CN114917149A - Nano carrier for encapsulating ceramide, preparation method and application thereof - Google Patents
Nano carrier for encapsulating ceramide, preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a nano-carrier for encapsulating ceramide, and a preparation method and application thereof. The nano-carrier for encapsulating ceramide provided by the invention is prepared by preparing a polymer solution and a ceramide solution, and dripping the polymer and the ceramide solution into water after mixing, thereby obtaining the nano-carrier for encapsulating ceramide. The nano carrier for encapsulating ceramide prepared by the preparation method provided by the invention has higher encapsulation efficiency and good stability on ceramide, and can solve the problems of low water solubility, poor transdermal absorbability and easiness in influencing the ceramide stability by the surrounding environment in the field of cosmetics.
Description
Technical Field
The invention belongs to the technical field of cosmetic raw materials, and particularly relates to a nano carrier for encapsulating ceramide, and a preparation method and application thereof.
Background
Ceramides, also known as sphingolipids, are a lipid present in the skin. Ceramide is one of important components of stratum corneum, and has physiological functions of moisturizing, maintaining skin barrier, resisting aging, resisting allergy, inducing apoptosis and the like. However, ceramide is an oil-soluble substance with high melting point and high crystallinity, and is directly applied to a cosmetic formula, so that the defects of low water solubility, poor transdermal absorbability, easy influence of the stability of the ceramide on the surrounding environment and the like exist, and the application of the ceramide in the fields of cosmetics and the like is limited.
In order to improve water solubility, transdermal absorption effect and stability of ceramide, various transdermal drug delivery systems, such as liposomes, nanoemulsions, polymeric micelles, etc., have been widely studied. The polymer micelle is used as a novel drug delivery carrier, has a plurality of advantages, and due to the unique core-shell structure, the hydrophobic micelle core can provide an entrapment place for hydrophobic drugs through hydrophobic-hydrophobic interaction force, and has solubilization and embedding effects on the hydrophobic drugs; the hydrophilic micelle shell can promote the water solubility of the micelle and also can be used as a protective layer to maintain the stability of the micelle. Generally, the polymer micelle is formed by self-assembling a single polymer, and as a hydrophobic drug carrier, the longer the hydrophobic block in the polymer structure is, which is beneficial to the entrapment of the self-assembled micelle on ceramide, but the increase of the hydrophobic block easily causes the decrease of the proportion of the hydrophilic block, and further causes the thinning of the micelle shell and even the insufficient embedding of the hydrophilic block on the micelle surface, which results in the low entrapment rate of the ceramide and the disintegration of the micelle. The polymer micelle in the prior art is easy to cause the problems of poor transdermal absorption and insufficient stability when being used for encapsulating ceramide.
Disclosure of Invention
In order to overcome the problems of poor water solubility, poor transdermal absorption and insufficient stability of ceramide in the prior art, the invention mainly aims to provide a preparation method of a nano carrier for encapsulating ceramide.
The invention also aims to provide the nano-carrier prepared by the method. Wherein, the nano-carrier is a polymer mixed micelle, and the polymer mixed micelle carries ceramide.
The invention further aims to provide application of the nano-carrier prepared by the method.
The preparation method of the nano-carrier for encapsulating ceramide, which is provided by the invention, comprises the following steps of:
(1) dissolving two different amphiphilic block polymers in polyol, heating and stirring, and obtaining a polymer solution after the amphiphilic block polymers are fully dissolved;
(2) dissolving ceramide in polyalcohol, heating and stirring, and obtaining a ceramide solution after the ceramide is fully dissolved;
(3) adding the ceramide solution into the polymer solution, and stirring to obtain a mixed solution;
(4) and (3) dripping the mixed solution into water under the stirring condition, continuing stirring after the dripping is finished, and performing dispersion treatment to obtain the ceramide-entrapped nano carrier.
Preferably, the nano carrier loaded with the ceramide is a polymer mixed micelle loaded with the ceramide.
Alternatively, in some embodiments of the invention, the two different amphiphilic block polymers in step (1) comprise polycaprolactone-b-polyethylene glycol monomethyl ether (polymer PCL) x -b-mPEG y ) Polylactic acid-b-polyethylene glycol monomethyl ether (polymer PLA) x -b-mPEG y ) Poly (lactic-co-glycolic acid) -b-polyethylene glycol monomethyl ether (polymer P (LA)) x -co-GA y )-b-mPEG z ) Polyethylene glycol monomethyl ether-b-N, N-diethylaminoethyl polymethacrylate (Polymer mPEG) x -b-PDEAEMA y ) Poly (lactic-co-glycolic acid) -b-polyethylene glycol monomethyl ether methacrylate (polymer P (LA) x -co-GA y )-b-PPEGMA z ) Polyoxyethylene-b-polyoxypropylene-b-polyoxyethylene (Polymer PEO) x -b-PPO y -b-PEO z ) Two kinds of (1).
Wherein x, y and z are polymerization degrees of corresponding repeating units in the polymer structure.
Optionally, in some embodiments of the invention, the polymeric PCL x -b-mPEG y Molecular weight M of n 6000-12000, the structural formula is:
x＝35-61，y＝45-113；
the polymer PLA x -b-mPEG y Molecular weight M of n 6000-12000, the structural formula is:
x＝28-48，y＝45-113；
the polymer P (LA) x -co-GA y )-b-mPEG z Molecular weight M of n 6000-12000, the structural formula is:
x＝42-78，y＝14-26，z＝45-113；
the polymer mPEG x -b-PDEAEMA y Molecular weight M of n 6000-12000, the structural formula is as follows:
x＝45-113，y＝23-41；
the polymer P (LA) x -co-GA y )-b-PPEGMA z Molecular weight M of n 6000-12000, the structural formula is as follows:
x＝42-78，y＝14-26，z＝5-13；
the Polymer PEO x -b-PPO y -b-PEO z Molecular weight M of n 6000-12000, the structural formula is:
x＝45-113，y＝34-135，z＝45-113。
alternatively, in some embodiments of the present invention, the mass percentages of the two amphiphilic block polymers in the nanocarrier are each relatively independently 0.2% to 15%, preferably 0.2% to 10%.
Alternatively, in some embodiments of the present invention, the polyhydric alcohol in step (1) and step (2) each independently comprises at least one of propylene glycol, isopropanol, dipropylene glycol, glycerol, butylene glycol, 1, 2-pentanediol, and 1, 2-hexanediol.
Alternatively, in some embodiments of the invention, the polyol in step (1) and step (2) is the same.
Optionally, in some embodiments of the invention, the total mass percentage of the polyol in the nanocarrier is 10% to 50%.
