CN102670509B - Liposomal formulation containing slightly solubility camptothecine and preparation method thereof - Google Patents

Abstract

The present invention relates to a kind of Liposomal formulation containing slightly solubility camptothecine and preparation method thereof.Described Liposomal formulation comprises slightly solubility camptothecine, phospholipid, salt and sugar or polyhydric alcohol, described salt is selected from buffer salt and/or inorganic salt, its concentration is 0.1mol/L～1.0mol/L, it is preferably 0.3mol/L～0.8mol/L, described sugar or polyhydric alcohol are selected from sucrose, trehalose, glucose, sorbose, lactose, fructose, sorbitol and mannitol, its concentration is 200mg/ml～1000mg/ml, preferably 300mg/ml～800mg/ml.The invention still further relates to comprise the pharmaceutical composition of described Liposomal formulation, and described Liposomal formulation is for preparing the purposes of antitumor drug.The Liposomal formulation envelop rate of the present invention is high, and preparation is simple, convenient, is suitable for large-scale production.

Description

Liposomal formulation containing slightly solubility camptothecine and preparation method thereof

Technical field

The invention belongs to technical field of medicine, be specifically related to a kind of liposome containing slightly solubility camptothecine Preparation and preparation method thereof.

Background technology

Camptothecine or derivatives thereof, also referred to as camptothecine, be DNA synthetic inhibitor, for kinds cancer disease Treatment.The kind of camptothecine has camptothecine, 9-hydroxy camptothecin, 9-aminocamptothecin, 10-hydroxyl in the market Camptothecine, nitrocamptothecin, 7-(β-trimethyl silyl) ethyl-camptothecin, 7-(tert-butoxy) formamino camptothecine, SN38 (SN-38), 9-nitrocamptothecin (9-NC) etc., mainly by modes such as vein, oral, sprayings It is administered.

Camptothecine, with topoisomerase as site of action, plays antitumaous effect by the synthesis of target suppression DNA, Being applicable to the tumor of the different speed of growth, cytotoxicity is strong, for multiple evils such as gastric cancer, hepatocarcinoma, osteocarcinoma, leukemia, bladder cancer The therapeutic effect of property tumor is obvious.Its mechanism of action is Selective depression DNA topoisomerase I (TOPO I).In mechanism In, camptothecine lactonic ring is opened, and the nucleophilic moiety of acyl group and TOPO II interacts, and by with TOPO I-DNA Cleavable complex Reversible binding form camptothecine-TOPOI-DNA ternary complex, thus stablize TOPO I-DNA Complex, suppression DNA untwists, and causes DNA di-phosphate ester bond fission, and then Apoptoais and death occurs.

Camptothecine has anti-tumor activity in vivo must keep the complete of hexa-atomic Alpha-hydroxy lactonic ring (ring E) Property, i.e. keep the Guan Bi of lactonic ring, lactonic ring to open, activity is substantially reduced or inactive.But slightly water-soluble camptothecin class medicine Alpha-hydroxy lactonic ring aqueous environments is had sensitivity, can be with hydrolysis in the aqueous environments that the pH such as blood are high so that it is Lose anti-tumor activity.And make natrium brine injection by open loop of being alkalized by camptothecine the most clinically and use, Though the method adds water solublity, but activity only has the most original l/10 even lower.In order to improve slightly solubility camptothecine Stability and drug effect, it may be considered that slightly solubility camptothecine is prepared as Liposomal formulation.

Liposome is the lipid bilayer that phospholipid is formed when being dispersed in water, and it is internal be the Guan Bi vesicle of aqueous phase, leads Liposome to be had the following characteristics that is a kind of lipid bilayer folliculus, and structure is similar with cell biological film, therefore has good Cell compatibility；Film material can biodegradation and avirulence and immunogenicity in vivo；Both can coated water-soluble medicine, can wrap again Wrapping up in fat-soluble medicine, the intravenously administrable for fat-soluble medicine provides possibility；Liposome can possess target function, reduces medicine Toxicity.Therefore, slightly solubility camptothecine is prepared as Liposomal formulation and can protect its lactonic ring, maintain its activity, fall Its toxic and side effects low.

