CN109718205A - A kind of preparation method and system of medicinal liposome - Google Patents
A kind of preparation method and system of medicinal liposome Download PDFInfo
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- CN109718205A CN109718205A CN201910181051.1A CN201910181051A CN109718205A CN 109718205 A CN109718205 A CN 109718205A CN 201910181051 A CN201910181051 A CN 201910181051A CN 109718205 A CN109718205 A CN 109718205A
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Abstract
This application involves field of pharmaceutical preparations more particularly to a kind of preparation methods of medicinal liposome, comprising: adjusts liquid carbon dioxide to supercriticality；Supercritical carbon dioxide in one pipeline is dissolved with core material drug, supercritical carbon dioxide in another pipeline is dissolved with wall material solution, and the temperature of the supercritical carbon dioxide dissolved with wall material solution is made to be higher than the temperature for being dissolved with the supercritical carbon dioxide of core material drug；The temperature supercritical carbon dioxide adjusted dissolved with core material drug is passed through granulation kettle from top, the temperature supercritical carbon dioxide adjusted dissolved with wall material solution is passed through granulation kettle from lower part, carries out liposome granulation；The pressure of supercritical carbon dioxide dissolved with core material drug and the pressure of the supercritical carbon dioxide dissolved with wall material solution are greater than the pressure in granulation kettle；Collect the liposome that embedding is completed.This method reduce the reunions of core material particles, the probability of liposome repeatedly embedded, and improve the encapsulation rate of liposome.
Description
Technical field
This application involves field of pharmaceutical preparations more particularly to the preparation methods and system of a kind of medicinal liposome.
Background technique
Liposome is a kind of artificial membrane, when being that amphiphatic molecule (such as: phosphatide and sphingolipid) is scattered in water phase, the hydrophobic tail of molecule
Portion, which tends to flock together, avoids water phase, and the hydrophilic head of molecule is exposed in water phase, and formation has bilayer knot
The vesicle of structure.Liposome can be used for transgenosis or drug, and the liposome medicament for drug refers to drug encapsulation in class
The miniature vesicular body formed in lipid bilayer.Specifically, liposome medicament can be melted with cell membrane using liposome
Drug is sent into cell interior by the characteristics of conjunction.
In the prior art, the method for producing liposome usually feeds intake by configured lotion or according to a certain percentage
Into overcritical kettle, supercriticality is opened, hydrophilic solution is then added, forms oil-in-water phospholipid bilayer structure.But
It is be easy to cause the reunion of core material particles, the multiple embedding of liposome during production liposome in the prior art, influences liposome
Embedding effect and embedding rate.
Therefore, the reunion of core material particles, the multiple embedding of liposome how are avoided, the embedding effect of liposome is improved, is
Those skilled in the art's technical problem urgently to be solved at present.
Summary of the invention
This application provides a kind of preparation method of medicinal liposome and systems, to reduce reunion, the lipid of core material particles
The multiple embedding of body improves the embedding effect of liposome.
In order to solve the above technical problems, the application provides the following technical solutions:
A kind of preparation method of medicinal liposome includes the following steps: to adjust liquid CO 2 to supercriticality；
By the supercritical carbon dioxide and core material drug mixed dissolution in a pipeline, by the supercritical carbon dioxide in another pipeline
With wall material solution mixed dissolution, and adjust temperature make dissolved with wall material solution supercritical carbon dioxide temperature be higher than dissolution
There is the temperature of the supercritical carbon dioxide of core material drug；By the temperature supercritical carbon dioxide adjusted dissolved with core material drug
It is passed through granulation kettle from top, the temperature supercritical carbon dioxide adjusted dissolved with wall material solution is passed through granulation from lower part
Kettle carries out liposome granulation；Wherein, the pressure of the supercritical carbon dioxide dissolved with core material drug and dissolved with wall material solution
The pressure of supercritical carbon dioxide is all larger than the pressure in granulation kettle；The liposome that embedding is completed is collected from carbon dioxide.
The preparation method of medicinal liposome as described above, wherein preferably, core material solution be menthol+acetone and
The mixed liquor of drug, menthol+acetone ratio are (4~2): 1.
