CN101129361A - Sirolimus lipidosome freeze-dried acanthopanax powder and technique of preparing the same - Google Patents
Sirolimus lipidosome freeze-dried acanthopanax powder and technique of preparing the same Download PDFInfo
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- CN101129361A CN101129361A CNA2007100163140A CN200710016314A CN101129361A CN 101129361 A CN101129361 A CN 101129361A CN A2007100163140 A CNA2007100163140 A CN A2007100163140A CN 200710016314 A CN200710016314 A CN 200710016314A CN 101129361 A CN101129361 A CN 101129361A
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Abstract
The invention discloses a xiluomosi liposome freeze dried and making technique, which comprises the following steps: selecting liposome component, buffer, organic solvent, antioxidant and freeze-drying protective as raw material; adopting film diffusion method to make the liposome turbid liquor with xiluomosi through high-pressure or hypersonic dispersing method evenly; drying the liposome to improve the storage stability obviously; dispersing the freeze dried at random proportion in the water evenly without any sediment and impurity; making the packing rate of liposome at 96% with the grain size at 50-250nm; improving the drug effect greatly in comparison with oral agent; lengthening the circulating time in the blood; elevating the biological utility of drug.
Description
Technical field:
The present invention relates to the preparation of sirolimus, that is to say to relate to a kind of Injectable liposomal lyophilized injectable powder and preparation method that contains sirolimus, is sirolimus lipidosome freeze-dried acanthopanax powder and preparation technology thereof specifically.
Background technology:
Sirolimus (Sirolimus, Rapamune, have another name called rapamycin) be earlier 1970s, the metabolite of the water absorption streptomycete AYB P44 that from the soil on island, Easter mountain, the Pacific Ocean, separates by Canadian Ayerst institute scientist, its relative molecular mass is 914.2, at first as hypotoxicity antifungal antibiotic.Report its immunosuppressive activity in rat assist agent arthritis and experimental allergic cerebrospinal meningitis model in 1978, and begin to carry out relevant rudimentary and clinical experiment.Experiment shows that it not only has significant curative effect for the various autoimmune sexual abnormality, and demonstrates the anti-rejection activity of significance on different types of organ transplantation animal model.Beginning in 1989 is tried out as the new drug of the rejection of treatment organ transplantation, drugs approved by FDA in 1999 with this medicine as kidney organ's transplantation immunity inhibitor in clinical practice, so far get the Green Light or register in more than 20 countries, be used for prevention of organ transplant patient's acute rejection.Discover, sirolimus mainly shows as suppressor T cell and T cell dependency B cell to the antigenic reaction of mortifier as the effect of immunosuppressant, mechanism of action is that sirolimus combines formation sirolimus FKBP-12 complex with FK506 albumen (FKBP-12), the latter again with mammals sirolimus target molecule (mTOR, a kind of adjusting kinases of key) combination, blocking-up T lymphocyte and other cells are by the process of G1 phase to the S phase, thus the generation depression effect.The pharmacological results shows that the immunosuppressive effect of sirolimus obviously is better than similar medicine tacrolimus at present, is 100 times of ciclosporin.Sirolimus is a kind of solid matter that is insoluble in water, is subject to the influence of light and heat under field conditions (factors) and degrades, so its preparation needs lucifuge cold preservation, and the production process of preparation need be carried out under the lucifuge condition.
External listing sirolimus dosage form is mainly oral liquid, and containing this product concentration is 1mg/ml, and specification has 60mL, two kinds of 150mL, and bioavailability just is about 15%.The sirolimus oral administration solution needs shading, sealing, and 4-8 ℃ of cold preservation is valid for one year, quantitatively also very inconvenience when the patient takes.Calendar year 2001 Elan company utilizes nanotechnology to develop the nanocrystal sheet of sirolimus.Compare with oral administration solution, though nanocrystal sheet taking convenience, bioavailability has only improved about 1 times, and the nano junction wafer production cycle is longer, and institute mills and also influences the quality of sirolimus easily the working medium high-strength and long time in the production process.