Alternatively, in some embodiments of the present invention,
the heating temperature in the step (1) and the heating temperature in the step (2) are respectively and independently 45-80 ℃;
the rotating speed of the stirring in the step (1) and the step (2) is 150-600rpm relatively independently;
the stirring time of the stirring in the step (1) and the step (2) is relatively and independently 2h-12 h.
Optionally, in some embodiments of the invention, the ceramide in step (2) comprises at least one of ceramide AP, ceramide AS, ceramide E (cetyl-PG hydroxyethylpalmitamide), ceramide NP;
optionally, in some embodiments of the invention, the weight percentage of the ceramide in the nano-carrier in the step (2) is 0.1% to 5%.
Alternatively, in some embodiments of the invention,
the rotating speed of the stirring in the step (3) is 150-600 rpm; and (4) stirring time of the stirring in the step (3) is 2-12 h.
Alternatively, in some embodiments of the present invention,
the rotating speed under the stirring condition in the step (4) is 150-600 rpm; the dropping speed of the peristaltic pump is 20-50 rpm;
in the step (4), the mass percent of the water in the nano carrier is 15-89.5%;
the rotating speed of the continuous stirring after the dropwise adding in the step (4) is 150-600 rpm; the stirring time for continuously stirring after the dropwise adding is 4-24 h;
the step (4) of dispersing treatment refers to that a high-shear homogenizing and emulsifying machine is adopted to carry out shearing homogenization, the power of the high-shear homogenizing and emulsifying machine is 500-1000w, the rotating speed of the high-shear homogenizing and emulsifying machine is 5000-8000rpm, and the high-shear homogenizing and emulsifying machine carries out high-speed shearing dispersion for 3-10 min.
The invention also provides application of the nano carrier for encapsulating ceramide in the field of cosmetics.
The cosmetics of the invention can be smoothing toner, emulsion, cream, facial mask, jelly, powder, spray, essence, washing and caring cosmetics and color cosmetics.
The weight percentage of the nano carrier for encapsulating the ceramide in the cosmetics is 1-20%.
Compared with the prior art, the invention has the following advantages and beneficial effects: the invention provides a nano carrier for encapsulating ceramide, and a preparation method and application thereof. The nano-carrier prepared by the preparation method of the nano-carrier provided by the invention is a polymer mixed micelle. The polymer mixed micelle adopts two kinds of amphiphilic block polymers and forms micelle in selective solvent through self-assembly. The polymer mixed micelle integrates a plurality of blocks with different functions into the same micelle system. Compared with the polymer micelle formed by self-assembly of single-component polymer, the polymer mixed micelle prepared by the invention has higher entrapment rate and good stability for ceramide, and can improve the problems of low water solubility, poor transdermal absorption and easy influence of the ceramide stability on the surrounding environment in the field of cosmetics. In addition, the preparation method of the nano-carrier for encapsulating ceramide provided by the invention is simple, is beneficial to saving the process flow and reducing the manufacturing cost, and is suitable for being used in various cosmetics.
Drawings
FIG. 1 is a graph showing the rate of change in particle size over 3 months for the products prepared in examples 1 to 4 and comparative examples 1 to 4.
FIG. 2 is a graph showing the rate of change in encapsulation efficiency over 3 months for the products prepared in examples 1 to 4 and comparative examples 1 to 4.
FIG. 3 is a graph showing the rate of change in particle size over 3 months for the products prepared in examples 1, 5-8.
FIG. 4 is a graph showing the rate of change in encapsulation efficiency over 3 months for the products prepared in examples 1, 5-8.
FIG. 5 is a graph showing the rate of change in particle size over 3 months for the products of examples 1, 9-12.
FIG. 6 is a graph showing the rate of change in encapsulation efficiency over 3 months for products prepared in examples 1, 9-12.
Detailed Description
The present invention will be described in further detail with reference to examples and drawings, but the embodiments of the present invention are not limited thereto. The examples, in which specific conditions are not specified, were carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by manufacturers, and are conventional products commercially available. The reagents used in the examples are commercially available without specific reference. It should be noted that, the mass percentages mentioned in the present application are mass percentages of the corresponding substances in the polymer mixed micelle solution.
In the examples of the present invention, the poly-hexaneEster-b-polyethylene glycol monomethyl ether (Polymer PCL) x -b-mPEG y ) Polylactic acid-b-polyethylene glycol monomethyl ether (polymer PLA) x -b-mPEG y ) Poly (lactic-co-glycolic acid) -b-polyethylene glycol monomethyl ether (polymer P (LA)) x -co-GA y )-b-mPEG z ) And polyoxyethylene-b-polyoxypropylene-b-Polyoxyethylene (PEO) x -b-PPO y -b-PEO z ) All can be purchased directly from the market.
Polyethylene glycol monomethyl ether-b-Poly (N, N-diethylaminoethyl methacrylate) (mPEG) x -b-PDEAEMA y ) Prepared by the following method (taking 1mmol of polyethylene glycol monomethyl ether-b-polymethacrylic acid N, N-diethylaminoethyl ester as an example):
(1) 1.0mmol of polyethylene glycol monomethyl ether (mPEG, 2.0-5.0g) was dissolved in dichloromethane (50mL), the reaction was cooled to 0 ℃ and 4.0mmol of 2-bromoisobutyryl bromide (0.92g) was added slowly under inert gas. The reaction system reacts for 2 to 4 hours in ice-water bath, and then continues to react for 12 to 48 hours at room temperature. After the reaction is finished, the reaction mixture is respectively treated by dilute hydrochloric acid solution (1.0mol/L) and saturated NaHCO 3 The solution was washed with deionized water and the organic phase was dried over anhydrous MgSO 4 Dried overnight. Taking supernatant, and concentrating by rotary evaporation. Precipitating the product by using excessive n-hexane solution, and drying to obtain a solid product mPEG-Br.
(2) 1.0mmol of mPEG-Br (2.14-5.14g), diethylaminoethyl methacrylate (DEAEMA, 4.50-8.5g) and 0.1mmol of N, N, N ', N,' N "-pentamethyldiethylenetriamine (PMDETA, 17mg) were dissolved in tetrahydrofuran (THF, 50 mL). Under an inert gas atmosphere, 0.1mmol of CuBr (15mg) was rapidly added to the reaction system. The reaction system is kept at 50-70 ℃ for reaction for 12-48 h. And after the reaction is finished, removing copper salt from the reaction mixture by a neutral alumina column (THF is used as eluent), performing rotary evaporation and concentration on the eluent, dripping the eluent into excessive n-hexane for precipitation, collecting a solid product, and drying to obtain the mPEG-PPEGMA.
