CN1493361A - Lipid nano-particle of glyceride behenate and its preparation method - Google Patents
Lipid nano-particle of glyceride behenate and its preparation method Download PDFInfo
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- CN1493361A CN1493361A CNA031506658A CN03150665A CN1493361A CN 1493361 A CN1493361 A CN 1493361A CN A031506658 A CNA031506658 A CN A031506658A CN 03150665 A CN03150665 A CN 03150665A CN 1493361 A CN1493361 A CN 1493361A
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- rikemal
- lipid nanoparticle
- aqueous dispersion
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Abstract
A lipid nanoparticle (size 100-200nm) of glyceride behenate is prepared by the combination of solvent-fusion method and high-pressure emulsifying, where the mixture of ATO and soybean phosphatide is used as carrier and the poloxamer 188 is used as suspending aid to make the medicine is wrapped by lipid nanoparticle to form uniform dispersed system in water. Its advantages are high biological utilization rate and stable absorptivity.
Description
Technical field
The present invention relates to a kind of pharmaceutical carrier, particularly a kind of Rikemal B 200 lipid nanoparticle that is used for fat-soluble medicine and preparation method thereof.
Background technology
In the pharmaceutical preparation field, fat-soluble medicine often exists administration artifact availability to cross low and absorbs shortcoming such as instability, and this has greatly limited the application clinically of this type of medicine.Developing rapidly and the application in pharmaceutics of nanotechnology significantly improved the deficiency after the fat-soluble medicine administration.
Usually, the size of nanoparticle is defined between 1～1000 nanometer in the pharmaceutics, mainly comprises nano-carrier and Nano medication two classes.Nano-carrier means medicine is stated from the different substrates material nano grain with the method bag of inlaying or adsorbing, as nanometer liposome, polymer nanocomposite capsule, nanosphere, polymer micelle etc.; Nano medication then is meant the nanoparticle that directly material medicine is processed into.
Lipid nanoparticle is earlier 1990s to rise one of nano-carrier, being solid-state lipid materials under the room temperature that it adopts and physiological compatibility is good is carrier, it is with the advantage of polymer nanoparticle such as polylactic acid (PLA) nanoparticle, as the release that can control medicine, avoid drug leakage etc., simultaneously, preparation method simple (as adopting the high pressure dispersing emulsification machine) is suitable for suitability for industrialized production, mainly is applicable to fat-soluble medicine.Lipid nanoparticle can quiet notes administration or oral administration, reaches the purpose that improves bioavailability or targeting.
Since lipid nanoparticle be a kind of have improve fat-soluble medicine administration artifact availability and absorbefacient pharmaceutical carrier, therefore, research and develop new lipid nanoparticle, become a focus in pharmaceutics field, also be that pharmaceutical field institute ten minutes is expected.
Summary of the invention
The technical issues that need to address of the present invention are the lipid nanoparticles that disclose a kind of Rikemal B 200, and it can significantly improve the absorption of fat-soluble medicine, and has passive targeting, to satisfy the needs of relevant department;
Another technical issues that need to address of the present invention provide the preparation method of the lipid nanoparticle of above-mentioned Rikemal B 200, so that suitability for industrialized production.
The lipid nanoparticle of Rikemal B 200 of the present invention is a kind of compositions, and its component and weight percent content comprise:
Rikemal B 200 50～60%
Soybean phospholipid 20～30%
Poloxamer (poloxamer) 188 20～30%
Particle diameter is between 100～200nm.
Said Rikemal B 200, its English trade name are compritol 888 ATO, are called for short ATO, its chemistry Rikemal B 200 by name.
Can adopt the commercially available prod, be main carrier material;
Said soybean phospholipid is a kind of lecithin that extracts from Semen sojae atricolor, can adopt the commercially available prod, and it mainly acts on is the affinity that increases the medicine lipid fused solution, is stabilizing agent of the present invention;
Said poloxamer188 is for mixing suspending agent, the commercial goods is called poloxamer 188, the chemical name of its standard is a polyoxyethylene poly-oxygen propylene aether, it is poly-(oxygen ethylene) a block copolymer of poly-(oxypropylene) b-of poly-(oxygen ethylene) a-of α-hydrogen-ω-hydroxyl, the model that can adopt Pu, Shanghai power film preparation adjuvant scientific and technological cooperation company to produce is Pluronic F68, and its molecular formula is: HO (C
2H
4O)
a(C
3H
6O)
b(C
2H
4O)
aH.