The preparation method of medicinal liposome as described above, wherein preferably, wall material solution is lecithin and hyalomitome
The ratio of the mixed liquor of acid, lecithin and hyaluronic acid is (0.1~1): 1.
The preparation method of medicinal liposome as described above, wherein preferably, will be overcritical dissolved with wall material solution
The temperature of carbon dioxide is adjusted between 30 DEG C~70 DEG C, and the temperature of the supercritical carbon dioxide dissolved with core material solution is adjusted
To between 50 DEG C~80 DEG C.
The preparation method of medicinal liposome as described above, wherein preferably, overcritical two dissolved with core material drug
The pressure of carbonoxide is 26Mpa, and the pressure of the supercritical carbon dioxide dissolved with wall material solution is 22Mpa, the pressure in kettle of pelletizing
Power is 7Mpa.
The preparation method of medicinal liposome as described above, wherein preferably, liposome granulation in granulation kettle is carried out
Protect control.
The preparation method of medicinal liposome as described above, wherein preferably, the temperature that control liposome is pelletized to 65
℃。
The preparation method of medicinal liposome as described above, wherein preferably, molten to being passed through by nozzle to granulation kettle
Solution has the supercritical carbon dioxide of core material drug, protects in nozzle interior to the supercritical carbon dioxide dissolved with core material drug
Temperature.
The preparation method of medicinal liposome as described above, wherein preferably, be dissolved with core wait be passed through in granulation kettle
The supercritical carbon dioxide of material drug gasifies, and after core material particles are precipitated, change the core material particles direction of motion and is allowed to ordered movement.
A kind of preparation system of medicinal liposome, comprising: granulation kettle；The lower part of granulation kettle and conveying are dissolved with wall material solution
Supercritical carbon dioxide pipe-line system connection, the temperature of supercritical carbon dioxide dissolved with wall material solution is adjusted
It is whole；The pipe-line system of the supercritical carbon dioxide of top and conveying dissolved with core material drug of granulation kettle is connect, to dissolved with core
The temperature of the supercritical carbon dioxide of material drug is adjusted；And adjust overcritical two dissolved with wall material solution after temperature
The temperature of carbonoxide is higher than the temperature of the supercritical carbon dioxide dissolved with core material drug after adjustment temperature；Wherein, it is dissolved with
The pressure of the supercritical carbon dioxide of core material drug and the pressure of the supercritical carbon dioxide dissolved with wall material solution are all larger than system
Pressure in grain kettle.
Relatively above-mentioned background technique, the preparation method of liposome provided by the present invention, comprising: by liquid CO 2 tune
It is whole to supercriticality；It, will be in another pipeline by the supercritical carbon dioxide and core material drug mixed dissolution in a pipeline
Supercritical carbon dioxide and wall material solution mixed dissolution, and adjust temperature and make the overcritical titanium dioxide dissolved with wall material solution
The temperature of carbon is higher than the temperature of the supercritical carbon dioxide dissolved with core material drug；Temperature is adjusted dissolved with core material drug
Supercritical carbon dioxide be passed through granulation kettle from top, by the temperature supercritical carbon dioxide adjusted dissolved with wall material solution
It is passed through granulation kettle from lower part, carries out liposome granulation；Wherein, the pressure of the supercritical carbon dioxide dissolved with core material drug and molten
Solution has the pressure of the supercritical carbon dioxide of wall material solution to be all larger than the pressure in granulation kettle；It collects and has embedded from carbon dioxide
At liposome.Specifically, core material particles from top to bottom move, wall material moves from the bottom to top, and wall material and core material particles are met shape
At stable embedding liposome bimolecular structure.Since the temperature of the supercritical carbon dioxide dissolved with wall material solution is higher than dissolution
There is the temperature of the supercritical carbon dioxide of core material drug, therefore the convection velocity of wall material and core material particles can be enhanced, and then make
It obtains wall material and the mixing of core material suspended particulate sufficiently, improves embedding effect and encapsulation rate, and the fast upward motion of wall material is also
It reduces core material suspended particulate and repeats the probability contacted with wall material, and then avoid core material suspended particulate and repeatedly embedded.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described, it should be apparent that, the accompanying drawings in the following description is only this
The some embodiments recorded in invention can also be obtained according to these attached drawings other for those of ordinary skill in the art
Attached drawing.
