CN1939315A - Ganglioside solid lipid nano-particle of monosialic acid tetrahexose and its preparation - Google Patents
Ganglioside solid lipid nano-particle of monosialic acid tetrahexose and its preparation Download PDFInfo
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- CN1939315A CN1939315A CN 200510086534 CN200510086534A CN1939315A CN 1939315 A CN1939315 A CN 1939315A CN 200510086534 CN200510086534 CN 200510086534 CN 200510086534 A CN200510086534 A CN 200510086534A CN 1939315 A CN1939315 A CN 1939315A
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Abstract
A solid liposome nanoparticle of tetrahexose monosialogandlioside (GM1) is proportionally prepared from GM1, medicinal phosphatide, lipoid material and emulsifier. Said lipoid material is chosen from fatty acid, vegetative oil, glyceride of fatty acid, steroid and wax.
Description
Technical field
The present invention relates to a kind of Monostalotetrahexosylgangliside pharmaceutical preparation, relate in particular to a kind of Monostalotetrahexosylgangliside nanometer formulation and preparation method thereof.
Background technology
Monostalotetrahexosylgangliside (Monosialotetrahexosylganglioside, GM1) be to contain sialic TANGSHEN through sphingolipid, be the constituent of mammalian cell membrane, the important physical effect is all played in the differentiation of pair cell, growth, axoplasm transportation and regeneration, its molecule is made up of a hydrophobic ceramide part and a hydrophilic sialyloligosaccharide group, and molecular weight is 1574 dalton.GM1 has the neural reconstruct of promotion, accelerator nerve cytothesis; Promote neuranagenesis, promote neural axon growth and synapse to form; Recover the innervation function, improve nerve conduction, promote the recovery of brain electrical acti and other neuroelectricity physical signs; The protection brain cell membrane promotes functions such as the various enzymatic activity recoveries of cell membrane.
At present, GM1 has been widely used in treating the nerve injury of various traumatic and cardiovascular and cerebrovascular diseases, the delayed ischemic neurological deficits in various chronic disease later stages, brain atrophy, alzheimer disease, dysnoesia etc. clinically.
Exogenous GM1 has fat-soluble, and evidence can be passed blood brain barrier after entering in the body, is gathered in impaired brain district, embeds in the cell membrane, and the function of imitation endogenous GM1 plays a role.Exogenous GM1 generally extract to obtain from Medulla Bovis seu Bubali or Medulla sus domestica, clinical present application be import injection water injection type.Though GM1 can enter cerebral tissue, but prove by pharmacokinetic study to GM1, after exogenous GM1 is expelled in the animal body, accumulate in the liver in a large number, only have 20% to enter internal organs such as brain, spinal cord, kidney, and serum half-life is shorter, entering intravital medicine only has and plays a role on a small quantity, service efficiency is low, clinically in order to reach the common large usage quantity of therapeutic effect.
Chinese patent application 00133077.2 discloses the process of the GM1 of separating and purifying high-purity from animal brain.This method mainly comprises with ORGANIC SOLVENT MIXTURES extracts total ganglioside, the total ganglioside of acid hydrolysis, and ion-exchange chromatography, in four steps such as reversed phase column chromatography, gained GM1 purity is greater than 98%.Because GM1 has been used for clinical treatment central nervous system injury disease.So the preparation method of GM1 of the present invention is suitable for large-scale production.
Chinese patent ZL02111387.4 discloses a kind of method of the GM1 of preparation preparation.The present invention is used in combination ultrafilter membrane isolation technics, Iatrobeads and DEAE Sephadex A-25 column chromatography, or be used in combination ultrafilter membrane isolation technics, Iatrobeads column chromatography, high performance liquid chromatography chromatographic technique, extraction, purifying ganglioside GM1 from Medulla sus domestica, purity reaches more than 95%.The present invention has reduced the link of traditional extraction, purification process, reduce cost and the use amount of harmful organic solvent, kept the amphipathic physicochemical characteristics of Ganglioside GM1 in the preparation process, preparation process is simple, environmental protection, cost degradation, and can improve the curative effect of Ganglioside GM1 preparation.
Chinese patent ZL 01132052.4 invention relates to the preparation method of GM1.The present invention adopts brevibacterium (Brevibacterium sp.) QL-1 strain, by microbial conversion process, other component fermentation decomposition and inversion in the ganglioside extract is become GM1, provides a kind of yield height, the preparation method of the GM1 that cost is low.
