CN113368055A - Preparation method of nano liposome emulsion - Google Patents
Preparation method of nano liposome emulsion Download PDFInfo
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Abstract
The invention relates to the technical field of liposome, in particular to a preparation method of a nano liposome emulsion. The invention discloses a preparation method of a nanoliposome emulsion, which comprises the steps of mixing phospholipid, an insoluble drug and cherry plant extract water to obtain suspension, dispersing at a proper temperature through high-speed shearing, and crushing the phospholipid and the insoluble drug to form a micron scale. Under the micron scale, after long-time shearing, the insoluble drug particles and the phospholipid particles interact to emulsify, and then self-assemble to form the micron-scale liposome. The preparation method can dissolve the fat-soluble medicine only by mechanical shearing action, and has unexpected effect. The preparation method does not use toxic and harmful organic solvents, and has safe and environment-friendly production process and high product safety. The invention takes the oriental cherry plant extract water as the solvent for preparing the liposome, so that the obtained liposome has natural preservative and antioxidant effects, and no preservative is required to be additionally added for preserving the liposome.
Description
Technical Field
The invention relates to the technical field of liposome, in particular to a preparation method of a nano liposome emulsion.
Background
In recent years, liposome has attracted much attention and is widely used in the fields of biomedicine, cosmetics, health foods and the like.
There are many methods for preparing liposomes of fat-soluble drugs, such as: the film method, the reverse phase evaporation method, the injection method and the like, and most preparation methods involve the use of organic solvents. The introduction of organic solvents may cause risks such as environmental pollution and product solvent residue, and directly affect the quality of products, so strict control and management are required in industrial production. Besides the thin film method, other traditional liposome preparation methods are generally not suitable for large-scale industrial production, thereby limiting the popularization and application of the liposome in industrialization.
In addition, the liposome needs to be additionally added with a preservative to prevent the pollution of the liposome in the preservation process, but the preservative also has the risk of causing pollution and residue.
Disclosure of Invention
In view of the above, the present invention provides a method for preparing a nanoliposome emulsion, which can prepare a lipid-soluble drug liposome simply and rapidly without using an organic solvent; in addition, the preparation method uses oriental cherry plant extract water as a solvent, so that the prepared liposome has natural preservative and antioxidant effects.
The specific technical scheme is as follows:
the invention provides a preparation method of a nanoliposome emulsion, which comprises the following steps:
step 1: mixing phospholipid, cholesterol, and medicine with cherry blossom plant extract water to form suspension; the drug comprises a fat-soluble drug;
step 2: shearing the suspension at a high speed under a heating and heat-preserving state to obtain emulsion;
the invention mixes phospholipid, insoluble drug and water to obtain suspension, which is dispersed by high speed shearing at proper temperature to pulverize phospholipid and insoluble drug to form micron scale. Under the micron scale, after long-time shearing, the insoluble drug particles and the phospholipid particles interact to emulsify, and then self-assemble to form the micron-scale liposome.
The method does not use toxic and harmful organic solvents in the process of preparing the fat-soluble drug liposome, and has safe and environment-friendly production process and high product safety; the preparation equipment and the process are simple, and the method is suitable for large-scale production and improves the production efficiency.
Cherry blossom (academic name: Cerasus sp.): is a general term of several plants in the genus of cerasus of the family Rosaceae, and is named as "Tokyo cherry blossom" in the newly revised name of "Chinese plant record", also called as "Japanese cherry blossom". The oriental cherry has extremely high ornamental value and also has the effects of medicine, skin care and the like. In the aspect of skin care, the cherry blossom has good effects of shrinking pores and balancing grease, contains rich natural vitamin A, B, E, and the cherry leaf flavone also has the effects of maintaining beauty, keeping young, strengthening mucous membrane and promoting sugar metabolism, and can be used for keeping young skin. Cherry blossom has the effects of tendering skin and brightening skin, is one of important raw materials of skin care products, is usually extracted and refined, experts extract the cherry blossom into cherry blossom tender oil by using a three-high fresh extraction technology, and the cherry blossom extract contains a component called cherry blossom enzyme which is commonly used for removing acnes.