The lipid nanoparticle of Rikemal B 200 of the present invention, preferred ingredients and weight percent content comprise:
Rikemal B 200 30～50%
Soybean phospholipid 20～40%
poloxamer188 20～40％
The invention still further relates to the aqueous dispersion that contains above-mentioned composition, wherein, the content of said compositions is: 30～70mg/ml, preferred 50mg/ml.
The preparation method of the lipid nanoparticle of Rikemal B 200 of the present invention comprises the steps:
(1) said ATO, soybean phospholipid are dissolved in the organic solvent of 60～90 ℃ of heat, preferred 85 ℃, continue heating, fling to organic solvent, in-10～0 ℃ freezing 1～5 hour;
Said organic solvent comprises dehydrated alcohol.
(2) poloxamer188 is scattered in the water, it is standby to form uniform water, and preferred concentration is 1～100mg/ml;
(3) with the water of the solid of step (1) preparation gained and step (2) gained at 0～10 ℃, preferred 3～5 ℃ of mixing, grinding to particle diameter 100 μ m, form uniform microgranule aqueous dispersion;
(4) with aqueous dispersion high pressure homogenize under the pressure of 700～1800bar of step (3) gained, be chilled to room temperature rapidly, can obtain to contain the aqueous dispersion of the lipid nanoparticle of 100～200nm.
(5) aqueous dispersion lyophilization under-25～-30 ℃ condition that step (4) is obtained can obtain lipid nanoparticle.
The lipid nanoparticle of Rikemal B 200 of the present invention can carry fat-soluble medicine with the method bag of inlaying, the finished product that obtains can directly apply to clinical, perhaps adopts art-recognized method to be prepared into tablet, pill, capsule, soft capsule and powder etc. and takes.The present invention is the carrier of the fat-soluble medicine medicine of 100～200nm nanoparticle, behind the medicine carrying, has passive targeting, after entering blood circulation, usually absorbed by mononuclear phagocyte system rapidly and from blood flow, remove, thereby in the organ that the distribution that makes its medicine be enriched in reticuloendothelial system is enriched, as liver, spleen etc.In addition, by methods such as control nanoparticle particle diameter or change nanoparticle surfaces characteristic, can make medicine be enriched in organs such as pulmonary and brain, improve the bioavailability after the fat-soluble medicine administration greatly and absorbed stability, significantly improve the deficiency after the fat-soluble medicine administration.
Description of drawings
Fig. 1 is the electromicroscopic photograph of the lipid nanoparticle of Rikemal B 200 of the present invention.
Fig. 2 is particle size distribution figure.
The specific embodiment
Embodiment 1
(1) get 2.0g ATO, 1.Sg soybean phospholipid, in 85 ℃ water-bath, heat, it is dissolved in the 15ml dehydrated alcohol, continue heating, fling to organic solvent after, in 0 ℃ freezing 2 hours rapidly, standby;
(2) poloxamer188 that gets 1.5g is scattered in 4 ℃ the 100ml water, and it is standby to form uniform water;
(3) solid of (1) preparation gained and 4 ℃ the water of (2) gained are mixed, grind (mortar, homogenizer), to particle diameter 100 μ m, (cross 180 mesh sieves), form uniform microgranule aqueous dispersion;
(4) with the aqueous dispersion of (3) gained pressure (the Niro Soavi high pressure homogenization machine that adopts GEA company to produce) high pressure homogenization cycles 5 times (3 minutes) at room temperature, 700bar, after aqueous dispersion is chilled to 10 ℃ with ice bath, rapid 5 times of recirculation (3 minutes), be chilled to room temperature rapidly, can make the aqueous dispersion that the 100ml particle diameter is the lipid nanoparticle of 100～200nm;
(5) aqueous dispersion with step (4) adopts conventional method lyophilization, can obtain lipid nanoparticle.Its electromicroscopic photograph is seen Fig. 1, and its particle size distribution is seen Fig. 2.
