CN106821988A - A kind of simple supersonically preparation method of the controllable liposoluble medicinal liposome of nanometer particle size - Google Patents
A kind of simple supersonically preparation method of the controllable liposoluble medicinal liposome of nanometer particle size Download PDFInfo
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- CN106821988A CN106821988A CN201710202471.4A CN201710202471A CN106821988A CN 106821988 A CN106821988 A CN 106821988A CN 201710202471 A CN201710202471 A CN 201710202471A CN 106821988 A CN106821988 A CN 106821988A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1277—Processes for preparing; Proliposomes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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Abstract
A kind of simple supersonically preparation method of the controllable liposoluble medicinal liposome of nanometer particle size, with cholesterol, DPPC and fat-soluble medicine as raw material, prepares a kind of liposoluble medicinal liposome of size tunable, and specific steps include：1）By the cholesterol of formula rate, DPPC, fat-soluble medicine mixed dissolution in alcohol solvent；2）Constant temperature vacuum distillation mixed solution, removes solvent；3）Vacuum drying mixture；4）With enough PBS aquation dispersions, suspension is obtained；5）By suspension under condition of ice bath, ultrasonic vibration obtains final product the controllable liposoluble medicinal liposome of nanometer particle size.It is of the invention compared with current common method, using alcohol solvent, safe toxic and side effect is small, and preparation section is simple, the best operating condition of Probe Ultrasonic Searching is most importantly determined, prepares that favorable dispersibility, homogeneous, nanometer particle size be small and drug-loaded liposome of good stability.
Description
Technical field
The present invention relates to a kind of simple supersonically preparation method of the controllable liposoluble medicinal liposome of nanometer particle size, belong to fat
Plastid or phospholipid capsule bubble preparation field.
Background technology
At present, the research of medicament-carried nano liposome turns into the biomedical, hot issue of physical chemistry association area.By medicine
Thing can improve the utilization rate of medicine, reduce drug toxicity and reach the effect of slow releasing pharmaceutical in being wrapped in liposome vesicle.
The preparation technology of the entrapment efficiency, stability and nanometer particle size and liposome of medicament-carried nano liposome has much relations.
The clinical practice availability of medicinal liposome is closely bound up with its nanometer particle size, therefore, to the preparation method of medicinal liposome
Optimization is a study hotspot all the time.For the liposome for containing fat-soluble medicine, how to control smaller scale and homogeneous receive
Grain of rice footpath and easy preparation method is operated to have not been reported.
The content of the invention
In order to overcome the above-mentioned deficiency of prior art, it is an object of the invention to provide a kind of controllable fat-soluble of nanometer particle size
The simple supersonically preparation method of medicinal liposome.The present invention uses alcohol solvent, and safe toxic and side effect is small, and preparation section is simple,
Prepare that favorable dispersibility, homogeneous, nanometer particle size be small and drug-loaded liposome of good stability.
To achieve these goals, the technical solution adopted in the present invention is：A kind of controllable fat-soluble medicine of nanometer particle size
The simple supersonically preparation method of composite lipidosome, with cholesterol, DPPC and fat-soluble medicine as raw material, passes through
Ultrasonic disperse, prepares a kind of liposoluble medicinal liposome of size tunable, comprises the following steps that：
1）The cholesterol of formula rate, DPPC, fat-soluble medicine mixed dissolution is molten in enough ethanol
In agent；
2）By step 1）At 40-50 DEG C, constant temperature vacuum distillation under 0.01 ~ 0.1MPa vacuums is removed the mixed solution for obtaining
Solvent；
3）Treat that solvent all volatilizees, by step 2）The mixture for obtaining is in 0.01 ~ 0.1Mpa vacuums, 25 ~ 30 DEG C of temperature conditionss
2 ~ 4h of lower vacuum drying；
4）With the PBS dispersion steps 3 of enough 10mM, pH7.4）The mixture for obtaining aquation 1 under the conditions of 35 ~ 45 DEG C
~ 3 hours, obtain suspension；
5）By step 4）Under condition of ice bath, 10 ~ 30min of ultrasonic vibration obtains final product liposoluble medicinal liposome to the suspension for obtaining.
