CN101584663A - Novel delivery system of Duoxitasai lipidosome for injection and preparation method thereof - Google Patents
Novel delivery system of Duoxitasai lipidosome for injection and preparation method thereof Download PDFInfo
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- CN101584663A CN101584663A CNA2008100976615A CN200810097661A CN101584663A CN 101584663 A CN101584663 A CN 101584663A CN A2008100976615 A CNA2008100976615 A CN A2008100976615A CN 200810097661 A CN200810097661 A CN 200810097661A CN 101584663 A CN101584663 A CN 101584663A
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Abstract
The invention relates to a novel delivery system of Duoxitasai lipidosome for injection and a preparation method thereof. The delivery system comprises Duoxitasai, phospholipid membrane materials, membrane stabilizing materials and pharmaceutically acceptable assistant agent, which respectively contains curative dose, wherein the membrane stabilizing material comprises ion-type amphiphilic substances, and the weight ratio of the Duoxitasai, the phospholipid membrane materials and the membrane stabilizing materials is 1:5:0.2-1:50:50. The preparation method comprises the following steps: (a) emulsification, i.e. dissolving the Duoxitasai, the phospholipid membrane materials and the membrane stabilizing materials in an organic solvent, then pouring the mixture into a water phase, and emulsifying the mixture into emulsion with an emulsifying apparatus; and (b) volatilization and dispersion, i.e. removing the organic solvent by volatilization, and then packaging the Duoxitasai in lipidosomes. The lipidosome prepared according to the method has small mean grain sizes, narrow distribution, high packaging rate, great drug loading amount and good reproduction quality and is suitable for the scaling-up of the industrial production.
Description
Technical field
The invention belongs to medical technical field, relate to a kind of used for intravenous injection docetaxel liposome drug-supplying system and novel preparation method.
Background technology
Liposome (liposome) or title lipoid bead, liquid crystal microcapsule are a kind of target medicine carriers.1971, people such as Britain Rymen began used as pharmaceutical carrier.Can have a liking for behind the cytophagy carrier and decomposed by enzyme and discharge medicine by infiltration or by huge, thereby play a role.It has the class cellularity, enter the autoimmune function that is mainly activated body in the animal body by reticuloendothelial system phagocytic, and the interior distribution of the body that changes encapsulated medicine, drug main will be put aside in histoorgans such as liver, spleen, lung and bone marrow, thereby improve the therapeutic index of medicine, reduce the toxicity of the therapeutic dose and the reduction medicine of medicine.
Liposome enters can be by the human body reticuloendothelial system phagocytic behind the human body, and main targeting contains the abundant organ of reticuloendothelial system liver, spleen etc., and is poor to other position targeting, exists easily to be caused seepage by destruction such as intravital albumen and problem such as affect the treatment.
When liposome was used the hydrophilic polymer coating of bonding, its physics, chemistry, biological stability all improved greatly.In this technology, contain polyglycol derivatization phospholipid (PEG-DSPE) in the composition of liposome, its effect be stop plasma protein absorption promptly conditioningization in the surface of liposome, thereby reduce the picked-up of mononuclear phagocyte, prolong the time of blood circulation, make liposome can effectively arrive diseased region, therefore can better bring into play curative effect, alleviate toxicity.
Docetaxel (Docetaxol) is the semisynthetic paclitaxel derivant of chemical compound that extracts in the needle by European yew, by the exploitation of Rhone-Poulenc Rorer company and the listing of France.Its mechanism of action and taxanes seemingly are assembled into microtubule by promoting the microtubule dimer, prevent the multimerization process simultaneously and make microtubule stable, and the retardance cell is in G2 and M phase, and suppressing cell further divides, thus the mitosis of anticancer and propagation.The Docetaxel antitumor spectra is wide, antitumor action is strong, and all more outstanding to the curative effect of intractable breast carcinoma, nonsmall-cell lung cancer etc., clinical practice has a high potential.