In the invention, the cherry flower extract water is obtained by distilling cherry flower petals at low temperature in vacuum; the distillation temperature is 30-65 ℃; the distillation pressure is-60 kPa-101 kPa; the distillation time is 3-10 h.
The invention uses the oriental cherry plant extract water as the solvent for preparing the liposome, and the obtained liposome is unexpectedly found to have the effects of antisepsis and antioxidation, so that the liposome is preserved without adding an additional preservative.
In step 1 of the present invention, the fat-soluble drug comprises: one or more of glabridin, ceramide, resveratrol and fat-soluble vitamins.
The phospholipid comprises one or more of soybean lecithin, egg yolk lecithin, hydrogenated lecithin, dilauroyl phosphatidylcholine, dimyristoyl phosphorylcholine, dipalmitoyl phosphorylcholine, distearoyl phosphatidylcholine, dioleoyl phosphatidylcholine, dilauroyl phosphatidylethanolamine, dimyristoyl phosphatidylethanolamine, dipalmitoyl phosphatidylethanolamine, distearoyl phosphatidylethanolamine and dioleoyl phosphatidylethanolamine.
The medicament further comprises: a water-soluble drug. The water-soluble medicine comprises one or more than two of sodium hyaluronate, nano metal colloid dispersion liquid and water-soluble vitamins.
Before mixing, the method also comprises the following steps: adding a surfactant. The addition of a surfactant can facilitate the solubilization of the fat-soluble drug.
The surfactant is ionic surfactant and/or nonionic surfactant, wherein the cationic surfactant comprises quaternary ammonium salt, the anionic surfactant comprises higher fatty acid salt or sulfate salt, and the nonionic surfactant comprises one or more than two of tween, span, PEG fatty acid ester and polyglycerol-10-stearate.
Before mixing, the method also comprises the following steps: the polyol is added. The addition of the polyol can further facilitate the dissolution of a portion of the fat-soluble drug. Glabridin has low solubility in polyhydric alcohol.
The polyhydric alcohol comprises one or more of glycerol, propylene glycol, butylene glycol, pentylene glycol, and isoprene glycol.
In the invention, according to the mass percentage,
2-15% of phospholipid;
0.01-5% of a medicament;
0-5% of cholesterol;
the balance being water.
Preferably, the amount of the surfactant is, in mass percent,
2-10% of phospholipid;
0.01-4% of a medicament;
0-4% of cholesterol;
the rest is cherry blossom plant extract water.
More preferably, the amount of the surfactant is, in mass percent,
2-8% of phospholipid;
0.1-3% of a medicament;
0-3% of cholesterol;
when the medicament is a fat-soluble medicament and a water-soluble medicament, the dosage ratio of the fat-soluble medicament and the water-soluble medicament is not particularly limited.
In the invention, the weight percentage of the surfactant is 0.1-20%, preferably 0.1-15%, and more preferably 0.1-8%; 5 to 60% of a polyol, preferably 5 to 45%, more preferably 5 to 30%.
In step 2 of the invention, the heating temperature of the suspension liquid needs to be higher than the phase transition temperature of the phospholipid. The heating temperature is 50-100 ℃, and preferably 50-70 ℃; then, maintaining the heating temperature for shearing, wherein a shearing disperser is adopted for shearing; the shearing rate is 8000-20000 rpm (rotor diameter is 13mm), the shearing time is more than 30min, preferably more than 60min at the shearing rate of 8000-15000 rpm (rotor diameter is 13mm), more preferably 60-90 min. The liposome obtained after shearing is micron-sized.