Fig. 1 is the preparation system schematic diagram of medicinal liposome provided by the embodiments of the present application；
Fig. 2 is the flow chart of medicine lipid preparation provided by the embodiments of the present application；
Fig. 3 is the structural schematic diagram of granulation kettle provided by the embodiments of the present application.
Wherein, 1- liquid carbon dioxide storage tank, the first high pressure valve of 2-, the second high pressure valve of 3-, 4- First Heat Exchanger, 5- second
Heat exchanger, the first high-pressure pump of 6-, the second high-pressure pump of 7-, the first HV XLPE power cables of 8-, the second HV XLPE power cables of 9-, 10- third are high
Press pump, the 4th high-pressure pump of 11-, 12- third heat exchanger, the 4th heat exchanger of 13-, 14- first pressure regulating valve, 15- second pressure
Regulating valve, the overcritical accumulator still of 16- wall material, 17- third high pressure valve, the 4th high pressure valve of 18-, 19- granulation kettle, 191- nozzle,
192- collecting chamber, 193- reaction chamber, 194- tube side heat exchanger, 195- prestore chamber, 196- insulation jacket, the micron-sized filtering of 197-
Web frame unit, 198- liposome discharge control valve, 199- supercritical carbon dioxide loop exit control valve, 20- hot water storage tank.
Specific embodiment
The embodiment of the present invention is described below in detail, examples of the embodiments are shown in the accompanying drawings, wherein from beginning to end
Same or similar label indicates same or similar element or element with the same or similar functions.Below with reference to attached
The embodiment of figure description is exemplary, and for explaining only the invention, and is not construed as limiting the claims.
As shown in Figure 1, this application provides a kind of preparation systems of medicinal liposome, comprising: granulation kettle 19, kettle 19 of pelletizing
Lower part connect with conveying dissolved with the pipe-line system of supercritical carbon dioxide of wall material solution, the top of granulation kettle 19 and conveying
The pipe-line system of supercritical carbon dioxide dissolved with core material drug connects.
Specifically, the pipe-line system of supercritical carbon dioxide of the conveying dissolved with wall material miscible fluid is as follows: liquid titanium dioxide
Carbon storage tank 1, the first high pressure valve 2, First Heat Exchanger 4, the first high-pressure pump 6 are successively linked in sequence, so as to be stored in liquid titanium dioxide
The liquid carbon dioxide of carbon storage tank 1 adjusts temperature and pressure to super through the first high pressure valve 2, First Heat Exchanger 4 and the first high-pressure pump 6
Critical state.First HV XLPE power cables 8 and third high-pressure pump 10 connect, so as to be stored in the wall material in the first HV XLPE power cables 8
Solution is pressurizeed by third high-pressure pump 10.First high-pressure pump 6 and third high-pressure pump 10 are connect with third heat exchanger 12, so that wall
Material liquid is dissolved in supercritical carbon dioxide, and further adjusts temperature to the supercritical carbon dioxide dissolved with wall material solution
Degree.Third heat exchanger 12 is successively linked in sequence with first pressure regulating valve 14, the overcritical accumulator still 16 of wall material, so as to further adjust
The supercritical carbon dioxide dissolved with wall material solution after whole temperature is stored to the overcritical accumulator still of wall material 16 with spare.Wall material is super
Critical accumulator still 16 is connect with third high pressure valve 17, is dissolved with wall material solution so as to be stored in the overcritical caching kettle 16 of wall material
Supercritical carbon dioxide by entering the lower part of granulation kettle 19 after third high pressure valve 17.