Docetaxel is insoluble in water, and fat-soluble also little, and this has just influenced its clinical practice greatly.At present the listing kind is a docetaxel injection only, is that to make solvent with tween 80 and ethanol formulated, easily causes more untoward reaction, as stimulation, haemolysis, anaphylaxis, neurotoxicity, Cardiovascular Toxicity or the like.And to use Claritin before using, bring great inconvenience and misery to the patient.
Chinese patent CN1931157A discloses a kind of can the injection or oral docetaxel liposome and solid preparation thereof.It is the underlying membrane material with phospholipid, cholesterol, adds suitable additives, adopts several different methods to prepare various types of liposomees, and the liposome particle diameter that makes is little, the envelop rate height, and good stability and toxic and side effects are low, have reached the clinical injection requirement substantially.But the liposome concentration of preparation is lower, needs the bigger container of volume during production, and the cost height is not suitable for heavy dose of administration.
Chinese patent CN1846692A and CN101057831A disclose a kind of docetaxel long-circulating liposome and preparation method thereof.It is a raw material with soybean phospholipid, hydrogenated soya phosphatide, cholesterol lengthening recycled material polyglycol derivatization phospholipid and pH regulator agent oleic acid etc., has prepared long circulating liposomes with film dispersion method, has improved the body-internal-circulation time of medicine.But the liposome drug loading of preparation is low, and uses long recycled material polyglycol derivatization phospholipid to make its cost too high because of a large amount of, is difficult to realize suitability for industrialized production.
Because the water insoluble and fat-soluble also not high characteristics of docetaxel.Make this type of medicine when being prepared into liposome, have that drug loading is low, when adding water after the problem of poor stability, the especially lyophilizing and rebuilding, medicine is easily separated out crystallization.This mainly is because fat-soluble medicine is when preparing liposome, medicine often is encapsulated on the film of liposome, and if medicine fat-soluble higher, the just easy high and metastable liposome of preparation drug loading, as Alprostadil, liposomees such as amycin are all more stable.For docetaxel, fat-soluble relatively poor because of it, and insoluble in the water, when adopting routine prescription and preparation method, exist drug loading low, make the unsettled shortcoming of liposome.Ideal liposome pattern is that medicine is wrapped in the liposome with crystallite or other insoluble state, thereby realize higher drug loading, but because docetaxel liposome also exists and easily separates out crystalline problem, therefore desire to make the relatively stable need of liposome of preparation that the material that forms liposome membrane is carried out deep improvement, itself and drug affinity are increased, stop medicine to pass, thereby improve the stability of liposome.
Summary of the invention
Based on the problems referred to above, the inventor adds the new membrane stabilizing material on recipe design, for example cholesterol sulfate sodium, dodecyl sodium sulfate plasma type amphiphilic substance; On preparation technology, proposition emulsifying is waved arching pushing and is prepared docetaxel liposome.
An object of the present invention is to provide a kind of novel delivery system of Duoxitasai lipidosome for injection and freeze-dried preparation thereof, described docetaxel liposome drug-supplying system is little to injection site irritation, circulation time is long and have a targeting in vivo.
Another object of the present invention provides a kind of new preparation method that is used for delivery system of Duoxitasai lipidosome for injection.Redissolve with water for injection when preparation of the present invention uses, available 5% glucose injection further disperses, and is used for intravenous injection.
According to the present invention, described docetaxel liposome drug-supplying system comprises docetaxel, immobilized artificial membrane material, film stabilizing material and the pharmaceutically acceptable adjuvant for the treatment of effective dose, wherein, described film stabilizing material comprises the ion-type amphiphilic substance, and the weight ratio of described docetaxel and described immobilized artificial membrane material and described film stabilizing material is 1: 5: 0.2～1: 50: 50.Described ion-type amphiphilic substance can be cholesterol sulfate sodium, cholesterol sodium phosphate, cholesterol sodium sulfonate, dodecyl sodium sulfate or its mixture, especially the adding of this new membrane stabilizing material of cholesterol sulfate sodium, fundamentally improve the quality of liposome, made its drug loading, envelop rate, particle size distribution and stability obviously be better than bibliographical information.