Chinese patent application 200410018280.5 discloses the preparation method of a kind of GM1.The fermented bacterium that the present invention prepares GM1 is Pseudomonas in distress (Oerskovia sp.), Oerskovia xanthineolytica (Oerskoviaxanthineolytica), be the wild strain that obtains of screening naturally from soil, can reach 60% the conversion ratio of no gm1 gangliosidosis substrate.Mutagenic strain is handed over Chinese typical culture collection center preservation, and its preserving number is CCTCC M204032.The present invention changes into GM1 by microbial conversion process with other component fermentation in the ganglioside extract, and extraction ratio improves 100% than existing methods.This method is easy and simple to handle, with low cost, for GM1 large-scale production provides possibility.
Solid lipid nanoparticle (solid lipid nanoparticle, SLN) be a kind of novel nanoparticle class drug-supplying system that is developing in recent years, be meant that with biocompatible high-melting-point lipid be the nanosphere that framework material is made, with solid-state natural or synthetic lipoid pharmaceutical pack be wrapped in the lipoid nuclear and make the solid micelle drug delivery system that particle diameter is 50～1000nm.Because framework material is a solid when room temperature, so SLN had both had the physical stability height of polymer nanocomposite ball, drug leakage is few, slow-releasing good, and stable in properties prepares easy characteristics, has the advantage that liposome toxicity is low, be easy to large-scale production again concurrently.High-melting-point lipid commonly used has saturated fatty acid glyceride, stearic acid, mixing lipid etc.SLN is different with the liposome bilayer structure that with phospholipid is main component, is the solid particle that is formed by multiple lipid materials, and it has certain slow releasing function simultaneously, can be used as the carrier of targeting location and controlled-release function.SLN a kind ofly shows the pharmaceutical carrier of good application prospect at pharmaceutical field, and has been applied to clinical.
Chinese patent application 03101154.3 discloses component, preparation technology and the application of GM1 liposome complex preparation.In this invention, described liposome complex is made of in proportion cholesterol, phospholipid and GM1.The GM1 that the experiment proved that the liposome form can significantly improve bioavailability in the body, can enter apace in the cerebral tissue, more effectively treats the acute and chronic central nervous system injury.But further improve bioavailability and the preparation stability of GM1, the targeting that especially improves specific part remains the problem that the GM1 dosage form research need solve.
Summary of the invention
One object of the present invention is to provide a kind of GM1 solid lipid nanoparticle, and it can increase the stability of GM1, improves bioavailability, reduces clinical using dosage.GM1 solid lipid nanoparticle provided by the invention is compared with liposome, has stability preferably.
Another object of the present invention is to provide the preparation method of this GM1 solid lipid nanoparticle.
Also purpose of the present invention is to provide the pharmaceutical preparation that comprises the GM1 solid lipid nanoparticle.
According to one object of the present invention, the invention provides a kind of GM1 solid lipid nanoparticle, it comprises Monostalotetrahexosylgangliside and pharmaceutically useful phospholipid, matrix material, emulsifying agent;
The weight ratio of described Monostalotetrahexosylgangliside, phospholipid, matrix material, emulsifying agent is followed successively by: 0.1～10: 0.2～50: 1～30: 0.5～80;
Described matrix material is for keeping solid-state at normal temperatures, and has the matrix material of biocompatibility.
Described matrix material is high-melting-point and tool biocompatibility, can keep solid-state at normal temperatures.When matrix material is that final prepared nanometer formulation is a nanoemulsions when being the material of liquid phase under a kind of room temperature; When matrix material is that final prepared nanometer formulation is a solid lipid nanoparticle when being the material of solid phase under a kind of room temperature; When matrix material was multiple mixtures of material, final prepared nanometer formulation was a nano structured lipid carrier.
Preferably, described matrix material is one or more of the above fatty acid of 12 carbochains, fatty glyceride, steroid, some wax apoplexy due to endogenous wind.
The above fatty acid of described 12 carbochains can be one or more that are selected from stearic acid, Palmic acid, docosanoic acid, myristic acid etc.; Described fatty glyceride can be one or more that are selected from glyceryl monostearate, three hard acid glyceride etc.; Described steroid can be cholesterol etc., and described wax class can be one or more that are selected from spermol cetylate, Cera Flava etc.
