexyl)phosphate spermaceti fat, the phospholipid amide one or more, modify lipid and can be polyethylene glycol-lactic acid, Polyethylene Glycol-DSPE, polyoxyethylene fatty acid ester, N-palmityl-L-homocysteine, the polyethylene glycol-caprolactone, polyethylene glycol-Acetic acid, hydroxy-, bimol. cyclic ester lactide, polyethylene glycol-cetyl cyanoacrylate, the polyoxyethylene fatty acid ester class, polyoxyethylene fatty acid ether, polyoxyethylene methyl Oleum Ricini ether one or more.
3, podophyllotoxin vesicle preparation method as claimed in claim 1 is characterized in that:
Get non-ionic surface active agent, stabilizing agent, modification lipid, podophyllotoxin and be dissolved in an amount of organic solvent dissolution, solution for standby; Other gets phosphate buffer, at 30-70 ℃ of constant temperature and under stirring, at the uniform velocity drips above-mentioned organic solvent solution, adds the back and continues to stir, wave to the greatest extent to ether, add phosphate buffer to full dose, ultrasonic or cross high pressure dispersing emulsification machine 1-3 time, filter, lyophilization or fill, promptly.
4, podophyllotoxin vesicle preparation method as claimed in claim 1 is characterized in that:
Get non-ionic surface active agent, stabilizing agent, modification lipid, podophyllotoxin and be dissolved in an amount of organic solvent, on Rotary Evaporators, 30-70 ℃ of vacuum evaporation adds phosphate buffer then to dry film, supersound process, promptly.
5, podophyllotoxin vesicle preparation method as claimed in claim 1 is characterized in that:
Get non-ionic surface active agent, stabilizing agent, modification lipid, podophyllotoxin and be dissolved in an amount of organic solvent, add phosphate buffer, supersound process, again mixed liquor reduction vaporization under 30-70 ℃ of water bath with thermostatic control is removed organic solvent to gel formation, add an amount of phosphate buffer, continue reduction vaporization to forming suspension.
6, as claim 3,4,5 described podophyllotoxin vesicle preparation methoies, it is characterized in that: phosphate buffer also can be ammonium sulfate buffer, the amino buffer of trihydroxy methyl or other buffer, and organic solvent can be ether, chloroform, ethanol, dichloromethane, n-amyl alcohol, isoamyl alcohol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200810106183XA CN101574319A (en) | 2008-05-09 | 2008-05-09 | Podophyllotoxin vesicle and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200810106183XA CN101574319A (en) | 2008-05-09 | 2008-05-09 | Podophyllotoxin vesicle and preparation method thereof |
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| CN101574319A true CN101574319A (en) | 2009-11-11 |
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| CNA200810106183XA Pending CN101574319A (en) | 2008-05-09 | 2008-05-09 | Podophyllotoxin vesicle and preparation method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104382856A (en) * | 2014-12-04 | 2015-03-04 | 中国药科大学 | Deoxidated podophyllotoxin long-circulating liposome freeze-drying preparation |
| CN104825395A (en) * | 2015-04-22 | 2015-08-12 | 合肥华方医药科技有限公司 | Total bufadienolide nonionic surfactant vesicles and preparation method thereof |
| CN106943308A (en) * | 2017-02-28 | 2017-07-14 | 西安科艺诗生物技术有限公司 | A kind of liposome lyophilized composition and purposes |
| CN107049932A (en) * | 2017-06-22 | 2017-08-18 | 四川大学 | A kind of small-molecule drug phase change gel slow-released system in situ and preparation method thereof |
-
2008
- 2008-05-09 CN CNA200810106183XA patent/CN101574319A/en active Pending
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104382856A (en) * | 2014-12-04 | 2015-03-04 | 中国药科大学 | Deoxidated podophyllotoxin long-circulating liposome freeze-drying preparation |
| CN104382856B (en) * | 2014-12-04 | 2017-11-14 | 中国药科大学 | A kind of deoxypodophyllotoxin long circulating liposome lyophilized formulations |
| CN104825395A (en) * | 2015-04-22 | 2015-08-12 | 合肥华方医药科技有限公司 | Total bufadienolide nonionic surfactant vesicles and preparation method thereof |
| CN104825395B (en) * | 2015-04-22 | 2018-02-27 | 合肥华方医药科技有限公司 | A kind of total toadpoison lactone nonionic surfactant vesicle and preparation method thereof |
| CN106943308A (en) * | 2017-02-28 | 2017-07-14 | 西安科艺诗生物技术有限公司 | A kind of liposome lyophilized composition and purposes |
| CN107049932A (en) * | 2017-06-22 | 2017-08-18 | 四川大学 | A kind of small-molecule drug phase change gel slow-released system in situ and preparation method thereof |
| CN108771657A (en) * | 2017-06-22 | 2018-11-09 | 四川大学 | A kind of small-molecule drug original position phase change gel slow-released system and preparation method thereof |
| CN109010261A (en) * | 2017-06-22 | 2018-12-18 | 四川大学 | A kind of small-molecule drug original position phase change gel slow-released system and preparation method thereof |
| CN109010261B (en) * | 2017-06-22 | 2020-11-06 | 四川大学 | Small molecule drug in-situ phase change gel sustained release system and preparation method thereof |
| CN108771657B (en) * | 2017-06-22 | 2020-11-06 | 四川大学 | Small molecule drug in-situ phase change gel sustained release system and preparation method thereof |
| CN107049932B (en) * | 2017-06-22 | 2020-11-06 | 四川大学 | Small molecule drug in-situ phase change gel sustained release system and preparation method thereof |
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Application publication date: 20091111 |