CN1823733A - Self asembled precusor liposome containing camptothecin kind medicine and its preparation method - Google Patents
Self asembled precusor liposome containing camptothecin kind medicine and its preparation method Download PDFInfo
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- CN1823733A CN1823733A CNA2006100376369A CN200610037636A CN1823733A CN 1823733 A CN1823733 A CN 1823733A CN A2006100376369 A CNA2006100376369 A CN A2006100376369A CN 200610037636 A CN200610037636 A CN 200610037636A CN 1823733 A CN1823733 A CN 1823733A
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Abstract
A self-assembled precursor liposome of camptothecine contained medicine is proportionally prepared from camptothecine contained medicine, phosphatide, polyethylene glycol and dispersing medium through mixing, dispersing, press filtering by millipore film, and pouring it in a container full of N2.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, relate to a kind of self-assembling proliposome that contains camptothecine, the invention still further relates to the preparation method of this self-assembling proliposome.
Background technology
In view of camptothecine and derivant thereof unique anticancer mechanism (specific blocking-up Top I enzyme synthetic), from over 1985, especially after entering the nineties, countries such as the U.S., Japan, Canada and Britain actively drop into great amount of manpower and material resources and carry out the research and development of camptothecine, make camptothecine become paclitaxel second important woody anticancer medicinal plants afterwards, popular research topic has become international.
Because camptothecine and derivant thereof mostly are insoluble in water, existing domestic listing kind is to utilize aqueous slkali that its lactonic ring is opened to form carboxylate and be prepared into injection and be applied to clinical at present.But the lactonic ring structure of camptothecine is the key position of its anti-tumor activity, and the lactone medicine of biologically active has determined that in the concentration of target site the curative effect of medicine, this preparation cause drug effect significantly to reduce and toxic and side effects increases.Clinical research as the hydroxy camptothecin liquid drugs injection shows that carboxylate (pH=7.4) under physiological condition can partly change into lactone type and drug effect takes place, but it accounts for 10%～20% of total dose.In the lactone type donor with biologically active with camptothecine and derivant thereof, Chinese scholars attempts utilizing many new drug delivery systems, has all obtained certain progress as liposome technology, self emulsifying technology etc.
Wherein, liposome technology is the middle made superminiature spheroid carrier preparation of thin film that drug encapsulation is formed in the class lipid bilayer.Chemotherapeutics is encapsulated in the class lipid bilayer and forms liposome-medicinal composition, is used for the plasma half-life that oncotherapy can prolong drug, improves curative effect, reduces toxic and side effects.Over nearly 20 years, liposome is as pharmaceutical carrier, and particularly the research of carrier in the drug-supplying system of medicine as cancer therapy drug has development rapidly.
At present, the feature of pastille Liposomal formulation is: (mean diameter＜1000nm) form is dispersed in and makes liquid preparation or solid (lyophilizing) preparation in liquid medium or the solid dielectric with nanoparticle with the pastille liposome.The feature of its preparation method is: phospholipid is disperseed (or dissolving) in suitable organic solvent, adopt film dispersion method or method for preparing lipidosome such as reverse evaporation or injection method, earlier drug encapsulation is prepared into micron grain (the pastille liposome turbid liquor of mean diameter＞1000nm) in liposome; Adopt methods such as ultrasonic, high pressure homogenize, microporous membrane filter pressing then, micron order pastille liposome is disperseed (or broken) become the nanoparticle (dispersion (as the 5-fluorouracil multiphasic liposomes) of mean diameter＜1000nm); Or the employing Freeze Drying Technique, above dispersion is made nanoparticle solid (lyophilizing) preparation (as the injection Paclitaxel liposome).But there is two large problems in above preparation method:
1, complicated process of preparation, easily microbiological contamination, poor reproducibility, be difficult to industrialized great production, and manufacturing cost height.
