CN104983591A - Double modified beta-carotene lipidosome and preparation method thereof - Google Patents
Double modified beta-carotene lipidosome and preparation method thereof Download PDFInfo
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- CN104983591A CN104983591A CN201510401943.XA CN201510401943A CN104983591A CN 104983591 A CN104983591 A CN 104983591A CN 201510401943 A CN201510401943 A CN 201510401943A CN 104983591 A CN104983591 A CN 104983591A
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Abstract
The invention discloses doubly-decorated beta-carotene lipidosome. The doubly-decorated beta-carotene lipidosome consists of the following components: egg yolk lecithin, dihexadecyl phosphate, mannitol, saccharose, beta-carotene, cholesterol, tween-80, VE, VC, chitosan and sodium hyaluronate. The invention also discloses a preparation method of the lipidosome. The preparation method comprises the following steps: preparing a beta-carotene lipidosome suspension, dropwise adding the suspension into a chitosan solution, centrifuging to obtain precipitates, dissolving the precipitates by utilizing distilled water, dropwise adding into a hyaluronic acid solution to obtain a hyaluronic acid-chitosan-lipidosome suspension, and freeze drying the suspension to obtain lipidosome powder. By virtue of effective ultrasonic oscillation, and membrane filtration and size stabilization, the particle size of the hyaluronic acid-chitosan-lipidosome is uniform and good in dispersity, and pores of the skin are unlikely to be blocked; by virtue of packaging layer by layer, the drug releasing time is long, and the sunscreen function can be active for a long time; the lipidosome exists in a form of powder by utilizing the freeze drying process, so that the long-term storage is facilitated; moreover, convenience in storage and application can be realized.
Description
Technical field
The invention belongs to Cosmetic Manufacture technical field, be specifically related to a kind of dual modified beta-carotenoid lipid body; The invention still further relates to the preparation method of this dual modified beta-carotenoid lipid body.
Background technology
Liposome is made up of lipid bilayer, and its inside is the closed imitated vesicle structure of aqueous phase, and due to the stuctures and properties of its uniqueness, liposome has been widely used and food, medicine and cosmetic field.
Beta-carotene has multiple double bond, oxidizable under the radical ion existent condition that light, heat, oxygen and activity are stronger, thus effectively prevent the oxidative damage of DNA and lipoprotein, maintain cell function, delaying body aging, is a generally acknowledged Natural antioxidant; Added in cosmetics, the double effects that cosmetics absorb ultraviolet and skin whitening can be given; But beta-carotene is insoluble or be difficult to dissolve in the cosmetics common solvent such as water, propylene glycol, glycerol, methanol and ethanol, strongly limit its use at cosmetic field.Utilize solubility microsphere to make beta-carotene liposome by coated for beta-carotene, and added in cosmetics, solve the problem of the insoluble or indissoluble of beta-carotene.The shortcomings such as but liposome is to the sensitivity such as sour, hot, easily assemble fused, flocculation at duration of storage, cause core to leak, in use procedure, release is too fast, and easily producing dashes forward releases, wayward.So need to modify with macromolecular material chitosan and hyaluronic acid, liposome can be improved to the sensitivity such as sour, hot by coating technology layer by layer, improve stability, control drug release rate, make beta-carotene not easy to leak.
Hyaluronic acid HA has been widely used in the production of cosmetics as natural moisture preserving agent, compared with traditional wetting agent, has higher moistening effect, and without shortcomings such as greasy feeling and obstruction skin pores.Hyaluronate sodium is the sodium-salt form of hyaluronic acid (HA), it is a kind of straight-chain polysaccharide of high molecular, be distributed widely in animal and human's body connective tissue cell epimatrix, its random coil state in the solution and its hydrodynamics feature give its important physical characteristic, i.e. height viscoelasticity, plasticity, permeability and good biocompatibility, it is a kind of broad-spectrum bioabsorbable material, therefore be wrapped in the outermost layer at beta-carotene liposome, in cosmetics, played unique effect as Moisture factor.And the sunscreen cream of commercial type and the longest sun-proof time of sunlight lotion are 4h at present; the sun-proof time is too short; beta-carotene is wrapped up layer by layer and can control its slow release speed; extend effective sun-proof time to 8h; and by wrapping up the contact reducing substance having sun-screening function and skin layer by layer; reduce its stimulation to skin, can better skin be protected.