The nano-scale liposome has better dispersibility and stability and better skin permeability. Therefore, after the high-speed shearing is performed in step 2 of the present invention, the method further comprises: homogenizing under high pressure. The high-pressure homogenization can crush and thin the micron-sized liposome to obtain the nano-sized liposome. The high-pressure homogenization specifically comprises the following steps: each cycle was carried out at a pressure of 400bar, 600bar, 800bar, 1000bar for 2 or more times.
According to the technical scheme, the invention has the following advantages:
the invention provides a preparation method of a nanoliposome emulsion, which comprises the steps of mixing phospholipid, insoluble drugs and oriental cherry plant extract water to obtain suspension, dispersing at a proper temperature through high-speed shearing, and crushing the phospholipid and the insoluble drugs to form a micron scale. Under the micron scale, after long-time shearing, the insoluble drug particles and the phospholipid particles interact to emulsify, and then self-assemble to form the micron-scale liposome. The preparation method can dissolve the fat-soluble medicine only by mechanical shearing action, and has unexpected effect. In addition, the preparation method does not use toxic and harmful organic solvents, the production process is safe and environment-friendly, and the product safety is high; the preparation equipment and the process are simple, and the method is suitable for large-scale production and improves the production efficiency. In addition, the cherry blossom plant extract water is used as a solvent for preparing the liposome, and the obtained liposome has natural preservative and antioxidant effects, so that the liposome is preserved without adding a preservative additionally.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to these drawings without inventive exercise.
FIG. 1 is an optical microscope photograph of liposomes in an emulsion prepared in step 1 of example 2 of the present invention;
FIG. 2 is an optical microscope photograph (3 μm on scale) of liposomes in the emulsion obtained in step 1 of example 3 of the present invention;
FIG. 3 is an optical microscope photograph (3 μm on scale) of liposomes in the emulsion obtained in step 1 of example 4 of the present invention;
FIG. 4 is an optical microscope photograph (3 μm on scale) of liposomes in the emulsion obtained in step 1 of example 5 of the present invention;
FIG. 5 is an optical microscope photograph (3 μm on scale) of liposomes in the emulsion obtained in step 1 of example 6 of the present invention;
FIG. 6 is an optical microscope photograph (3 μm on scale) of liposomes in an emulsion prepared in step 1 of example 7 of the present invention;
FIG. 7 is an optical microscope photograph (3 μm on scale) of liposomes in an emulsion prepared in step 1 of example 9 of the present invention;
FIG. 8 is a transmission electron micrograph (100 nm on a scale) of glabridin liposome prepared in step 2 of example 9 of the present invention;
FIG. 9 is a graph showing the results of B16 experiments in which Glabradin is Glabridin, GL is Glabridin liposome, and GL-S is Glabridin liposome-formulated oriental cherry plant water, according to Experimental example 3 of the present invention;
FIG. 10 is a histogram of melanin content in B16 cells according to Experimental example 3, wherein Glabradin is Glabridin, GL is Glabridin liposome, and GL-S is Glabridin liposome-compounded oriental cherry plant water.
Detailed Description
In order to make the objects, features and advantages of the present invention more obvious and understandable, the technical solutions in the embodiments of the present invention will be clearly and completely described below, and it should be apparent that the embodiments described below are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The reagents in the examples of the present invention are all commercially available.
Wherein, the high-speed homogeneous dispersion machine of experimental type: IKA, Germany.
Experimental high-pressure homogenizer: suzhou ATS Inc.
Zeta nanometer particle size analyzer: malvern, uk.
Reagent:
soybean lecithin: PC > 95%, Sigma-Aldrich Sigma Aldrich trade company, Shanghai.
Glabridin: HPLC purity is more than or equal to 90 percent, Qinghai lake pharmaceutical industry Co.
Cholesterol: purity > 96%, Sigma-Aldrich Sigma Aldrich trade ltd.
Polyglycerol-10-stearate: heliochemical trade (shanghai) limited.
Butanediol: purity > 98%, manufactured by Nippon Daiillo Co., Ltd.