At present, the report of the Liposomal formulation of existing multiple camptothecine, the patent of Publication No. CN1537534A Report a kind of liposome containing phospholipid, cholesterol, freeze drying protectant and 10-hydroxycamptothecine and preparation method thereof；Public The patent that the number of opening is CN1980671A discloses a kind of lipid system containing phospholipid, fatty acid and slightly water-soluble camptothecin Agent；The patent of Publication No. CN101003556A discloses a kind of 10-hydroxycamptothecine derivant, its Liposomal formulation and preparation Method；Publication No. CN1650864A, the patent of CN1582932A, CN101019834A all disclose a kind of camptothecine or its class Patent like the liposome of thing.But owing to slightly water-soluble camptothecin class medicine is usually, water is insoluble, fat slightly solubility, with fat such as phospholipid The affinity of matter is poor, and the liposome encapsulation therefore using said method to prepare is the most relatively low, less than 50%.To this end, specially Profit CN1562021A discloses a kind of method improving envelop rate by regulation foreign minister pH, and first the method is by such medicine Alkaline solution dissolves, regulates foreign minister pH again after being then encapsulated into liposome with solution (open loop) form and make camptothecine Become precipitation (closed loop) form to be wrapped in liposome interior, thus can improve the envelop rate of medicine, but the method is still limited to wrap Envelope rate is elevated above 75% by the 10%-30% of prior art.

If the envelop rate of slightly solubility camptothecine liposome can be improved further, it is beneficial to it as antitumor Medicine application in clinic.

Summary of the invention

In order to improve the envelop rate of slightly solubility camptothecine liposome preparation further, inventor is by substantial amounts of reality Test, it was demonstrated that in the preparation process of liposome, add the salt of high concentration and sugar can make more drug encapsulation in liposome, This completes the present invention.Camptothecine owing to the present invention relates to belongs to water not fat melting insoluble drug, at water and having Dissolubility in machine solvent is the most relatively low, and the phospholipid forming liposome belongs to amphipathic nature material, adds high concentration in aqueous phase Salt and sugar cause the increase of solution ion strength, reduce medicine dissolubility in aqueous phase, promote the medicine in aqueous phase to fat Distribution in plastid, thus improve the envelop rate of medicine.

One aspect of the present invention relates to a kind of Liposomal formulation, its comprise slightly solubility camptothecine, phospholipid, salt with And sugar or polyhydric alcohol, it is characterised in that the concentration of described salt is 0.1mol/L～1.0mol/L, preferably 0.3mol/L～ 0.8mol/L, in embodiments of the invention, is 0.3,0.5 or 0.7mol/L；The concentration of described sugar or polyhydric alcohol is 200mg/ml～1000mg/ml, preferably 300mg/ml～800mg/ml, in embodiments of the invention, described sugar or many The concentration of unit's alcohol is 300mg/ml, 400mg/ml or 500mg/ml.

Wherein said slightly solubility camptothecine refers to water-insoluble fat slightly solubility camptothecine, it include but It is not limited to camptothecine, 9-hydroxy camptothecin, 9-aminocamptothecin, 10-hydroxycamptothecine, nitrocamptothecin, 7-(β-trimethyl first Silylation) ethyl-camptothecin, 7-(tert-butoxy) formamino camptothecine and SN38, and they Pharmaceutical salts.In embodiments of the invention, described slightly solubility camptothecine include 10-hydroxycamptothecine, 9-aminocamptothecin and SN-38。