Preferably, the weight ratio of described GM1, phospholipid, matrix material, emulsifying agent is followed successively by: 0.1～10:0.2～20: 1～30: 20～80.
Preferably, the weight ratio of described GM1, phospholipid, matrix material, emulsifying agent is followed successively by: 0.1～8: 0.5～10: 1～15: 1～50.
Preferably, the weight ratio of described GM1, phospholipid, matrix material, emulsifying agent is followed successively by: 0.5～8: 20～50: 2～30: 20～50.
Preferably, the weight ratio of described GM1, phospholipid, matrix material, emulsifying agent is followed successively by: 0.1～10: 0.2～20: 10～30: 50～80.
Preferred, the weight ratio of described GM1, phospholipid, matrix material, emulsifying agent is followed successively by: 0.1～2.5: 1.5～3: 1～5: 3～25, as 0.1: 2: 1: 3,0.1: 1.5: 2: 6,1: 3: 5: 25,2.5: 1.5: 1.3: 20 etc.
Described phospholipid can be one or more that are selected from soybean lecithin, Ovum Gallus domesticus Flavus lecithin, two Laurel phosphatidyl cholines, two myristoyl phosphatidylcholines, dipalmitoyl phosphatidyl choline, distearoyl phosphatidylcholine, dioleoyl phospholipid phatidylcholine, two myristoyl PHOSPHATIDYL ETHANOLAMINE, two palmityl sphingomyelins, 1-stearoyl-2-palmitoylphosphatidyl choline, two palmityl phosphatidyl glycerols, two myristoyl phosphatidic acid etc.
Preferably, described emulsifying agent is a nonionic surfactant, for example tween, span, polyoxyl stearate, poloxamer, sodium dehydrocholate etc.
Preferably, described GM1 solid lipid nano-particle preparation also can further comprise additives.Described additives can be one or more of glycerol, propylene glycol, ethanol, mannitol etc.
The effect of phospholipid, emulsifying agent, additives is to form stable emulsifying agent film with packaging medicine and matrix material, and wherein additives are omissible sometimes; Matrix material is the carrier material as GM1.Additives of the present invention have been meant the pharmaceutical adjunct of Stabilization and/or auxiliary emulsification, also can be called stabilizing agent or coemulsifier, can be used as excipient simultaneously in preparation.
Different ingredients or component, need select for use corresponding matrix material as pharmaceutical carrier, and contain the carrier of different pharmaceutical, need screening suitable phospholipid, emulsifying agent, additives kind, especially the ratio of phospholipid, emulsifying agent, additives and matrix material is to form the basis of stablizing the GM1 solid lipid nanoparticle.
According to another object of the present invention, the invention provides the preparation method of described GM1 solid lipid nanoparticle, it can adopt the conventional method of existing various preparation solid lipid nanoparticles in the prior art, for example solvent emulsion method, the even method of high pressure breast, thin-film ultrasonic dispersion method, high-speed homogenization method, microemulsion dilution method etc.
Described preparation method can comprise the steps: for the solvent emulsion method
GM1, matrix material, phospholipid are dissolved in organic solvent constitute organic facies;
With emulsifying agent formation water soluble in water;
Described organic facies and water are heated to uniform temp respectively, under stirring condition organic facies are injected aqueous phase, form transparent system;
Organic solvent is removed in described transparent system decompression concentrated, mix then in 0～2 ℃ of aqueous phase and stir cooling, form the suspension of solid lipid nanoparticle.
Preferably, described organic solvent is chloroform, methanol etc.
The preferred for preparation prescription is as follows:
Raw material weight percentage ratio
GM1 0.5～8％
Phosphatidase 12 0～50%
Matrix material 2～30%
Emulsifying agent 20～50%
Described preparation method also can comprise the steps: for the even method of high pressure breast
Take by weighing a certain amount of matrix material and emulsifying agent respectively, mix post-heating to 60～80 ℃, obtain liquid oil phase;
A certain amount of GM1 is joined in the liquid oil phase that makes, be stirred to and be even clear state;
Join then in a certain amount of synthermal distilled water, adopt the high pressure dispersing emulsification machine under 200～500 atmospheric pressure,, promptly get GM1 solid lipid nanoparticle suspension after the cooling through 2～5 circulations.