Therefore, how beta-carotene being made beta-carotene liposome, and carry out beta-carotene liposome coated layer by layer, is the problem needing solution badly.
Summary of the invention
The object of the present invention is to provide a kind of dual modified beta-carotenoid lipid body, solve beta-carotene liposome when adding in cosmetics, can cause release too fast, easily produce prominent releasing and problem that is wayward and cosmetics poor stability.
Another object of the present invention is to the preparation method providing this dual modified beta-carotenoid lipid body, preparation technology is simple, easily realizes.
The technical solution adopted in the present invention is; a kind of dual modified beta-carotenoid lipid body; composed of the following components by mass percentage: Ovum Gallus domesticus Flavus lecithin 15% ~ 30%; Dihexadecylphosphate 1% ~ 3%; protective agent 30% ~ 60%, beta-carotene crystal 0.1% ~ 1%, cholesterol 5% ~ 9%; tween 80 10% ~ 20%, V
e0.5% ~ 1%, V
c0.5% ~ 1%, chitosan 1% ~ 3%, hyaluronate sodium 1% ~ 3%, above constituent mass percentage ratio sum is 100%.
Feature of the present invention is also,
In Ovum Gallus domesticus Flavus lecithin, phosphatidylcholine content is greater than 90%, and protective agent is the mixture of sucrose and mannitol, and wherein, the mass ratio of sucrose and mannitol is 6:4; Hyaluronic molecular weight is 10-100 ten thousand.
Liposome is freeze-dried powder, and mean diameter is 240.45 ± 0.28nm, and cell in vitro drug release time is 8 ~ 10h.
Another technical scheme of the present invention is, a kind of preparation method of dual modified beta-carotenoid lipid body, and concrete steps are as follows:
Step 1, takes Ovum Gallus domesticus Flavus lecithin 15% ~ 30% respectively, Dihexadecylphosphate 1% ~ 3%, protective agent 30% ~ 60%, beta-carotene crystal 0.1% ~ 1%, and cholesterol is 5% ~ 9%, tween 80 10% ~ 20%, V
e0.5% ~ 1%, V
c0.5% ~ 1%, chitosan 1% ~ 3%, hyaluronate sodium 1% ~ 3%, above constituent mass percentage ratio sum is 100%;
Step 2, gets Ovum Gallus domesticus Flavus lecithin, beta-carotene crystal, cholesterol, tween 80 that step 1 weighs, Dihexadecylphosphate, V
eand V
cbe dissolved in organic solvent, room temperature magnetic force is stirred to each medicine and dissolves completely, by dissolve completely rear solution pour into round-bottomed flask temperature be 40 DEG C, pressure in a rotary evaporator after rotary evaporation, obtains liposome membrane under being 0.008Mpa condition;
Step 3, it is in the Tris buffer of 0.1mol/L that protective agent step 1 taken is dissolved in concentration, is stirred to and dissolves completely; To join in step 2 gained liposome membrane containing protectant Tris buffer and carry out washing film, obtain thick liposome turbid liquor, by gained suspension at 45 DEG C ~ 55 DEG C water-bath magnetic agitation 40min ~ 60min, then, after ice-water bath effective ultrasonic vibration process 15min ~ 20min, beta-carotene liposome turbid liquor is obtained;
Step 4, it is in the citric acid solution of 4% that low-molecular weight chitoglycan step 1 taken is dissolved in concentration, leaves standstill 8 ~ 16h, after making it fully dissolve, obtains the chitosan solution that concentration is 0.685mg/mL ~ 2.055mg/mL, for subsequent use;
Step 5, getting step 3 gained beta-carotene liposome is added drop-wise in step 4 gained chitosan solution with the speed of 0.1mL/s, 40min ~ 60min is stirred under 500rmp speed, after making its mix homogeneously, by mixture effective ultrasonic vibration 10min ~ 15min in ice bath, be placed on 8 ~ 16h in 3 ~ 4 DEG C of environment, then by its centrifugal treating 30min under the rotating speed of 15000rpm, finally the precipitate distilled water after centrifugal treating is dissolved, obtain chitosan-Bao liposome solutions;
Step 6, hyaluronate sodium step 1 taken is dissolved in distilled water, leaves standstill 8 ~ 16h, makes it fully dissolve, obtain the hyaluronic acid solution that concentration is 0.685mg/mL ~ 2.055mg/mL;
Step 7, step 5 gained chitosan-Bao liposome solutions is added drop-wise in step 6 gained hyaluronic acid solution with the speed of 0.1mL/s, drip rear continuation and stir 40min ~ 60min, the effective ultrasonic vibration 10min ~ 15min of ice bath, obtain hyaluronic acid-chitosan-liposome turbid liquor, then 0.45 μm of micro-filtration membrane and 0.22 μm of micro-filtration membrane carry out granulate excessively successively;
Step 8, step 7 is filtered hyaluronic acid-chitosan-liposome turbid liquor of obtaining freeze-thaw two to three times repeatedly under-60 ± 1 DEG C and 10 ± 1 DEG C of environmental conditions, to be distributed in cillin bottle under-60 ± 1 DEG C of environmental condition after pre-freeze 30h, again-52 ± 2 DEG C, vacuum is less than lyophilization 25h ~ 30h under the environmental condition of 100mT, obtains lipid freeze-dry powder.