6) step 5）In ultrasound condition be work 2-4s, interval 3-5s, power 200-220W, obtain particle diameter 160nm
The liposome of left and right.
In described cholesterol, DPPC, fat-soluble medicine formula, 1 part of each component of formula rubs
You are at proportioning：
Cholesterol：1 part；
DPPC：3-4 parts；
Fat-soluble medicine：3 ~ 4 parts；
Described fat-soluble medicine is the one kind in the tetrahydrofuran solution or resveratrol of amphotericin B.
In the tetrahydrofuran solution of the amphotericin B, the tetrahydrofuran solution of 1 part of amphotericin B contains 1 part of both sexes
Mycin B and enough tetrahydrofurans.
The step 2）In vacuum distillation use Rotary Evaporators, the evaporation solvent under 45 DEG C of constant temperature.
The step 4）In, aquation mistake of the accelerating mixture in PBS cushioning liquid by the way of rotation or stirring
Journey.
The step 5）Ultrasonic vibration use ultrasonic cell disrupte instrument, by every 3s work 2s in the way of, in power
Disperseed under conditions of 200W.
Compared with prior art, the beneficial effect that the present invention is obtained is：
1st, the organic solvent in the present invention is ethanol, is had no toxic side effect.
2nd, the preparation method in the present invention is simple.
3rd, the liposome that the ultrasound condition and mode in the present invention are obtained, disperses homogeneous, and nanometer particle size is controllable.
Brief description of the drawings
Fig. 1 is the grain size distribution of the product that embodiment 1 is obtained；
Fig. 2 is the grain size distribution of the product that embodiment 2 is obtained；
Fig. 3 is the grain size distribution of the product that embodiment 3 is obtained.
Specific embodiment
Present disclosure is described in further detail below by specific implementation example with reference, but these realities
Apply example and be not intended to limit protection scope of the present invention.
Embodiment 1
The mmol of cholesterol 2.5, the mmol of DPPC 8.7 are weighed, mixed dissolution is in enough alcohol solvents；
The mmol of amphotericin B 9 is dissolved in enough tetrahydrofuran solvents；Material is all poured into 100ml flasks, is sufficiently mixed.
Solution after being sufficiently mixed is moved into eggplant type bottle, using vacuum rotary evaporator under 40 DEG C of constant temperature evaporation solvent, constantly carry
Vacuum is risen, complete to solvent volatilization, vacuum reaches more than 0.08Mpa.Eggplant type bottle with mixture is placed in vacuum drying
In case, 25 DEG C, dry 2h under the conditions of 0.01MPa.During the PBS of enough 10mM, pH 7.4 added into eggplant type bottle, 35
Aquation is rotated under the conditions of DEG C 1 hour, obtain suspension, then use ultrasonic cell disrupte instrument, under 0 DEG C of condition of ice bath, Probe Ultrasonic Searching
15 min, work 2s, interval 3s, power 200W.Unilamelar liposome vesica of the particle diameter in 160nm or so is obtained after ultrasound.
Embodiment 2
The mmol of cholesterol 2.5 is weighed, the mmol of DPPC 8.7, the mmol mixed dissolutions of resveratrol 7.6 exist
In enough alcohol solvents, material is all poured into 100ml flasks, be sufficiently mixed.Solution after being sufficiently mixed moves into eggplant
In type bottle, using vacuum rotary evaporator under 50 DEG C of constant temperature evaporation solvent, constantly lift vacuum, it is complete to solvent volatilization,
Vacuum reaches more than 0.08Mpa.Eggplant type bottle with mixture is placed in vacuum drying chamber, 30 DEG C, do under the conditions of 0.1MPa
Dry 4h.By in the PBS addition eggplant type bottle of enough 10mM, pH 7.4, aquation is rotated 1 hour under the conditions of 45 DEG C, obtained
To suspension, then ultrasonic cell disrupte instrument is used, under 0 DEG C of condition of ice bath, the min of Probe Ultrasonic Searching 30, work 4s, interval 5s, power
220W.Unilamelar liposome vesica of the particle diameter in 160nm or so is obtained after ultrasound.