According to the present invention, new membrane stabilizing material cholesterol sulfate sodium is to be derived behind Sulfation by cholesterol, has overcome the weak shortcoming of cholesterol hydrophilic, has kept the strong advantage of its lipotropy, the composition of liposome membrane can be participated in, the function of the flowability of cholesterol regulation film can be played; Can form one deck charge layer at surface of liposome again, increase the repulsion between the liposome microgranule, avoid liposome to merge the effect of the liposome of playing stably.
According to the present invention, described immobilized artificial membrane material can be egg yolk lecithin, soybean lecithin, phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, hydrolecithin or its mixture of purity more than 80%, and preferably soya lecithin.
According to the present invention, described film stabilizing material comprises long circulation adjuvant.Described long circulation adjuvant be polyglycol derivatization phospholipid (for example, PEG2000-DSPE).In the structure of described polyglycol derivatization phospholipid, phospholipid moiety is selected from one or more in the group of being made up of stearic acid PHOSPHATIDYL ETHANOLAMINE, cholesterol succinate, PHOSPHATIDYL ETHANOLAMINE, phosphatidylcholine, phosphatidylinositols, phosphatidyl silk amino acid, diphosphatidylglycerol and the sour phospholipid that contracts, and the molecular weight of Polyethylene Glycol is 200～20000, preferred 500～10000, more preferably 1000～5000, most preferably 2000.
According to the present invention, described film stabilizing material comprises the fish oil material.Described fish oil material is selected from one or more in the group of being made up of fish oil, fish oil ethyl ester, EPA-E and docosahexaenoic acid ethyl; And the weight ratio of described fish oil material and described phospholipid is 1: 1～1: 50, is preferably 1: 4.5～1: 12.5.
According to the present invention, described film stabilizing material is selected from fish oil material, polyglycol derivatization phospholipid, cholesterol sulfate sodium, cholesterol sodium phosphate, cholesterol sodium sulfonate, dodecyl sodium sulfate, and it can use separately, also can unite use.According to the present invention, in described delivery system of Duoxitasai lipidosome for injection, described ion-type amphiphilic substance (cholesterol sulfate sodium, cholesterol sodium phosphate, cholesterol sodium sulfonate, dodecyl sodium sulfate or its mixture) is 0.2: 1～10: 1 with the weight ratio of described docetaxel, is preferably 1: 1～1.3: 1.
According to the present invention, also can further comprise the acceptable adjuvant of pharmacy, for example antioxidant, pH value regulator and freeze drying protectant.
According to the present invention, described pH value regulator can suppress or stop the release of medicine from liposome, the pH value of this moment is not the pH value of drug solubility minimum, but under the prerequisite that guarantees envelop rate, suitably improve the dissolubility of medicine, to strengthen the chemical potential of medicine at aqueous phase, balance is moved to oil phase, the buffer of this pH value also is known as " discharging inhibition type buffer ".Sort buffer liquid has very strong buffer capacity, and the energy maintenance system reaches the pH value of expectation.Preferred buffer is the Tris-HCl buffer of pH value between 4.0～9.0, and most preferably pH value is between 7.2～7.8.
The prepared liposome of the present invention can comprise freeze drying protectant; described freeze drying protectant comprises sugar and polyhydric alcohol; freeze drying protectant generally is a hydrophilic compounds; mainly contain saccharide, carbamide, dextran, albumin or polyvinyl alcohol etc.; can prevent the rearrangement of lipid in the liposome, most of principal agent still is wrapped in the liposome after the lyophilizing like this.Freeze drying protectant generally is strong hydrogen bond acceptor, has representational spatial chemistry feature, helps preventing the intramolecularly spatial distribution of composition in the duplicature.Saccharide mainly comprises mannose, galactose, trehalose, maltose, sucrose, lactose and glucose etc., most preferably is lactose; Based on docetaxel liposome drug-supplying system gross weight, its consumption most preferably is 10% between 5%～20%.In the polyalcohols, relatively more commonly used is mannitol and sorbitol.The present invention is surprised to find when using sorbitol or mannitol separately, can not successfully keep the particle diameter of liposome.Mannitol can with any collaborative use of mentioning saccharide, most preferred combinations is and glucose most preferred ratio 2: 3 (w/w).