Summary of the invention:
The objective of the invention is to, overcome the deficiencies in the prior art part, for solving the low problem of sirolimus bioavailability, a kind of good stability, envelop rate height, cost is low and toxic and side effects is little sirolimus Injectable liposomal freeze-dried powder are provided, a kind of preparation technology of this Injectable liposomal freeze-dried powder is provided simultaneously.A kind of sirolimus lipidosome freeze-dried acanthopanax powder of the present invention, this is a kind of new formulation for the injection application.The notion of liposome (liposomes) is proposed in nineteen sixty-five by Bingham the earliest, and people such as late 1960s Rahman at first use it as pharmaceutical carrier.Liposome is that pharmaceutical pack is rolled in the miniature vesicle structure that forms in the phospholipid bilayer.Liposome has the dissolubility that improves insoluble drug as a kind of good pharmaceutical carrier, improves encapsulated stability of drug, reduces advantages such as drug toxicity and prolong drug action time.The carrier material of liposome has the good tissue cell compatibility, can safety be used for drug administration by injection, this has just improved bioavailability of medicament greatly.
Sirolimus liposome of the present invention, its liposome membrane has certain permeability, and under liquid condition, the medicine of sealing easily is penetrated into outside the film.In addition, under liquid condition, oxidation, hydrolysis easily take place in material phospholipid, the cholesterol of liposome, go mouldy etc., and the particle gathering that easily sticks together, and these have all influenced the quality of liposome, have limited the suitability for industrialized production of liposome and application clinically.Sirolimus lipidosome freeze-dried acanthopanax powder of the present invention and preparation technology thereof; this preparation is to select liposome component, buffer, organic solvent, antioxidant and freeze drying protectant for use; adopt film dispersion method, even or ultrasonic dispersing method is handled the liposome turbid liquor of making uniform parcel sirolimus through the high pressure breast.The sirolimus liposome is made freeze-dried powder through lyophilization, has significantly improved bin stability.Lyophilized powder can be used arbitrary proportion water for injection homodisperse, does not produce any precipitation and impurity, and after disperseing, liposome encapsulation reaches 96%, and particle diameter is 50-250nm.Pharmacodynamic experiment shows, compares with oral injection, and lipidosome injection has improved the curative effect of medicine greatly.Pharmacokinetic experiment shows, compare with oral injection, the lipidosome injection significant prolongation medicine in the sanguimotor time, and improved bioavailability of medicament greatly.
For solving the stability problem of liposome, the present invention adopts Freeze Drying Technique, and liposome preparation is become the lyophilization powder, has invented a kind of stable sirolimus liposome injection solid freeze-dried powder.After the sirolimus liposome made the solid freeze-dried powder, stability improved greatly, stored simply, disperseed to get final product with an amount of water for injection dilution before using, and had improved the stability of encapsulated sirolimus, can safe drug administration by injection.Special needs to be pointed out is, liposome is after injection enters blood circulation, alternative concentrates on the abundant organ of mononuclear phagocyte system, as liver, spleen etc., this has just significantly reduced the cardiac toxicity of sirolimus, and can be in liver, spleen slowly release, significant prolongation drug treating time.
Technical scheme of the present invention is the characteristic according to liposome, selects for use the film dispersion method preparation to wrap up the liposome of Xi Luomosi.The present invention adds an amount of vitamin E as antioxidant in prescription, prevent the oxidation deterioration of lipid components, strengthens the chemical stability of liposome.The weight ratio of vitamin E and phospholipid is 0.001: 10.1: 1.The sirolimus liposome aqueous suspension that obtains belongs to the submicron system of high degree of dispersion; has higher surface energy; liquid condition is preserved interparticle adhesion, gathering is easily taken place down; the present invention adds freeze drying protectant in the liposome aqueous suspension; adopt Freeze Drying Technique, prepared sirolimus lipidosome freeze-dried acanthopanax powder.
Resulting sirolimus lipidosome freeze-dried acanthopanax powder can significantly improve preparation stored stability, can guarantee that again sirolimus lipidosome freeze-dried acanthopanax powder can add water for injection with arbitrary proportion and dilute dispersion again, and not produce any insoluble substance or precipitation.In addition, because the height cell compatibility of selected matrix material, the liposome turbid liquor that obtains through dilution can safety drug administration by injection, enter blood circulation after, alternative concentrates on the abundant organ of mononuclear phagocyte system, as liver, spleen etc., this has just significantly reduced the cardiac toxicity of sirolimus, and can be in liver, spleen slowly release, significant prolongation drug treating time, improved medicine bioavailability in vivo.