Described phospholipid can be saturated phospholipid, it is also possible to for unsaturated phospholipid, can be natural phospholipid, it is also possible to for closing Become phospholipid, can be common phospholipid, it is also possible to for modify after phospholipid such as hydrophilic group modification phospholipid or there is special nature Phospholipid such as has the phospholipid of long circulating character and have the phospholipid of sensitive characteristic, described phospholipid include but not limited to egg yolk lecithin, Soybean phospholipid, hydrogenated soya phosphatide, hydrogenation egg yolk lecithin, DSPG, DSPE, list Distearoylphosphatidic acid choline, dipalmitoyl phosphatidyl choline, distearoyl phosphatidylcholine, 1,2-Dierucoyl-Sn- Glycero-3-phosphocholine, DOPC, DSPE, two palmityl phosphatidyls Ethanolamine, DOPE, DPPG, DSPG, sphingomyelin, phosphorus Acyl serine, phosphatidic acid, lysophosphatide, MPPC, MSPC, different molecular weight The phospholipid of Pegylation, cephalin, Yolk lecithin, phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, phosphatidylinositols, phospholipid Acyl glycerol, Phosphatidylserine, two myristoyl lecithin, PHOSPHATIDYL ETHANOLAMINE, phosphatidylcholine, two Cetyl Phosphates, two Palmityl phosphatidic acid, two Laurel phosphatidylcholines, distearoyl phosphatidylcholine, two mustard acyl group lecithin, distearyl phospholipid Acyl glycerol, two capryl lecithin, DOPC, MPPC, 1-myristoyl-2- Stearoyl lecithin, PMPC, PSPC, 1-stearoyl-2-meat Myristoyl lecithin, SPPC, 1-myristoyl-2-oleoyllecithin, 1-palmityl-2-oleoyl Lecithin, myristoyl LYSOLECITHIN SUNLECITHIN A, palmityl LYSOLECITHIN SUNLECITHIN A, stearoyl LYSOLECITHIN SUNLECITHIN A, two lauroyl phosphatidyls are sweet Oil, GLYCEROL,DIMYRISTOYL PHOSPHATIDYL, DPPG, DSPG, dioleoyl phospholipid acyl are sweet Oil, two mustard acyl phospholipids acyl glycerol, 1-palmityl-2-oleoylphosphatidyl glycerol, two myristoyl phosphatidic acid, two palmityl phospholipid Acid, G 12S3P, DMPEA, DPPE, distearoylphosphatidyl Ethanolamine, DOPE, two mustard acylphosphatidyl ethanolamines, 1-palmityl-2-oleoylphosphatidyl ethanolamine, two Myristoyl Phosphatidylserine, distearoylphosphatidyl serine, two palmityl Phosphatidylserine, dioleoyl phospholipid acyl silk Propylhomoserin, distearyl ethanolamine-Polyethylene Glycol or its two or more mixture.

In embodiments of the invention, described phospholipid is dipalmitoyl phosphatidyl choline DPPC and long circulating phospholipid two is hard The mixture of acyl ethanolamine-Macrogol 2000, unsaturated phospholipid Ovum Gallus domesticus Flavus lecithin or Ovum Gallus domesticus Flavus lecithin and distearyl The mixture of ethanolamine-Macrogol 2000.

In the present invention, described slightly solubility camptothecine is 0.0001: 1～1: 1 with the percentage by weight of phospholipid； It is preferably 0.005: 1～0.1: 1.

In the present invention, described salt be the one in soluble-salt, for example, buffer salt and/or soluble inorganic salt or Multiple, for example, in phosphate, carbonate, acetate, citrate, oxalates, sulfate, sulphite or hydrochlorate Planting or multiple, preferably phosphate, in embodiments of the invention, described salt is sodium ascorbyl phosphate or potassium phosphate/sodium salt.

In the present invention, described sugar or polyhydric alcohol are in monosaccharide and disaccharide, soluble polysaccharide and small molecule polyol One or more, preferably one or more in monosaccharide and disaccharide and small molecule polyol, for example, sucrose, trehalose, Portugal One or several in grape sugar, sorbose, lactose, fructose, sorbitol and mannitol, in embodiments of the invention, described Sugar or polyhydric alcohol be sucrose or trehalose.