Feature of the present invention is also,
In step 1, in Ovum Gallus domesticus Flavus lecithin, phosphatidylcholine content is greater than 90%, and the amount ratio of Ovum Gallus domesticus Flavus lecithin and Dihexadecylphosphate is 10:1; The amount ratio of cholesterol and Dihexadecylphosphate is 2.5:1; The amount ratio of protective agent and Ovum Gallus domesticus Flavus lecithin is 2:1; Protective agent is the mixture of sucrose and mannitol, and wherein, the mass ratio of sucrose and mannitol is 6:4; Hyaluronic molecular weight is 10-100 ten thousand.
In step 2, organic solvent is the mixture of dehydrated alcohol and chloroform, and wherein the volume ratio of dehydrated alcohol and chloroform is 1:2.
In step 4, chitosan is low-molecular weight chitoglycan, and its molecular weight is 50,000 ~ 190,000.
In step 5, the volume ratio of beta-carotene liposome turbid liquor and chitosan solution is 1:1.
In step 7, the volume ratio of hyaluronic acid solution and chitosan-Bao liposome turbid liquor is 1:1.
The invention has the beneficial effects as follows, utilize effective ultrasonic vibration and the process of filter membrane granulate, make the size of hyaluronic acid-chitosan-liposome even, good dispersion, not easily blocks the pore of skin; Coated drug release time is long layer by layer, can be sun-proof for a long time, and reduces the exposure concentration of sun-prevention component and skin after parcel, decreases its stimulation to skin; Adopt freeze-dry process make liposome with Powdered existence, be conducive to long-term preservation, and storage, easy to use.
Accompanying drawing explanation
Fig. 1 is preparation technology's flow chart of the present invention's dual modified beta-carotenoid lipid body;
Fig. 2 is the grain size distribution of the embodiment of the present invention 1 gained liposome;
Fig. 3 is the grain size distribution of comparative example gained liposome of the present invention;
Fig. 4 is the embodiment of the present invention 1 and comparative example gained Via Liposomes cell slow release figure;
Fig. 5 is the sunscreen cream spf value phenogram utilizing the embodiment of the present invention 1 gained liposomal preparation;
Fig. 6 is the ultraviolet permeability change curve of the sunscreen cream utilizing the embodiment of the present invention 1 gained liposomal preparation.
Detailed description of the invention
Descend and the present invention is described in detail with detailed description of the invention by reference to the accompanying drawings.