Specifically, the pipe-line system of supercritical carbon dioxide of the conveying dissolved with core material drug is as follows: liquid carbon dioxide
Storage tank 1, the second high pressure valve 3, the second heat exchanger 5, the second high-pressure pump 7 are successively linked in sequence, so as to be stored in liquid carbon dioxide
The liquid carbon dioxide of storage tank 1 adjusts temperature and pressure through the second high pressure valve 3, the second heat exchanger 5 and the second high-pressure pump 7 and faces to super
Boundary's state.Second HV XLPE power cables 9 and the connection of the 4th high-pressure pump 11, so as to be stored in the core material medicine in the second HV XLPE power cables 9
Object is pressurizeed by the 4th high-pressure pump 11.Second high-pressure pump 7 and the 4th high-pressure pump 11 are connect with the 4th heat exchanger 13, so that core material
Drug, which is dissolved in supercritical carbon dioxide, forms inclusion compound, and further to the overcritical titanium dioxide for being dissolved with core material drug
After carbon adjusts temperature, also, the temperature of the supercritical carbon dioxide dissolved with wall material solution after whole temperature is higher than adjustment temperature
The supercritical carbon dioxide dissolved with core material drug temperature.4th high-pressure pump 11 and second pressure regulating valve the 15, the 4th are high
Pressure valve 18 is successively linked in sequence, so that the supercritical carbon dioxide dissolved with core material drug passes through second pressure regulating valve 15 and the
Enter the top of granulation kettle 19 after four high pressure valves 18.
Pelletize kettle 19 top from top to bottom with supercritical carbon dioxide loop exit control valve and liposome control of export
Valve connection, the liposome of carbon dioxide and embedding completion is discharged.
In addition, the preparation system of medicinal liposome further include: the hot water being connect with First Heat Exchanger 4 and the second heat exchanger 5
Storage tank 20 provides heat source, certain hot water storage tank 20 or third heat exchanger 12 for First Heat Exchanger 4 and the second heat exchanger 5
Heat source is provided with the 4th heat exchanger 13.
As shown in Fig. 2, including the following steps: this application provides a kind of preparation method of medicinal liposome
Step S210, liquid carbon dioxide is adjusted to supercriticality；
Specifically, the liquid carbon dioxide in liquid CO 2 storage tank 1 is entered the first heat exchange by the first high pressure valve 2
In device 4, while being entered in the second heat exchanger 5 by the second high pressure valve 3, is changed by the First Heat Exchanger 4 and second of two pipelines
Hot device 5 heats the liquid carbon dioxide of two pipelines.
Then, the carbon dioxide after being heated by First Heat Exchanger 4 passes through the first high-pressure pump 6, while passing through the second heat exchange
Carbon dioxide after device 5 heats passes through the second high-pressure pump 7, after the first high-pressure pump 6 and the pressurization of the second high-pressure pump 7, two pipes
Carbon dioxide in road is in a supercritical state.
Step S220, by the supercritical carbon dioxide and core material drug mixed dissolution in a pipeline, by another pipeline
In supercritical carbon dioxide and wall material solution mixed dissolution, and adjust temperature and make the overcritical dioxy dissolved with wall material solution
The temperature for changing carbon is higher than the temperature of the supercritical carbon dioxide dissolved with core material drug；
Wherein, core material drug is the mixed liquor of menthol+acetone and drug.Menthol+acetone is proportionally (4~2): 1
It is configured, proportionally 3:1 is configured preferred menthol+acetone.
Specifically, configuring core material drug according to aforementioned proportion, and core material drug is mixed in the second HV XLPE power cables 9
It closes.Mixed core material drug is after the pressurization of the 4th high-pressure pump 11 and in one article of pipeline after the pressurization of the second high-pressure pump 7
Supercritical carbon dioxide mixed dissolution, i.e., it is pressurized after core material drug be dissolved to it is pressurized after supercritical carbon dioxide in shape
At inclusion compound.Then, the supercritical carbon dioxide dissolved with core material drug carries out temperature adjustment through the 4th heat exchanger 13, is dissolved with
After temperature adjusts, temperature is maintained between 30 DEG C~70 DEG C the supercritical carbon dioxide of core material drug；Its preferred temperature
It is maintained between 40 DEG C~60 DEG C；Further preferably its temperature is maintained between 45 DEG C~50 DEG C.Then, super dissolved with core material drug
Critical carbon dioxide carries out pressure adjustment using second pressure regulating valve 15 after temperature adjusts.