The preferred for preparation prescription is as follows:
Raw material weight percentage ratio
GM1 0.1～10％
Phosphatidase 10 .2～20%
Matrix material 10～30%
Emulsifying agent 50～80%
According to also aspect of the present invention, the invention provides a kind of pharmaceutical preparation for the treatment of nerve injury, it comprises above-mentioned GM1 solid lipid nanoparticle and pharmaceutically acceptable carrier, excipient and/or the protective agent for the treatment of effective dose.
Also can further add other in described pharmaceutical preparation can play synergistic medicine in treatment aspect the nerve injury with GM1, as dihydropyridine calcium ion antagonist etc., to make compound preparation.、
Described pharmaceutical preparation can be freeze-dried powder injection, oral enteric preparation, spray, injection etc., and it can adopt this area conventional formulation method to prepare.
When described pharmaceutical preparation is freeze-dried powder injection, preparation method can for:
To add a certain proportion of excipient through the GM1 solid lipid nanoparticle suspension that one of said method obtains; be sub-packed in 2ml, the 5ml cillin bottle; specification is respectively 20mg, 100mg; place freezer dryer-40 ℃ pre-cooling; set suitable lyophilizing program; observe the state in the freeze-drying process, up to obtaining the white loose sprills.
The excipient that adds in the lyophilized injectable powder is one or more of mannitol, dextran, glycine etc.The unit dose of described lyophilized injectable powder can be 20～100mg.
When described pharmaceutical preparation is the oral enteric preparation, preparation method can for:
To add a certain proportion of protective agent through the GM1 solid lipid nanoparticle suspension that one of said method obtains; place freezer dryer-40 ℃ pre-cooling; set suitable lyophilizing program; observe the state in the freeze-drying process, up to obtaining the white loose sprills, this powder is the intermediate of making the GM1 capsule; according to the assay result; take by weighing an amount of freeze dried GM1 solid lipid nanoparticle, add the certain proportion medical starch, the enteric coated capsule of packing into after mixing sieves.
Prepare the protective agent that adds in the capsular lyophilized powder and be one or more of sucrose, trehalose, maltose, lactose, sorbitol etc.The unit dose of described oral enteric preparation can be 20～100mg, is preferably 20～40mg.
Morphology is investigated the result and is shown that described nanoparticle is spherical in shape, and dispersity is good, and average diameter is 80～140nm.
Envelop rate is investigated the result and is shown that the envelop rate of described nanoparticle is more than 85%.
Outward appearance and stability observing result show that described GM1 solid lipid nanoparticle is the milky suspension, is positioned over room temperature after 6 months, the outward appearance no change; Carry out room temperature high speed centrifugation 5000rpm then, 10min does not have precipitation and lamination and takes place.And Chinese patent application 03101154.3 disclosed GM1 liposome is milky colloid solution or milky white solution, and stability test shows that 4 ℃ of cold preservations are after 3 months, and high speed centrifugation 10min does not have precipitation and layering takes place.Therefore, GM1 solid lipid nanoparticle of the present invention is compared with liposome, has better stability.
With respect to the conventional liposome preparation, GM1 solid lipid nanoparticle envelop rate height provided by the invention, mean diameter is littler, absorb fast, it is fast to see through various biomembranous speed, and the area that medicine plays a role is big, and the time that medicine stops in vivo is long, increase the bioavailability of GM1, reduce clinical medicine dose and toxic and side effects; Can change the physiological disposition of medicine, increase the target that becomes, improve the therapeutic index of medicine nervous tissue; Simultaneously have smaller antigenic, thereby use has safety preferably in vivo for the microgranule in this nano-scale range.
In order to understand essence of the present invention better,, describe in detail but do not limit the present invention below by description to better embodiment of the present invention.
The specific embodiment
The used test material of the present invention if no special instructions, is commercially available purchase product.
The used GM1 of the present invention can be prepared according to disclosed method in the prior art document, perhaps buys from commercial channels to obtain.