Example 1
This example is the preparation of cherry blossom Water extract
Weighing fresh petal of oriental cherry 50kg, cutting into size of 4-5 mm with a cutter, placing into drying equipment at low temperature of 150L, setting vacuum degree at-90 kPa, extracting temperature at about 40 deg.C, stirring speed at 30rpm, and extracting time at 6 h. Condensing and collecting the cherry blossom cell water, and filtering the cherry blossom cell water through a 0.22um filter membrane to obtain the cherry blossom cell water, wherein the yield of the cherry blossom cell water is 74.6 percent.
Example 2
The preparation formula of glabridin liposome in this example is shown in table 1, and the specific preparation steps are as follows:
(1) adding phospholipid (PC 95%), glabridin and cholesterol into cherry blossom extract water, heating in water bath at 50 deg.C, and high-speed shearing with experiment type IKA high-speed shearing disperser at 10000rpm for 30min to obtain uniform emulsion.
(2) And (2) homogenizing the uniform emulsion obtained in the step (1) under high pressure, and circulating for 2 times under 400/600/800/1000bar pressure respectively to obtain uniform glabridin liposome.
As can be seen in FIG. 1, after high shear in step 1, a multi-lamellar globular structure resembling liposomes is observed in the emulsion in step 1.
Examples 3 to 5
The preparation formula of glabridin liposome in this example is shown in table 1, and the specific preparation steps are as follows:
(1) adding phospholipid (PC 95%), glabridin and cholesterol into cherry blossom extract water, heating in water bath at 60 deg.C, and high-speed shearing with experiment type IKA high-speed shearing disperser at 10000rpm for 60min to obtain uniform emulsion.
(2) And (2) homogenizing the uniform emulsion obtained in the step (1) under high pressure, and circulating for 2 times under 400/600/800/1000bar pressure respectively to obtain uniform glabridin liposome.
As can be seen from FIGS. 2 to 4, after the high-speed shearing in step 1, a multi-layer spherical structure similar to liposome can be observed in the emulsion in step 1.
Example 6
The preparation formula of glabridin liposome in this example is shown in table 1, and the specific preparation steps are as follows:
(1) adding phospholipid (PC 95%), polyglycerol-10-stearate, glabridin and cholesterol into oriental cherry plant extraction water, heating in water bath at 50 deg.C, and high-speed shearing with experiment type IKA high-speed shearing disperser at 10000rpm for 30min to obtain uniform emulsion.
(2) And (2) homogenizing the uniform emulsion obtained in the step (1) under high pressure, and circulating for 2 times under 400/600/800/1000bar pressure respectively to obtain uniform glabridin liposome.
As can be seen in FIG. 5, after high shear in step 1, a multi-lamellar globular structure resembling liposomes is observed in the emulsion in step 1.
Examples 7 to 8
The preparation formula of glabridin liposome in this example is shown in table 1, and the specific preparation steps are as follows:
(1) adding phospholipid (PC 95%), polyglycerol-10-stearate, glabridin and cholesterol into the mixture of oriental cherry extract water and butanediol, heating in water bath at 50 deg.C, and high-speed shearing with an experimental IKA high-speed shearing disperser at 10000rpm for 30min to obtain uniform emulsion.
(2) And (2) homogenizing the uniform emulsion obtained in the step (1) under high pressure, and circulating for 2 times under 400/600/800/1000bar pressure respectively to obtain uniform glabridin liposome.
As can be seen in FIG. 6, in example 7, after high shear in step 1, a multi-lamellar globular structure resembling liposomes is observed in the emulsion in step 1.
Example 9
The preparation formula of glabridin liposome in this example is shown in table 1, and the specific preparation steps are as follows:
(1) adding phospholipid (PC 95%), polyglycerol-10-stearate, glabridin and cholesterol into cherry blossom extract water, heating in water bath at 60 deg.C, and high-speed shearing with experiment type IKA high-speed shearing disperser at 10000rpm for 60min to obtain uniform emulsion.