In addition, wall material solution is the mixed liquor of lecithin and hyaluronic acid.Wherein, lecithin is the lecithin from yolk
Rouge (1- palmityl -2- oleolyl phosphatidyl Serine choline), lecithin content is 90% or more.Hyaluronic acid (D- grape
Uronic acid and N-acetyl-glucosamine), since it can achieve target spot conveying in conjunction with the binding site of drug.Specifically, ovum
The ratio of phosphatide and hyaluronic acid is (0.1~1): 1, the ratio of preferred lecithin and hyaluronic acid is (0.5~0.8): and 1,
The ratio of lecithin and hyaluronic acid further preferably is (0.6~0.7): 1.
Specifically, configuring wall material solution according to aforementioned proportion, and wall material solution is mixed in the first HV XLPE power cables 8
It closes.Mixed wall material solution is after the pressurization of third high-pressure pump 10 and in a pipeline after the pressurization of the first force (forcing) pump 6
Supercritical carbon dioxide mixed dissolution, i.e., it is pressurized after wall material solution be dissolved to it is pressurized after supercritical carbon dioxide in.
Then, the supercritical carbon dioxide dissolved with wall material solution carries out temperature adjustment through third heat exchanger 12, is dissolved with wall material solution
Supercritical carbon dioxide after temperature adjusts, temperature is maintained between 50 DEG C~80 DEG C, its preferred temperature is maintained at 60
DEG C~70 DEG C between；Further preferably its temperature is maintained between 65 DEG C~68 DEG C.Then, the overcritical dioxy dissolved with wall material solution
Change carbon pressure is adjusted using first pressure regulating valve 14 after temperature adjusts, reach the overcritical accumulator still 16 of wall material with
It is spare.
Such as: core material medicine preparation: 100 grams of drug are accurately weighed, 1730 grams of menthol, 270 grams of acetone, is heated at 40 DEG C
Lower dissolution is stirred evenly and is forced into after 20mpa homogeneous for use, and above-mentioned stand-by drug is dissolved in supercritical carbon dioxide
It is middle to form the supercritical carbon dioxide for being dissolved with core material drug, reach 45 DEG C by heat exchanger heating, is reached by high-pressure pump pressurization
To 26Mpa；
Wall material solution preparation: weighing 780 grams of lecithin and 1300 grams of hyaluronic acids in the yolk source of 94% content, dissolves
The supercritical carbon dioxide for being dissolved with wall material solution is formed in supercritical carbon dioxide, heating reaches 65 DEG C, and pressure reaches
22Mpa。
Step S230, the temperature supercritical carbon dioxide adjusted dissolved with core material drug is passed through granulation from top
The temperature supercritical carbon dioxide adjusted dissolved with wall material solution is passed through granulation kettle from lower part, carries out lipid system by kettle
Grain, wherein the pressure of the supercritical carbon dioxide dissolved with core material drug and supercritical carbon dioxide dissolved with wall material solution
Pressure is all larger than the pressure in granulation kettle；
After second pressure regulating valve 15 carries out pressure adjustment, the supercritical carbon dioxide dissolved with core material drug passes through
4th high pressure valve 18 is sprayed into granulation kettle 19 by the top of nozzle from granulation kettle 19, due to overcritical dissolved with core material drug
The pressure of carbon dioxide is higher than the pressure in granulation kettle 19, therefore enters overcritical dissolved with core material drug in granulation kettle 19
Carbon dioxide expands rapidly, gasifies, since solubility of the core material in supercritical carbon dioxide is lower, dissolved core material
Just it is precipitated in the form of fine particle, forms the granule particles of suspension.It is stored in being dissolved in the overcritical accumulator still 16 of wall material
The supercritical carbon dioxide of wall material solution enters granulation kettle 19 by the lower part of third high pressure valve 17 from granulation kettle 19.Core material particles
It from top to bottom moves, wall material moves from the bottom to top, and wall material and core material particles meet to form stable embedding liposome bimolecular knot
Structure.Since the temperature of the supercritical carbon dioxide dissolved with wall material solution is higher than the supercritical carbon dioxide dissolved with core material drug
Temperature, therefore the convection velocity of wall material and core material particles can be enhanced, so that wall material and the mixing of core material suspended particulate are filled
Point, embedding effect and encapsulation rate are improved, and the fast upward motion of wall material also reduces core material suspended particulate and wall material weight
The chance of multiple connection touching, and then the probability that core material suspended particulate is repeatedly embedded is avoided, also avoid traditional liposomal preparation work
Solvent is largely used in skill.
