CN101991538A

Movatterモバイル変換

Info

Publication number: CN101991538A
Application number: CN2009101016078A
Authority: CN
Inventors: 熊素彬; R·J·李; 尹小东
Original assignee: Zhejiang University of Technology ZJUT
Current assignee: Zhejiang University of Technology ZJUT
Priority date: 2009-08-14
Filing date: 2009-08-14
Publication date: 2011-03-30
Anticipated expiration: 2029-08-14
Also published as: CN101991538B

Abstract

The invention discloses a tocopheryl polyethylene glycol succinate (TPGS)-containing liposome composition and application thereof. The liposome composition consists of a phospholipid compound, a cholesterol compound and TPGS. The weight ratio of the phospholipid compound to the cholesterol compound to the TPGS is 5 to 95:0 to 50:0.1 to 60. The TPGS-containing liposome composition is applied to preparing medicine-loading liposomes, can improve the stability of liposome medicaments and the curative effect of the medicaments.

Description

A kind of liposome composition and application thereof that contains TPGS

Technical field

The present invention relates to the liposome composition of a kind of TPGS of containing, and by its drug-loaded liposome for preparing.

Background technology

The bilayer structure of the similar cell membrane that liposome mainly is made up of phospholipid and cholesterol.Liposome can be divided three classes: little single chamber (layer) liposome, and particle diameter is 20～80nm; Large unilamellar vesicle, particle diameter is about 100～1000nm; Multicell (layer) liposome, particle diameter is about 1000～5000nm.Conventional liposome has been experienced in the development of liposome, and the PEG modified liposome is to receptor or ligand modified liposome.The liposome of clinical practice at present is mainly conventional liposome (as DaunoXome) and PEG modified liposome (as Doxil).Compare with conventional liposome, the PEG modified liposome has the particle diameter that reduces liposome, improves the stability of liposome, and the extension body circulation time improves advantages such as cancer therapy drug targeting.Liposome PEG dressing agent commonly used is mainly PEG (2000)-DSPE, modifies Evacet listing product Doxil as PEG; Still the surfactant that has some to contain PEG in addition, as Tween80, Poloxmer188, etc.

The preparation method of liposome has multiple, according to the character of medicine maybe needs select.(1) film dispersion method: be that film materials such as phospholipid are dissolved in an amount of chloroform or other organic solvent, fat-soluble medicine can be added in the organic solvent, under the decompression rotation, remove then and desolvate, make lipid after wall forms thin film, add the buffer solution or other solution that do not contain or contain water soluble drug, carry out jolting, then can form multilamellar liposome.(2) injection method: matrix materials such as phospholipid and fat-soluble medicine are dissolved in (oil phase) in the organic solvent, then the oil phase average rate are expelled in the water (containing or do not contain water soluble drug), eliminate the method that organic solvent obtains liposome.Difference according to solvent can be divided into ethanol or tert-butyl alcohol injection method and ether injection method etc.(3) reverse phase evaporation: be that matrix materials such as phospholipid are dissolved in organic solvent, in chloroform, mix with the buffer of pastille by a certain percentage again, emulsifying that the pressure reducing and steaming organic solvent can form liposome then.This method is suitable for water soluble drug, macromole active substance, and the liposome preparation as insulin etc. can improve envelop rate.Freeze-drying and fusion method are still arranged in addition.The 5 kinds of methods in front disperse formed liposome mostly to be multilamelar liposome, available various mechanical means further disperses, to reduce particle diameter and to form small unilamellar vesicle: a) the ultrasonic method big multilamellar liposome ultrasonoscope supersound process that will obtain, according to the ultransonic intensity of adopt and action time length obtain small unilamellar vesicle.B) the homogenize method big multilamellar liposome that will obtain becomes liposome than small particle diameter by tissue mashing machine or the homogenize of high pressure dispersing emulsification machine.C) under high pressure continuously by behind the poly-carbonic acid fibrous membrane of aperture 1.0-0.05 μ m, the size distribution of liposome is tending towards homogeneous to the squeezing and pressing method big multilamellar liposome that will obtain, and mostly is unilamelar liposome.