The preparation of GM1 solid lipid nanoparticle
[embodiment 1] solvent emulsion method
10mg GM1 and 100mg stearic acid are dissolved in the chloroform, and the 200mg soybean lecithin is dissolved in an amount of ethanol, two parts mix organic facies, heating in water bath to 75 ℃.F-68 is dissolved in distilled water with the 300mg poloxamer, is water, and this water is placed on agitating heating and puts, and adds magneton and stirs and be heated to 75 ℃, keeps constant temperature.With glue head dropper organic facies is dropwise added aqueous phase, constant temperature is stirred to and forms transparent system.Change this system over to the Rotary Evaporators reduction vaporization and remove organic solvent, and be concentrated into 1/2 volume.Concentrated solution is added 0 ℃ of aqueous phase fast, stir cooling 2 hours fast, form the suspension of solid lipid nanoparticle.
[embodiment 2] solvent emulsion method
10mg GM1 and 200mg stearic acid are dissolved in the chloroform, and the 150mg soybean lecithin is dissolved in an amount of ethanol, two parts mix organic facies, heating in water bath to 75 ℃.F-68 is dissolved in distilled water with the 600mg poloxamer, is water, and this water is placed on agitating heating and puts, and adds magneton and stirs and be heated to 75 ℃, keeps constant temperature.With glue head dropper organic facies is dropwise added aqueous phase, constant temperature is stirred to and forms transparent system.Change this system over to the Rotary Evaporators reduction vaporization and remove organic solvent, and be concentrated into 1/2 volume.Concentrated solution is added 0 ℃ of aqueous phase fast, stir cooling 2 hours fast, form the suspension of solid lipid nanoparticle.
The even method of [embodiment 3] high pressure breast
Take by weighing 500mg stearic acid, 300mg soybean lecithin, be heated to 75 ℃, fully stirring and evenly mixing obtains liquid oil phase.Take by weighing 100mg GM1 and join in the liquid oil phase, be stirred well to clarification evenly.Take by weighing 2500mg polyoxyl stearate S-40, add the 100ml distilled water, put that agitating heating puts heating and constant temperature is water in 75 ℃.With glue head dropper 75 ℃ the settled solution that contains GM1 is dropwise joined aqueous phase, adopt magneton to stir simultaneously.Adopt high pressure dispersing emulsification machine emulsifying 5 minutes behind the mix homogeneously, be cooled to the solid lipid nanoparticle that room temperature promptly gets GM1.
The even method of [embodiment 4] high pressure breast
Take by weighing 130mg stearic acid, 150mg soybean lecithin, be heated to 75 ℃, fully stirring and evenly mixing obtains liquid oil phase.Take by weighing 250mg GM1 and join in the liquid oil phase, be stirred well to clarification evenly.Take by weighing 2000mg polyoxyl stearate S-40, add the 100ml distilled water, put that agitating heating puts heating and constant temperature is water in 75 ℃.With glue head dropper 75 ℃ the settled solution that contains GM1 is dropwise joined aqueous phase, adopt magneton to stir simultaneously.Adopt high pressure dispersing emulsification machine emulsifying 5 minutes behind the mix homogeneously, be cooled to the solid lipid nanoparticle that room temperature promptly gets GM1.
The preparation of GM1 solid lipid nano-particle preparation
[embodiment 5] freeze-dried powder injection
It is 3% that the mannitol that will add certain mass through the GM1 solid lipid nanoparticle suspension 1000ml that embodiment 1,2,3 or 4 obtains makes its final concentration; be sub-packed in 2ml, the 5ml cillin bottle; specification is respectively 20mg, 100mg; place freezer dryer-40 ℃ pre-cooling; set the lyophilizing program; observe the state in the freeze-drying process, up to obtaining the white loose sprills.
[embodiment 6] oral enteric preparation
To add 30g sucrose through embodiment 1,2,3 or the 4 GM1 solid lipid nanoparticle suspension 1000ml that obtain; place freezer dryer-40 ℃ pre-cooling; set suitable lyophilizing program; observe the state in the freeze-drying process; up to obtaining the white loose sprills; this powder is the intermediate of making the GM1 capsule; according to the assay result; take by weighing an amount of freeze dried GM1 solid lipid nanoparticle; it is 5% that the adding medical starch makes its final concentration; mixing is crossed the enteric coated capsule of packing into behind 100 mesh sieves, and specification is respectively: 20mg, 40mg.