The said sirolimus lipidosome freeze-dried acanthopanax powder of the present invention is characterized in that being made up of the raw material of following weight ratio:
Sirolimus 500mg-5g
Phosphatidase 11 g-100g
Cholesterol 100mg-50g
Antioxidant 1mg-10g
Freeze drying protectant 30g-400g
Sodium chloride 9g
Satisfy simultaneously: the weight ratio of sirolimus and phospholipid is 0.05: 1-0.5: 1, and the weight ratio of cholesterol and phospholipid is 0.1: 11: 1.
Described sirolimus lipidosome freeze-dried acanthopanax powder, wherein phospholipid can be homemade injection soybean phospholipid, Ovum Gallus domesticus Flavus lecithin, cephalin, Phosphatidylserine, distearoyl phosphatidylcholine, dipalmitoyl phosphatidyl choline, dimyristoyl phosphatidyl choline, also can be poloxamer, ceramide, pool, Kaifeng class nonionic surfactant; Cholesterol is homemade injection cholesterol.
Described sirolimus lipidosome freeze-dried acanthopanax powder, wherein antioxidant can be a vitamin E, the weight ratio of itself and phospholipid is 0.001: 1-0.1: 1.
Described sirolimus lipidosome freeze-dried acanthopanax powder, wherein freeze drying protectant is mannitol, sorbitol, sucrose, lactose, trehalose, glucose, polyvinylpyrrolidone or their mixture, its content is 3-40%.Described sirolimus lipidosome freeze-dried acanthopanax powder, its dosage form is a lyophilized powder.
Described sirolimus lipidosome freeze-dried acanthopanax powder is characterized in that the method for preparing liposome comprises following steps:
1) purchase the raw material of following weight or volume:
Sirolimus 500mg-5g
Phosphatidase 11 g-100g
Cholesterol 100mg-50g
Vitamin E 1mg-10g
Buffer 100ml-500ml
Freeze drying protectant 30g-400g
Organic solvent 400ml-800ml
Sodium chloride 9g
Water for injection 1000ml
2) sirolimus, phospholipid, cholesterol, vitamin E are dissolved in chloroform or the chloroform-ethanol mixed solvent and mix homogeneously; With Rotary Evaporators the decompression of the organic solvent in the solution is removed, on the vial wall, form lipid membrane.
3) (p H6-7.4 0.01mol/L), stirs 30min, at room temperature places 2h, makes the thin film imbibition to add isoosmotic phosphate buffer; At room temperature stir 2h again, obtain the liposome aqueous suspension.The liposome aqueous suspension that obtains is even or ultrasonic dispersing processing through the high pressure breast, the homogenize liposome.
4) add freeze drying protectant, ooze water for injection with grade and be settled to 1000ml, the degerming of process filtering with microporous membrane, be sub-packed in the cillin bottle.
5) lyophilization obtains the lyophilized powder of sirolimus liposome, 0-4 ℃ of storage.
Described sirolimus lipidosome freeze-dried acanthopanax powder preparation method, the Laemmli buffer system Laemmli that it is characterized in that preparing liposome is a phosphate buffer, pH is 6-7.4.
Described sirolimus lipidosome freeze-dried acanthopanax powder preparation method, the organic solvent that it is characterized in that preparing liposome is chloroform, ethanol or their mixture.
Described sirolimus lipidosome freeze-dried acanthopanax powder preparation method is characterized in that the homogenize liposome adopts the even method of high pressure breast, and condition is 500bar, 2-5 time; Perhaps adopt the ultrasonic dispersing method to handle 2min (every processing 0.5min is 0.5min intermittently).
Described sirolimus lipidosome freeze-dried acanthopanax powder preparation method, the sterilizing methods that it is characterized in that preparing liposome is a filtering with microporous membrane.
Described sirolimus lipidosome freeze-dried acanthopanax powder preparation method, it is characterized in that lyophilization be at first with the sirolimus liposome turbid liquor in-80 ℃ of following freezing 24-48h, at-40--60 ℃, carry out under the condition of 0.5-0.1mPa then.
Described sirolimus lipidosome freeze-dried acanthopanax powder preparation method is characterized in that all operations all carry out under the lucifuge environment.