Embodiment 1
Step 1, takes 2.400g Ovum Gallus domesticus Flavus lecithin, 0.240g Dihexadecylphosphate, 0.047g beta-carotene crystal, 0.600g cholesterol, 1.471g tween 80,0.075gV respectively
eand 0.075gV
cbe dissolved in the mixture of 30mL dehydrated alcohol and chloroform, in mixture, the volume ratio of dehydrated alcohol and chloroform is 1:2, room temperature magnetic force is stirred to each medicine and dissolves completely, by dissolve completely rear solution pour into round-bottomed flask temperature be 40 DEG C, pressure in a rotary evaporator after rotary evaporation, obtains liposome membrane under being 0.008Mpa condition;
Step 2, takes 1.920g mannitol and 2.880g sucrose dissolved is in the Tris buffer of 0.1mol/L in 150mL concentration, is stirred to and dissolves completely, must contain protectant Tris buffer; To join in step 1 gained liposome membrane containing protectant Tris buffer and wash film, obtain thick liposome turbid liquor, by gained suspension at 55 DEG C of water-bath magnetic agitation 55min, then effective ultrasonic vibration process 15min (each effective ultrasonic 5min, interval 5min) after, obtain beta-carotene liposome turbid liquor;
Step 3, getting 0.146g low-molecular weight chitoglycan, to be dissolved in 146mL concentration be in the citric acid solution of 4% (w/v), leaves standstill 12h, after making it fully dissolve concentration be the chitosan solution of 1mg/mL; The beta-carotene liposome turbid liquor getting 100mL step 2 obtained is added drop-wise in the above-mentioned chitosan solution of 100mL with the speed of 0.1mL/s, 55min is stirred under 500rmp speed, after making its mix homogeneously, by mixture effective ultrasonic vibration 15min (each ultrasonic 5min in ice bath, interval 5min), sealing is placed on 16h in 4 DEG C of environment, then by its centrifugal treating 30min under the rotating speed of 15000rpm, finally the 100mL distilled water of the precipitate after centrifugal treating is dissolved, obtain chitosan-Bao liposome solutions;
Step 4, by molten for 0.146g hyaluronate sodium, solution, in 146mL distilled water, leaves standstill 8h, makes it fully dissolve, obtain the hyaluronic acid solution that concentration is 1mg/mL; Chitosan-Bao the liposome solutions getting 100mL step 3 obtained is added drop-wise in 100mL hyaluronic acid solution with the speed of 0.1mL/s, drip rear continuation and stir 55min, ice bath effective ultrasonic vibration 15min (each ultrasonic 5min, interval 5min), obtain hyaluronic acid-chitosan-liposome turbid liquor, then 0.45 μm of micro-filtration membrane and 0.22 μm of micro-filtration membrane carry out granulate excessively successively; Hyaluronic acid-chitosan-liposome turbid liquor of obtaining freeze-thaw twice repeatedly under-60 ± 1 DEG C and 10 ± 1 DEG C of environmental conditions will be filtered, to be distributed in cillin bottle under-60 ± 1 DEG C of environmental condition after pre-freeze 30h, again-52 ± 2 DEG C, vacuum is less than lyophilization 25h under the environmental condition of 100mT, obtains lipid freeze-dry powder.
Embodiment 2
Step 1 takes 2.200g Ovum Gallus domesticus Flavus lecithin, 0.220g Dihexadecylphosphate, 0.100g beta-carotene crystal, 0.550g cholesterol, 1.730g tween 80,0.100gV respectively
eand 0.100gV
cbe dissolved in the mixture of 30mL dehydrated alcohol and chloroform, in mixture, the volume ratio of dehydrated alcohol and chloroform is 1:2, and room temperature magnetic force is stirred to each medicine and dissolves completely.By dissolve completely rear solution pour into round-bottomed flask temperature be 40 DEG C, pressure in a rotary evaporator after rotary evaporation, obtains liposome membrane under being 0.008Mpa condition;
Step 2, takes 1.760g mannitol and 2.640g sucrose dissolved is in the Tris buffer of 0.1mol/L in 150mL concentration, is stirred to and dissolves completely, must contain protectant Tris buffer; Film is washed by joining containing protectant Tris buffer in the obtained liposome membrane of upper step rotary evaporation, obtain thick liposome turbid liquor, by gained suspension at 45 DEG C of water-bath magnetic agitation 60min, then at ice-water bath effective ultrasonic vibration process 15min (each ultrasonic 5min, interval 5min) after, obtain beta-carotene liposome turbid liquor;
Step 3, getting 0.300g low-molecular weight chitoglycan, to be dissolved in 146mL concentration be in the citric acid solution of 4% (w/v), leaves standstill 8h, after making it fully dissolve, obtain the chitosan solution that concentration is 2.055mg/mL; The beta-carotene liposome turbid liquor getting 100mL step 2 obtained is added drop-wise in 100mL chitosan solution with the speed of 0.1mL/s, 60min is stirred under 500rmp speed, after making its mix homogeneously, by mixture effective ultrasonic vibration 15min (each ultrasonic 5min in ice bath, interval 5min), sealing is placed on 16h in 4 DEG C of environment, then by its centrifugal treating 30min under the rotating speed of 15000rpm, finally the 100mL distilled water of the precipitate after centrifugal treating is dissolved, obtain chitosan-Bao liposome solutions;
Step 4, is dissolved in 0.300g hyaluronate sodium in 146mL distilled water, leaves standstill 12h, makes it fully dissolve, obtain the hyaluronic acid solution that concentration is 2.055mg/mL; Chitosan-Bao the liposome solutions getting 100mL step 3 obtained is added drop-wise in 100mL hyaluronic acid solution with the speed of 0.1mL/s, drip rear continuation and stir 60min, ice bath effective ultrasonic vibration 10min (ultrasonic 5min, interval 5min), obtain hyaluronic acid-chitosan-liposome turbid liquor, then 0.45 μm of micro-filtration membrane and 0.22 μm of micro-filtration membrane carry out granulate excessively successively; To the suspension that obtains be filtered under-60 ± 1 DEG C and 10 ± 1 DEG C of environmental conditions repeatedly after freeze-thaw three times, to be distributed in cillin bottle under-60 ± 1 DEG C of environmental condition after pre-freeze 30h, again-52 ± 2 DEG C, vacuum is less than lyophilization 30h under the environmental condition of 100mT, obtains lipid freeze-dry powder.