Embodiment 2
Adopt embodiment 1 identical method to be prepared, the addition of ATO is that 1.0g, soybean phospholipid are 2.5g, and poloxamer188 is 1.5g.
Embodiment 3
Adopt embodiment 1 identical method to be prepared, the addition of ATO is that 3.0g, soybean phospholipid are 0.5g, and poloxamer188 is 1.5g.
Embodiment 4
Adopt embodiment 1 identical method to be prepared, the addition of ATO is that 2.0g, soybean phospholipid are 1.0g, and poloxamer188 is 2.0g.
Embodiment 5
Adopt the identical method of embodiment 1, adding 120mg schizandrin in step (1) can obtain to be loaded with the lipid nanoparticle of the Rikemal B 200 of fat-soluble medicine.
Claims (9)
1. the lipid nanoparticle of a Rikemal B 200 is characterized in that, component and weight percent content comprise:
Rikemal B 200 20～60%
Soybean phospholipid 20～30%
poloxamer188 20～30％。
2. the lipid nanoparticle of Rikemal B 200 according to claim 1 is characterized in that, preferred ingredients and weight percent content comprise:
Rikemal B 200 20～60%
Soybean phospholipid 20～30%
poloxamer188 20～30％。
3. aqueous dispersion that contains the lipid nanoparticle of claim 1 or 2 described Rikemal B 200s.
4. the aqueous dispersion of the lipid nanoparticle of Rikemal B 200 according to claim 3 is characterized in that, wherein, the content of the lipid nanoparticle of Rikemal B 200 is 30～70mg/ml.
5. the aqueous dispersion preparation method of the lipid nanoparticle of Rikemal B 200 according to claim 3 is characterized in that, comprises the steps:
(1) said Rikemal B 200, soybean phospholipid are dissolved in the organic solvent, organic solvent is flung in heating, and is freezing;
(2) poloxamer188 is scattered in the water, it is standby to form uniform water, and preferred concentration is 1～100mg/ml;
(3) with the water of the solid of step (1) preparation gained and step (2) gained mixing, grinding, form uniform microgranule aqueous dispersion;
(4) with the aqueous dispersion of step (3) gained homogenizing under pressure, be chilled to room temperature, can obtain to contain the aqueous dispersion of the lipid nanoparticle of 100～200nm at 700～1800bar.
6. method according to claim 5 is characterized in that, said Rikemal B 200, soybean phospholipid are dissolved in the organic solvent, and organic solvent is flung in heating, and is freezing in-10～0 ℃.
7. method according to claim 5 is characterized in that said organic solvent comprises dehydrated alcohol.
8. method according to claim 5 is characterized in that, poloxamer188 is scattered in the water to form concentration be the uniform water of 1～100mg/ml.
9. method according to claim 5 is characterized in that, after the aqueous dispersion homogenize with step (3) gained, is chilled to room temperature rapidly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031506658A CN1493361A (en) | 2003-08-29 | 2003-08-29 | Lipid nano-particle of glyceride behenate and its preparation method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031506658A CN1493361A (en) | 2003-08-29 | 2003-08-29 | Lipid nano-particle of glyceride behenate and its preparation method |
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| Publication Number | Publication Date |
|---|---|
| CN1493361A true CN1493361A (en) | 2004-05-05 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA031506658A Pending CN1493361A (en) | 2003-08-29 | 2003-08-29 | Lipid nano-particle of glyceride behenate and its preparation method |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1771911B (en) * | 2005-11-10 | 2010-05-12 | 浙江大学 | Re-dispersible nanometer particle of insoluble medicine and its preparation |
| WO2011086574A3 (en) * | 2010-01-18 | 2011-11-10 | Concept Medical Research Private Limited | Formulations of nano-carriers and methods of preparing the same |
-
2003
- 2003-08-29 CN CNA031506658A patent/CN1493361A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1771911B (en) * | 2005-11-10 | 2010-05-12 | 浙江大学 | Re-dispersible nanometer particle of insoluble medicine and its preparation |
| WO2011086574A3 (en) * | 2010-01-18 | 2011-11-10 | Concept Medical Research Private Limited | Formulations of nano-carriers and methods of preparing the same |
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