Poly (lactic-co-glycolic acid) -b-polyethylene glycol monomethyl ether methacrylate (P (LA) x -co-GA y )-b-PPEGMA z ) Prepared by the following method (to prepare 1mmol of poly (lactic acid-co-hydroxyethyl)Acid) -b-polyethylene glycol monomethyl ether methacrylate as an example):
(1) 1.0mmol of 1-propanol (0.06g), lactide (0.8-1.5g) and glycolide (3.0-6.0g) are sequentially reacted in a bottle, and stannous octoate (69mg, the mass fraction is 1 percent of the total amount of the fed lactide and glycolide) is added. Under the protection of inert gas, the reaction system is kept at the temperature of 100 ℃ and 150 ℃ for reaction for 5-10 h. After the reaction is finished, CH is added 2 Cl 2 Dissolving the crude product (50mL), dripping into excessive n-hexane for purification, and drying the solid precipitate to obtain a solid product P (LA-co-GA).
(2) Dissolving P (LA-co-GA) (3.0-8.0g) in CH 2 Cl 2 (50mL), the reaction was cooled to 0 ℃ and 2-bromoisobutyryl bromide (0.92g) was added under an inert atmosphere. The reaction system reacts for 2 to 4 hours in ice-water bath, and then continues to react for 12 to 48 hours at room temperature. After the reaction is finished, the reaction mixture is respectively treated by dilute hydrochloric acid solution (1.0mol/L) and saturated NaHCO 3 The solution was washed with deionized water and the organic phase was dried over anhydrous MgSO 4 Dry overnight. Taking supernatant, and concentrating by rotary evaporation. Precipitating the product with excessive n-hexane solution, and drying to obtain solid product P (LA-co-GA) -Br.
(3) P (LA-co-GA) -Br (3.14-8.1g), polyethylene glycol acrylate (PEGMA, 2.0-5.5g) and PMDETA (17mg) were dissolved in THF (50 mL). Under inert gas atmosphere, CuBr (15mg) was rapidly added to the reaction system. The reaction system is kept at 50-70 ℃ for reaction for 12-48 h. After the reaction is finished, the copper salt of the reaction mixture is removed through a neutral alumina column (THF is used as eluent), the eluent is concentrated through rotary evaporation, and then is dripped into excessive n-hexane for precipitation, and a solid product is collected and dried to obtain the P (LA-co-GA) -PPEGMA.
In the present invention, 1mmol of amphiphilic block polymer is prepared as an example, and the amount of the raw material added may be adjusted according to actual needs when the amphiphilic block polymer is actually prepared, and the amount of the raw material added is not limited in the present invention.
Example 1
Block polymer PCL 44 -b-mPEG 113 (1% by mass, Mn 10000) and P (LA) 54 -co-GA 18 )-b-PPEGMA 13 (1% by mass, Mn. RTM. 10000) was dissolved in 10% by mass of butanediol, and magnetic stirring (150 rpm) was maintained at 60 ℃ for 4 hours. After the polymer is sufficiently dissolved, a polymer solution is obtained. Dissolving 3% by mass of ceramide E in 10% by mass of butanediol, keeping magnetic stirring (the rotating speed is 150rpm) for 4 hours at 60 ℃, and obtaining a ceramide E solution after the ceramide E is fully dissolved. The ceramide E solution is added into the polymer solution, and the mixture is magnetically stirred (the rotating speed is 150rpm) for 4 hours to obtain a mixed solution. And under the stirring condition (the rotating speed is 150rpm), uniformly dropping the mixed solution into deionized water with the mass percentage of 75% by using a peristaltic pump (the dropping speed is 30rpm), continuing stirring (300rpm) for 12h after the dropping is finished, and then carrying out high-speed shearing dispersion for 5min (the rotating speed is 8000rpm) to obtain the nano carrier for encapsulating the ceramide E. Specifically, the nano-carrier is a polymer mixed micelle.
Example 2
Block polymer PCL 44 -b-mPEG 113 (mass% is 1%, M n 10000) and PLA 35 -b-mPEG 113 (mass% is 1%, M n 10000) is dissolved in propylene glycol with the mass percentage of 15 percent, magnetic stirring is kept at 60 ℃ (the rotating speed is 150rpm) for 4 hours, and after the polymer is fully dissolved, a polymer solution is obtained. And dissolving 5% by mass of ceramide E in 15% by mass of propylene glycol, keeping magnetic stirring (rotating speed of 150rpm) for 4 hours at 60 ℃, and obtaining a ceramide E solution after the ceramide E is fully dissolved. The ceramide E solution is added into the polymer solution, and the mixture is magnetically stirred (the rotating speed is 150rpm) for 4 hours to obtain a mixed solution. Under the stirring condition (the rotating speed is 150rpm), uniformly dropping the mixed solution into 63 mass percent of deionized water by using a peristaltic pump (the dropping speed is 30rpm), continuing stirring (the rotating speed is 300rpm) for 12h after the dropping is finished, and shearing and dispersing at a high speed for 5min (the rotating speed is 8000rpm) to obtain the nano carrier for encapsulating the ceramide E. Specifically, the nano-carrier is a polymer mixed micelle.
Example 3
Block polymer PCL 62 -b-mPEG 113 (mass percentage)At a ratio of 1%, M n 12000) and PLA 49 -b-mPEG 113 (1% by mass, M) n 12000) was dissolved in 25% by mass of propylene glycol, and magnetic stirring (300rpm) was maintained at 60 ℃ for 4 hours to obtain a polymer solution after the polymer was sufficiently dissolved. And dissolving 5% by mass of ceramide E in 25% by mass of propylene glycol, keeping magnetic stirring (rotating speed of 300rpm) for 4 hours at 60 ℃, and obtaining a ceramide E solution after the ceramide E is fully dissolved. The ceramide solution E is added into the polymer solution, and the mixture is magnetically stirred (the rotating speed is 300rpm) for 4 hours to obtain a mixed solution. Under the stirring condition (the rotating speed is 300rpm), uniformly dropping the mixed solution into deionized water with the mass percentage of 43% by using a peristaltic pump (the dropping speed is 30rpm), continuing stirring (the rotating speed is 450rpm) for 12h after the dropping is finished, and shearing and dispersing at a high speed for 5min (the rotating speed is 8000rpm) to obtain the nano carrier for encapsulating the ceramide E. Specifically, the nano-carrier is a polymer mixed micelle.