Embodiment 3
Step 1 takes 2.600g Ovum Gallus domesticus Flavus lecithin, 0.260g Dihexadecylphosphate, 0.030g beta-carotene crystal, 0.650g cholesterol, 1.000g tween 80,0.030gV respectively
eand 0.030gV
cbe dissolved in the mixture of 30mL dehydrated alcohol and chloroform, in mixture, the volume ratio of dehydrated alcohol and chloroform is 1:2, and room temperature magnetic force is stirred to each medicine and dissolves completely.By dissolve completely rear solution pour into round-bottomed flask temperature be 40 DEG C, pressure in a rotary evaporator after rotary evaporation, obtains liposome membrane under being 0.008Mpa condition;
Step 2, to take 2.080g mannitol and 3.120g sucrose dissolved be 150mL concentration in concentration is in the Tris buffer of 0.1mol/L, is stirred to and dissolves completely, must contain protectant Tris buffer; Film is washed by joining containing protectant Tris buffer in the obtained liposome membrane of upper step rotary evaporation, obtain thick liposome turbid liquor, by gained suspension at 50 DEG C of water-bath magnetic agitation 40min, then effective ultrasonic vibration process 15min (each ultrasonic 5min, interval 5min) after, obtain beta-carotene liposome turbid liquor;
Step 3, getting 0.100g low-molecular weight chitoglycan, to be dissolved in 146mL concentration be in the citric acid solution of 4% (w/v), leaves standstill 16h, after making it fully dissolve, obtain the chitosan solution that concentration is 0.685mg/mL; The beta-carotene liposome turbid liquor getting 100mL step 2 obtained is added drop-wise in 100mL chitosan solution with the speed of 0.1mL/s, 1h is stirred under 500rmp speed, after making its mix homogeneously, by mixture effective ultrasonic vibration 15min (each ultrasonic 5min in ice bath, interval 5min), be placed on 16h in 4 DEG C of environment, then by its centrifugal treating 30min under the rotating speed of 15000rpm, finally the precipitate distilled water after centrifugal treating is dissolved, obtain chitosan-Bao liposome solutions;
Step 4, is dissolved in 0.100g hyaluronate sodium in 146mL distilled water, leaves standstill 16h, makes it fully dissolve, obtain the hyaluronic acid solution that concentration is 0.685mg/mL; Chitosan-Bao the liposome solutions getting 100mL step 3 obtained is added drop-wise in 100mL hyaluronic acid solution with the speed of 0.1mL/s, drip rear continuation and stir 60min, ice bath effective ultrasonic vibration 10min (each ultrasonic 5min, interval 5min), obtain hyaluronic acid-chitosan-liposome turbid liquor, then 0.45 μm of micro-filtration membrane and 0.22 μm of micro-filtration membrane carry out granulate excessively successively; To the suspension that obtains be filtered under-60 ± 1 DEG C and 10 ± 1 DEG C of environmental conditions repeatedly after freeze-thaw three times, to be distributed in cillin bottle under-60 ± 1 DEG C of environmental condition after pre-freeze 30h, again-52 ± 2 DEG C, vacuum is less than lyophilization 30h under the environmental condition of 100mT, obtains nanometer liposome powder.