Specifically, as shown in figure 3, granulation kettle 19 is divided into three cavitys from the bottom to top.After temperature adjusts, it is dissolved with core material
The supercritical carbon dioxide of drug runs through the collecting chamber 192 on top by nozzle 191, protrudes into the reaction chamber 193 at middle part, preferably
Stretch to the middle and upper part of reaction chamber 193.Since carbon dioxide gasification takes away heat, the temperature in reaction chamber 193 is reduced rapidly, and is
Avoid the nozzle 191 because caused by reducing temperature from blocking, can to mix in reaction chamber 193 core material drug, wall material solution
It is kept the temperature with carbon dioxide.Specifically, be provided with tube side heat exchanger 194 in reaction chamber 193, by tube side heat exchanger
The medium with certain temperature is passed through in 194 to play the work to core material, wall material and carbon dioxide heat preservation in reaction chamber 193
With.Preferably, nozzle 191 is extend into 194 middle part of tube side heat exchanger in reaction chamber 193, it is ensured that dissolved with core material solution
The moment that supercritical carbon dioxide gushes out from nozzle will not because of temperature reduction and lead to the reunions of core material particles.
In addition, nozzle 191 blocks in order to prevent, can also face dissolved with the super of core material drug what is circulated in nozzle 191
Boundary's carbon dioxide is kept the temperature.Specifically, heating chamber can be arranged inside nozzle 191, being passed through into heating chamber has centainly
Temperature heating oil, by heat oil heated, so as to prevent to flow through the fluid in nozzle 191 in advance gasify cool down from
And stopped nozzles 191.
On the basis of the above, due to being carried out to the supercritical carbon dioxide dissolved with core material drug to circulate in nozzle 191
Heat preservation, and also the fluid being passed through in granulation kettle 19 is kept the temperature, therefore avoid spray caused by carbon dioxide gasification cooling
Mouth 191 blocks, it is possible to the spouting velocity of further supercritical carbon dioxide of the control dissolved with core material drug.Specifically
, there is certain pressure due to the supercritical carbon dioxide dissolved with core material drug, so by reducing opening for nozzle 191
Mouth size, to improve spouting velocity, that is, increases the intensity of expansion, therefore ensure that core material particles in granulation kettle
Distribution without " dead zone ", to further improve embedding effect and encapsulation rate.And due also to reducing opening for nozzle 191
Mouth size, ensure that the partial size of core material particles is smaller, so that the liposome particle average grain diameter of production is smaller, such as:
Between 40nm~80nm, achieve the effect that nanometer is pelletized, much smaller than the production particle size of conventional liposome.
In order to further guarantee that the wall material in the supercritical carbon dioxide dissolved with wall material solution can quickly rise,
Namely to guarantee have between the carbon dioxide dissolved with wall material solution and the supercritical carbon dioxide dissolved with core material drug
Scheduled temperature difference, therefore to ensure that the temperature of the supercritical carbon dioxide dissolved with wall material solution is scheduled temperature, therefore
The chamber 195 that prestores for prestoring the supercritical carbon dioxide dissolved with wall material solution of lower part is kept the temperature, such as is prestoring chamber 195
It is external insulation jacket 196 is set, by being passed through the medium of predetermined temperature into insulation jacket 196, to realize to being dissolved with
The adjustment of the temperature of the supercritical carbon dioxide of wall material solution.
On the basis of the above, the supercritical carbon dioxide gasification dissolved with core material drug wait be passed through in granulation kettle 19, core
After material is precipitated with fine particle, change the core material particles of disordered motion, and be allowed to ordered movement, to reduce between core material particles
Collision, so that the reunion between core material particles is reduced, so that the embedding of liposome is more stable.Specifically, passing through
Baffle plate, such as segmental baffle are set in the reaction chamber at the middle part of granulation kettle 19, so that core material particles movement is orderly,
The agglomeration for reducing core material particles, improves the stability of embedding.