Beneficial effect of the present invention is, the sirolimus lipidosome freeze-dried acanthopanax powder that the present invention makes, outward appearance is a kind of faint yellow loose spongy very thin powder, add water for injection gently jolting dilute at once and disperse to be even suspension, particle diameter is between 100-200nm, envelop rate can reach 96%, and free sirolimus seldom is generally less than 4%.Phospholipid, cholesterol carrier material use homemade injection phospholipid, cholesterol in the present invention's prescription, greatly reduce product cost, make the preparation that meets China's actual conditions.The present invention adds vitamin E as antioxidant in prescription, improved the chemical stability of sirolimus liposome greatly.In addition, the present invention adopt the even method of high pressure breast or ultrasonic dispersing method further even the size of liposome particles, and the even liposome turbid liquor that obtains adopts Freeze Drying Technique to make the solid freeze-dried powder, cryopreservation has further improved the physical stability of sirolimus liposome.The obtained freeze-drying powder-product of the present invention 1 year stability test result that keeps in Dark Place under 0-4 ℃ shows that the rate of change of its mean diameter and envelop rate is all less than 3%.The sirolimus lipidosome freeze-dried acanthopanax powder that the present invention makes uses simple, and preceding being uniformly dispersed with an amount of water for injection dilution of injection gets final product, and consumption is followed the doctor's advice.
Description of drawings:
Curve when accompanying drawing 1 is sirolimus oral liquid single dose administration rat plasma Chinese medicine; Curve when accompanying drawing 2 is sirolimus lipid freeze-dry powder rat tail vein injection blood plasma Chinese medicine.
The specific embodiment:
Referring now to accompanying drawing 1 and accompanying drawing 2, be described as follows in conjunction with the embodiments:
Pharmacodynamic experiment of the present invention:
60 mices after renal transplantation are divided into two groups at random, irritate stomach for one group and give sirolimus oral liquid (Rapamune , Wyeth company, lot number 08587), the sirolimus lipidosome freeze-dried acanthopanax powder of another group tail vein injection after the water for injection dilution, the result shows, oral liquid ED50 is 15mgkg-1, the ED50 of liposome then is 2mgkg-1, as seen compares with oral injection, and lipidosome injection has improved the curative effect of medicine greatly.
Pharmacokinetic experiment of the present invention:
Get body weight and be 10 of the healthy Wistar male rats of (200 ± 2) g, be divided into two groups at random, one group of gastric infusion sirolimus oral liquid (Rapamune , Wyeth company, lot number 08587), one group of tail vein injection sirolimus lipidosome freeze-dried acanthopanax powder after the water for injection dilution is all by the dosed administration of 25mgkg-1.Respectively at 0.25,0.5,1,2,6,12,24,36 and the 48h eye socket get blood 1.5-2.0mL, add inner mark solution 20 μ l (internal standard substance is a 32-de-methoxy sirolimus) the vortex mixing of 1g/ml, add each 1ml of 5% solution of zinc sulfate and acetone, centrifugal behind the vortex mixing (3000r/min) 10min, get supernatant 1ml, dry up the back and add mobile phase 0.5ml dissolving, filter back sample introduction 10 μ l and measure.
The HPLC chromatographic condition: chromatographic column is C8 post (250mm * 4.6mm, 5.6 μ m), mobile phase be methanol-water-acetonitrile (30: 30: 40, V/V), 40 ℃ of column temperatures, flow velocity 1.5ml/min, the detection wavelength is 277nm.
Table 1 sirolimus rat pharmacokinetic parameter relatively
Cmax(ug·ml-1) Tmax(h) AUC(h·ug·ml-1) MRT(h)
Oral liquid 0.73 1.4 10.6 12.34
Injection--99.7 23.68
As shown in Table 1, compare with oral liquid, the liposome significant prolongation medicine mean residence time in vivo, brought up to 23.68h by 12.34h.AUC has also increased nearly 10 times.
The present invention is further elaborated by the following examples, but institute is not a limitation of the present invention as embodiment.