Comparative example
Step 1, takes 2.400g Ovum Gallus domesticus Flavus lecithin, 0.240g Dihexadecylphosphate, 0.047g beta-carotene crystal, 0.600g cholesterol, 1.471g tween 80,0.075gV respectively
eand 0.075gV
cbe dissolved in the mixture of 30mL dehydrated alcohol and chloroform, in mixture, the volume ratio of dehydrated alcohol and chloroform is 1:2, room temperature magnetic force is stirred to each medicine and dissolves completely, by dissolve completely rear solution pour into round-bottomed flask temperature be 40 DEG C, pressure in a rotary evaporator after rotary evaporation, obtains liposome membrane under being 0.008Mpa condition;
Step 2, takes 1.920g mannitol and 2.880g sucrose dissolved is in the Tris buffer of 0.1mol/L in 150mL concentration, is stirred to and dissolves completely, must contain protectant Tris buffer; To join in step 1 gained liposome membrane containing protectant Tris buffer and wash film, obtain thick liposome turbid liquor, by gained suspension at 55 DEG C of water-bath magnetic agitation 55min, then effective ultrasonic vibration process 15min (each effective ultrasonic 5min, interval 5min) after, obtain beta-carotene liposome turbid liquor;
Step 3, getting 0.146g low-molecular weight chitoglycan, to be dissolved in 146mL concentration be in the citric acid solution of 4% (w/v), leaves standstill 12h, after making it fully dissolve concentration be the chitosan solution of 1mg/mL; The beta-carotene liposome turbid liquor getting 100mL step 2 obtained is added drop-wise in the above-mentioned chitosan solution of 100mL with the speed of 0.1mL/s, 55min is stirred under 500rmp speed, after making its mix homogeneously, by mixture effective ultrasonic vibration 15min (each ultrasonic 5min in ice bath, interval 5min), sealing is placed on 16h in 4 DEG C of environment, then by its centrifugal treating 30min under the rotating speed of 15000rpm, finally the 100mL distilled water of the precipitate after centrifugal treating is dissolved, obtain chitosan-Bao liposome solutions.
Fig. 1 is the preparation flow figure of the present invention's dual modified beta-carotenoid lipid body, effective ultrasonic vibration is utilized in the present invention's dual modified beta-carotenoid lipid production procedure, cross the effect of film granulate, make hyaluronic acid-chitosan-liposomal particle size size even, good dispersion, not easily blocks the pore of skin.Mean diameter is 240.45 ± 0.28nm, and Zeta potential is-36.3 ± 2.5mV; The grain size distribution of the embodiment of the present invention 1 gained liposome, as shown in Figure 2, the particle size range of gained liposome is 210 ~ 270nm; Comparative example is that its grain size distribution as shown in Figure 3 only with the liposome of Chitosan-coated; Fig. 4 is the embodiment of the present invention 1 and comparative example gained liposome cell in vitro slow release figure, carry out Release Performance test in the environment of the simulated skin pH of pH=5.5, after result shows 2h through chitosan and the coated liposome medicine realeasing rate of hyaluronic acid be 48%, and only the liposome release rate of encasement polysaccharide is 80%, the stability of multilayer coating structure liposome is better than only with the liposome of Chitosan-coated as seen from the figure; Therefore, the liposome slow-release time of modifying through chitosan and hyaluronic acid bilayer is long, has long-time sun-screening function.
Chitosan is dissolved with citric acid in the present invention, and make the chitosan solution that concentration is 0.685mg/mL ~ 2.055mg/mL, because citric acid belongs to the one of fruit acid, its effect is mainly accelerated cutin and is upgraded, the renewal of cutin contributes to melanic in skin peeling off, the receipts of pore are thin, the dissolving etc. of blackhead.And the chitosan solution generally prepared with acetate dissolution chitosan is flavoursome pungent, and there is very large zest to skin.In addition, the chitosan modified liposome that the present invention's citric acid dissolves is compared with generally using the chitosan modified liposome of acetate dissolution, little to the injury of skin.
The beta-carotene selected in the present invention has sun-proof function, and the surface that Dihexadecylphosphate is incorporated as obtained liposome provides negative charge, is combined by electrostatic interaction with positively charged chitosan, makes the liposome stability that obtains better.The V added
cand V
ealso there is very strong antioxidation, better sun-proof result can be reached, and add wetting agent hyaluronic acid, while sun-proof, also there is moisture-keeping function, better can protect skin.