Example 4
Block polymer PCL 35 -b-mPEG 45 (1%, Mn. RTM. 6000) and PLA 28 -b-mPEG 45 (1%, Mn. RTM. 6000) was dissolved in 15% by mass of propylene glycol, and magnetic stirring (150 rpm) was maintained at 45 ℃ for 4 hours to obtain a mixed polymer solution after the polymer was sufficiently dissolved. Dissolving 3% by mass of ceramide E in 15% by mass of propylene glycol, keeping magnetic stirring (rotating speed of 150rpm) for 4h at 45 ℃, and obtaining a ceramide E solution after the ceramide E is fully dissolved. The ceramide E solution is added into the polymer solution, and the mixture is magnetically stirred (the rotating speed is 150rpm) for 4 hours to obtain a mixed solution. Under the stirring condition (the rotating speed is 150rpm), uniformly dripping the mixed solution into 65 percent deionized water by using a peristaltic pump (the dripping speed is 30rpm), continuously stirring (the rotating speed is 300rpm) for 12 hours after finishing dripping, and shearing and dispersing at a high speed for 5min (8000rpm) to obtain the nano carrier for encapsulating the ceramide E. Specifically, the nano-carrier is a polymer mixed micelle.
Example 5
The procedure of example 1 for preparing a nanocarrier entrapping ceramide E was repeated except for modifying ceramide E of example 1 having a mass percentage of 3% to ceramide E having a mass percentage of 0.1%, while modifying the amount of deionized water to be 77.9% so that the total mass percentage is 100%, and the remaining conditions were not changed.
Example 6
The procedure of example 1 for preparing a nanocarrier encapsulating ceramide E was repeated except that 3% by mass of ceramide E in example 1 was modified to 1% by mass of ceramide E, while the amount of deionized water was modified to 77% so that the total mass% was 100%, and the remaining conditions were not changed.
Example 7
The procedure of example 1 for preparing a nanocarrier entrapping ceramide E was repeated except that 3% by mass of ceramide E in example 1 was modified to 5% by mass of ceramide E, while the amount of deionized water was modified to 73% so that the total mass percentage was 100%, and the remaining conditions were not changed.
Example 8
The procedure of example 1 for preparing a nanocarrier entrapping ceramide E was repeated except that 3% by mass of ceramide E in example 1 was modified to 7% by mass of ceramide E, while the amount of deionized water was modified to 71% so that the total mass percentage was 100%, and the remaining conditions were not changed.
Example 9
Example 1 the procedure for preparing a nanocarrier entrapping ceramide E in example 1 was repeated except that example 1 included PCL in an amount of 1% by mass 44 -b-mPEG 113 And 1% by mass of P (LA) 54 -co-GA 18 )-b-PPEGMA 13 Modified to 0.25 percent of PCL by mass percentage 44 -b-mPEG 113 And 0.25% by mass of P (LA) 54 -co-GA 18 )-b-PPEGMA 13 Meanwhile, the amount of the deionized water is modified to 76.5% so that the total mass percentage is 100%, and the rest conditions are not changed.
Example 10
Example 1 preparation was repeatedA step of entrapping a nanocarrier of ceramide E, except that PCL of example 1 was used in an amount of 1% by mass 44 -b-mPEG 113 And 1% by mass of P (LA) 54 -co-GA 18 )-b-PPEGMA 13 PCL with the mass percent of 5 percent is changed 44 -b-mPEG 113 And 5% by mass of P (LA) 54 -co-GA 18 )-b-PPEGMA 13 Meanwhile, the amount of the deionized water is modified to 67% so that the total mass percentage is 100%, and the rest conditions are unchanged.
Example 11
Example 1 the procedure for preparing a nanocarrier entrapping ceramide E in example 1 was repeated except that example 1 included PCL in an amount of 1% by mass 44 -b-mPEG 113 And 1% by mass of P (LA) 54 -co-GA 18 )-b-PPEGMA 13 Modified into PCL with the mass percentage of 10 percent 44 -b-mPEG 113 And 10% by mass of P (LA) 54 -co-GA 18 )-b-PPEGMA 13 Changing the butanediol with the mass percent of 10% in the steps (1) and (2) into the butanediol with the mass percent of 15%, and simultaneously changing the using amount of the deionized water into 47% so that the total mass percent is 100%, wherein the rest conditions are not changed.
Example 12
Example 1 the procedure for preparing a nanocarrier entrapping ceramide E in example 1 was repeated except that example 1 included PCL in an amount of 1% by mass 44 -b-mPEG 113 And 1% by mass of P (LA) 54 -co-GA 18 )-b-PPEGMA 13 Modified into PCL with the mass percentage of 15 percent 44 -b-mPEG 113 And 15% by mass of P (LA) 54 -co-GA 18 )-b-PPEGMA 13 Changing the butanediol with the mass percent of 10% in the steps (1) and (2) into the butanediol with the mass percent of 20%, and simultaneously changing the using amount of the deionized water into 27% so that the total mass percent is 100%, and keeping the rest conditions unchanged.
Example 13
Block polymer PEO 113 -b-PPO 34 -b-PEO 113 (1% by mass, M) n 12000) and P (LA) 54 -co-GA 18 )-b-PPEGMA 13 (1% by mass, M) n 10000) was dissolved in 15% by mass of isopropyl alcohol, and magnetic stirring (300rpm) was maintained at 45 c for 4 hours to obtain a polymer solution after the polymer was sufficiently dissolved. Dissolving 5% by mass of ceramide E in 15% by mass of isopropanol, maintaining magnetic stirring (rotation speed of 400rpm) at 45 ℃ for 4h, and obtaining a ceramide E solution (oil phase B) after the ceramide E is fully dissolved. The ceramide E solution is added into the polymer solution, and the mixture is magnetically stirred (the rotating speed is 150rpm) for 4 hours to obtain a mixed solution. Under the stirring condition (the rotating speed is 150rpm), uniformly dripping the mixed solution into deionized water with the mass percent of 63% by using a peristaltic pump (the dripping speed is 30rpm), continuously stirring (the rotating speed is 300rpm) for 12h after finishing dripping, and shearing and dispersing at a high speed for 10min (the rotating speed is 5000rpm) to obtain the ceramide E-loaded nano carrier. Specifically, the nano-carrier is a polymer mixed micelle.
Example 14
Block polymer PCL 44 -b-mPEG 113 (3% by mass, M) n 10000) and PLA 35 -b-mPEG 113 (3% by mass, M) n 10000) was dissolved in 15% by mass of glycerin, and magnetic stirring (150 rpm) was maintained at 45 ℃ for 4 hours to obtain a polymer solution after the polymer was sufficiently dissolved. Dissolving 4% by mass of ceramide E in 15% by mass of glycerol, maintaining magnetic stirring (rotating speed of 600rpm) for 4h at 45 ℃, and obtaining a ceramide E solution after the ceramide E is fully dissolved. The ceramide E solution is added into the polymer solution, and the mixture is magnetically stirred (the rotating speed is 300rpm) for 4 hours to obtain a mixed solution. Under the stirring condition (the rotating speed is 300rpm), uniformly dropping the mixed solution into deionized water with the mass percentage of 60% by using a peristaltic pump (the dropping speed is 30rpm), continuing stirring (the rotating speed is 300rpm) for 12h after the dropping is finished, and performing high-speed shearing dispersion for 10min (the rotating speed is 5000rpm) to obtain the nano carrier for encapsulating the ceramide E. Specifically, the nano-carrier is a polymer mixed micelle.