When the preparation drug-loaded liposome, according to the character of medicine, the mechanism difference of loading can be divided into " initiatively medicine carrying " and " passive medicine carrying " two big classes.So-called " passive medicine carrying ", promptly at first medicine is soluble in the aqueous phase or organic facies (fat-soluble medicine) in, prepare drug-loaded liposome by selected method for preparing lipidosome then.For fat-soluble, with the high medicine of immobilized artificial membrane affinity, " passive medicine carrying " method is comparatively suitable.So-called " initiatively medicine carrying " promptly carries out medicine carrying by the different ions or the chemical compound gradient of water inside and outside the liposome, mainly is applicable to amphiphatic medicine.Active loading method mainly comprises (1) pH gradient method; (2) ammonium sulphate gradient; (3) calcium acetate gradient method or other ion gradient methods.

Ammonium sulphate gradient promptly earlier is wrapped in water in the liposome with ammonium sulfate, then the ammonium sulfate of water outward of the method weeding of grease plastid by dialysis, gel chromatography or ultrafiltration.Because the difference of ion pair bilayer infiltration coefficient, (0.13cm/s) is higher for the amino molecule infiltration coefficient, can be diffused into outer aqueous phase very soon; H⁺Infiltration coefficient much smaller than amino molecule, make that water is acid in the liposome, form the pH gradient, gradient magnitude is by [NH₄⁺] outer water/[NH₄⁺] interior water relatively determines, makes the contrary ammonium sulphate gradient of medicine be written into liposome like this.Medicine enters behind the liposome and SO₄^2-The sulfate that forms reduces the bilayer infiltration coefficient, thereby makes weakly basic drugs have very high envelop rate and have good stable.

The calcium acetate gradient method makes a large amount of protons be transported to the outside pH of generation gradient from liposome interior by the calcium acetate concentration gradient (inner concentration is higher than the outside) of the transmembrane movement generation of calcium acetate.The permeability parameters (6.6 * 10 of acetic acid^-4Cms^-1) compare Ca²⁺(2.5 * 10^-11Cms^-1) big 7 orders of magnitude, so Ca²⁺Seldom pass through bimolecular film and stay liposome interior, acetic acid molecule has then participated in the proton transhipment.The Concentraton gradient that the calcium acetate transmembrane movement produces (inner concentration is higher than the outside) causes a large amount of protons to produce the pH gradient to the outside from the internal forwarding of liposome, and the imbalance of pH is carried for bag and the gathering weak acidic drug provides high efficiency drive power.

Initiatively medicine carrying with the common feature of passive medicine carrying is: the inside and outside water of liposome or the drug level basically identical on the bimolecular tunic in loading process, the factor that determines its envelop rate be medicine with interior water volume, liposome number and the medicine fat of the composition of the active force of immobilized artificial membrane, film material, liposome than (medicine and immobilized artificial membrane material compare) etc.

Vitamin E polyethylene glycol succinic acid ester (TPGS) is the soluble derivative of the vitamin E that formed through esterification by vitamin e succinate and cetomacrogol 1000, comprises d-alpha-tocopherol succinic acid macrogol ester (d-TPGS) and dl-alpha-tocopherol succinic acid macrogol ester (dl-TPGS).Reports such as Youk are prepared into TPGS with vitamin E, has certain antitumaous effect (Youk HJ, et al.Enhanced anticancer efficacy ofa-tocopheryl succinate by conjugation with polyethylene glycol.JControl Rel, 2005,107:43-52.).Yamagata etc. discover that TPGS can suppress the effect of P-gp among the drug resistance breast cancer cell MDCK-II and significantly promotes the picked-up of anticarcinogen mitoxantrone, improve anticancer therapeutic (Yamagata T, et al.Effect of excipients on breastcancer resistance protein substrate uptake activity.J Control Rel, 2007,124:1-5).Report TPGS such as Zhao can promote modified with folic acid PLGA nanoparticle at the picked-up of tumor cell and the cytotoxicity of medicine (Zhao H, et al.Addition ofTPGS tofolate-conjugated polymer micelles for selective tumor targeting.JBiomed Mater Res A.2008, epub).Cao etc. form carrier micelle with amycin and TPGS by chemical bond, the free amycin half-life prolongs 4.5 times of (Cao N, et al.Doxorubicin conjugated to D-a-tocopheryl polyethylene glycol 1000succinate (TPGS): Conjugation chemistry, characterization, in vitro andin vivo evaluation.Biomaterials，2008，29：3856-65)。In addition, TPGS can promote Transdermal absorption (the Chen CH of medicine, et al.Simultaneous effects of tocopherylpolyethylene glycol succinate (TPGS) on local hair growth promotionand systemic absorption of topically applied minoxidil in a mouse model.Int J Pharm.2005,306 (1-2): 91-8.) and promote oral absorption (Mu L, the et al.Mixed micelles made of poly (ethyleneglycol)-phosphatidylethanolamine conjugate and d-alpha-tocopherylpolyethylene glycol 1000 succinate as pharmaceutical nanocarriers forcamptothecin.Int J Pharm.2005 306 (1-2): 142-9.) of medicine

