CN1311189A - Synthesis of poly glycol monomethyl ether cholesterol succinate derivative and its preparation - Google Patents
Synthesis of poly glycol monomethyl ether cholesterol succinate derivative and its preparation Download PDFInfo
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- CN1311189A CN1311189A CN 00110157 CN00110157A CN1311189A CN 1311189 A CN1311189 A CN 1311189A CN 00110157 CN00110157 CN 00110157 CN 00110157 A CN00110157 A CN 00110157A CN 1311189 A CN1311189 A CN 1311189A
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- monomethyl ether
- preparation
- glycol monomethyl
- poly glycol
- succinate derivative
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Abstract
This invention is a synthesis of polyglycol monomethyl ether cholesterol succinate derivative and its preparation; it can coat the lipoid, emulsion and micro m capsule (granule), prolong thier invo half-life period and circulating period in blood, and improve the physical stability of the preparation. It is made up by using succinic anhydride and cholesterol as raw-materials through reflux reaction, and its structural formala is as the above diagram where n=10-200. This invention is simple in technology and easy for realization.
Description
The present invention relates to medical technical field, exactly it is the synthetic and preparation of poly glycol monomethyl ether cholesterol succinate derivative.
Classic liposome, emulsion or nanocapsule (grain), very easy by scavenger cell identification in the body, engulf, cause short target tissue limitation of transformation period in its body, more be unfavorable for combining with means such as temperature-sensitive, magnetosensitive, immunity, set up in recent years, utilizing the PEG lipid derivate that this class preparation is carried out the technology of dressing, is the technology that a utmost point has using value.Modal material is the PEG phosphatidyl ethanolamine derivant, but the expensive and purification difficult of phosphatidylethanolamine valency, comparatively speaking, cholesterol is inexpensive and easily refining, report is arranged, by ehter bond PGE is linked to each other with cholesterol, after made PEG cholesterol derivative carries out dressing to liposome, prolonged the transformation period in the rat body.Because the more difficult in vivo metabolism of ehter bond, fracture, its toxicity may be bigger, and the easy enzymolysis of ester bond.Therefore, we have invented the synthetic method of poly glycol monomethyl ether cholesterol succinate derivative.
The synthetic method and the preparation thereof that the purpose of this invention is to provide a kind of poly glycol monomethyl ether cholesterol succinate derivative, it can carry out surface coatings to dosage surface, has greatly prolonged cycling time in the blood, has improved the physical stability of preparation.
The objective of the invention is to be achieved by the following scheme, it is that raw material is made with succinyl oxide and cholesterol, it is characterized in that structural formula is:
N=10-200 in the formula, preferred values are n=20-50.Utilize poly glycol monomethyl ether cholesterol succinate derivative to liposome, emulsion, nanocapsule (grain) carry out dressing.
Advantage of the present invention is, with low cost, technology is simple, and to lipid, emulsion and nanocapsule (grain) carry out dressing with this, greatly prolonged the transformation period in its body, prolonged cycling time in its blood, improved the physical stability of preparation.
Below in conjunction with embodiment the present invention is done further detailed description.
Embodiment 1: poly glycol monomethyl ether cholesterol succinate derivative synthetic.
Be dissolved in succinyl oxide and cholesterol in the anhydrous methylene chloride jointly, back flow reaction 8 hours, reaction solution reclaims solvent, products therefrom toluene recrystallization, get Cholesteryl hemisuccinate, itself and thionyl chloride back flow reaction in anhydrous methylene chloride were added poly glycol monomethyl ether and continued back flow reaction 5 hours after 5 hours, reclaim solvent, promptly get product.
Embodiment 2: dressing liposome preparation and mouse body internal dynamics.
Calcium yellowish green disorderly (CF) solution is prepared liposome by reverse phase evaporation, and, carry out former grain respectively by the millipore filtration of 0.45,0.30,0.22 μ m.Get by Sephadex G.50 post remove the liposome of free CF, after pressing 10ml/kg dosage mouse tail vein injection, get blood plasma in different time, survey the concentration of CF, the gained data are handled with 3P87, obtain t1/2 and AUC, the t1/2 of CF solution, the classical liposome of CF and CF dressing liposome is respectively as a result: 38.1,134.7 and 206.9 minutes AUC ratio is respectively 1,6.5 and 17.5.