In the present invention, described Liposomal formulation is possibly together with additive, and described additive is solid selected from antioxidant, gallbladder In alcohol, surfactant, magnetisable material, antibody, part, stabilizer, charged species, pH adjusting agent and high molecular polymer one Plant or several.In one embodiment of the invention, described additive is antioxidant vitamin E；In the present invention one In embodiment, described additive is cholesterol.

Described antioxidant such as vitamin E, sodium sulfite, sodium sulfite etc. have the material of antioxidation；Institute The surfactant stated such as poloxamer, tween, span etc. have the material of surface-active action；Described magnetisable material such as three Aoxidize two ferrum, ferroso-ferric oxide etc. and there is magnetisable material；Described antibody be can specific effect in the material of some receptor, as The antibody F105 etc. of AntiHIV1 RT activity；Described part refer to can specific effect in the little molecule of some receptor material such as mannitol, Galactose etc.；Described charged species is the material per se with electric charge, as phosphatidic acid (PA), Phosphatidylserine (PS), ten Eight amine etc.；Described pH adjusting agent is to regulate the material of pH, such as citric acid, hydrochloric acid, phosphoric acid, triethylamine etc.；Described height Molecularly Imprinted Polymer can be dextran, Polyethylene Glycol etc..

Those skilled in the art can add different additives according to actual needs, and obtained liposome can be general Logical liposome, long circulating liposomes, thermal sensitive liposome, long circulating thermal sensitive liposome, magnetic liposome or immunoliposome.

In the present invention, the envelop rate of described Liposomal formulation can reach more than 85%, after multigelation, encapsulates Rate can reach more than 90%, even close to 100%.

Another aspect of the present invention relates to a kind of pharmaceutical composition, and it contains the lipid system of the present invention of therapeutically effective amount Agent, and pharmaceutically acceptable carrier or excipient.

The further aspect of the present invention relates to the preparation method of the Liposomal formulation of the present invention, and it can use Passive loading skill Prepared by art, including film dispersion method, organic solvent lyophilization, spray drying method, fluidized bed coating, single phase soln lyophilization, Reverse phase evaporation, second emulsifying method, alcohol injection or cross-current injection；In specific embodiments of the present invention, described system Preparation Method is film dispersion method and spray drying method, specifically includes following steps:

(1) slightly solubility camptothecine, phospholipid and additive are dissolved in organic solvent, such as chloroform and/or methanol In；

(2) in evaporation (1), gained solution, to remove organic solvent, obtains mixed powder or thin film；Or by (1) gained solution It is spray-dried, obtains mixed powder；

(3) in (2), in gained mixed powder or thin film or (1), gained solution adds containing salt and the solution of sugar, aquation Or after emulsifying, suspension is removed, ultrasonic or homogenizing crosses film, degerming, obtains liposome；Optionally, before degerming, multigelation is added Step.

In one embodiment of the invention, described slightly solubility camptothecine liposome preparation uses thin film to divide Prepared by arching pushing, will medicine, phospholipid and other additives be dissolved in organic solvent, ultrasonic dissolution.Rotary evaporation removes organic Solvent, puts in vacuum drying oven and adds after certain time containing high salt concentration and the solution of sugar, removed by suspension after aquation, ultrasonic Or homogenizing crosses film, obtain liposome.

In another embodiment of the present invention, described slightly solubility camptothecine liposome preparation uses spraying Prepared by seasoning, will medicine, phospholipid and other additives be dissolved in organic solvent, ultrasonic dissolution.Be spray-dried i.e. obtain mixed Close powder, put in vacuum drying oven and add after certain time containing high salt concentration and the solution of sugar, after aquation, suspension is removed, ultrasonic Or homogenizing crosses film, obtain liposome.

Described liposome stores after can being directly over filtering bacterium after prepared by distinct methods or uses, it is also possible to repeatedly Freeze thawing, to increase the envelop rate of liposome further, is then passed through filtering bacterium and stores or use.

Described liposome can make injection, lyophilized injectable powder, infusion solutions or spray further.