2, quality of the pharmaceutical preparations poor stability.Its principal character is: the unstable or reduction of entrapment efficiency, it is big that liposome particle diameter instability or particle diameter become.Its main cause is:
(1) disperse (or broken) to become in the preparation process such as nanoparticle liposome or liquid lyophilizing at liposomal encapsulated medicine, micron grain liposome, the fluctuation of (or broken) or freeze-dry process condition, parameter owing to seal, disperse must influence the size of liposome and to the envelop rate of medicine.
(2) pastille liposome liquid body preparation objectively exists at duration of storage: medicine causes entrapment efficiency to reduce or instability from the phenomenon of liposome to liquid medium diffusion (or seepage); The trend of upper state nanoparticle cohesion (or gathering) also causes the liposome particle diameter to become big or unsettled key factor.
(3) in before use dissolving of pastille lipidosome solid (lyophilizing) preparation, the dispersive process since the liposome nano granule local dissolution not exclusively, disperse inhomogeneously, cause liposome to be assembled or particle diameter becomes big; Or liposome breaks, drug leakage, causes the pastille liposome encapsulation to descend.
In view of existing Liposomal formulation objectively exists envelop rate, particle diameter instability, is difficult for problems such as industrialization and expensive, high price, cause the commercialization process of pastille liposome to be walked with difficulty.
Pro-liposome (proliposomes) notion is proposed by Anye at first, and its preparation method can reduce according to existing reported in literature: thin-film carrier sedimentation, freeze-drying, spray drying method, powder bed polishing, fluidized bed process, vacuum circumgyration etc.Its basic feature is: phospholipid is dissolved in the organic solvent (as ethanol, ether etc.); after removing organic solvent with certain method (as distillation, drying etc.); phospholipid is dispersed in water insoluble particulate skeleton surface with form of film, faces with before adding hydration medium to reassemble into liposome microgranule or nanoparticle.In view of in preparation solid type pro-liposome process, removing organic solvent technology is the major technique bottleneck of realizing industrialization, and the hydro-combination process of solid type pro-liposome is also slower with the objective reality hydration rate, problems such as local dissolution is incomplete, dispersion is inhomogeneous, thereby cause main quality index such as entrapment efficiency and mean diameter to be difficult for effectively control, be difficult to satisfy clinical instructions for use.In existing publication, research document and the report of preparation liposome and pro-liposome, do not find directly to adopt the formulation preparation technology of liquid-type self-assembling proliposome as yet.
Summary of the invention
The objective of the invention is provides a kind of self-assembling proliposome that contains camptothecine at the problems referred to above.
Another object of the present invention provides the preparation method of this self-assembling proliposome.
The objective of the invention is to realize by following measures:
A kind of self-assembling proliposome that contains camptothecine, contain following components in weight percentage in the prescription of this self-assembling proliposome:
0.01～5% camptothecine, 1～50% phospholipid, 10～90% disperse medium, 0.1～30% polyethyleneglycol modified dose, 0.1～40% dispersant.
Described self-assembling proliposome, wherein camptothecine is meant camptothecine, hydroxy camptothecin, nitrocamptothecin and derivant thereof.
Described self-assembling proliposome, wherein phospholipid adopts natural phospholipid, perhaps adopts semi-synthetic or complete synthesis phospholipid, perhaps adopt the mixture of natural phospholipid and semi-synthetic or complete synthesis phospholipid, and the content of phosphatidylcholine is between 50%～99%.
Described self-assembling proliposome, the natural phospholipid during wherein natural phospholipid is selected from the natural materials such as Semen sojae atricolor, egg yolk, brain or spinal cord.
Described self-assembling proliposome, wherein polyethyleneglycol modified dose is the polyoxyethylene-type non-ionic surface active agent, be selected from the following material one or more: the carbowax modifier of Tweens, poloxamer class, brejs or Myrij class polyoxyethylene-type non-ionic surface active agent, polyoxyethylated alkyl phenol, polyoxyethylene castor oil, polyoxyethylene hydrogenated Oleum Ricini or phospholipid, or the derivant of above-mentioned substance.