According to the present invention, described liposome administration system can be the preparation of lyophilized powder form.Wherein, particle diameter is 10nm～1000nm, is preferably 10nm～300nm; The weight ratio of docetaxel and immobilized artificial membrane material is that medicine fat weight ratio is 1: 50～1: 5, is preferably 1: 8.5～1: 7.0; Long circulation adjuvant and immobilized artificial membrane material weight ratio are 1: 100～20: 100, are preferably 3: 100～7: 100; The preparation ultimate density that reaches docetaxel is 1～10mg/mL, is preferably 3～5mg/mL.
According to the present invention, adopt emulsifying to wave arching pushing first and prepare liposome, described method comprises: a) emulsifying step: docetaxel, liposome membrane material and film stabilizing material are dissolved in the organic solvent, pour aqueous phase then into, form Emulsion through emulsifying device emulsifying; And b) wave stroll suddenly: waving looses removes organic solvent, and entrapped drug is in liposome then.Organic solvent of stating for example can be dichloromethane, chloroform, ether or ethyl acetate etc. not miscible and boiling point be relatively low with water and be easy to wave diffusing organic solvent.Wherein, preferred dichloromethane.Preferably in described emulsifying step, can be by ultrasonic, homogenizing, nanometer machine Processing of Preparation Emulsion.In described emulsifying step, described Emulsion is the O/W Emulsion that forms through suitable emulsifying device emulsifying, because the film material mostly is two parent's property materials greatly, so mainly is present in after the emulsifying on the interfacial film of Emulsion, wave loose remove organic solvent after, medicine can effectively be encapsulated in the liposome.The characteristics of this method are, adopt emulsifying and wave two step process that loose, and method is simple and reliable, favorable reproducibility.Liposome mean diameter little (between 50～150nm), the narrow diameter distribution (200nm) of preparation, envelop rate height (95%), drug loading height (12%), stability also significantly improves.
According to the present invention, described medicine can also be paclitaxel, capecitabine, doxorubicin, pirarubicin, gemcitabine, etoposide, Vinorebine and vinorelbine.
Liposome storage form of the present invention is the lyophilized powder form.Institute's goods are color and luster homogeneous, the full block of outward appearance, face with preceding and can rebuild liposome with the water for injection dilution.This dosage form increases substantially liposome stability, helps the storage and the transportation of liposome product.
The present invention adopts new method for preparing lipidosome and membrane stability material bag to carry docetaxel.Because the adding of film stabilizing material such as fish oil, cholesterol sulfate sodium, dodecyl sodium sulfate and pH regulator agent, especially the adding of this new membrane stabilizing material of cholesterol sulfate sodium, fundamentally improve the quality of liposome, made its drug loading, envelop rate, particle size distribution and stability obviously be better than bibliographical information.
In the development of the inventive method, we also find, as not adding the cholesterol sulfate sodium in the film stabilizing material used herein in the film material, dodecyl sodium sulfate plasma type two close materials, the dissolution with solvents liquid of phospholipid can't with water or buffer emulsifying, and the formation paste, adding tween 80, still can't disperse during surfactants such as pluronic F-68, but by adding cholesterol sulfate sodium or dodecyl sodium sulfate plasma type amphiphilic substance, can be dispersed into the uniform Emulsion of particle diameter, and can be by changing ultrasonic time, modes such as profit phase ratio are controlled particle diameter, thereby prepare the different liposome of particle diameter.In preparation process, also find in the liposome material, to add fish oil or fish oil ethyl ester in addition, the liposome drug loading of preparation is obviously improved.