GM1 solid lipid nanoparticle character is investigated
[embodiment 7] nanoparticle outward appearance and stability observing
The GM1 solid lipid nanoparticle that makes is the milky suspension.Each 10 parts in GM1 solid lipid nanoparticles that the embodiment 1,2,3 or 4 that learns from else's experience respectively obtains and barren SLN suspension sample, wherein 5 parts are positioned over room temperature, other 5 parts are positioned in 4 ℃ of refrigerators, place and observe its outward appearance in 24 hours, 1 month, 3 months, 6 months, find no cosmetic variation; Carry out room temperature high speed centrifugation 4000rpm, 5000rpm, 10000rpm, the centrifugal 10min of 15000rpm then, do not have precipitation and lamination and take place.
[embodiment 8] nanoparticle morphology is investigated
The GM1 solid lipid nanoparticle suspension that the embodiment 1,2,3 or 4 that learns from else's experience respectively makes is an amount of, adds the distilled water dilution, drips on the copper mesh that covers carbon film the Sodium phosphotungstate liquid negative staining with 2%, photo under transmission electron microscope then.Photo shows that nanoparticle is spherical in shape, and dispersity is good, and arithmetic mean diameter is respectively: 108nm (embodiment 1), 102nm (embodiment 2), 90nm (embodiment 3), 95nm (embodiment 4).
[embodiment 9] nanoparticle envelop rate is investigated
The GM1 solid lipid nanoparticle suspension that the embodiment 1,2,3 or 4 that learns from else's experience respectively makes is put in the centrifuge tube in right amount, and the centrifugal 15min of 100000rpm draws supernatant, supplies volume with distilled water, and the centrifugal 15min of 100000rpm draws supernatant once more.Merge supernatant twice, measure wherein GM1 content, be calculated as follows envelop rate and be respectively 87.31% (embodiment 1) and 92.28% (embodiment 2), 88.66% (embodiment 3) and 89.02% (embodiment 4) with the HPLC method
More than the description of better embodiment of the present invention is not limited the present invention, those skilled in the art can make various changes or distortion according to the present invention, only otherwise break away from spirit of the present invention, all should belong to the scope of claims of the present invention.
Claims (12)
1, a kind of Monostalotetrahexosylgangliside solid lipid nanoparticle is characterized in that,
Comprise Monostalotetrahexosylgangliside and pharmaceutically useful phospholipid, matrix material, emulsifying agent;
The weight ratio of described Monostalotetrahexosylgangliside, phospholipid, matrix material, emulsifying agent is followed successively by: 0.1～10: 0.2～50: 1～30: 0.5～80;
Described matrix material is for keeping solid-state at normal temperatures, and has the matrix material of biocompatibility.
2, the described solid lipid nanoparticle of claim 1 is characterized in that, the weight ratio of described Monostalotetrahexosylgangliside, phospholipid, matrix material, emulsifying agent is followed successively by: 0.1～10: 0.2～20: 1～30: 20～80.
3, the described solid lipid nanoparticle of claim 1 is characterized in that, the weight ratio of described Monostalotetrahexosylgangliside, phospholipid, matrix material, emulsifying agent is followed successively by: 0.1～8: 0.5～10: 1～15: 1～50.
4, the described solid lipid nanoparticle of claim 1 is characterized in that, described solid lipid nanoparticle further comprises additives, and described additives are to be selected from glycerol, propylene glycol, ethanol, the mannitol one or more.
5, the described solid lipid nanoparticle of claim 1, it is characterized in that, described matrix material for be selected from stearic acid, Palmic acid, docosanoic acid, myristic acid, glyceryl monostearate, three hard acid glyceride, cholesterol, spermol cetylate, mellisic one or more.
6, the described solid lipid nanoparticle of claim 1, it is characterized in that described phospholipid is to be selected from one or more of soybean lecithin, Ovum Gallus domesticus Flavus lecithin, two Laurel phosphatidyl cholines, two myristoyl phosphatidylcholines, dipalmitoyl phosphatidyl choline, distearoyl phosphatidylcholine, dioleoyl phospholipid phatidylcholine, two myristoyl PHOSPHATIDYL ETHANOLAMINE, two palmityl sphingomyelins, 1-stearoyl-2-palmitoylphosphatidyl choline, two palmityl phosphatidyl glycerols, two myristoyl phosphatidic acid.
7, the described solid lipid nanoparticle of claim 1 is characterized in that, described emulsifying agent is a nonionic surfactant.