It is characterized in that Tweens polyoxyethylene-type non-ionic surface active agent is the mixture of polyoxyethylene sorbitan monolaurate, polyethenoxy sorbitan monopalmitate, polyethenoxy sorbitan monostearate, polyoxyethylene sorbitan monooleate dehydration, polyethenoxy sorbitan list trioleate or above-mentioned substance; Poloxamer class non-ionic surface active agent is the polyoxyethylene polyoxypropylene block copolymer of polyoxyethylene chain segment molecular weight ratio between 10%～80% or the mixture of above-mentioned substance; Brejs polyoxyethylene-type non-ionic surface active agent is the mixture of Brij30, polyoxyethylene lauryl ether, polyoxyethylene oleate ether, Polyoxyethylene cetyl ether or above-mentioned substance; Myrij class polyoxyethylene-type non-ionic surface active agent is the mixture of Myrj 45, polyoxyethylene 40 monostearates or above-mentioned substance; The polyoxyethylated alkyl phenol class is the mixture of polyoxyethylene nonylphenol ether, polyoxyethylene octylphenol ether or above-mentioned substance; Polyoxyethylene castor oil is that Cremophor EL, polyoxyethylene hydrogenated Oleum Ricini are that the carbowax modifier of CremophorRH40, Cremophor RH60 or its mixture, phospholipid is the mixture of methoxy poly (ethylene glycol) 350 PHOSPHATIDYL ETHANOLAMINE, methoxy poly (ethylene glycol) 550 PHOSPHATIDYL ETHANOLAMINE, methoxy poly (ethylene glycol) 750 PHOSPHATIDYL ETHANOLAMINE, methoxy poly (ethylene glycol) 1000 PHOSPHATIDYL ETHANOLAMINE, methoxy poly (ethylene glycol) 2000 PHOSPHATIDYL ETHANOLAMINE or above-mentioned substance.
Described self-assembling proliposome, wherein disperse medium is selected from the mixture of propylene glycol, ethanol, Polyethylene Glycol, isopropyl alcohol, glycerol, dimethyl formamide, dimethyl acetylamide, dimethyl sulfoxide or above-mentioned substance and water.
Described self-assembling proliposome, wherein dispersant is selected from the organic alcohol of chain, ring-type or aromatics that contains 4～7 carbon atoms.
Described self-assembling proliposome, the organic alcohol of chain, ring-type or aromatics that wherein contains 4～7 carbon atoms are one or more in n-butyl alcohol, the tert-butyl alcohol, n-amyl alcohol, benzyl alcohol, cyclopentanol or the Hexalin.
Described self-assembling proliposome also contains 0.1～10% stabilizing agent in its prescription.
Described self-assembling proliposome, wherein stabilizing agent is selected from one or more in cholesterol, oleic acid, polyvidone, ethyl lactate, benzyl benzoate, vitamin E, butylated hydroxyarisol, dibutyl paracresol, phenol, citric acid, cholic acid and its esters, deoxycholic acid and its esters.
The preparation method of described self assembly liposome comprises the following steps:
Get each raw material by prescription and place container, make its mixing, dispersion (regulating pH in case of necessity is 3～6), get clear liquid, 0.1～0.8 μ m microporous filter membrane filter pressing (available in case of necessity active carbon depyrogenation, take off filter pressing behind the charcoal), the filtrate embedding obtains containing the self-assembling proliposome of camptothecine in filling nitrogen cascade.
The above-mentioned self-assembling proliposome that contains camptothecine, each raw material also can adopt packing or assembly packaging respectively in its formula combination, faces with the form that before is mixed into pro-liposome.
A kind of liposome that contains camptothecine, this liposome are that the hydration medium of above-mentioned self-assembling proliposome with an amount of (10～250 times of amounts (v/v)) disperseed to dilute the Liposomal formulation that forms, and mean diameter＜1000nm, envelop rate＞80%.Preferred mean diameter is 100～800nm, envelop rate＞90%.
Described liposome, wherein hydration medium is selected from water for injection, pure water, aqueous phosphatic, D/W or glucose sodium chloride aqueous solution.
The above-mentioned self-assembling proliposome of camptothecine or the Liposomal formulation after the hydration of containing can be used for drug administration by injection or cavity/canal drug administration.