Example 15
Block polymer PCL 44 -b-mPEG 113 (5% by mass, M) n 10000) and PLA 35 -b-mPEG 113 (5% by mass, M) n 10000) is dissolved in 1, 2-hexanediol with the mass percentage of 15 percent, magnetic stirring (the rotating speed is 150rpm) is kept for 4 hours at the temperature of 60 ℃, and after the polymer is fully dissolved, a polymer solution is obtained. Dissolving 5% by mass of ceramide AP in 15% by mass of 1, 2-hexanediol, and keeping magnetic stirring (rotating speed of 600rpm) for 4h at 60 ℃ to obtain a ceramide E solution after the ceramide AP is fully dissolved. The ceramide AP solution is added into the polymer solution, and the mixture is magnetically stirred (the rotating speed is 600rpm) for 4 hours to obtain a mixed solution. Under the stirring condition (the rotating speed is 600rpm), uniformly dripping the mixed solution into deionized water with the mass percent of 55% by using a peristaltic pump (the dripping speed is 30rpm), continuing stirring (the rotating speed is 600rpm) for 12h after finishing dripping, and shearing and dispersing at a high speed for 5min (the rotating speed is 8000rpm) to obtain the ceramide AP-loaded nano carrier. Specifically, the nano-carrier is a polymer mixed micelle.
Example 16
Block polymer PCL 44 -b-mPEG 113 (5% by mass, M) n 10000) and PLA 35 -b-mPEG 113 (5% by mass, M) n 10000) was dissolved in 15% by mass of dipropylene glycol, and magnetic stirring (400 rpm) was maintained at 60 ℃ for 6 hours to obtain a polymer solution after the polymer was sufficiently dissolved. And dissolving 5% by mass of ceramide AS in 15% by mass of dipropylene glycol, and keeping magnetic stirring (rotating speed of 400rpm) at 60 ℃ for 6 hours to obtain a ceramide AS solution after the ceramide AS is fully dissolved. The ceramide AS solution is added into the polymer solution, and the mixture is obtained after magnetic stirring (the rotating speed is 400rpm) for 4 hours. Under the stirring condition (the rotating speed is 400rpm), uniformly dropping the mixed solution into deionized water with the mass percentage of 55% by using a peristaltic pump (the dropping speed is 30rpm), continuing stirring (the rotating speed is 400rpm) for 12h after the dropping is finished, and shearing and dispersing at a high speed for 5min (the rotating speed is 8000rpm) to obtain the nano carrier for encapsulating the ceramide AS. Specifically, the nano carrier is a polymer mixtureMicelles.
Example 17
Block polymer PEO 113 -b-PPO 34 -b-PEO 113 (3% by mass, M) n 12000) and P (LA) 54 -co-GA 18 )-b-PPEGMA 13 (3% by mass, M) n 10000) is dissolved in 1, 2-pentanediol with the mass percentage of 15%, magnetic stirring (the rotating speed is 500rpm) is kept for 4 hours at the temperature of 60 ℃, and after the polymer is fully dissolved, a polymer solution is obtained. Dissolving 3% by mass of ceramide NP in 15% by mass of 1, 2-pentanediol, and keeping magnetic stirring (rotating speed of 500rpm) for 4h at 60 ℃, so as to obtain a ceramide NP solution after the ceramide NP is fully dissolved. The ceramide NP solution is added into the mixed polymer solution, and the mixed solution is obtained by magnetic stirring (the rotating speed is 500rpm) for 4 hours. Under the stirring condition (the rotating speed is 500rpm), uniformly dropping the mixed solution into deionized water with the mass percentage of 61% by using a peristaltic pump (the dropping speed is 30rpm), continuing stirring (the rotating speed is 500rpm) for 12h after the dropping is finished, and shearing and dispersing at a high speed for 5min (the rotating speed is 8000rpm) to obtain the nano carrier for encapsulating the ceramide NP. Specifically, the nano-carrier is a polymer mixed micelle.
Comparative example 1
Mixing polymer P (LA) 54 -co-GA 18 )-b-PPEGMA 13 (2%, Mn: 10000) was dissolved in butanediol of 10% by mass, and magnetic stirring (150 rpm) was maintained at 60 ℃ for 4 hours to obtain a polymer solution after the polymer was sufficiently dissolved. Dissolving 3% by mass of ceramide E in 10% by mass of butanediol, keeping magnetic stirring (rotating speed of 150rpm) for 4h at 60 ℃, and obtaining a ceramide E solution after the ceramide E is fully dissolved. The ceramide E solution is added into the polymer solution, and the mixture is magnetically stirred (the rotating speed is 150rpm) for 4 hours to obtain a mixed solution. Under the stirring condition (the rotating speed is 150rpm), uniformly dripping the mixed solution into deionized water with the mass percentage of 75% by using a peristaltic pump (the dripping speed is 30rpm), continuing stirring (the rotating speed is 300rpm) for 12h after finishing dripping, and shearing and dispersing at a high speed for 5min (the rotating speed is 8000rpm) to obtain the ceramide E-encapsulated nanoA rice carrier.
Comparative example 1 differs from example 1 in that only P (LA) is used in comparative example 1 54 -co-GA 18 )-b-PPEGMA 13 Preparing the nano carrier for encapsulating the ceramide E as a raw material.
Comparative example 2
Mixing polymer PCL 44 -b-mPEG 113 (2%, Mn. about.10000) was dissolved in 10% by mass of butanediol, and magnetic stirring (150 rpm) was maintained at 45 ℃ for 4 hours to obtain a polymer solution after the polymer was sufficiently dissolved. Dissolving 5% by mass of ceramide E in 10% by mass of butanediol, keeping magnetic stirring (rotating speed of 150rpm) for 4h at 45 ℃, and obtaining a ceramide E solution after the ceramide E is fully dissolved. The ceramide E solution is added into the polymer solution, and the mixture is magnetically stirred (the rotating speed is 150rpm) for 4 hours to obtain a mixed solution. Under the stirring condition (the rotating speed is 150rpm), uniformly dropping the mixed solution into deionized water with the mass percentage of 73% by using a peristaltic pump (the dropping speed is 30rpm), continuing stirring (the rotating speed is 300rpm) for 12h after the dropping is finished, and performing high-speed shearing dispersion for 5min to obtain the nano carrier for encapsulating the ceramide E.