Use this method, be possible not only to prepare conventional liposome, it is also possible to be prepared as long circulating liposomes, long circulating temperature-sensitive Liposome and other actively or passively target liposomes, can increase the stability of medicine, improves pharmaceutically active, can increase Medicine, in the release of target area, improves curative effect, it is also possible to reduces the medicine distribution at systemic circulation system, thus reduces total medication Amount, reduces whole body toxic and side effects simultaneously.

Another aspect of the present invention relates to the Liposomal formulation of present invention purposes in preparing antitumor drug.

The beneficial effect of the invention

The present invention, in the Liposomal formulation of slightly solubility camptothecine, adds salt and the sugar of high concentration so that protecting While card pharmaceutically active, substantially increase the envelop rate containing slightly solubility camptothecine liposome preparation, its envelop rate Can reach more than 85%, and after multigelation, envelop rate can reach more than 90%, close to 100%.Slightly solubility camptothecine Medicine lisposome preparation envelop rate be greatly improved the application that would be even more beneficial to such medicine in clinical treatment tumour.

Meanwhile, this Liposomal formulation preparation method is simple, convenient, it is not necessary to medicine first changes into inactive open loop form It is encapsulated in the most again in liposome or reconvert becomes closed loop, but can directly such medicine be encapsulated in closed loop In liposome, it is suitable for large-scale production.

Accompanying drawing explanation

The grain size distribution of the liposome of Fig. 1 embodiment 1 preparation.

Wherein vertical coordinate " cumulative distribution " represents cumulative distribution, and unit is %, " density Distribution " represent Density Distribution；Abscissa " particle size " represents granularity, and unit is nanometer (nm).

Detailed description of the invention

Below in conjunction with embodiment, embodiment of the present invention are described in detail, but those skilled in the art will Understanding, the following example is merely to illustrate the present invention, and should not be taken as limiting the scope of the invention.In embodiment unreceipted specifically Condition person, the condition advised according to normal condition or manufacturer is carried out, or (prunus mume (sieb.) sieb.et zucc. is made the country prosperous with reference to " microcarrier drug delivery system " Compiling, on November 1st, 2009 publishes, publishing house of the Central China University of Science and Technology).Agents useful for same or instrument unreceipted production firm person, be Can by city available from conventional products.

The preparation of embodiment 110-hydroxy camptothecin long circulation thermal sensitive liposome

Use thin film dispersion-homogenizing to cross embrane method and prepare liposome: by 10-hydroxycamptothecine 1g, DPPC (two palmityl ovum Phospholipid) 46g, distearyl ethanolamine-Macrogol 2000 3.0g, it is dissolved in chloroform: methanol=1: in 1, ultrasonic to the most molten Solving, the rotating speed rotary evaporation 40min of 55 DEG C of 150rpm, to remove organic solvent, is vacuum dried 3h, adds containing 500mg/ml sea In the phosphate sodium solution of 0.3M, pH5.0 of algae sugar, under the conditions of 50 DEG C of 100rpm after aquation 40min, homogenizing crosses the poly-of 0.15 μm Carbonic ester film, the mixed liquor after then crossing 0.22 μm film is divided into 2 parts, and portion directly stores use, a through following program Store after freeze thawing and use, obtain the long circulating thermal sensitive liposome of 10-hydroxycamptothecine.

Freeze thawing program:

Freeze thawing program-70 DEG C 50 DEG C-70 DEG C 50 DEG C-70 DEG C 50 DEG C-20 DEG C

Time 2h 10min 2h 10min 2h 10min preserves

The preparation of embodiment 210-Hydroxycamptothecin liposome

By 10-hydroxycamptothecine 2g, Ovum Gallus domesticus Flavus lecithin 47.5g, vitamin E 0.5g, it is dissolved in chloroform: methanol=2: in 1, Ultrasonic to being completely dissolved, the rotating speed rotary evaporation 40min of 45 DEG C of 150rpm, to remove organic solvent, is vacuum dried 3h, and addition contains Have in the phosphate sodium solution of 0.5M, pH5.0 of 400mg/ml sucrose, under the conditions of 45 DEG C of 100rpm after aquation 40min, homogenizing mistake The polycarbonate membrane of 0.10 μm, stores after multigelation and uses, obtain 10-hydroxycamptothecine liposome.