Beneficial effect of the present invention:
The present invention directly is dispersed or dissolved in slightly solubility cancer therapy drug-camptothecine and contains in the phospholipid, polyethyleneglycol modified dose, disperse medium, dispersant, makes liquid type pastille pro-liposome.When this liquid type pro-liposome is diluted with suitable hydration medium, needn't adopt homogenize technology or machinery (as ultrasonic technique, homogenizer etc.) in the hydro-combination process, (in 60 seconds) are self-assembled into high envelop rate (envelop rate can reach more than 95%) fast, evenly (mean diameter can reach 100～800nm) nanoscale pastille Liposomal formulation to particle diameter.This preparation method adopts the common process equipment of preparation liquid preparation or injection, but scale, high efficiency production, and constant product quality, syringeability is good, and its effective storage period is more than 2 years; The liposome that forms after the hydration is stable and controllable for quality, can satisfy the needs of clinical administration fully.This method is that technology is simple, cost is low, has solved " bottleneck " problem that existing liposome is difficult to the high efficiency suitability for industrialized production.
Used various compositions are physiological compatibility among the present invention, and safety and be easy to buy uses homemade goods all can reach requirement; And by adjusting the ratio of each component in the prescription, can regulate the dissolubility and the dilution stability of medicine within the specific limits, and the may command size (can effectively be controlled mean diameter＜1000nm), to adapt to various medication requirements.
The physicochemical characteristics of the finished product that makes according to the present invention (pressing embodiment 1):
[finished product character]: this product is yellow clear solution.
[hydration dispersibility]: this product is disperseed and can self assembly be formed the blue opalescent nanometer disperse system of semi-transparent zone through jolting in as 5% glucose injection at solvent for injection.
[particle size distribution]: this product, is pressed clinical dosage dilution back and is measured particle diameter (Malvern Zetasizer3000HS) with the PCS method as retarder thinner with 5% glucose injection, and particle size distribution figure sees Fig. 2, and mean diameter is 343.2 ± 8.42nm.
[morphology investigation]: this product with 5% glucose injection as retarder thinner, observe under transmission electron microscope by clinical dosage dilution back, blank does not present hollow cryptomere or spherical during medicine carrying, and visible medicine obviously is wrapped in the lipid capsule (ball) (the results are shown in Figure 3) behind the medicine carrying.
[entrapment efficiency determination]:
Liposome Chinese medicine content assaying method: chromatographic column: Diamonsil C
18(200mm * 4.6mm * 5 μ m); Mobile phase: methanol: water=60: 40; Detect wavelength: 266nm; Column temperature: 30 ℃; Flow velocity: 1ml/min; Sample size: 20 μ l.
The entrapment efficiency determination method: with the double distilled water is eluting solvent, take from the populated Sephadex gel column of sample on the liposome solutions after the assembling, access and wherein be with blue opalescence part, methanol constant volume, it is M that the peak area substitution mark Qu Fangcheng of HPLC method mensuration 10-hydroxycamptothecine gets dose
1, the direct standardize solution of liposome solutions that other gets equal volume with the HPLC method measure total dose M
2
Envelop rate %=M
1/ M
2* 100%
Measurement result: 10-hydroxycamptothecine self-assembling proliposome of the present invention is 98.68 ± 0.55% (n=3) through the envelop rate that self assembly forms liposome.
Description of drawings
Fig. 1 is preparation technology's flow chart of camptothecine self-assembling proliposome.
The 10-hydroxycamptothecine self-assembling proliposome that Fig. 2 prepares for embodiment 1 is self-assembled into the particle size distribution figure of liposome after the hydration in 5% glucose injection, mean diameter is 343.2 ± 8.42nm.
Fig. 3 for the 10-hydroxycamptothecine medicine carrying of embodiment 1 preparation after self-assembling proliposome in 5% glucose injection, be self-assembled into the transmission electron microscope photo (40,000 times) of liposome after the hydration.
The specific embodiment
Below be embodiments of the invention, these examples also do not mean that limitation of the present invention.