In view of TPGS is a kind of multi-functional pharmaceutic adjuvant.The present invention is intended to utilize the PEG chain (molecular weight 1000) and the hydrophobic vitamin E chain of TPGS possess hydrophilic property, and the hydrophobic chain of vitamin E can insert the hydrophobic layer of liposome, to form the PEG modified liposome.Utilize simultaneously TPGS the effect of inhibition P-gp glycoprotein, promote characteristic such as cellular uptake and drug absorption and design the drug-loaded liposome prescription that contains TPGS.

Summary of the invention

First technical problem that the present invention will solve is to provide a kind of novel liposome composition that contains TPGS, and it can not only improve liposome medicament stability, and can improve the curative effect of medicine.

For solving the problems of the technologies described above, the present invention adopts following technical scheme:

A kind of liposome composition that contains TPGS is made up of phospholipids compounds, cholesterol chemical compound and TPGS, and the weight portion ratio phospholipids compounds of each component: cholesterol chemical compound: TPGS is 5～95: 0～50: 0.1～60.Wherein the expression of the weight portion lower limit " 0 " of cholesterol chemical compound can be substantially equal to zero, but is not 0.

The weight portion ratio phospholipids compounds of the preferred described component of the present invention: cholesterol chemical compound: TPGS is 50～90: 10～40: 1～40.

The weight portion ratio phospholipids compounds of further preferred described component: cholesterol chemical compound: TPGS is 60～90: 10～30: 5～30.

It is one of following that cholesterol chemical compound of the present invention can be selected from: cholesterol, Cholesteryl hemisuccinate (CHEMS), cholesterol sulfate sodium, DC-chol (3 β-[N-(N '; the N-dimethyl aminoethyl) amido formoxyl] cholesterol), be preferably cholesterol, CHEMS or DC-chol.

Second technical problem that the present invention will solve provides the application of liposome composition in the preparation drug-loaded liposome of the described TPGS of containing, and promptly by liposome composition and medication preparation drug-loaded liposome, this drug-loaded liposome can significantly improve the curative effect of medicine.

The medicine that the present invention is suitable for can be various types of medicines, can be divided into following a few class according to its solubility property: water solublity, amphiphilic, fat-soluble.Water soluble drug comprises: nucleic acid class, protide and micromolecular water soluble drug class such as cisplatin, carboplatin, fluorouracil, cantharidin, norcantharidin, oxymatrine etc.; Amphiphilic medicine comprises: weakly basic drugs example hydrochloric acid amycin, daunorubicin hydrochloride, mitoxantrone hydrochloride, vincristine sulfate, Arechin (Polfa), Farmorubine Hydrochloride etc., weak acidic drug such as prednisolone sodium succinate, Inflamase, dexamethasone sodium phosphate, hydrocortisone sodium succinate, diclofenac sodium, Urbason Solubile, Protophenicol (Proto)., betamethasone sodium phosphate etc.; Fat-soluble medicine comprises: emodin, chrysophanic acid, amphotericin B, paclitaxel, Docetaxel, vitamin C succinate, sodium L-ascorbate-2-phosphate, Vitamin E acetate, vitamin A palmitate, camptothecine, hydroxy camptothecin etc.Preferably in the preparation of drug-loaded liposome, the weight of described medicine is 1～40% of liposome composition weight in the present invention, and is preferred 1～30%, more preferably 1～20%.