Novelty of the present invention proposes emulsifying and waves arching pushing, by adding new membrane stabilizing material such as cholesterol sulfate sodium, adopts emulsifying and waves two step process that loose and prepare liposome, for the innovation of method for preparing lipidosome provides reference.And successfully prepared little, the narrow diameter distribution of mean diameter, the liposome of drug loading height, envelop rate height, good stability with this method.
The specific embodiment
The specific embodiment of the invention, by following embodiment explanation, following example mainly is to be used to further specify preparation of the present invention, but protection domain of the present invention is not limited thereto.
Embodiment 1
Soybean lecithin 2.45g
Fish oil ethyl ester 0.51g
Docetaxel 0.33g
Cholesterol sulfate sodium 0.24g
PEG2000-DSPE 0.20g
Dichloromethane 20.0mL
Tris-HCl buffer (0.005M, pH=7.6) 100.0mL
Preparation process
Precision takes by weighing above-mentioned each component of formula ratio, puts in the 50mL beaker, adds the dichloromethane of formula ratio, ultrasonic dissolution; Other get a 250mL beaker add 100mL Tris-HCl buffer (0.005M, pH=7.6).In dichloromethane phase impouring buffering liquid phase,, put in the constant temperature blender with magnetic force with cell pulverization machine supersound process 3～10min, 40～45 ℃ of water-baths, and the 600r/min stirring, organic solvent promptly gets the transparent liposome turbid liquor of blue opalescence after waving and using up, and the microporous filter membrane degerming of 0.22 μ m is promptly excessively.
The lyophilizing prescription
Docetaxel liposome suspension 90mL
Lactose 10g
(0.005M pH=7.6) adds to 100mL to the Tris-HCl buffer
The lactose of formula ratio is added in the docetaxel liposome suspension, is stirred to dissolving, add the Tris-HCl buffer (0.005M pH=7.6) to 100mL, crosses the microporous filter membrane degerming of 0.22 μ m, be sub-packed in the cillin bottle, then to the freeze dryer lyophilization promptly.
Freeze-drying process
Get made liposome solutions 5mL and pack in the cillin bottle of 10mL capacity, clog with plug.Freeze dryer is put into cold-trap, pre-freeze 6h with these pipe cillin bottles after condenser temperature is-40 ℃ of following pre-cooling 1h.Treat to drain 30 hours after product freezes in fact, draining pressure under stablizing is 50.5Pa, the vacuum gland.
Experimental result 1
According to three batches in embodiment 1 preparation sample, add and carry out physicochemical constant research, result such as following table 1 after water is rebuild.
Table 1
Embodiment 2
Ovum Gallus domesticus Flavus lecithin 2.28g
Fish oil ethyl ester 0.51g
Docetaxel 0.33g
Cholesterol sulfate sodium 0.24g
PEG2000-DSPE 0.20g
Dichloromethane 20.0mL
Tris-HCl buffer (0.005M, pH=7.6) 100.0mL
All the other processes are with embodiment 1
Experimental result 2
According to embodiment 2 preparation samples, add and carry out physicochemical constant research, result such as following table 2 after water is rebuild.
Table 2
Embodiment 3
Soybean lecithin 2.45g
EPA-E and docosahexaenoic acid ethyl (1: 1 weight ratio) 0.51g
Docetaxel 0.33g
Cholesterol sulfate sodium 0.36g
PEG2000-DSPE 0.20g
Dichloromethane 20.0mL
Tris-HCl buffer (0.005M, pH=7.6) 100.0mL
All the other processes are with embodiment 1
According to embodiment 3 preparation samples, add and carry out physicochemical constant research, result such as following table 3 after water is rebuild.
Table 3
Embodiment 4
Soybean lecithin and phosphatidylcholine (weight ratio 5: 1) 2.45g
Fish oil ethyl ester 0.26g
Docetaxel 0.33g
Cholesterol sulfate sodium 0.24g
PEG2000-DSPE 0.15g
Dichloromethane 20.0mL
Tris-HCl buffer (0.005M, pH=7.6) 100.0mL
All the other processes are with embodiment 1
According to embodiment 4 preparation samples, add and carry out physicochemical constant research, result such as following table 4 after water is rebuild.