Embodiment 1
Prescription: 10-hydroxycamptothecine 1g
Soybean phospholipid 180g
Poloxamer 188 (trade name F-68) 5g
Benzyl alcohol 250g
Dehydrated alcohol adds to 1000ml
Preparation technology: be dissolved in the adequate amount of ethanol by the process chart of Fig. 1 soybean phospholipid with recipe quantity, add the ethanol of medicine, poloxamer 188, benzyl alcohol and the surplus of recipe quantity subsequently, after treating that medicine and other components all disperse or dissolve, 0.22 after the degerming of μ m filtering with microporous membrane, in under the aseptic condition with the filtrate embedding in filling nitrogen ampoule bottle or cillin bottle, promptly get the 10-hydroxycamptothecine self-assembling proliposome.
Face with preceding by clinical get dilution in 5% glucose solution that the 10-hydroxycamptothecine self-assembling proliposome is added to 150 times of amounts (v/v), disperse with dosage after, can form the 10-hydroxycamptothecine liposome solutions fast, mean diameter＜600nm, envelop rate＞95%.
Embodiment 2
Prescription: camptothecine 1g
Egg phosphatide 200g
Tween 80 5g
N-butyl alcohol 150g
Vitamin E 2g
PEG400 adds to 1000ml
Preparation technology: the egg phosphatide of recipe quantity is dissolved in an amount of PEG400, add the medicine of recipe quantity subsequently, Tween 80, the PEG400 of n-butyl alcohol, vitamin E and surplus, after treating that medicine and other components all disperse or dissolve, 0.22 the degerming of μ m filtering with microporous membrane, under the aseptic condition with the filtrate embedding in filling nitrogen ampoule bottle or cillin bottle, promptly get the camptothecine self-assembling proliposome.
Face with preceding by clinical get dilution in 5% glucose solution that the camptothecine self-assembling proliposome is added to 200 times of amounts (v/v), disperse with dosage after, can form the camptothecine liposome solutions fast, mean diameter＜800nm, envelop rate＞90%.
Embodiment 3
Prescription: 10-hydroxycamptothecine 0.8g
Hydrogenated phospholipid 200g
Polyoxyethylene hydrogenated Oleum Ricini (Cremophor RH40) 2g
Benzyl alcohol 120g
Deoxycholic acid 0.8g
Propylene glycol 200g
Dehydrated alcohol adds to 1000ml
Preparation technology: the hydrogenated phospholipid of recipe quantity is dissolved in the adequate amount of ethanol, add the ethanol of medicine, polyoxyethylene hydrogenated Oleum Ricini Cremophor RH40, benzyl alcohol, propylene glycol, deoxycholic acid and the surplus of recipe quantity subsequently, after treating that medicine and other components all disperse or dissolve, 0.22 μ m filtering with microporous membrane degerming, in under the aseptic condition with the filtrate embedding in filling nitrogen ampoule bottle or cillin bottle, promptly get the 10-hydroxycamptothecine self-assembling proliposome.
Face with preceding by clinical with dosage get the 10-hydroxycamptothecine self-assembling proliposome be added to 50 times of amounts (v/v) aqueous solution for injection dilution, disperse after, can form the 10-hydroxycamptothecine liposome solutions fast, mean diameter＜600nm, envelop rate＞90%.
Embodiment 4
Prescription: camptothecine 1g
Egg phosphatide 95g
Polyoxyethylene hydrogenated Oleum Ricini (Cremophor RH60) 1g
Tween 80 2g
Benzyl alcohol 350g
Cholesterol 5g
Vitamin E 1g
PEG400 100g
Ethanol adds to 1000ml
Preparation technology: the egg phosphatide of recipe quantity is dissolved in the adequate amount of ethanol, add the medicine of recipe quantity subsequently, Tween 80, the ethanol of polyoxyethylene hydrogenated Oleum Ricini Cremophor RH60, cholesterol, Tween 80, benzyl alcohol, vitamin E, PEG400 and surplus, after treating that medicine and other components all disperse or dissolve, 0.22 the degerming of μ m filtering with microporous membrane, embedding promptly gets the camptothecine self-assembling proliposome under the aseptic condition in ampoule bottle.