8, the preparation method of the described solid lipid nanoparticle of claim 1 comprises the steps:
Monostalotetrahexosylgangliside, matrix material, phospholipid are dissolved in organic solvent constitute organic facies;
With emulsifying agent formation water soluble in water;
Described organic facies and water are heated to uniform temp respectively, under stirring condition organic facies are injected aqueous phase, form transparent system;
Organic solvent is removed in described transparent system decompression concentrated, mix then in 0～2 ℃ of aqueous phase and stir cooling, form the suspension of solid lipid nanoparticle.
9, the preparation method of the described solid lipid nanoparticle of claim 1 comprises the steps:
Take by weighing matrix material and emulsifying agent respectively, mix post-heating to 60～80 ℃, obtain liquid oil phase;
Monostalotetrahexosylgangliside is joined in the liquid oil phase that makes, be stirred to and be even clear state;
Join then in a certain amount of synthermal distilled water, adopt the high pressure dispersing emulsification machine under 200～500 atmospheric pressure,, promptly get GM1 solid lipid nanoparticle suspension after the cooling through 2～5 circulations.
10, a kind of pharmaceutical preparation for the treatment of nerve injury is characterized in that, comprises the described Monostalotetrahexosylgangliside solid lipid nanoparticle of claim 1 and pharmaceutically acceptable carrier, excipient and/or protective agent.
11, the described pharmaceutical preparation of claim 10 is characterized in that, described pharmaceutical preparation is freeze-dried powder injection or oral enteric preparation.
12, the described pharmaceutical preparation of claim 11 is characterized in that,
When pharmaceutical preparation was freeze-dried powder injection, described excipient was one or more in mannitol, dextran, the glycine;
When pharmaceutical preparation was the oral enteric preparation, described protective agent was one or more in sucrose, trehalose, maltose, lactose, the sorbitol.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101700230B (en) * | 2009-11-06 | 2012-02-01 | 山东大学 | Monosialote rahexosylganglioside microsphere and preparing method thereof |
| CN102366408A (en) * | 2011-09-14 | 2012-03-07 | 海南灵康制药有限公司 | Monosialotetrahexosyl ganglioside sodium liposome injection |
| CN106361718A (en) * | 2016-10-14 | 2017-02-01 | 珠海赛隆药业股份有限公司 | Colon-specific bioadhesive tablet containing monosialotetrahexosyl ganglioside sodium |
| CN106619545A (en) * | 2016-10-14 | 2017-05-10 | 珠海赛隆药业股份有限公司 | Monosialotetrahexosyl ganglioside sodium oral preparation stabilized in gastrointestinal tract and preparation method |
| CN107115321A (en) * | 2017-04-16 | 2017-09-01 | 新疆维吾尔自治区药物研究所 | Creeping thistle glycosides solid lipid nanoparticle and preparation method thereof |
| CN110755405A (en) * | 2019-10-25 | 2020-02-07 | 南昌大学 | Application of ganglioside GM3 with targeting property in preparing medicine for treating atherosclerosis |
-
2005
- 2005-09-28 CN CN 200510086534 patent/CN1939315A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101700230B (en) * | 2009-11-06 | 2012-02-01 | 山东大学 | Monosialote rahexosylganglioside microsphere and preparing method thereof |
| CN102366408A (en) * | 2011-09-14 | 2012-03-07 | 海南灵康制药有限公司 | Monosialotetrahexosyl ganglioside sodium liposome injection |
| CN106361718A (en) * | 2016-10-14 | 2017-02-01 | 珠海赛隆药业股份有限公司 | Colon-specific bioadhesive tablet containing monosialotetrahexosyl ganglioside sodium |
| CN106619545A (en) * | 2016-10-14 | 2017-05-10 | 珠海赛隆药业股份有限公司 | Monosialotetrahexosyl ganglioside sodium oral preparation stabilized in gastrointestinal tract and preparation method |
| CN106361718B (en) * | 2016-10-14 | 2019-01-25 | 珠海赛隆药业股份有限公司 | The colon target biology adhesion tablet of monosialotetrahexose ganglioside sodium |
| CN107115321A (en) * | 2017-04-16 | 2017-09-01 | 新疆维吾尔自治区药物研究所 | Creeping thistle glycosides solid lipid nanoparticle and preparation method thereof |
| CN110755405A (en) * | 2019-10-25 | 2020-02-07 | 南昌大学 | Application of ganglioside GM3 with targeting property in preparing medicine for treating atherosclerosis |
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