(2) And (2) homogenizing the uniform emulsion obtained in the step (1) under high pressure, and circulating for 2 times under 400/600/800/1000bar pressure respectively to obtain uniform glabridin liposome.
As can be seen in FIG. 7, after high shear in step 1, a multi-lamellar globular structure resembling liposomes is observed in the step 1 emulsion.
As can be seen from fig. 8, glabridin was successfully encapsulated in liposomes.
Example 10
The preparation formula of glabridin liposome in this example is shown in table 1, and the specific preparation steps are as follows:
(1) adding phospholipid (PC 95%), polyglycerol-10-stearate, glabridin and cholesterol into the mixture of oriental cherry plant extract water and butanediol, heating in water bath at 50 deg.C, and high-speed shearing with experiment type IKA high-speed shearing disperser at 8000rpm for 30min to obtain uniform emulsion.
(2) And (2) homogenizing the uniform emulsion obtained in the step (1) under high pressure, and circulating for 2 times under 400/600/800/1000bar pressure to obtain transparent and uniform glabridin liposome.
Example 11
The preparation formula of glabridin liposome in this example is shown in table 1, and the specific preparation steps are as follows:
(1) adding phospholipid (PC 95%), polyglycerol-10-stearate, glabridin and cholesterol into the mixture of oriental cherry plant extract water and butanediol, heating in water bath at 60 deg.C, and high-speed shearing with an experimental IKA high-speed shearing disperser at 10000rpm for 30min to obtain uniform emulsion.
(2) And (2) homogenizing the uniform emulsion obtained in the step (1) under high pressure, and circulating for 2 times under 400/600/800/1000bar pressure to obtain transparent and uniform glabridin liposome.
Example 12
The preparation formula of glabridin liposome in this example is shown in table 1, and the specific preparation steps are as follows:
(1) adding phospholipid (PC 95%), polyglycerol-10-stearate, glabridin and cholesterol into the mixture of oriental cherry plant extract water and butanediol, heating in water bath at 50 deg.C, and high-speed shearing with an experimental IKA high-speed shearing disperser at 10000rpm for 60min to obtain uniform emulsion.
(2) And (2) homogenizing the uniform emulsion obtained in the step (1) under high pressure, and circulating for 2 times under 400/600/800/1000bar pressure to obtain transparent and uniform glabridin liposome.
Example 13
The preparation formula of glabridin liposome in this example is shown in table 1, and the specific preparation steps are as follows:
(1) adding phospholipid (PC 95%), polyglycerol-10-stearate, glabridin and cholesterol into the mixture of oriental cherry plant extract water and butanediol, heating in water bath at 50 deg.C, and high-speed shearing with an experimental IKA high-speed shearing disperser at 10000rpm for 90min to obtain uniform emulsion.
(2) And (2) homogenizing the uniform emulsion obtained in the step (1) under high pressure, and circulating for 2 times under 400/600/800/1000bar pressure to obtain transparent and uniform glabridin liposome.
Comparative example 1
The preparation formula of glabridin liposome in this example is shown in table 1, and the specific preparation steps are as follows:
(1) adding phospholipid (PC 95%), glabridin and cholesterol into water, heating in water bath at 60 deg.C, and high-speed shearing with experiment type IKA high-speed shearing disperser at 10000rpm for 60min to obtain uniform emulsion.
(2) And (2) homogenizing the uniform emulsion obtained in the step (1) under high pressure, and circulating for 2 times under 400/600/800/1000bar pressure respectively to obtain uniform glabridin liposome.
Comparative examples 2 to 3
The comparative example is the preparation of glabridin liposome, the formula is shown in table 1, and the preparation steps are as follows:
(1) dissolving phospholipid (PC 95%), polyglycerol-10-stearate, glabridin and cholesterol in 200g methanol-chloroform (mass ratio of 62:38) to obtain clear and transparent solution, and performing rotary evaporation to remove organic solvent to obtain the film.