Face with preceding by clinical get dilution in the aqueous phosphatic that the camptothecine self-assembling proliposome adds 100 times of amounts (v/v), dispersion with dosage after, can form the camptothecine liposome solutions fast, mean diameter＜800nm, envelop rate＞90%.
Claims (15)
1, a kind of self-assembling proliposome that contains camptothecine is characterized in that containing in the prescription of this self-assembling proliposome the following material of percentage by weight:
0.01～5% camptothecine, 1～50% phospholipid, 10～90% disperse medium, 0.1～30% polyethyleneglycol modified dose, 1～40% dispersant.
2, self-assembling proliposome according to claim 1 is characterized in that described camptothecine is meant camptothecine, hydroxy camptothecin, nitrocamptothecin and derivant thereof.
3, self-assembling proliposome according to claim 1, it is characterized in that phospholipid adopts natural phospholipid, perhaps adopt semi-synthetic or complete synthesis phospholipid, perhaps adopt the mixture of natural phospholipid and semi-synthetic or complete synthesis phospholipid, and the content of phosphatidylcholine is between 50%～99%.
4, self-assembling proliposome according to claim 3 is characterized in that described natural phospholipid is selected from the natural phospholipid in Semen sojae atricolor, egg yolk, brain or the spinal cord.
5, self-assembling proliposome according to claim 1, it is characterized in that described polyethyleneglycol modified dose is the polyoxyethylene-type non-ionic surface active agent, be selected from the following material one or more: the carbowax modifier of Tweens, poloxamer class, brejs or Myrij class polyoxyethylene-type non-ionic surface active agent, polyoxyethylated alkyl phenol, polyoxyethylene castor oil, polyoxyethylene hydrogenated Oleum Ricini or phospholipid, or the derivant of above-mentioned substance.
6, self-assembling proliposome according to claim 5 is characterized in that Tweens polyoxyethylene-type non-ionic surface active agent is the mixture of polyoxyethylene sorbitan monolaurate, polyethenoxy sorbitan monopalmitate, polyethenoxy sorbitan monostearate, polyoxyethylene sorbitan monooleate dehydration, polyethenoxy sorbitan list trioleate or above-mentioned substance; Poloxamer class non-ionic surface active agent is the polyoxyethylene polyoxypropylene block copolymer of polyoxyethylene chain segment molecular weight ratio between 10%～80% or the mixture of above-mentioned substance; Brejs polyoxyethylene-type non-ionic surface active agent is the mixture of Brij30, polyoxyethylene lauryl ether, polyoxyethylene oleate ether, Polyoxyethylene cetyl ether or above-mentioned substance; Myrij class polyoxyethylene-type non-ionic surface active agent is the mixture of Myrj 45, polyoxyethylene 40 monostearates or above-mentioned substance; The polyoxyethylated alkyl phenol class is the mixture of polyoxyethylene nonylphenol ether, polyoxyethylene octylphenol ether or above-mentioned substance; Polyoxyethylene castor oil is that Cremophor EL, polyoxyethylene hydrogenated Oleum Ricini are Cremophor RH40, Cremophor RH60 or its mixture; The carbowax modifier of phospholipid is the mixture of methoxy poly (ethylene glycol) 350 PHOSPHATIDYL ETHANOLAMINE, methoxy poly (ethylene glycol) 550 PHOSPHATIDYL ETHANOLAMINE, methoxy poly (ethylene glycol) 750 PHOSPHATIDYL ETHANOLAMINE, methoxy poly (ethylene glycol) 1000 PHOSPHATIDYL ETHANOLAMINE, methoxy poly (ethylene glycol) 2000 PHOSPHATIDYL ETHANOLAMINE or above-mentioned substance.
7, self-assembling proliposome according to claim 1 is characterized in that described disperse medium is selected from the mixture of propylene glycol, ethanol, Polyethylene Glycol, isopropyl alcohol, glycerol, dimethyl formamide, dimethyl acetylamide, dimethyl sulfoxide or above-mentioned substance and water.