The described medicine of the concrete recommendation of the present invention is an emodin.

The present invention is concrete to recommend described drug-loaded liposome to be made by following component: 48～87 parts of Ovum Gallus domesticus Flavus lecithins, 11～24 parts in cholesterol, 2～38 parts of TPGS, 5 parts of emodins.

Drug-loaded liposome of the present invention can adopt the conventional method preparation, can select voluntarily according to the character and the needs of medicine, such as using injection method, film dispersion method etc., the mode that is written into of medicine can adopt initiatively medicine carrying or passive medicine carrying, in general, fat-soluble medicine can adopt passive medicine carrying mode, and amphipathic medicine can adopt initiatively medicine carrying mode, and initiatively the medicine carrying mode can be selected ammonium sulphate gradient, calcium acetate gradient method etc. for use according to pharmaceutical properties.Water soluble drug both can adopt initiatively medicine carrying mode, also can adopt passive medicine carrying mode.

When medicine is amphiphilic weakly basic drugs, recommend to be prepared by the following method: phospholipids compounds, cholesterol and TPGS are dissolved in the ethanol or the tert-butyl alcohol, inject (NH fast₄)₂SO₄In the aqueous solution, form multilamelar liposome, N₂Be pressed through 200nm and 100nm polycarbonate membrane down successively, get unilamelar liposome.(NH in buffer ultrafiltration such as reuse aqueous sucrose solution or the phosphate displacement liposome disperse medium₄)₂SO₄, inside and outside the formation liposome bimolecular filmDegree gets blank unilamelar liposome; Then that amphiphilic weakly basic drugs is soluble in water, add in the blank unilamelar liposome, under the 37-65 ℃ of water bath condition, medicine is at NH₄⁺Enter the liposome medicine carrying under the effect of gradient, obtain drug-loaded liposome.

When medicine is amphiphilic weak acidic drug, recommend to be prepared by the following method: phospholipids compounds, cholesterol and TPGS are dissolved in the ethanol or the tert-butyl alcohol, inject the calcium acetate aqueous solution fast, form multilamelar liposome, N₂Be pressed through 200nm and 100nm polycarbonate membrane down successively, get unilamelar liposome.Calcium acetate in buffer ultrafiltration such as reuse aqueous sucrose solution or the acetate displacement liposome disperse medium forms the inside and outside calcium ion concentration gradient of liposome bimolecular film, gets blank unilamelar liposome; Then that amphiphilic weak acidic drug is soluble in water, add in the blank unilamelar liposome, under the 37-65 ℃ of water bath condition, medicine enters the liposome medicine carrying under the effect of calcium ion concentration gradient, obtain drug-loaded liposome.

When medicine is fat-soluble medicine, described drug-loaded liposome recommends to adopt following method to be prepared: phospholipids compounds, cholesterol, TPGS and fat-soluble medicine are placed reactor, adding organic solvent (preferred alcohol and/or chloroform) dissolves, the decompression rotary evaporation forms thin film, add normal saline or glycerine water solution hydrated films and form multilamelar liposome, N₂Be pressed through 200nm and 100nm polycarbonate membrane down successively, get the single chamber drug-loaded liposome.

When medicine is water soluble drug, described drug-loaded liposome recommends to adopt following method preparation: phospholipids compounds, cholesterol chemical compound and TPGS are placed reactor, adding organic solvent (preferred chloroform, dichloromethane, ethanol) dissolves, the decompression rotary evaporation forms thin film, add the normal saline hydrated films that contains water soluble drug and form multilamelar liposome, N₂Be pressed through 200nm and 100nm polycarbonate membrane down successively, get the single chamber drug-loaded liposome.

The drug-loaded liposome that the present invention makes is applicable to drug administration by injection, oral administration, percutaneous drug delivery and other mode administration.