(2) And (2) placing the film obtained in the step (1) in a water bath at 60 ℃, and adding a mixed solution of the oriental cherry plant extraction water and butanediol in a prescription amount while stirring to obtain a crude emulsion. Homogenizing the crude emulsion under high pressure, and circulating for 2 times under 400/600/800/1000bar pressure to obtain glabridin liposome.
Comparative example 4
The comparative example is the preparation of glabridin liposome, the formula is shown in table 1, and the preparation steps are as follows:
(1) adding phospholipid (PC 95%), polyglycerol-10-stearate, glabridin and cholesterol into a mixture of water and butanediol, heating in water bath at 30 deg.C, and high-speed shearing with an experimental IKA high-speed shearing disperser at 10000rpm for 30min to obtain uniform emulsion.
(2) And (2) homogenizing the uniform emulsion obtained in the step (1) under high pressure, and circulating for 2 times under 400/600/800/1000bar pressure to obtain transparent and uniform glabridin liposome.
TABLE 1 example and comparative example formulations
Test example 1
The glabridin liposomes prepared in example 9 and comparative example 1 were dispersed using PBS as a dispersant, and the average particle diameter was measured using a Zeta sizer; separating the encapsulated and free glabridin by an ultrafiltration centrifugal tube, detecting the glabridin content by HPLC and calculating the encapsulation rate. Test results are shown in table 2.
As is clear from the results in Table 2, glabridin liposome was successfully obtained in examples 1 to 13. Example 9 compared with the glabridin liposome prepared in comparative example 1, there was substantially no difference in appearance, average particle size, and glabridin content, which indicates that the effect of liposome prepared by using oriental cherry plant extract water instead of pure water in the example was substantially uniform, and the liposome was able to replace pure water as a solvent. The glabridin liposome prepared by the liposome preparation method of comparative example 4 is in a yellow turbid state in appearance, and insoluble particles exist; the sample has larger particle size, the encapsulation efficiency of the glabridin medicament is obviously reduced, which shows that when the temperature is insufficient, the phospholipid phase cannot be fully converted into the liquid crystal phase, and fat-soluble medicaments such as glabridin and the like are difficult to fully react with phospholipid molecules, so that the particle size is increased, the encapsulation efficiency is reduced, and the quality of a liposome preparation is reduced.
Table 2 characterization of glabridin liposomes of example 9 and comparative example 1
Test example 2
The glabridin liposomes prepared in the examples and the comparison were subjected to preservative challenge test.
Inoculating certain amount of bacteria and fungi, and detecting microbial quantity change at intervals of 0 day, 7 days, 14 days, 21 days and 28 days according to the detection method of the microbial preservative efficacy test of United states Pharmacopeia USP32<51 >.
As can be seen from Table 3, the sakura cell glabridin liposome prepared in each example has a preservative effect.
Table 3 preservative challenge testing of glabridin liposomes of examples 2, 6, 8, 9, 10
Test example 3
Microorganism detection was carried out for example 9 and comparative example 1 according to the national Standard GB7918.2-87 "Standard test method for microorganisms for cosmetics
As can be seen from table 4, the sakura cell glabridin prepared in example 9 has a certain preservative effect.
TABLE 4
Test example 4
The glabridin liposome prepared in example 9 and comparative example 1 was subjected to MTT toxicity test and melanin content test on mouse melanoma cells B16 cells.
1. B16 cells were plated in 96-well plates at 5X 10 cells per well3Cells were seeded at density and incubated with 5% CO in a 37 ℃ incubator2Treating glabridin liposome and pure glabridin with different concentrations for 24 hr. Then, 20. mu.L of MTT solution (5mg/mL) was added to each well, and the cells were maintained at 37 ℃ for 3 h. The supernatant was carefully aspirated and its absorbance at 570nm was measured by a microplate reader (Bio-Rad, USA) to calculate the cell inhibition rate.