The preparation of embodiment 39-amino camptothecin long circulating liposomes

By 9-aminocamptothecin 4g, Ovum Gallus domesticus Flavus lecithin 43g, distearyl ethanolamine-Macrogol 2000 2.5g, cholesterol 0.5g, is dissolved in chloroform: methanol=2: in 1, ultrasonic to being completely dissolved, the rotating speed rotary evaporation 40min of 50 DEG C of 150rpm is to remove Organic solvent, is vacuum dried 3h, adds in the phosphate sodium solution of 0.7M, pH5.0 of containing 300mg/ml sucrose, 45 DEG C Under the conditions of 100rpm after aquation 40min, homogenizing crosses the polycarbonate membrane of 0.10 μm, stores and uses, obtain 9-after multigelation Amino camptothecin long circulating liposomes.

The preparation of embodiment 4SN-38 long circulating thermal sensitive liposome

By SN-38 (SN38) 2g, DPPC46g, distearyl ethanolamine-Macrogol 2000 2.0g, joins in ethanol, ultrasonic to being completely dissolved, and is spray-dried to obtain dried object, add the 0.3M containing 500mg/ml sucrose, In potassium phosphate/sodium salt (potassium/sodium=1: the 4) solution of pH5.0, under the conditions of 45 DEG C of 100rpm after aquation 40min, homogenizing crosses 0.15 μm Polycarbonate membrane, after multigelation store use, obtain the long circulating thermal sensitive liposome of SN-38.

The mensuration of embodiment 5 liposome encapsulation

Take liposome appropriate, being placed in 12000rpm under Super High Speed Condition and be centrifuged 8min, if there being precipitation, being centrifuged repeatedly, until Occur without precipitation, take supernatant, add appropriate methanol or add the methanol rupture of membranes of suitable Triton aqueous solution, then through HPLC Method measures the content of drug in solution, and before and after being centrifuged by contrast, the cubage envelop rate of lipidosome Chinese traditional medicine thing, the results are shown in Table 1。

The mensuration of table 1 liposome encapsulation

From result above, each embodiment gained envelop rate is the highest, more than 85%, and through multigelation After, envelop rate can reach more than 90%, close to 100%.

Embodiment 6 liposomal particle size and the detection of stability

Taking liposome or the liposome after dilution is appropriate, use appropriate distilled water diluting, the population making final concentration is 40- 120cps (the number of each second；Characters per second), it is placed on nano particle size analyzer mensuration.

Pick and place the liposome putting different time and the liposome diluted through different multiples (carries out dilute with glucose injection Release) appropriate, measure its change of size, investigate placement and the dilution stability of liposome.Particle diameter and stability result such as table 2 institute Show.

Table 2 liposome places the change of size of different time after dilution different multiples

From result above, the particle diameter of prepared each batch liposome places 24h without significant change in room temperature, each batch Secondary liposome particle diameter after glucose injection dilutes 20 times and 50 times, also without significant change, places 24h in room temperature after dilution Rear particle diameter, also without significant change, illustrates that the room temperature shelf-stability of liposome and dilution stability are preferable.

Although the detailed description of the invention of the present invention has obtained detailed description, it will be understood to those of skill in the art that.Root According to disclosed all teachings, those details can be carried out various amendment and replacement, these change all the guarantor of the present invention Within the scope of protecting.The four corner of the present invention is given by claims and any equivalent thereof.