Comparative example 2 differs from example 1 in that only PCL is used in comparative example 2 44 -b-mPEG 113 Preparing the nano carrier for encapsulating the ceramide E as a raw material.
Comparative example 3
Dissolving 1% soybean lecithin, 0.1% cholesterol and 5% ceramide E in 30% ethanol by mass, and stirring at 60 deg.C (150 rpm) for 3 hr. The ethanol solution was removed from the mixed solution by evaporation with a rotary evaporator (40 ℃ C., rotation speed: 250 rpm). After the ethanol is completely removed, adding 93.9 percent by mass of deionized water, dispersing for 30min by ultrasonic waves (600w), and finally passing through an organic microporous filter membrane with the aperture of 0.45 mu m to obtain the ceramide E-encapsulated liposome.
Comparative example 3 differs from example 1 in that comparative example 3 entraps ceramide E in liposomes.
Comparative example 4
Mixing 5% of ceramide E and 15% of caprylic/capric triglyceride by mass, heating to 85 ℃ until the ceramide E is completely dissolved, and then adding 10% of butanediol by mass to obtain an oil phase component. And (3) dropping deionized water with the mass percent of 70% into the oil phase components through a peristaltic pump (the dropping speed is 30rpm), and after the dropping is finished, shearing the mixed solution at a high speed of 15000 rpm. And then circularly treating for 5 times through high-pressure homogenization (1000bar) to obtain the nanoemulsion coated with the ceramide E.
Comparative example 4 differs from example 1 in that comparative example 4 carries ceramide E in a nanoemulsion.
The samples prepared in examples 1-12 were subjected to particle size characterization, encapsulation efficiency characterization and stability testing.
The test method comprises the following steps:
(1) and (3) characterization of particle size: a Malvern Nano ZS90 particle size potential detector is adopted to represent the particle size and the particle size dispersion coefficient (PDI) of the sample, the test angle is 90 degrees, the test temperature is 25 ℃, each group of experiments are carried out three times of parallel experiments, and the arithmetic mean value of the experiment results is taken.
(2) And (3) determining the encapsulation efficiency: collecting 200 μ L of the micelle solution, centrifuging by low temperature (4 deg.C) ultrafiltration (9000rpm, 30min), collecting 5 μ L of filtrate, and measuring ceramide content in the filtrate by high performance liquid chromatography (HPLC, Shimadzu Japan), i.e. content of uncoated free ceramide in the micelle solution. Taking the micelle solution, adding a methanol solution, and mixing the micelle solution: and (3) ultrasonically demulsifying the methanol at a ratio of 1:9(v/v) for 30min, filtering by using a filter membrane, and measuring the content of the ceramide, namely the total content of the ceramide in the micelle solution, by using a high performance liquid chromatograph (HPLC, Shimadzu, Japan) from 5 mu L of sample solution. The Entrapment Efficiency (EE) of the ceramide-entrapped polymer mixed micelle was calculated according to formula (1). An analytical column used in the HPLC system is a nonpolar C18 column, a mobile phase is 100% methanol, the flow rate is 1.0mL/min, the column temperature of a chromatographic column is 25 ℃, quantitative detection is carried out according to a standard curve of ceramide, each group of experiments are carried out with three parallel experiments, and the arithmetic mean value of the experiment results is taken.
C 1 Represents the concentration of unencapsulated free ceramide in the micellar solution; c 0 The total concentration of ceramide in the micelle system after the methanol ultrasonic demulsification is shown.
(3) Standing the sample at room temperature for one month, two months and three months respectively, and then measuring the particle size and the encapsulation efficiency respectively.
TABLE 1 particle size and encapsulation efficiency of examples 1-12, comparative example 1 and comparative example 2 samples
| Sample (I) | Particle size (nm) | PDI | Encapsulation efficiency (%) |
| Example 1 | 72.8(±1.1) | 0.253 | 80.3(±1.1) |
| Example 2 | 91.5(±0.8) | 0.261 | 86.5(±0.8) |
| Example 3 | 102.7(±1.5) | 0.274 | 73.9(±0.6) |
| Example 4 | 86.4(±1.2) | 0.226 | 72.1(±1.4) |
| Example 5 | 75.4(±0.8) | 0.253 | 83.6(±1.2) |
| Example 6 | 83.2(±1.4) | 0.237 | 78.2(±1.1) |
| Example 7 | 93.1(±0.7) | 0.242 | 73.6(±0.9) |
| Example 8 | 92.5(±1.2) | 0.312 | 53.3(±1.0) |
| Example 9 | 70.5(±0.8) | 0.291 | 72.7(±1.2) |
| Example 10 | 95.2(±1.3) | 0.274 | 82.0(±1.4) |
| Example 11 | 101.6(±0.9) | 0.275 | 75.3(±1.2) |
| Example 12 | 126.8(±0.6) | 0.246 | 80.5(±0.8) |
| Comparative example 1 | 120.5(±2.2) | 0.345 | 63.2(±2.5) |
| Comparative example 2 | 114.7(±1.9) | 0.288 | 55.5(±1.2) |
| Comparative example 3 | 135.3(±1.7) | 0.302 | 53.5(±1.4) |
| Comparative example 4 | 158.4(±0.8) | 0.284 | 51.8(±1.0) |
TABLE 2 stability test results for samples of examples 1-12, comparative example 1 and comparative example 2
Particle size and encapsulation efficiency results for the samples of examples 1-12, comparative example 1 and comparative example 2 are shown in table 1. The results of particle size and stability tests for the samples of examples 1-12, comparative example 1 and comparative example 2 are shown in table 2.
