CN102871936B - Nano-carrier loaded with rhodiola rosea extract and preparation method and application thereof - Google Patents
Nano-carrier loaded with rhodiola rosea extract and preparation method and application thereof Download PDFInfo
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- CN102871936B CN102871936B CN201210434701.7A CN201210434701A CN102871936B CN 102871936 B CN102871936 B CN 102871936B CN 201210434701 A CN201210434701 A CN 201210434701A CN 102871936 B CN102871936 B CN 102871936B
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Abstract
The invention relates to a nano-carrier loaded with a rhodiola rosea extract. The nano-carrier comprises the following components according to the weight ratio: 0.5% to 3% of rhodiola rosea extract, 20% to 30% of solvent, 40% to 50% of emulsifier and 18% to 35% of lipid material; the lipid material is a solid and liquid mixture of a liquid lipid material and a solid lipid material, and the emulsifier comprises a water-in-oil emulsifier and an oil-in-water emulsifier. A preparation method of the nano-carrier with the rhodiola rosea extract comprises the following steps: mixing the lipid material and the emulsifier as an oil phase; adding the water-in-oil emulsifier into the solvent as an internal aqueous phase; adding internal aqueous water into a liquid state oil phase; uniformly mixing and solidifying after being cooled to room temperature; adding the water-in-oil emulsifier, uniformly mixing to obtain a lipid system, solidifying after being cooled to room temperature to obtain the nano-carrier loaded with the rhodiola rosea extract. The invention has the following advantages: the nano-carrier loaded with the rhodiola rosea extract is jointly utilized with a technology of multiple emulsion and lipid nanoparticles, the traditional liquid state oil is replaced by the mixture of the solid state oil and the liquid state oil, the internal aqueous phase as the rhodiola rosea extract is more stable than the traditional multiple emulsion, and the obtained nano-carrier loaded with the rhodiola rosea extract as a material can be added into the cosmetics and foods, so that the existing application defects are effectively solved.
Description
Technical field
The invention belongs to the carrier system technical field in cosmetics and food technology of preparing, relate to a kind of preparation method of nano carrier, particularly a kind of nano structured lipid carrier take Radix Rhodiolae extract as active component and its production and use.
Background technology
Lipid nanoparticle (Lipid Nanoparticles, LN) technology is a kind ofly to adopt glyceride type matrix material that physiological compatibility is high as carrier material, the nano carrier system that can be used for supported active composition that adopts modern nanotechnology to prepare.Lipid nanoparticle has following characteristics: 1, realize the probability that controlled drug release and targeting discharge; 2, improved medicine stability; 3, drug loading is higher; 4, oleophylic and hydrophilic drugs all can facilitate the introduction of; 5, carrier does not have bio-toxicity; 6, avoided the use of organic solvent; 7, can carry out large-scale production and sterilizing.
Crassulaceae plants rhodiola (Rhodioala L.) various plants is Tibetan medicine and pharmacology common drug.Recent studies shows: Radix Rhodiolae has anti-hypoxia, radioprotective, antiviral, adjusting Radical Metabolism, slow down aging, resisting fatigue, raising motor capacity, improves intelligence, mediator's body immunity function, improves the effects such as cardiac function.Be called " plateau Radix Ginseng ", its main chemical compositions has rhodioside, butyl alcohol and Radix Rhodiolae polysaccharide, and contains flavone compound, phenolic compound, protein, fat, trace volatile oil and trace element, aminoacid etc.Its common commercial form is Radix Rhodiolae extracting solution (solvent is water) or Radix Rhodiolae extract (Powdered), and active component is wherein mainly rhodioside.
Rhodioside is major function composition wherein, has the health-care effecies such as antioxidation, resisting fatigue, resisting microwave radiation, inhibition blood sugar increasing, anti-peroxidation.The health product of Rhodiola species are extensively taken by the practitioner of the special industries such as spaceman, mountaineer, driver.But at present in application process, exist bottleneck as follows: there is no slow-release function, the active substance defects such as easily oxidized, bioavailability is low.
The parcel dosage form that water-soluble active ingredient is conventional has liposome, multiple emulsion (W/O/W), and w/o type emulsion, liposome structure load water-soluble active ingredient limited amount, and structure is stable relatively not; Multiple emulsion technology is used usually used as a kind of dosage form; W/o type emulsion periphery continuous phase is oil phase, is of limited application.
Summary of the invention
Technical problem to be solved by this invention is to combine uses multiple emulsion and lipid nanoparticle technology, and a kind of nano-carrier of load Radix Rhodiolae extract is provided.
Another technical problem to be solved by this invention is the preparation method of the nano-carrier that above-mentioned load Radix Rhodiolae extract is provided.
A technical problem more to be solved by this invention is the purposes of the nano-carrier that above-mentioned load Radix Rhodiolae extract is provided.
The present invention solves the problems of the technologies described above taked technical scheme and is to provide a kind of nano-carrier of load Radix Rhodiolae extract, Radix Rhodiolae extract is made through extraction, filtering and concentrating, absorb-elute by Radix Rhodiolae, and the nano-lipid carrier of described load Radix Rhodiolae extract comprises following component by its weight percent meter:
Radix Rhodiolae extract 0.5～3%
Solvent 20～30%
Matrix material 18～35%;
Described matrix material is the solidliquid mixture of liquid lipoid material and solid lipid material, liquid lipoid material is one or both in macadimia nut oil, Semen pruni armeniacae oil, and described solid lipid material is one or both in glyceryl monostearate, glycerol monolaurate; Described solvent is one or more the mixed solvent in Lubrajel oil, 1,3 butylene glycol, glyceryl cocoate.