Fig. 9 is a graph showing the results of the B16 cell inhibition ratio test provided in this test example. The higher the cytostatic rate, the higher the cell death rate. Generally, the inhibition rate is below 20%, and no toxicity is considered. As shown in FIG. 9, the inhibition rate of pure glabridin is much higher than that of liposome, and the safety of liposome is better than that of pure glabridin.
2. B16 cells were plated at 2X 10 per well5Individual cells were seeded at a density in 12-well plates and then incubated at 37 ℃ and 5% CO2Incubate for 24 hours. Adding different concentrations of pure glabridin, the liposome of example 6 and the liposome of example 11 respectively, and adding 200nM alpha-MSH respectively for 48 hoursThereafter, the cells were lysed in 1mL of 1M NaOH (containing 10% DMSO) for 30 minutes, incubated in a water bath at 80 ℃ for 1h, and then centrifuged at 3000rpm for 20 minutes. The control group was subjected to the above experiment using deionized water. The relative amount of melanin in the cells was calculated by measuring the Optical Density (OD) of the supernatant at 475nm by an ELISA reader.
Melanin content (%) ═ ODs/OD 0X 100
OD0 is control ODs is sample group optical density
FIG. 10 is a histogram of melanin content of B16 cells provided in this test example. As shown in fig. 10, before the sample is added, the black content of the melanoma cells is about 100%, and after different samples with different concentrations are added, the melanin can be significantly reduced, wherein the liposome prepared by using the oriental cherry extract water has the most significant effect, which indicates that the liposome has a certain whitening synergistic effect.
The above-mentioned embodiments are only used for illustrating the technical solutions of the present invention, and not for limiting the same; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.
Claims (10)
1. A method for preparing a nanoliposome emulsion, comprising the steps of:
step 1: mixing phospholipid, cholesterol, and medicine with cherry blossom plant extract water to form suspension; the drug comprises a fat-soluble drug;
step 2: and shearing the suspension at high speed under the heating and heat preservation state to obtain the nano liposome emulsion.
2. The method according to claim 1, wherein the shearing rate in step 2 is 8000rpm or more and the time is 30min or more.
3. The method according to claim 1 or 2, wherein the temperature of the heating and holding in step 2 is not lower than the phase transition temperature of the phospholipid.
4. The process according to claim 1, wherein the fat-soluble drug comprises: one or more of glabridin, ceramide, resveratrol and fat-soluble vitamins;
the phospholipid comprises one or more of soybean lecithin, egg yolk lecithin, hydrogenated lecithin, dilauroyl phosphatidylcholine, dimyristoyl phosphorylcholine, dipalmitoyl phosphorylcholine, distearoyl phosphatidylcholine, dioleoyl phosphatidylcholine, dilauroyl phosphatidylethanolamine, dimyristoyl phosphatidylethanolamine, dipalmitoyl phosphatidylethanolamine, distearoyl phosphatidylethanolamine and dioleoyl phosphatidylethanolamine.
5. The method of claim 1, wherein the medicament further comprises: a water-soluble drug.
6. The method according to claim 5, wherein the water-soluble drug includes one or more of sodium hyaluronate, nano-metal colloid dispersion, and water-soluble vitamin.
7. The method according to claim 1, wherein the reaction mixture is, in mass percent,
2-15% of phospholipid;
0.01-5% of a medicament;
0-5% of cholesterol;
the rest is cherry blossom plant extract water.
8. The method of claim 1, wherein the step 2 further comprises, before obtaining the liposome emulsion: homogenizing under high pressure;
the high-pressure homogenization specifically comprises the following steps: each cycle was carried out at a pressure of 400bar, 600bar, 800bar, 1000bar for 2 or more times.
9. The method according to claim 1, wherein the step 1 further comprises, before the mixing: adding a surfactant.
10. The method according to claim 1 or 9, wherein the step 1, before the mixing, further comprises: the polyol is added.
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