Compared with prior art, beneficial effect of the present invention is: the present invention utilizes the multifunctionality design PEG modified liposome of TPGS.Utilize the PEG chain (molecular weight 1000) and the hydrophobic vitamin E chain of TPGS possess hydrophilic property, the hydrophobic chain of vitamin E can insert the hydrophobic layer of liposome, to form the PEG modified liposome, improves liposome stability and has the circulation of prolong drug body.Utilize simultaneously TPGS suppress the P-gp glycoprotein effect, promote characteristic such as cellular uptake and drug absorption and design contain TPGS the drug-loaded liposome prescription to improve curative effect of medication.Compare with existing PEG2000-DSPE modified liposome, short, sterically hindered little than the PEG chain of PEG2000-DSPE (PEG molecular weight 2000) because of PEG chain among the TPGS (molecular weight 1000), easy and cells contacting is also absorbed; And TPGS also has the function that suppresses P-gp, promotes drug absorption and has certain antitumaous effect; TPGS is ratified as pharmaceutic adjuvant by FDA simultaneously, and price is cheap than PEG-DSPE, and its application at liposome will reduce production costs to a great extent.In a word, liposome composition of the present invention and drug-loaded liposome owing to added TPGS, more help bringing into play curative effect of medication.

Description of drawings

Emodin liposome that the emodin liposome that Fig. 1 modifies for PEG-DSPE, TPGS modify and the cytotoxicity figure of free emodin medicine andL1210 cytosis 24h;

Emodin liposome that the emodin liposome that Fig. 2 modifies for PEG-DSPE, TPGS modify and the cytotoxicity figure of free emodin medicine andL1210 cytosis 48h;

Emodin liposome that the emodin liposome that Fig. 3 modifies for PEG-DSPE, TPGS modify and the cytotoxicity figure of free emodin medicine andL1210 cytosis 72h.

The specific embodiment

With specific embodiment technical scheme of the present invention is described further below, but protection scope of the present invention is not limited thereto:

Embodiment 1: the emodin liposome prescription that contains TPGS

Table 1 contains the emodin liposome prescription of TPGS

	Formula I	Formula I I	Formula I II	Formula I V
					Prescription	mg	mg	mg	mg
EPC	87	65	56	48
					Cholesterol	11	24	22	14
TPGS	2	12	22	38
					Emodin	5	5	5	5

Lecithin, cholesterol, TPGS and emodin are placed round-bottomed flask, add the ethanol of 15ml and chloroform (2: 8, V/V) mixed solution lipin dissolving and medicine, the decompression rotary evaporation forms thin film, add the normal saline hydrated films and form multilamelar liposome, the ultimate density that makes emodin is 0.5mg/ml.N₂Be pressed through 200nm and 100nm polycarbonate membrane down successively, get the single chamber drug-loaded liposome, outward appearance is light yellow turbid shape liquid.

Embodiment 2:PEG-DSPE modifies the comparison of modifying the emodin liposome with TPGS

Respectively the EPC/Chol/TPGS (55/40/5) of identical mol ratio and EPC/Chol/PEG-DSPE (55/40/5) are prepared the emodin liposome by the method for embodiment 1, final emodin concentration is 0.5mg/ml, envelop rate is all more than 90% as a result, about mean diameter 100nm, 4 ℃ of refrigerators were placed 6 months, and stability is all good.Compare the cytotoxicity behind two kinds of liposomees and free emodin and the L1210 cytosis different time, the results are shown in Figure 1-3.From Fig. 1-3 as seen, the emodin liposome of free emodin of the emodin liposome cytotoxicity of TPGS modification and PEG-DSPE modification significantly improves.