Claims (15)

1. a Liposomal formulation, its comprise slightly solubility camptothecine, phospholipid, salt and sugar or polyhydric alcohol, its feature exists In, this Liposomal formulation is prepared by following preparation method, and this preparation method comprises the following steps:

(1) slightly solubility camptothecine, phospholipid and additive are dissolved in organic solvent；

(2) in evaporation (1), gained solution, to remove organic solvent, obtains mixed powder or thin film；Or (1) gained solution is carried out It is spray-dried, obtains mixed powder；

(3) by suspension after in (2), gained mixed powder or thin film addition contain salt and sugar or the solution of polyhydric alcohol, aquation or emulsifying Removal, ultrasonic or homogenizing crosses film, degerming, obtains liposome；

Optionally, before degerming, add the step of multigelation,

The concentration of described salt is 0.3mol/L～0.8mol/L；The pH value of described salt is 5.0；The concentration of described sugar or polyhydric alcohol is 300mg/ml～800mg/ml,

Described additive is selected from antioxidant, cholesterol, surfactant, magnetisable material, antibody, part, stabilizer, charged thing One or several in matter, pH adjusting agent and high molecular polymer.

2. the Liposomal formulation of claim 1, wherein said slightly solubility camptothecine is selected from camptothecine, 9-hydroxy-camptothecin Alkali, 9-aminocamptothecin, 10-hydroxycamptothecine, nitrocamptothecin, 7-(β-trimethyl silyl) ethyl-camptothecin, 7-(uncle Butoxy) formamino camptothecine and SN38, and their pharmaceutical salts.

3. the Liposomal formulation of claim 1, wherein said salt is soluble-salt.

4. the Liposomal formulation of claim 1, wherein said salt is buffer salt and/or soluble inorganic salt.

5. the Liposomal formulation of claim 3, wherein said soluble-salt is selected from phosphate, carbonate, acetate, citric acid One or more in salt, oxalates, sulfate, sulphite and hydrochlorate.

6. the Liposomal formulation of claim 1, wherein said organic solvent is chloroform and/or methanol.

7. the Liposomal formulation of claim 1, wherein said sugar or polyhydric alcohol selected from monosaccharide and disaccharide, soluble polysaccharide and One or more in small molecule polyol.

8. the Liposomal formulation of claim 1, wherein said sugar or polyhydric alcohol are in monosaccharide and disaccharide and small molecule polyol One or more.

9. the Liposomal formulation of claim 7, wherein said sugar or polyhydric alcohol are selected from sucrose, trehalose, glucose, Pyrusussuriensis One or more in sugar, lactose, fructose, sorbitol and mannitol.

10. the Liposomal formulation of claim 1, wherein said slightly solubility camptothecine with the percentage by weight of phospholipid is 0.0001:1～1:1.

The Liposomal formulation of 11. claim 1, wherein said slightly solubility camptothecine with the percentage by weight of phospholipid is 0.005:1～0.1:1.

12. pharmaceutical compositions, it contains the Liposomal formulation of any one of claim 1-11 of therapeutically effective amount, and pharmaceutically Acceptable carrier or excipient.

The preparation method of the Liposomal formulation of 13. any one of claim 1-11, it comprises the following steps:

(1) slightly solubility camptothecine, phospholipid and additive are dissolved in organic solvent；

(2) in evaporation (1), gained solution, to remove organic solvent, obtains mixed powder or thin film；Or (1) gained solution is carried out It is spray-dried, obtains mixed powder；

(3) by suspension after in (2), gained mixed powder or thin film addition contain salt and sugar or the solution of polyhydric alcohol, aquation or emulsifying Removal, ultrasonic or homogenizing crosses film, degerming, obtains liposome；

Optionally, before degerming, add the step of multigelation,

The concentration of described salt is 0.3mol/L～0.8mol/L, and the pH value of described salt is 5.0；The concentration of described sugar or polyhydric alcohol is 300mg/ml～800mg/ml,

Described additive is selected from antioxidant, cholesterol, surfactant, magnetisable material, antibody, part, stabilizer, charged thing One or several in matter, pH adjusting agent and high molecular polymer.

The preparation method of 14. claim 13, wherein said organic solvent is chloroform and/or methanol.

The Liposomal formulation of 15. any one of claim 1-11 purposes in preparing antitumor drug.