Embodiment 3
The mmol of cholesterol 2.5 is weighed, the mmol of DPPC 8.7, the mmol mixed dissolutions of resveratrol 7.6 exist
In enough alcohol solvents, material is all poured into 100ml flasks, be sufficiently mixed.Solution after being sufficiently mixed moves into eggplant
In type bottle, using vacuum rotary evaporator under 45 DEG C of constant temperature evaporation solvent, constantly lift vacuum, it is complete to solvent volatilization,
Vacuum reaches more than 0.08Mpa.Eggplant type bottle with mixture is placed in vacuum drying chamber, 28 DEG C, do under the conditions of 0.08MPa
Dry 3h.By in the PBS addition eggplant type bottle of enough 10mM, pH 7.4, aquation is rotated 1 hour under the conditions of 40 DEG C, obtained
To suspension, then ultrasonic cell disrupte instrument is used, under 0 DEG C of condition of ice bath, Probe Ultrasonic Searching 20min, work 3s, interval 4s, power
210W.Unilamelar liposome vesica of the particle diameter in 160nm or so is obtained after ultrasound.
Embodiment 4
The nanometer particle size evaluation of liposome.
The controllable liposoluble medicinal liposome of the nanometer particle size that embodiment 1 ~ 3 is obtained is detected using laser particle analyzer.Tool
Body step is as follows：5 parts of liposome is obtained, takes equal appropriate, PBS is used respectively（pH=7.4）After 5 times of dilution, using laser
Particle size analyzer is detected and recorded.
Testing result as shown in Fig. 1 ~ 3, wherein, Fig. 1 is the grain size distribution of product that embodiment 1 is obtained, and Fig. 2 is to implement
The grain size distribution of the product that example 2 is obtained, Fig. 3 is the grain size distribution of the product that embodiment 3 is obtained.
Testing result shows, the controllable liposoluble medicinal liposome of nanometer particle size prepared by the present invention, average grain diameter
160nm.Above test result shows, the controllable liposoluble medicinal liposome of nanometer particle size prepared by the present invention, particle diameter distribution
Uniformly, nanometer particle size is controllable, with preferable dispersiveness and homogeneity.
Claims (6)
1. the simple supersonically preparation method of the controllable liposoluble medicinal liposome of a kind of nanometer particle size, with cholesterol, two palmityls
Phosphatid ylcholine and fat-soluble medicine are raw material, by ultrasonic disperse, prepare a kind of fat-soluble medicine lipid of size tunable
Body, it is characterised in that specific steps include：
1）The cholesterol of formula rate, DPPC, fat-soluble medicine mixed dissolution is molten in enough ethanol
In agent；
2）By step 1）At 40-50 DEG C, constant temperature vacuum distillation under 0.01 ~ 0.1MPa vacuums is removed molten the mixed solution for obtaining
Agent；
3）Treat that solvent all volatilizees, by step 2）The mixture for obtaining is in 0.01 ~ 0.1Mpa vacuums, 25 ~ 30 DEG C of temperature conditionss
2 ~ 4h of lower vacuum drying；
4）With the PBS dispersion steps 3 of enough 10mM, pH7.4）The mixture for obtaining, the aquation under the conditions of 35 ~ 45 DEG C
1 ~ 3 hour, obtain suspension；
5）By step 4）Under condition of ice bath, 10 ~ 30min of ultrasonic vibration obtains final product liposoluble medicinal liposome to the suspension for obtaining；
6) step 5）In ultrasound condition be work 2-4s, interval 3-5s, power 200-220W, obtain particle diameter 160nm or so
Liposome.
2. a kind of controllable liposoluble medicinal liposome of nanometer particle size according to claim 1 it is simple ultrasound preparation side
Method, it is characterised in that in described cholesterol, DPPC, fat-soluble medicine formula, 1 part of each group of formula
Point mol ratio be：
Cholesterol：1 part；
DPPC：3-4 parts；
Fat-soluble medicine：3-4 parts；
Wherein, described fat-soluble medicine is the one kind in the tetrahydrofuran solution or resveratrol of amphotericin B.