Embodiment 2: the amphiphilic alkalescent medicine liposome prescription that contains TPGS

Table 2-1 contains parents' part alkalescent medicine liposome formula I of TPGS

Prescription	mg
		HSPC	74
Cholesterol	25
		TPGS	1
Mitoxantrone hydrochloride	10

Table 2-2 contains the amphiphilic alkalescent medicine liposome formula I I of TPGS

Prescription	mg
		HSPC	48
Cholesterol	15
		TPGS	38
Doxorubicin hydrochloride	?7

Table 2-3 contains the amphiphilic alkalescent medicine liposome formula I II of TPGS

Prescription	mg
		DSPC	81
Cholesterol	17
		TPGS	2
Vincristine sulfate	19

Table 2-4 contains the amphiphilic alkalescent medicine liposome formula I V of TPGS

Prescription	mg
		EPC	56
Cholesterol	22

TPGS	22
		Arechin (Polfa)	7

Table 2-5 contains the amphiphilic alkalescent medicine liposome prescription V of TPGS

Prescription	mg
		DPPC	54
Cholesterol	16
		TPGS	30
Daunorubicin hydrochloride	8

Phospholipid, cholesterol and TPGS are dissolved in the ethanol of 1ml, inject 5ml fast and contain 300mM pH4.0 (NH₄)₂SO₄Solution in, form multilamelar liposome, N₂Be pressed through 200nm and 100nm polycarbonate membrane down successively, get unilamelar liposome.Reuse contains the (NH in the aqueous solution ultrafiltration displacement liposome disperse medium of 10% sucrose₄)₂SO₄, form the inside and outside NH of liposome bimolecular film₄⁺Gradient gets blank unilamelar liposome, and the lipid total concentration is 20mg/ml, and mean diameter is all less than 100nm.

The above-mentioned Chinese medicine of respectively writing out a prescription is soluble in water, add in the blank unilamelar liposome, 55 ℃ of water-bath 1h, medicine is at NH₄⁺Enter the liposome medicine carrying under the effect of gradient, envelop rate is all more than 90%.

Embodiment 3: the amphiphilic acidic drug liposome prescription that contains TPGS

Table 3-1 contains the amphiphilic acidic drug liposome formula I of TPGS

Prescription	mg
		HSPC	73
Cholesterol	25
		TPGS	2
Prednisolone sodium succinate	7

Table 3-2 contains the amphiphilic acidic drug liposome formula I I of TPGS

Prescription	mg
		HSPC	55

Cholesterol	23
		TPGS	22
Dexamethasone sodium phosphate	10

Phospholipid, cholesterol and TPGS are dissolved in the 1ml ethanol, inject the solution that 5ml contains the 200mM calcium acetate fast, form multilamelar liposome, N₂Be pressed through 200nm and 100nm polycarbonate membrane down successively, get unilamelar liposome.Calcium acetate in the reuse 10% sucrose solution dialysis displacement liposome disperse medium forms the inside and outside calcium ion gradient of liposome bimolecular film, gets blank unilamelar liposome, and the lipid total concentration is 20mg/ml, and mean diameter is less than 100nm.

Medicine in the above-mentioned prescription is water-soluble, add in the blank unilamelar liposome that makes, 65 ℃ of water-bath 1h, medicine enter the liposome medicine carrying under the effect of calcium ion gradient, and envelop rate is more than 85%.

Embodiment 4: the water-soluble pesticide composite lipidosome prescription that contains TPGS

Table 4-1 contains the water-soluble pesticide composite lipidosome prescription of TPGS

Prescription	mg
		HSPC	65
CHEMS	25
		TPGS	10
Cisplatin	5

Phospholipid, cholesterol and TPGS are placed round-bottomed flask, add chloroform 15ml lipin dissolving, the decompression rotary evaporation forms thin film, adds cisplatin normal saline hydrated films and forms multilamelar liposome, N₂Be pressed through 200nm and 100nm polycarbonate membrane down successively, get the single chamber drug-loaded liposome, the lipid total concentration is 20mg/ml, and mean diameter is less than 100nm, and envelop rate is more than 85%.

Embodiment 5: the hard-soluble medicine liposome prescription that contains TPGS

Table 5-1 contains the hard-soluble medicine liposome formula I of TPGS

Prescription	mg
		DPPC	69
Cholesterol	11
		TPGS	20

Paclitaxel

3.5

Table 4-2 contains the hard-soluble medicine liposome formula I I of TPGS

Prescription	mg
		?HSPC	58
?DSPG	23
		Cholesterol	14
?TPGS	4
		Amphotericin B	15

Phospholipid, cholesterol, TPGS and medicine are placed round-bottomed flask, add 15ml ethanol and chloroform (2: 8, V/V) mixed solution lipin dissolving and medicine, the decompression rotary evaporation forms thin film, adds the normal saline hydrated films and forms multilamelar liposome, N₂Be pressed through 200nm and 100nm polycarbonate membrane down successively, get the single chamber drug-loaded liposome, the lipid total concentration is 20mg/ml, and mean diameter is less than 100nm, and envelop rate is more than 85%.