Table 4
Embodiment 5
Soybean lecithin and hydrogenated soy phosphatidyl choline (weight ratio 5: 1) 2.45g
Fish oil ethyl ester 0.41g
Docetaxel 0.33g
Cholesterol sulfate sodium 0.24g
PEG2000-DSPE 0.20g
Dichloromethane 20.0mL
Tris-HCl buffer (0.005M, pH=7.6) 100.0mL
All the other processes are with embodiment 1
According to embodiment 5 preparation samples, add and carry out physicochemical constant research, result such as following table 5 after water is rebuild.
Table 5
Embodiment 6
Soybean lecithin 2.45g
Fish oil ethyl ester 0.51g
Docetaxel 0.33g
Cholesterol phosphate ester sodium 0.24g
PEG2000-DSPE 0.20g
Dichloromethane 20.0mL
Tris-HCl buffer (0.005M, pH=7.6) 80.0mL
All the other processes are with embodiment 1
According to embodiment 6 preparation samples, add and carry out physicochemical constant research, result such as following table 6 after water is rebuild.
Table 6
Embodiment 7
Soybean lecithin 2.45g
Fish oil ethyl ester 0.51g
Docetaxel 0.33g
Cholesterol sulfate sodium 0.24g
PEG2000-DSPE 0.15g
Dichloromethane 17.0mL
Tris-HCl buffer (0.005M, pH=7.6) 80.0mL
All the other processes are with embodiment 1
According to embodiment 7 preparation samples, add and carry out physicochemical constant research, result such as following table 7 after water is rebuild.
Table 7
Embodiment 8
Soybean phospholipid 2.45g
Fish oil ethyl ester 0.51g
Docetaxel 0.33g
Sodium lauryl sulphate 0.15g
PEG2000-DSPE 0.20g
Dichloromethane 20.0mL
Tris-HCl buffer (0.005M, pH=7.6) 100.0mL
All the other processes are with embodiment 1
According to embodiment 8 preparation samples, add and carry out physicochemical constant research, result such as following table 8 after water is rebuild.
Table 8
Above embodiment all proves: delivery system of Duoxitasai lipidosome for injection of the present invention, the preparation liposome drug loading and stable aspect certain advantage is all arranged, has the drug loading height, the characteristics of good stability, the docetaxel liposome drug loading of conventional method preparation is difficult to reach more than 5%, and be easy to separate out medicine, and delivery system of Duoxitasai lipidosome for injection drug loading of the present invention can reach more than 10%, can not separate out medicine in general 24 hours, and the liposome mean diameter that the preparation method among employing the present invention makes little (between 50～150nm), narrow diameter distribution (200nm), envelop rate height (95%), drug loading height (12%), stability also significantly improves.
Claims (16)
1, a kind of delivery system of Duoxitasai lipidosome for injection, described delivery system of Duoxitasai lipidosome for injection comprises docetaxel, immobilized artificial membrane material, film stabilizing material and the pharmaceutically acceptable adjuvant for the treatment of effective dose, wherein, described film stabilizing material comprises the ion-type amphiphilic substance, and the weight ratio of described docetaxel and described immobilized artificial membrane material and described film stabilizing material is 1: 5: 0.2～1: 50: 50.
2, delivery system of Duoxitasai lipidosome for injection according to claim 1, wherein, described immobilized artificial membrane material is Ovum Gallus domesticus Flavus lecithin, soybean lecithin, phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, hydrolecithin or its mixture.
3, delivery system of Duoxitasai lipidosome for injection according to claim 1, wherein, described ion-type amphiphilic substance is cholesterol sulfate sodium, cholesterol sodium phosphate, cholesterol sodium sulfonate, dodecyl sodium sulfate or its mixture, and the weight ratio of described docetaxel and described ion-type amphiphilic substance is 1: 0.2～1: 10.