Embodiment 1:
Purchase the raw material of following weight or volume:
Sirolimus 500mg
Soybean phospholipid 2.3g
Cholesterol 1g
Vitamin E 21mg
Phosphate buffer (p H7.4,0.01mol/L) 300ml
Mannitol 100g
Chloroform 400ml
Sodium chloride 9g
Water for injection 1000ml
Weight ratio according to raw material in the prescription is dissolved in the chloroform sirolimus, phospholipid, cholesterol, vitamin E and mix homogeneously; With Rotary Evaporators the decompression of the organic solvent in the solution is removed (temperature is not higher than 40 ℃), on the vial wall, form lipid membrane; Add isoosmotic phosphate buffer (pH6-7.4,0.01mol/L contain 0.9%Nacl) 300ml, stir 30min, at room temperature place 2h, make the thin film imbibition; At room temperature stir 2h again, obtain the liposome aqueous suspension; The liposome aqueous suspension that obtains is handled (the high pressure dispersing emulsification machine is furnished with condensing tube, the cold water that the pipe internal recycle is 0 ℃), pressure 500bar, even 5 times of breast, homogenize liposome through the high pressure dispersing emulsification machine; The mannitol that adds formula ratio in the even liposome turbid liquor of gained oozes water for injection with grade and is settled to 1000ml, stirs, through 0.22 μ m filtering with microporous membrane degerming, be sub-packed in the cillin bottle (sterilization) of 200 10ml specifications; With sirolimus liposome turbid liquor freezing 48h under-80 ℃, then at-40 ℃, carry out lyophilization under the condition of 0.5-0.1mPa, obtain the lyophilized powder of sirolimus liposome, store 0-4 ℃ of lucifuge; Above-mentioned all operations step is all carried out under lucifuge; Product through arbitrarily than the water for injection dilution after, jolting can be separated into uniform suspension gently; Measure through the laser particle Particle Size Analyzer, mean diameter is 105nm, and it is 96% that the low temperature supercentrifugation records envelop rate.
Embodiment 2:
Purchase the raw material of following weight or volume:
Sirolimus 1000mg
Ovum Gallus domesticus Flavus lecithin 7g
Distearoyl phosphatidylcholine 5g
Cholesterol 7g
Vitamin E 100mg
Phosphate buffer (p H7.4,0.01mol/L) 300ml
Mannitol 150g
Chloroform 500ml
Sodium chloride 9g
Water for injection 1000ml
According to the weight ratio of raw material in the prescription sirolimus, phospholipid, cholesterol, vitamin E are dissolved in chloroform-alcohol mixed solvent of 2: 1 and mix homogeneously; With Rotary Evaporators the decompression of the organic solvent in the solution is removed (temperature is not higher than 40 ℃), on the vial wall, form lipid membrane; Add isoosmotic phosphate buffer (p H6-7.4,0.01mol/L contains 0.9%Nacl) 300ml, stir 30min, at room temperature place 2h, make the thin film imbibition; At room temperature stir 2h again, obtain the liposome aqueous suspension; The liposome aqueous suspension that obtains is handled (the high pressure dispersing emulsification machine is furnished with condensing tube, the cold water that the pipe internal recycle is 0 ℃), pressure 500bar, even 5 times of breast, homogenize liposome through the high pressure dispersing emulsification machine; The mannitol that adds formula ratio in the even liposome turbid liquor of gained oozes water for injection with grade and is settled to 1000ml and stirs, through 0.22 μ m filtering with microporous membrane degerming, be sub-packed in the cillin bottle (sterilization) of 200 10ml specifications; With sirolimus liposome turbid liquor freezing 48h under-80 ℃, then at-40 ℃, carry out lyophilization under the condition of 0.5-0.1mPa, obtain the lyophilized powder of sirolimus liposome, store 0-4 ℃ of lucifuge; Above-mentioned all operations step is all carried out under lucifuge; Product through arbitrarily than the water for injection dilution after, jolting can be separated into uniform suspension gently; Measure through the laser particle Particle Size Analyzer, mean diameter is 80nm, and it is 96% that the low temperature supercentrifugation records envelop rate.