The present invention adopts freeze drying process, with sucrose and mannitol for protective agent, lyophilized powder can be made to maintain original volume, do not subside, shrinkage, and any surface finish, redispersibility is better, and particle shape is also protected relatively good.After freeze drying process, make freeze-dried powder be conducive to long-term preservation, when preparing sunscreen cream, redissolved by dual modified beta good for lyophilizing-carotenoid lipid body lyophilized powder deionized water, concussion is to dissolving completely gently, then directly adds in sunscreen cream.Wherein, the addition of lyophilized powder in sunscreen cream is 1% ~ 10%, transports and uses more convenient.
Efficacy test:
Dual modified beta-carotenoid lipid the body of the embodiment of the present invention 1 gained is added in sunscreen cream, makes the sunscreen cream with long-time sun-proof function, and its sun-proof result is tested.
1. effective sun-proof time test: select 40 without the age of skin sensitivity history in the women in 25-45 year, dryness, neutrality, oily skin volunteer quantity are substantially identical, choosing volunteer's inner forearm region is recipient site, and the application area of each experimenter must not be less than 30cm
2.
One place's irradiation area is selected to experimenter's left forearm inside skin, 40 seconds are irradiated with solar UV simulator UVB, observed after 20 hours, occur that the minimum exposure dose of erythema is the med value of this experimenter's normal skin with skin, be the med value measured in advance, then mensuration volunteer smears the med value being added with the sunscreen cream of dual modified beta-carotenoid lipid prepared by the present invention, and calculates spf value with following formula:
The integer part of getting the meansigma methods of the spf value of 40 volunteers is the spf value of this sample, and concrete measurement result is shown in Fig. 5, and the sunscreen cream that as can be seen from the figure the present invention is made effective sun-proof time can continue 8h, and the best sun-proof time is 6h.
2. UV transparent rate: be dissolved in the bottle of 50mL capacity by sunscreen cream sample accurate weighing 100mg, adds dehydrated alcohol and absolute ether makes solution by the proportioning concentration of 1:1 as solvent.By the solution made down in the quartz cuvette pond of 1cm × 1cm × 5cm, in the ultra-violet and visible spectrophotometer debugged, measure the wave-length coverage UV transparent rate of 290 ~ 400nm.Test result as shown in Figure 6, as can be seen from the figure, the ultraviolet light of dual modified beta prepared by the present invention-carotenoid lipid body sunscreen cream is that the light transmittance within the scope of UVB or UVA is all no more than 20%, matches, illustrate that its sun-proof result is better with human test results above.
Claims (9)
1. dual modified beta-carotenoid lipid body; it is characterized in that; composed of the following components by mass percentage: Ovum Gallus domesticus Flavus lecithin 15% ~ 30%; Dihexadecylphosphate 1% ~ 3%; protective agent 30% ~ 60%, beta-carotene crystal 0.1% ~ 1%, cholesterol 5% ~ 9%; tween 80 10% ~ 20%, V
e0.5% ~ 1%, V
c0.5% ~ 1%, chitosan 1% ~ 3%, hyaluronate sodium 1% ~ 3%, above constituent mass percentage ratio sum is 100%.
2. one according to claim 1 dual modified beta-carotenoid lipid body, it is characterized in that, in Ovum Gallus domesticus Flavus lecithin, phosphatidylcholine content is greater than 90%, and protective agent is the mixture of sucrose and mannitol, and wherein, the mass ratio of sucrose and mannitol is 6:4; Hyaluronic molecular weight is 10-100 ten thousand.
3. one according to claim 1 dual modified beta-carotenoid lipid body, is characterized in that, liposome is freeze-dried powder, and mean diameter is 240.45 ± 0.28nm, and cell in vitro drug release time is 8 ~ 10h.