The polymer micelles of examples 1 to 4 and comparative examples 1 and 2, the liposomes of comparative example 3, and the nanoemulsion of comparative example 4 were analyzed. The mixed polymer micelles of examples 1 to 4 had ceramide entrapment rates of 80.3%, 86.5%, 73.9% and 72.1%, the liposomes of comparative example 3 had an entrapment rate of 53.5%, and the nanoemulsion of comparative example 4 had an entrapment rate of 51.8%, respectively, whereas the single polymer micelle P (LA) was used 54 -co-GA 18 )-b-PPEGMA 13 (comparative example 1) or PCL 44 -b-mPEG 113 (comparative example 2) the ceramide encapsulation efficiencies were 63.2% and 55.5%, respectively, and the polymer of example 1 was selected from P (LA) 54 -co-GA 18 )-b-PPEGMA 13 And PCL 44 -b-mPEG 113 Compared with liposome, nanoemulsion and single polymer micelle, the mixed polymer micelle has a better coating effect on ceramide, and is more favorable for improving the stability of ceramide. Further, the particle sizes of the samples of examples 1 to 4 were 72.8nm, 91.5nm, 102.7nm and 86.4nm, respectively, while those of the samples of comparative examples 1 to 4 were 120.5nm, 114.7nm, 135.3nm and 158.4nm, respectively, and the particle sizes of the samples of examples 1 to 4 were smaller than those of comparative examples 1 to 4, respectively, indicating that the mixed polymer is more advantageous in preparing micelles having smaller particle sizes. The smaller the particle size of the nanocarrier is, the easier the transdermal absorption performance of the nanocarrier is exerted. Therefore, the mixed polymer micelles of examples 1 to 4 showed more excellent transdermal absorption than the single polymer micelles, liposomes and nanoemulsions of comparative examples 1 to 4And (4) performance recovery. Wherein the particle size of the samples of example 1, example 2 and example 4 are all less than 100 nm. Generally, when the particle size of the nanocarrier is less than 100nm, the transdermal absorption property of the nanocarrier is more excellent. It can be seen that the particle size of the samples of example 1, example 2 and example 4 is more favorable for transdermal absorption than the particle size of the sample of example 3.
Wherein the particle size change rates of the samples of examples 1 to 4 were 4.26%, 1.86%, 5.84% and 6.83% in 3 months, respectively (calculated by subtracting the particle size of the sample of month 0 from the particle size of the sample of month 3 in the examples to obtain a sample particle size difference, and dividing the sample particle size difference by the particle size of the sample of month 0 to obtain the particle size change rate). The particle size change rates of the samples of comparative examples 1 and 2 were 16.93% and 26.59%, respectively, over 3 months. The change rates of the encapsulation efficiencies of examples 1 to 4 were 9.09%, 2.20%, 11.3% and 12.21%, respectively (calculated by subtracting the encapsulation efficiency of month 0 from the encapsulation efficiency of month 3 in the examples to obtain an encapsulation efficiency difference, and dividing the encapsulation efficiency difference by the encapsulation efficiency of month 0 to obtain the change rates of the encapsulation efficiencies). The samples of comparative examples 1-4 had encapsulation efficiency changes of 25.47%, 25.77%, 19.25%, and 18.15%, respectively. As shown in fig. 1 and 2, the absolute values of the rate of change in particle size and the rate of change in encapsulation efficiency of examples 1 to 4 in 3 months were smaller than those of comparative examples 1 and 2 in 3 months. The stability of the samples of examples 1-4 is significantly better than that of comparative examples 1-4. Compared with single polymer micelle, liposome and nanoemulsion, the sample of the mixed polymer micelle coated with ceramide has better stability.
The polymer mixed micelles of examples 1, 5 to 8 were analyzed. The polymer mixed micelles of examples 1, 5 to 8 were different in the amount of the entrapped ceramide, and examples 5, 6, 1, 7, 8 were 0.1%, 1%, 3%, 5% and 7%, respectively. However, the encapsulation efficiencies of the polymer mixed micelles of examples 5, 6, 1, 7, and 8 were 83.6%, 78.2%, 80.3%, 73.6%, and 53.3%, respectively. The encapsulation efficiency of the polymer mixed micelles of example 8 was lower than that of examples 1 and 5 to 7. As shown in FIGS. 3 and 4, the absolute values of the rate of change in particle size and the rate of change in encapsulation efficiency of the polymer mixed micelles of examples 1, 5 to 7 were less than those of the polymer mixed micelle of example 8 within 3 months, indicating that the amount of ceramide used affects the encapsulation efficiency and stability of the polymer mixed micelle. When the addition amount of the ceramide exceeds 5%, the encapsulation rate of the polymer mixed micelle on the ceramide is low, and after the polymer mixed micelle is prevented for a period of time, the polymer mixed micelle is agglomerated, the particle size is increased, and the stability of the polymer mixed micelle is influenced.
The polymer mixed micelles of examples 1, 9 to 12 were analyzed. The polymer mixed micelles of examples 1, 9 to 12 were different in the amount of the amphiphilic block polymer charged and the amount of the polyol used. The amounts of amphiphilic block polymers of examples 9, 1, 10, 11, 12 charged were 0.5%, 2%, 10%, 20%, and 30%, respectively. However, examples 11 and 12 used more butanediol than 1, 9 and 10, which illustrates that more alcohol was required to solubilize the amphiphilic block polymer when it was added more. As can be seen from fig. 5 and fig. 6, the more the polymer is added, the larger the particle size of the polymer mixed micelle becomes, and the larger the particle size of the polymer mixed micelle still becomes within 3 months of standing, which indicates that the more the polymer is added, the system is more easily agglomerated into particles, and the encapsulation efficiency of the polymer mixed micelle also shows a downward trend. When the input amount of the amphiphilic block polymer reaches 30%, the encapsulation efficiency of the polymer mixed micelle is sharply reduced.
The invention provides a nano carrier for encapsulating ceramide and a preparation method thereof. The polymer mixed micelle integrates a plurality of blocks with different functions into the same micelle system. Compared with the polymer micelle formed by self-assembly of a single-component polymer, the nano-carrier prepared by the invention has smaller particle size, higher entrapment rate on ceramide and good stability, and improves the water solubility, transdermal absorbability and stability of ceramide. Meanwhile, the preparation method of the nano-carrier for encapsulating ceramide provided by the invention is simple, is beneficial to saving the process flow and reducing the manufacturing cost, and is suitable for being used in various cosmetics.
The invention also provides a nano carrier for encapsulating ceramide. The nano-carrier for encapsulating ceramide provided by the invention is prepared by the preparation method.
The nano-carrier for encapsulating ceramide provided by the invention adopts micelles formed by self-assembly of two amphiphilic block polymers in a selective solvent. The polymer mixed micelle integrates a plurality of blocks with different functions into the same micelle system. The nano carrier for encapsulating ceramide prepared by the invention is a polymer mixed micelle for encapsulating ceramide. Compared with the polymer micelle formed by self-assembly of a single-component polymer, the polymer mixed micelle prepared by the invention has higher entrapment rate and good stability on ceramide, and improves the water solubility, the transdermal absorbability and the stability of the ceramide.
The invention also provides application of the nano carrier for encapsulating ceramide in the field of cosmetics. The cosmetics of the invention can be smoothing toner, emulsion, cream, facial mask, jelly, powder, spray, essence, washing and caring cosmetics and color cosmetics.