Embodiment 6: functional cosmetics liposome prescription

Table 6-1 contains the functional cosmetics liposome formula I of TPGS

Prescription	mg
		SPC	87
Cholesterol	11
		TPGS	2
TheVc cetylate	10

Table 6-2 contains the functional cosmetics liposome formula I I of TPGS

Prescription	mg
		EPC	85
Cholesterol	5
		TPGS	10

Vitamin E acetate

15

Table 6-3 contains the functional cosmetics liposome formula I II of TPGS

Prescription	mg
		SPC	61
Cholesterol	4
		TPGS	34
TheVA cetylate	20

Lecithin, cholesterol, TPGS and medicine are placed round-bottomed flask, add 20ml ethanol and chloroform (3: 7, V/V) mixed solution lipin dissolving and medicine, the decompression rotary evaporation forms thin film, glycerol adding aqueous solution hydrated films forms multilamelar liposome, N₂Be pressed through 200nm and 100nm polycarbonate membrane down successively, get the single chamber drug-loaded liposome, the lipid total concentration is 40mg/ml, and mean diameter is less than 100nm, and envelop rate is more than 90%.

Claims

1. a liposome composition that contains TPGS is made up of phospholipids compounds, cholesterol chemical compound and TPGS, and the weight portion ratio phospholipids compounds of each component: cholesterol chemical compound: TPGS is 5～95: 0～50: 0.1～60.

2. the liposome composition that contains TPGS as claimed in claim 1, it is characterized in that the weight portion ratio phospholipids compounds of described component: cholesterol chemical compound: TPGS is 50～90: 10～40: 1～40.

3. the liposome composition that contains TPGS as claimed in claim 2, it is characterized in that the weight portion ratio phospholipids compounds of described component: cholesterol chemical compound: TPGS is 60～90: 10～30: 5～30.

4. as the described liposome composition that contains TPGS of one of claim 1～3, it is characterized in that described phospholipids compounds is selected from following a kind of or several combination arbitrarily: phosphatidylcholine class, PHOSPHATIDYL ETHANOLAMINE class, phosphatidyl glycerol class, Phosphatidylserine class.

5. the liposome composition that contains TPGS as claimed in claim 4, it is one of following to it is characterized in that described phospholipids compounds is selected from: Ovum Gallus domesticus Flavus lecithin, soybean lecithin, hydrogenated soya phosphatide phatidylcholine, two myristic acid phosphatidylcholines, two Palmic acid phosphatidylcholines, distearyl acid phosphatidylcholine.

6. as the described liposome composition of one of claim 1～3, it is one of following to it is characterized in that described cholesterol chemical compound is selected from: cholesterol, Cholesteryl hemisuccinate, cholesterol sulfate sodium, DC-chol.

7. the application of liposome composition in the preparation drug-loaded liposome that contains TPGS as claimed in claim 1, it is characterized in that described medicine is amphiphilic medicine, water soluble drug or fat-soluble medicine, the weight of described medicine is 1～40% of liposome composition weight.

8. the application of liposome composition in the preparation drug-loaded liposome that contains TPGS as claimed in claim 7, the weight that it is characterized in that described medicine is 1～30% of liposome composition weight.

9. the application of liposome composition in the preparation drug-loaded liposome that contains TPGS as claimed in claim 7 is characterized in that described medicine is an emodin.

10. the application of liposome composition in the preparation drug-loaded liposome that contains TPGS as claimed in claim 9, it is characterized in that described drug-loaded liposome made by following component: 48～87 parts of Ovum Gallus domesticus Flavus lecithins, 11～24 parts in cholesterol, 2～38 parts of TPGS, 5 parts of emodins.