3. a kind of controllable liposoluble medicinal liposome of nanometer particle size according to claim 2 it is simple ultrasound preparation side
Method, it is characterised in that in the tetrahydrofuran solution of the amphotericin B, the tetrahydrofuran solution of 1 part of amphotericin B contains 1 part
Amphotericin B and enough tetrahydrofurans.
4. a kind of controllable liposoluble medicinal liposome of nanometer particle size according to claim 1 it is simple ultrasound preparation side
Method, it is characterised in that the step 2）In vacuum distillation use Rotary Evaporators, the evaporation solvent under 45 DEG C of constant temperature.
5. a kind of controllable liposoluble medicinal liposome of nanometer particle size according to claim 1 it is simple ultrasound preparation side
Method, it is characterised in that the step 4）In, accelerating mixture is in PBS cushioning liquid by the way of rotation or stirring
Hydration process.
6. a kind of controllable liposoluble medicinal liposome of nanometer particle size according to claim 1 it is simple ultrasound preparation side
Method, it is characterised in that the step 5）Ultrasonic vibration use ultrasonic cell disrupte instrument, with every 3-5s work 2-4s side
Formula, is disperseed under conditions of power 200-220W.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710202471.4A CN106821988A (en) | 2017-03-30 | 2017-03-30 | A kind of simple supersonically preparation method of the controllable liposoluble medicinal liposome of nanometer particle size |
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| CN201710202471.4A CN106821988A (en) | 2017-03-30 | 2017-03-30 | A kind of simple supersonically preparation method of the controllable liposoluble medicinal liposome of nanometer particle size |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107412165A (en) * | 2017-08-02 | 2017-12-01 | 上海上药新亚药业有限公司 | A kind of preparation method of AM Bison |
| CN115227650A (en) * | 2022-08-23 | 2022-10-25 | 苏州永健生物医药有限公司 | Preparation method of selaginella tamariscina essential oil liposome |
Citations (5)
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| CN103142481A (en) * | 2011-12-06 | 2013-06-12 | 国家纳米科学中心 | Drug-loaded liposome overcoming tumor drug resistance, preparation method and application thereof |
| CN103494773A (en) * | 2013-10-12 | 2014-01-08 | 南京医科大学 | ZL006 liposome and preparation method thereof |
| CN103655474A (en) * | 2012-09-11 | 2014-03-26 | 国家纳米科学中心 | Compound drug-carrying liposome as well as preparation method and application thereof |
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2017
- 2017-03-30 CN CN201710202471.4A patent/CN106821988A/en active Pending
Patent Citations (5)
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|---|---|---|---|---|
| CN103142481A (en) * | 2011-12-06 | 2013-06-12 | 国家纳米科学中心 | Drug-loaded liposome overcoming tumor drug resistance, preparation method and application thereof |
| CN103655474A (en) * | 2012-09-11 | 2014-03-26 | 国家纳米科学中心 | Compound drug-carrying liposome as well as preparation method and application thereof |
| CN103494773A (en) * | 2013-10-12 | 2014-01-08 | 南京医科大学 | ZL006 liposome and preparation method thereof |
| CN103919729A (en) * | 2014-03-20 | 2014-07-16 | 燕山大学 | Wedelolactone nanoliposome modified by combining chitosan and polyethylene glycol and its preparation method |
| CN105796496A (en) * | 2016-04-26 | 2016-07-27 | 北京大学 | Fenofibrate-containing nano-liposome as well as preparation method and application thereof |
Non-Patent Citations (3)
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107412165A (en) * | 2017-08-02 | 2017-12-01 | 上海上药新亚药业有限公司 | A kind of preparation method of AM Bison |
| CN115227650A (en) * | 2022-08-23 | 2022-10-25 | 苏州永健生物医药有限公司 | Preparation method of selaginella tamariscina essential oil liposome |
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Application publication date: 20170613 |