4. a preparation method for dual modified beta-carotenoid lipid body, it is characterized in that, concrete steps are as follows:
Step 1, takes Ovum Gallus domesticus Flavus lecithin 15% ~ 30% respectively, Dihexadecylphosphate 1% ~ 3%, protective agent 30% ~ 60%, beta-carotene crystal 0.1% ~ 1%, cholesterol 5% ~ 9%, tween 80 10% ~ 20%, V
e0.5% ~ 1%, V
c0.5% ~ 1%, chitosan 1% ~ 3%, hyaluronate sodium 1% ~ 3%, above constituent mass percentage ratio sum is 100%;
Step 2, gets Ovum Gallus domesticus Flavus lecithin, beta-carotene crystal, cholesterol, Dihexadecylphosphate, V that step 1 weighs
eand V
cbe dissolved in organic solvent, room temperature magnetic force is stirred to each medicine and dissolves completely, by dissolve completely rear solution pour into round-bottomed flask temperature be 40 DEG C, pressure in a rotary evaporator after rotary evaporation, obtains liposome membrane under being 0.008Mpa condition;
Step 3, it is in the Tris buffer of 0.1mol/L that protective agent step 1 taken is dissolved in concentration, is stirred to and dissolves completely, must contain protectant Tris buffer; To join in step 2 gained liposome membrane containing protectant Tris buffer and carry out washing film, obtain thick liposome turbid liquor, by gained suspension at 45 DEG C ~ 55 DEG C water-bath magnetic agitation 40min ~ 60min, then, after effective ultrasonic vibration process 15min ~ 20min, beta-carotene liposome turbid liquor is obtained;
Step 4, it is in the citric acid solution of 4% that chitosan step 1 taken is dissolved in concentration, leaves standstill 8 ~ 16h, after making it fully dissolve, obtains the chitosan solution that concentration is 0.685mg/mL ~ 2.055mg/mL, for subsequent use;
Step 5, getting step 3 gained beta-carotene liposome turbid liquor is added drop-wise in step 4 gained chitosan solution with the speed of 0.1mL/s, 40min ~ 60min is stirred under 500rmp speed, after making its mix homogeneously, by mixture effective ultrasonic vibration 10min ~ 15min in ice bath, be placed on 8 ~ 16h in 3 ~ 4 DEG C of environment, then by its centrifugal treating 30min under the rotating speed of 15000rpm, finally the precipitate distilled water after centrifugal treating is dissolved, obtain chitosan-Bao liposome solutions;
Step 6, hyaluronate sodium step 1 taken is dissolved in distilled water, leaves standstill 8 ~ 16h, makes it fully dissolve, obtain the hyaluronic acid solution that concentration is 0.685mg/mL ~ 2.055mg/mL;
Step 7, step 5 gained chitosan-Bao liposome solutions is added drop-wise in step 6 gained hyaluronic acid solution with the speed of 0.1mL/s, drip rear continuation and stir 40min ~ 60min, the effective ultrasonic vibration 10min ~ 15min of ice bath, obtain hyaluronic acid-chitosan-liposome turbid liquor, then 0.45 μm of filter membrane and 0.22 μm of filter membrane carry out granulate excessively successively;
Step 8, step 7 is filtered hyaluronic acid-chitosan-liposome turbid liquor of obtaining freeze-thaw two to three times repeatedly under-60 ± 1 DEG C and 10 ± 1 DEG C of environmental conditions, to be distributed in cillin bottle under-60 ± 1 DEG C of environmental condition after pre-freeze 30h, again-52 ± 2 DEG C, vacuum is less than lyophilization 25h ~ 30h under the environmental condition of 100mT, obtains lipid freeze-dry powder.
5. the preparation method of a kind of dual modified beta-carotenoid lipid body according to claim 4, it is characterized in that, in step 1, in Ovum Gallus domesticus Flavus lecithin, phosphatidylcholine content is greater than 90%, and the amount ratio of Ovum Gallus domesticus Flavus lecithin and Dihexadecylphosphate is 10:1; The amount ratio of cholesterol and Dihexadecylphosphate is 2.5:1; The amount ratio of protective agent and Ovum Gallus domesticus Flavus lecithin is 2:1; Protective agent is the mixture of sucrose and mannitol, and wherein, the mass ratio of sucrose and mannitol is 6:4; Hyaluronic molecular weight is 10-100 ten thousand.
6. the preparation method of a kind of dual modified beta-carotenoid lipid body according to claim 4, is characterized in that, in step 2, organic solvent is the mixture of dehydrated alcohol and chloroform, and wherein the volume ratio of dehydrated alcohol and chloroform is 1:2.
7. the preparation method of a kind of dual modified beta-carotenoid lipid body according to claim 4, is characterized in that, in step 4, chitosan is low-molecular weight chitoglycan, and its molecular weight is 50,000 ~ 190,000.
8. the preparation method of a kind of dual modified beta-carotenoid lipid body according to claim 4, is characterized in that, in step 5, the volume ratio of beta-carotene liposome turbid liquor and chitosan solution is 1:1.
9. the preparation method of a kind of dual modified beta-carotenoid lipid body according to claim 4, is characterized in that, in step 7, the volume ratio of hyaluronic acid solution and chitosan-Bao liposome turbid liquor is 1:1.
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