Such as: the supercritical carbon dioxide dissolved with core material drug is from top to bottom sprayed into granulation kettle by nozzle, system
The pressure control of grain kettle is opened wall material high pressure valve (third autoclave), in 7Mpa by (pre- by being passed through in insulation jacket again
Determine the medium of temperature) reach after heat exchange adjustment 65 DEG C of the supercritical carbon dioxide dissolved with wall material solution enter in kettle of pelletizing into
Row granulation, and the pressure of the supercritical carbon dioxide dissolved with wall material solution is controlled in 22Mpa.Step S204, from titanium dioxide
The liposome that embedding is completed is collected in carbon.
Since the application preparation method can guarantee there is stable liposome embedded effect, encapsulation rate, the application
Liposome is prepared in reaction chamber 193, carbon dioxide has a stable temperature change before reaction and after reaction, it is possible to
By measuring the temperature change of carbon dioxide, so that it is determined that whether liposome embeds completion, that is, the embedding of liposome is determined
Whether rate reaches scheduled embedding effect, encapsulation rate.
After the completion of determining liposome embedded in reaction kettle 193 by measuring temperature, liposome discharge control valve is opened
198, supercritical carbon dioxide loop exit control valve 199, liposome and carbon dioxide flow upward to collecting chamber 192, titanium dioxide
The micron-sized filter screen structure unit 197 that carbon is arranged out of collecting chamber 192, which continues up, to be flowed through carbon dioxide recycle and goes out
The pipeline outflow that mouth control valve 199 controls, and the intercepted pipeline controlled from liposome discharge control valve 198 of liposome is collected.
Such as: it pelletizes in granulation kettle after twenty minutes, the temperature by measuring carbon dioxide reaches predetermined temperature, opens super
Critical carbon dioxide loop exit control valve reduces pressure and opens simultaneously to 6.5Mpa so that carbon dioxide carries out circulation discharge
Liposome discharge control valve.Liposome is made: 3940 grams, carrying drug ratio 2.5%, encapsulation rate reaches 94%, and average grain diameter 75 ±
15nm, index of polyphenol 0.55, current potential: -25.9 ± 0.5/mV.
It is obvious to a person skilled in the art that invention is not limited to the details of the above exemplary embodiments, Er Qie
In the case where without departing substantially from spirit or essential attributes of the invention, the present invention can be realized in other specific forms.Therefore, no matter
From the point of view of which point, the present embodiments are to be considered as illustrative and not restrictive, and the scope of the present invention is by appended power
Benefit requires rather than above description limits, it is intended that all by what is fallen within the meaning and scope of the equivalent elements of the claims
Variation is included within the present invention.Any reference signs in the claims should not be construed as limiting the involved claims.
In addition, it should be understood that although this specification is described in terms of embodiments, but not each embodiment is only wrapped
Containing an independent technical solution, this description of the specification is merely for the sake of clarity, and those skilled in the art should
It considers the specification as a whole, the technical solutions in the various embodiments may also be suitably combined, forms those skilled in the art
The other embodiments being understood that.
Claims (10)
1. a kind of preparation method of medicinal liposome, which comprises the steps of:
Liquid CO 2 is adjusted to supercriticality；
By the supercritical carbon dioxide and core material drug mixed dissolution in a pipeline, by the overcritical dioxy in another pipeline
Change carbon and wall material solution mixed dissolution, and adjusting temperature is higher than the temperature of the supercritical carbon dioxide dissolved with wall material solution
The temperature of supercritical carbon dioxide dissolved with core material drug；
The temperature supercritical carbon dioxide adjusted dissolved with core material drug is passed through granulation kettle from top, after temperature is adjusted
The supercritical carbon dioxide dissolved with wall material solution be passed through granulation kettle from lower part, carry out liposome granulation；
Wherein, the pressure of the supercritical carbon dioxide dissolved with core material drug and supercritical carbon dioxide dissolved with wall material solution
Pressure be all larger than granulation kettle in pressure；
The liposome that embedding is completed is collected from carbon dioxide.
2. the preparation method of medicinal liposome according to claim 1, which is characterized in that core material solution is menthol+the third
The mixed liquor of ketone and drug, menthol+acetone ratio are (4~2): 1.