Embodiment 3: the interior medicine dynamics of Zorubicin dressing liposome.
After Zorubicin made different dosage form (Zorubicin solution, the classical liposome of Zorubicin and Zorubicin dressing liposome), press 10mg/kg dosage, the mouse tail vein administration, get blood in different time, measure doxorubicin concentration in the blood plasma, calculate the moving parameter of medicine, the t1/2 of three kinds of preparations is respectively as a result: 1.1,2.6 and 14.3 hours, AUC ratio was respectively 1.0,10.0 and 70.7.
Claims (4)
1, the synthetic and preparation of poly glycol monomethyl ether cholesterol succinate derivative, it is produced through back flow reaction by succinyl oxide and cholesterol, it is characterized in that, and structural formula is:
2, the synthetic and preparation of a kind of poly glycol monomethyl ether cholesterol succinate derivative according to claim 1 is characterized in that: n=10-200.
3, a kind of synthetic and preparation of poly glycol monomethyl ether cholesterol succinate derivative, it is characterized in that: be dissolved in succinyl oxide and cholesterol in the anhydrous methylene chloride jointly, back flow reaction 8 hours, reaction solution reclaims solvent, products therefrom toluene recrystallization, Cholesteryl hemisuccinate, with itself and thionyl chloride back flow reaction after 5 hours in anhydrous methylene chloride, add poly glycol monomethyl ether and continued back flow reaction 5 hours, reclaim solvent.
4, the synthetic and preparation of a kind of poly-ethanol monomethyl ether cholesterol succinate derivative according to claim 1, it is characterized in that: utilize poly glycol monomethyl ether cholesterol succinate derivative to liposome, emulsion, nanocapsule (grain) carry out dressing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 00110157 CN1311189A (en) | 2000-03-01 | 2000-03-01 | Synthesis of poly glycol monomethyl ether cholesterol succinate derivative and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 00110157 CN1311189A (en) | 2000-03-01 | 2000-03-01 | Synthesis of poly glycol monomethyl ether cholesterol succinate derivative and its preparation |
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| CN1311189A true CN1311189A (en) | 2001-09-05 |
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| CN 00110157 Pending CN1311189A (en) | 2000-03-01 | 2000-03-01 | Synthesis of poly glycol monomethyl ether cholesterol succinate derivative and its preparation |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102068701A (en) * | 2011-01-18 | 2011-05-25 | 沈阳药科大学 | Application of cleavable polyethylene glycol (PEG) lipid derivative to preparation |
| JP2013515693A (en) * | 2009-12-23 | 2013-05-09 | ノバルティス アーゲー | Lipids, lipid compositions and methods for their use |
| CN104163915A (en) * | 2013-05-16 | 2014-11-26 | 沈阳药科大学 | Cholesterol-poloxamer-cholesterol triblock copolymer, preparation method and application thereof |
| US10342761B2 (en) | 2014-07-16 | 2019-07-09 | Novartis Ag | Method of encapsulating a nucleic acid in a lipid nanoparticle host |
-
2000
- 2000-03-01 CN CN 00110157 patent/CN1311189A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013515693A (en) * | 2009-12-23 | 2013-05-09 | ノバルティス アーゲー | Lipids, lipid compositions and methods for their use |
| US9301923B2 (en) | 2009-12-23 | 2016-04-05 | Novartis Ag | Lipids, lipid compositions, and methods of using them |
| CN102068701A (en) * | 2011-01-18 | 2011-05-25 | 沈阳药科大学 | Application of cleavable polyethylene glycol (PEG) lipid derivative to preparation |
| CN102068701B (en) * | 2011-01-18 | 2012-11-07 | 沈阳药科大学 | Application of cleavable polyethylene glycol (PEG) lipid derivative in preparation |
| CN104163915A (en) * | 2013-05-16 | 2014-11-26 | 沈阳药科大学 | Cholesterol-poloxamer-cholesterol triblock copolymer, preparation method and application thereof |
| CN104163915B (en) * | 2013-05-16 | 2016-09-28 | 沈阳药科大学 | Cholesterol-poloxamer-cholesterol triblock copolymer and its preparation method and application |
| US10342761B2 (en) | 2014-07-16 | 2019-07-09 | Novartis Ag | Method of encapsulating a nucleic acid in a lipid nanoparticle host |
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