4, delivery system of Duoxitasai lipidosome for injection according to claim 1, wherein, described film stabilizing material comprises polyglycol derivatization phospholipid.
5, delivery system of Duoxitasai lipidosome for injection according to claim 4, wherein, in the structure of described polyglycol derivatization phospholipid, phospholipid moiety is to be selected from the group of being made up of stearic acid PHOSPHATIDYL ETHANOLAMINE, cholesterol succinate, PHOSPHATIDYL ETHANOLAMINE, phosphatidylcholine, phosphatidylinositols, phosphatidyl silk amino acid, diphosphatidylglycerol and the sour phospholipid that contracts one or more, and the molecular weight of Polyethylene Glycol is 200～20000.
6, delivery system of Duoxitasai lipidosome for injection according to claim 1, wherein, described film stabilizing material comprises the fish oil material.
7, delivery system of Duoxitasai lipidosome for injection according to claim 6, wherein, described fish oil material is selected from one or more in the group of being made up of fish oil, fish oil ethyl ester, EPA-E and docosahexaenoic acid ethyl, and the weight ratio of described fish oil material and described immobilized artificial membrane material is 1: 1～1: 50.
8, delivery system of Duoxitasai lipidosome for injection according to claim 1, wherein, described pharmaceutically acceptable adjuvant comprises antioxidant, pH value regulator and freeze drying protectant.
9, delivery system of Duoxitasai lipidosome for injection according to claim 8, wherein, to be selected from pH be 4.0～9.0 Tris-HCl buffer, citric acid-sodium citrate buffer, acetic acid-sodium-acetate buffer or phosphate buffer to described pH value regulator.
10, delivery system of Duoxitasai lipidosome for injection according to claim 8, wherein, described freeze drying protectant comprises sugar and polyhydric alcohol, and the gross weight that the amount of described freeze drying protectant accounts for described drug-supplying system is 1%～20%.
11, delivery system of Duoxitasai lipidosome for injection according to claim 8, wherein, described freeze drying protectant is a lactose.
12, docetaxel liposome drug-supplying system according to claim 1, wherein, described liposome administration system is that particle diameter is that the preparation ultimate density of 10nm～1000nm and docetaxel is the preparation of the lyophilized powder form of 1～10mg/mL.
13, a kind of preparation method that is used for delivery system of Duoxitasai lipidosome for injection, it comprises:
A) emulsifying step: docetaxel, immobilized artificial membrane material and film stabilizing material are dissolved in the organic solvent, pour aqueous phase then into, form Emulsion through emulsifying device emulsifying; With
B) wave stroll suddenly: waving looses removes organic solvent, seals docetaxel then in liposome.
14, the preparation method of delivery system of Duoxitasai lipidosome for injection according to claim 13, wherein, in described emulsifying step, the O/W type Emulsion of described Emulsion for being processed into by ultrasonic, homogenizing, nanometer machine.
15, the preparation method of delivery system of Duoxitasai lipidosome for injection according to claim 13, wherein, described organic solvent is dichloromethane, chloroform, ether or ethyl acetate.
16, the preparation method of delivery system of Duoxitasai lipidosome for injection according to claim 13 can be used for preparing other anticarcinogen paclitaxel, vinorelbine, Vinorebine.
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Family Cites Families (4)
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| CN1846692A (en) * | 2006-05-15 | 2006-10-18 | 沈阳药科大学 | Long circulation liposome prepn of polyene taxol and its prepn process |
| CN100496609C (en) * | 2006-12-30 | 2009-06-10 | 上海艾力斯医药科技有限公司 | Stable liposome composition |
-
2008
- 2008-05-22 CN CN 200810097661 patent/CN101584663B/en not_active Expired - Fee Related
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| CN104856955A (en) * | 2015-05-06 | 2015-08-26 | 刘星言 | Docetaxel loaded lipid vesicle drug delivery system and production method thereof |
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| CN114948875B (en) * | 2021-12-28 | 2023-11-28 | 河南省儿童医院郑州儿童医院 | Argatroban liposome injection and preparation method thereof |
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