8, self-assembling proliposome according to claim 1 is characterized in that described dispersant is selected from the organic alcohol of chain, ring-type or aromatics that contains 4～7 carbon atoms.
9, self-assembling proliposome according to claim 8, the organic alcohol of chain, ring-type or aromatics that it is characterized in that containing 4～7 carbon atoms are one or more in n-butyl alcohol, the tert-butyl alcohol, n-amyl alcohol, benzyl alcohol, cyclopentanol or the Hexalin.
10, self-assembling proliposome according to claim 1 is characterized in that also containing 0.1～10% stabilizing agent in its prescription.
11, self-assembling proliposome according to claim 10 is characterized in that described stabilizing agent is selected from one or more in cholesterol, oleic acid, polyvidone, ethyl lactate, benzyl benzoate, vitamin E, butylated hydroxyarisol, dibutyl paracresol, phenol, citric acid, cholic acid and its esters, deoxycholic acid and its esters.
12, as the preparation method of claim 1 or 10 described self-assembling proliposomes, it is characterized in that comprising the following steps:
Get each raw material by prescription and place container, make its mixing, dispersion, get clear liquid, 0.1～0.8 μ m microporous filter membrane filter pressing, the filtrate embedding obtains containing the self-assembling proliposome of camptothecine in filling nitrogen cascade.
13, a kind of liposome that contains camptothecine, it is characterized in that this liposome is the Liposomal formulation that disperses dilution to form with an amount of hydration medium by claim 1 or 10 described self-assembling proliposomes, and mean diameter＜1000nm, envelop rate＞80%.
14, the liposome of camptothecine according to claim 13 is characterized in that the preferred mean diameter of this liposome is 100～800nm, envelop rate＞90%.
15, liposome according to claim 13 is characterized in that described hydration medium is selected from water for injection, pure water, aqueous phosphatic, D/W or glucose sodium chloride aqueous solution.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100376369A CN1823733A (en) | 2006-01-06 | 2006-01-06 | Self asembled precusor liposome containing camptothecin kind medicine and its preparation method |
| CNB2006100638802A CN100518738C (en) | 2006-01-06 | 2006-12-31 | Self-assembly precursor liposome containing camptothecine medicine, and its preparing method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100376369A CN1823733A (en) | 2006-01-06 | 2006-01-06 | Self asembled precusor liposome containing camptothecin kind medicine and its preparation method |
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| CN1823733A true CN1823733A (en) | 2006-08-30 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102256596A (en) * | 2008-11-21 | 2011-11-23 | 医源治疗公司 | Liposomal composition for convection-enhanced delivery to the central nervous centre |
| CN106214641A (en) * | 2016-08-22 | 2016-12-14 | 沈阳鑫泰格尔医药科技开发有限公司 | A kind of liposome being applicable to water soluble drug and preparation method thereof |
| CN111132753A (en) * | 2017-09-04 | 2020-05-08 | 一丸自然美建有限公司 | pH-sensitive liposome and method for producing same |
-
2006
- 2006-01-06 CN CNA2006100376369A patent/CN1823733A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102256596A (en) * | 2008-11-21 | 2011-11-23 | 医源治疗公司 | Liposomal composition for convection-enhanced delivery to the central nervous centre |
| CN102256596B (en) * | 2008-11-21 | 2014-10-22 | 医源治疗公司 | Liposomal composition for convection-enhanced delivery to the central nervous centre |
| CN106214641A (en) * | 2016-08-22 | 2016-12-14 | 沈阳鑫泰格尔医药科技开发有限公司 | A kind of liposome being applicable to water soluble drug and preparation method thereof |
| CN111132753A (en) * | 2017-09-04 | 2020-05-08 | 一丸自然美建有限公司 | pH-sensitive liposome and method for producing same |
| CN111132753B (en) * | 2017-09-04 | 2022-05-27 | 一丸自然美健有限公司 | pH-sensitive liposome and method for producing same |
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