Embodiment 3:
Purchase the raw material of following weight or volume:
Sirolimus 1000mg
Soybean phospholipid 3g
Distearoyl phosphatidylcholine 5g
Cholesterol 7g
Vitamin E 100mg
Phosphate buffer (pH7.4,0.01mol/L) 300ml
Mannitol 150g
Chloroform 500ml
Sodium chloride 9g
Water for injection 1000ml
According to the weight ratio of raw material in the prescription sirolimus, phospholipid, cholesterol, vitamin E are dissolved in chloroform-alcohol mixed solvent of 2: 1 and mix homogeneously; With Rotary Evaporators the decompression of the organic solvent in the solution is removed (temperature is not higher than 40 ℃), on the vial wall, form lipid membrane; Add isoosmotic phosphate buffer (pH6-7.4,0.01mol/L contain 0.9%Nacl) 300ml, stir 30min, at room temperature place 2h, make the thin film imbibition; At room temperature stir 2h again, obtain the liposome aqueous suspension; The liposome aqueous suspension that obtains is through ultrasonic dispersing 2min (every ultrasonic 0.5min of place just is immersed in 0 ℃ of cold water discontinuous 0.5min), homogenize liposome; The mannitol that adds formula ratio in the even liposome turbid liquor of gained oozes water for injection with grade and is settled to 1000ml and stirs, through 0.22 μ m filtering with microporous membrane degerming, be sub-packed in the cillin bottle (sterilization) of 200 10ml specifications; With sirolimus liposome turbid liquor freezing 48h under-80 ℃, then at-40 ℃, carry out lyophilization under the condition of 0.5-0.1mPa, obtain the lyophilized powder of sirolimus liposome, store 0-4 ℃ of lucifuge; Above-mentioned all operations step is all carried out under lucifuge; Product through arbitrarily than the water for injection dilution after, jolting can be separated into uniform suspension gently; Measure through the laser particle Particle Size Analyzer, mean diameter is 80nm, and it is 96% that the low temperature supercentrifugation records envelop rate.
Claims (7)
1. sirolimus lipidosome freeze-dried acanthopanax powder is characterized in that being made up of the raw material of following weight ratio:
Sirolimus 500mg-5g
Phosphatidase 11 g-100g
Cholesterol 100mg-50g
Antioxidant 1mg-10g
Freeze drying protectant 30g-400g
Sodium chloride 9g
Satisfy simultaneously: the weight ratio of sirolimus and phospholipid is 0.05: 1-0.5: 1, and the weight ratio of cholesterol and phospholipid is 0.1: 1-1: 1.
2. sirolimus lipidosome freeze-dried acanthopanax powder according to claim 1, the lipid components that it is characterized in that preparing liposome can be homemade injection soybean phospholipid, Ovum Gallus domesticus Flavus lecithin, cephalin, Phosphatidylserine, distearoyl phosphatidylcholine, dipalmitoyl phosphatidyl choline, dimyristoyl phosphatidyl choline, poloxamer, ceramide, pool, Kaifeng class nonionic surfactant, cholesterol.
3. sirolimus lipidosome freeze-dried acanthopanax powder according to claim 1, the antioxidant that it is characterized in that preparing liposome is a vitamin E, the weight ratio of itself and phospholipid is 0.001: 1-0.1: 1.
4. sirolimus lipidosome freeze-dried acanthopanax powder according to claim 1; the freeze drying protectant that it is characterized in that preparing liposome can be mannitol, sorbitol, sucrose, lactose, trehalose, glucose, polyvinylpyrrolidone or their mixture, and its content is 3-40%.
5. sirolimus lipidosome freeze-dried acanthopanax powder according to claim 1 is characterized in that the method for preparing liposome comprises following steps:
1) purchase the raw material of following weight or volume:
Sirolimus 500mg-5g
Phosphatidase 11 g-100g
Cholesterol 100mg-50g
Vitamin E 1mg-10g
Buffer 100ml-500ml
Freeze drying protectant 30g-400g
Organic solvent 400ml-800ml
Sodium chloride 9g
Water for injection 1000ml
2) sirolimus, phospholipid, cholesterol, vitamin E are dissolved in chloroform or the chloroform-ethanol mixed solvent and mix homogeneously; With Rotary Evaporators the decompression of the organic solvent in the solution is removed, on the vial wall, form lipid membrane;
3) (pH6-7.4 0.01mol/L), stirs 30min, at room temperature places 2h, makes the thin film imbibition to add isoosmotic phosphate buffer; At room temperature stir 2h again, obtain the liposome aqueous suspension; The liposome aqueous suspension that obtains is even or ultrasonic dispersing processing through the high pressure breast, the homogenize liposome;
4) add freeze drying protectant, and stir, ooze water for injection with grade and be settled to 1000ml, the degerming of process filtering with microporous membrane, be sub-packed in the cillin bottle;
5) lyophilization obtains the lyophilized powder of sirolimus liposome, 0-4 ℃ of storage.
6. sirolimus lipidosome freeze-dried acanthopanax powder preparation method according to claim 5, the Laemmli buffer system Laemmli that it is characterized in that preparing liposome is a phosphate buffer, pH is 6-7.4.
7. sirolimus lipidosome freeze-dried acanthopanax powder preparation method according to claim 5, the organic solvent that it is characterized in that preparing liposome is chloroform, ethanol or their mixture.
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