3. the preparation method of medicinal liposome according to claim 2, which is characterized in that wall material solution be lecithin and thoroughly
The ratio of the mixed liquor of bright matter acid, lecithin and hyaluronic acid is (0.1~1): 1.
4. the preparation method of medicinal liposome according to claim 1-3, which is characterized in that wall material will be dissolved with
The temperature of the supercritical carbon dioxide of solution is adjusted between 30 DEG C~70 DEG C, will be dissolved with the overcritical titanium dioxide of core material solution
The temperature of carbon is adjusted between 50 DEG C~80 DEG C.
5. the preparation method of medicinal liposome according to claim 1-3, which is characterized in that be dissolved with core material medicine
The pressure of the supercritical carbon dioxide of object is 26Mpa, and the pressure of the supercritical carbon dioxide dissolved with wall material solution is 22Mpa,
Pressure in granulation kettle is 7Mpa.
6. the preparation method of medicinal liposome according to claim 1-3, which is characterized in that rouge in granulation kettle
Plastid granulation carries out guarantor's control.
7. the preparation method of medicinal liposome according to claim 6, which is characterized in that the temperature of control liposome granulation
To 65 DEG C.
8. the preparation method of medicinal liposome according to claim 1-3, which is characterized in that by nozzle to
Granulation kettle is passed through the supercritical carbon dioxide dissolved with core material drug, in nozzle interior to overcritical two dissolved with core material drug
Carbonoxide is kept the temperature.
9. the preparation method of medicinal liposome according to claim 1-3, which is characterized in that granulation kettle to be passed through
In dissolved with core material drug supercritical carbon dioxide gasification, core material particles be precipitated after, change the core material particles direction of motion make
Ordered movement.
10. a kind of preparation system of medicinal liposome characterized by comprising granulation kettle；The lower part of granulation kettle and conveying are dissolved
There is the pipe-line system of the supercritical carbon dioxide of wall material solution to connect, to the temperature of the supercritical carbon dioxide dissolved with wall material solution
Degree is adjusted；The pipe-line system of the supercritical carbon dioxide of top and conveying dissolved with core material drug of granulation kettle is connect, right
The temperature of supercritical carbon dioxide dissolved with core material drug is adjusted；And adjust after temperature dissolved with wall material solution
The temperature of supercritical carbon dioxide is higher than the temperature of the supercritical carbon dioxide dissolved with core material drug after adjustment temperature；Its
In, the pressure of the pressure of the supercritical carbon dioxide dissolved with core material drug and the supercritical carbon dioxide dissolved with wall material solution
The pressure being all larger than in granulation kettle.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910181051.1A CN109718205B (en) | 2019-03-11 | 2019-03-11 | Preparation method and system of drug liposome |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910181051.1A CN109718205B (en) | 2019-03-11 | 2019-03-11 | Preparation method and system of drug liposome |
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| Publication Number | Publication Date |
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| CN109718205A true CN109718205A (en) | 2019-05-07 |
| CN109718205B CN109718205B (en) | 2021-04-06 |
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| CN111012671A (en) * | 2019-11-25 | 2020-04-17 | 上海强德食品科技有限公司 | Physical preparation method of microcapsule |
| CN113143885A (en) * | 2021-04-13 | 2021-07-23 | 广东普萃特医生物工程有限公司 | Supercritical emulsification granulation process of lutein |
| CN114950289A (en) * | 2022-05-13 | 2022-08-30 | 成都科建生物医药有限公司 | Preparation device and preparation method of glutathione liposome |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111012671A (en) * | 2019-11-25 | 2020-04-17 | 上海强德食品科技有限公司 | Physical preparation method of microcapsule |
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| CN113143885A (en) * | 2021-04-13 | 2021-07-23 | 广东普萃特医生物工程有限公司 | Supercritical emulsification granulation process of lutein |
| CN114950289A (en) * | 2022-05-13 | 2022-08-30 | 成都科建生物医药有限公司 | Preparation device and preparation method of glutathione liposome |
| CN114950289B (en) * | 2022-05-13 | 2023-02-28 | 成都科建生物医药有限公司 | Preparation device and preparation method of glutathione liposome |
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