Wherein, the addition amount of the nano carrier for encapsulating the ceramide in the cosmetic is 1-20%. The above-mentioned addition amount is a safe addition amount. When the addition amount of the nano carrier for encapsulating the ceramide in the cosmetic is less than 1%, the nano carrier for encapsulating the ceramide cannot exert the effect. When the addition amount of the nano-carrier encapsulating ceramide in the cosmetic is more than 20%, the addition amount of the nano-carrier encapsulating ceramide is too large, which easily causes skin problems.
The preparation method of the nano-carrier for encapsulating ceramide provided by the invention is described in detail above, and the embodiments of the application are explained by applying specific examples, and the description of the examples is only used for helping to understand the method and the core idea of the application; meanwhile, for those skilled in the art, according to the idea of the present application, the specific implementation manner and the application scope may be changed, and in summary, the content of the present specification should not be construed as a limitation to the present application.
Claims (10)
1. A preparation method of a nano carrier for encapsulating ceramide is characterized by comprising the following steps:
(1) dissolving two different amphiphilic block polymers in polyol, heating and stirring, and obtaining a polymer solution after the amphiphilic block polymers are fully dissolved;
(2) dissolving ceramide in polyalcohol, heating and stirring, and obtaining a ceramide solution after the ceramide is fully dissolved;
(3) adding the ceramide solution into the polymer solution, and stirring to obtain a mixed solution;
(4) and (3) dripping the mixed solution into water under the stirring condition, continuing stirring after the dripping is finished, and performing dispersion treatment to obtain the ceramide-entrapped nano carrier.
2. The method for preparing the ceramide-encapsulated nano-carrier according to claim 1, wherein the two different amphiphilic block polymers in the step (1) are selected from two of polycaprolactone-b-polyethylene glycol monomethyl ether, polylactic acid-b-polyethylene glycol monomethyl ether, poly (lactic acid-co-glycolic acid) -b-polyethylene glycol monomethyl ether, polyethylene glycol monomethyl ether-b-poly N, N-diethylaminoethyl methacrylate, poly (lactic acid-co-glycolic acid) -b-polyethylene glycol monomethyl ether methacrylate, and polyoxyethylene-b-polyoxypropylene-b-polyoxyethylene.
3. The method for preparing the nano-carrier entrapping the ceramide according to claim 2, wherein the polycaprolactone-b-polyethylene glycol monomethyl ether PCL x -b-mPEG y Molecular weight M of n 6000-12000, the structural formula is:
x＝35-61，y＝45-113；
the polylactic acid-b-polyethylene glycol monomethyl ether PLA x -b-mPEG y Molecular weight M of n 6000-12000, the structural formula is as follows:
x＝28-48，y＝45-113；
the poly (lactic acid-co-glycolic acid) -b-polyethylene glycol monomethyl ether P (LA) x -co-GA y )-b-mPEG z Molecular weight M of n 6000-12000, the structural formula is:
x＝42-78，y＝14-26，z＝45-113；
the polyethylene glycol monomethyl ether-b-poly N, N-diethylaminoethyl methacrylate mPEG x -b-PDEAEMA y Molecular weight M of n 6000-12000, the structural formula is as follows:
x＝45-113，y＝23-41；
the poly (lactic acid-co-glycolic acid) -b-polyethylene glycol monomethyl ether methacrylate P (LA) x -co-GA y )-b-PPEGMA z Molecular weight M of n 6000-12000, the structural formula is:
x＝42-78，y＝14-26，z＝5-13；
the polyoxyethylene-b-polyoxypropylene-b-polyoxyethylene PEO x -b-PPO y -b-PEO z Molecular weight M of n 6000-12000, the structural formula is as follows:
x＝45-113，y＝34-135，z＝45-113。
4. the method for preparing the nano carrier coated with the ceramide as claimed in claim 1, wherein the two amphiphilic block polymers are relatively independent in the nano carrier in a mass percentage of 0.2-15%.
5. The method for preparing the nano carrier coated with the ceramide as claimed in claim 1, wherein the polyhydric alcohol in the step (1) and the polyhydric alcohol in the step (2) respectively and independently comprise at least one of propylene glycol, isopropanol, dipropylene glycol, glycerol, butanediol, 1, 2-pentanediol and 1, 2-hexanediol;
the total mass percentage of the polyhydric alcohol in the nano carrier is 10% -50%.
6. The method for preparing the nano-carrier encapsulating the ceramide AS claimed in claim 1, wherein the ceramide in the step (2) comprises at least one of ceramide AP, ceramide AS, ceramide E and ceramide NP;
in the step (2), the mass percentage of the ceramide in the nano-carrier is 0.1-5%.
7. The method for preparing the ceramide-encapsulated nanocarrier according to claim 1, wherein the nanocarrier is a ceramide-encapsulated nanocarrier,
the heating temperature in the step (1) and the heating temperature in the step (2) are respectively and independently 45-80 ℃;
the stirring in the step (1) and the step (2) is magnetic stirring, and the rotating speed of the stirring is 150-600rpm relatively independently;
the stirring time in the step (1) and the stirring time in the step (2) are respectively and independently 2h-12 h;
in the step (3), the stirring is magnetic stirring, and the rotating speed is 150-600 rpm; stirring for 2-12h in the step (3);
dropwise adding the mixed solution into water through a peristaltic pump, wherein the dropwise adding speed of the peristaltic pump is 20-50 rmp;
in the step (4), the mass percent of the water in the nano carrier is 15-89.5%;
the stirring in the step (4) and the rotating speed of the continuous stirring after the dropwise adding are 150-600 rpm; the stirring time for continuously stirring after the dropwise adding is 4-24 h;
the dispersion treatment in the step (4) is high-speed shear dispersion, the used equipment is a high-shear homogenizing emulsifying machine, the power of the high-shear homogenizing emulsifying machine is 500-1000w, the rotating speed of the high-shear homogenizing emulsifying machine is 5000-8000rpm, and the high-speed shear dispersion time of the high-shear homogenizing emulsifying machine is 3-10 min.
8. A ceramide-entrapped nanocarrier prepared by the method of any of claims 1 to 7.
9. Use of the ceramide-encapsulated nanocarrier of claim 8 in the cosmetic field.
10. The use according to claim 9, wherein the ceramide-encapsulating nanocarrier is present in the cosmetic product in an amount of 1% to 20% by weight.
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| CN109106611A (en) * | 2018-11-01 | 2019-01-01 | 苏州纳康生物科技有限公司 | A kind of ceramide liposome and preparation method thereof |
| CN112006986A (en) * | 2020-08-07 | 2020-12-01 | 厦门大学 | Vitamin E succinate polyethylene glycol nano micelle and preparation method and application thereof |
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