Concrete, in nano-lipid carrier,
The content of Radix Rhodiolae extract can be 0.5,1,1.5,2,2.5 or 3%;
The content of solvent can be 20,21,22,23,24,25,26,27,28,29 or 30%;
The content of emulsifying agent can be 40,41,42,43,44,45,46,47,48,49 or 50%;
The content of matrix material can be 18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34 or 35%.
On the basis of such scheme, in described matrix material, liquid lipoid material accounts for 8～15% of nano-lipid carrier percentage by weight; Solid lipid material accounts for 10～20% of nano-lipid carrier percentage by weight.
Concrete, the content of liquid lipoid material can be 8,9,10,11,12,13,14 or 15%; The content of solid lipid material can be 10,11,12,13,14,15,16,17,18,19 or 20%.
On the basis of such scheme, described emulsifier package is drawn together water-in-oil emulsifier and oil-water emulsifiers.
On the basis of such scheme, described water-in-oil emulsifier is one or both in Polyethylene Glycol-30 dimerization hydroxyl stearic acid ester, polyglycereol-3 diisopstearate, accounts for 25～30% of nano-lipid carrier percentage by weight.
Concrete, the content of water-in-oil emulsifier can be 25,26,27,28,29 or 30%.
On the basis of such scheme, described oil-water emulsifiers is one or both in polyoxyethylene lauryl ether, Tween 80, accounts for 15～20% of nano-lipid carrier percentage by weight.
Concrete, the content of oil-water emulsifiers can be 15,16,17,18,19 or 20%.
For the preparation method of the nano-carrier of above-mentioned load Radix Rhodiolae extract, comprise the steps:
The first step: matrix material is mixed with water-in-oil emulsifier, and 50～70 ℃ dissolve and stir, as oil phase; Radix Rhodiolae extract is added to solvent, and 50～70 ℃ stir, and obtain the solution containing Radix Rhodiolae extract, as interior water;
Second step: add interior water in liquid oil phase, mix homogeneously, is cooled to room temperature and solidifies;
The 3rd step: add oil-water emulsifiers, 50～70 ℃ stir and obtain lipid system, and cool to room temperature solidifies, and obtains the nano-lipid carrier of load Radix Rhodiolae extract.
On the basis of such scheme, the preparation method of described Radix Rhodiolae extract is: by 20～80% alcohol-pickled extractions for Radix Rhodiolae, ethanol consumption is 5～20 times of Radix Rhodiolae weight, obtains extracting solution; After extracting liquid filtering, concentrate 10～50 times, concentrated solution is purified with absorption with macroporous adsorbent resin; With the repeatedly eluting of ethanol of mass concentration 10%～95%, collect eluent, make Radix Rhodiolae extract.
For the purposes of the nano-carrier of above-mentioned load Radix Rhodiolae extract, for the preparation of skin care cosmetics or medicine, described cosmetics or medicine are cream, emulsion, astringent or facial film.
On the basis of such scheme, the weight percentage of the nano-carrier of described load Radix Rhodiolae extract in cosmetics or medicine is 3～8%.
Concrete, the consumption of load Radix Rhodiolae extract can be 3,3.5,4,4.5,5,5.5,6,6.5,7,7.5 or 8%.
On the basis of such scheme, the preparation method of described Radix Rhodiolae extract is: by 20～80% alcohol-pickled extractions for Radix Rhodiolae, ethanol consumption is 5～20 times of Radix Rhodiolae weight, obtains extracting solution; After extracting liquid filtering, concentrate 10～50 times, concentrated solution is purified with absorption with macroporous adsorbent resin; With the repeatedly eluting of ethanol of mass concentration 10%～95%, collect eluent, make Radix Rhodiolae extract.
The invention has the beneficial effects as follows:
The present invention is as a kind of new preparation technique, combine multiple emulsion and the lipid nanoparticle technology used, it is the traditional fluid oil of mixture replacing that oil phase in multiple emulsion is selected solid oil and fluid oil, interior water is Radix Rhodiolae extracting solution, the multiple emulsion that this structure is more traditional is more stable, and the nano-carrier of the load Radix Rhodiolae extract obtaining can be used as a kind of material, be added among cosmetics and food, effectively solve existing applied defect.
Accompanying drawing explanation
Fig. 1 is that cosmetics containing the nano-carrier of load Radix Rhodiolae extract are to cytoactive protective effect schematic diagram.
The specific embodiment
Below in conjunction with specific embodiment, such scheme is described further.These embodiment are not limited to limit the scope of the invention for the present invention is described.The implementation condition adopting in embodiment can be done further adjustment according to the condition of concrete producer, and not marked implementation condition is generally the condition in normal experiment.
Composite formula:
Weight
Radix Rhodiolae extract 2.5g
Solvent: Lubrajel Oil 25g
Water-in-oil emulsifier: Polyethylene Glycol-30 dimerization hydroxyl stearic acid ester 20g
Polyglycereol-3 diisopstearate 7g
Liquid lipoid material: macadimia nut oil 10g
Solid lipid material: glyceryl monostearate 17.5g
Oil-water emulsifiers: Tween 80 18g
Amount to 100g
The preparation method of described Radix Rhodiolae extract is: at room temperature, get 100 kilogram of 50% alcohol-pickled extraction 32 hours for 10 kilograms of Radix Rhodiolaes, obtain extracting solution; Extracting solution concentrates 20 times after 200 mesh filter screens filter, D101 macroporous resin adsorption purification on concentrated solution; Use again the ethanol eluting of mass concentration 40%, collect eluent, make Radix Rhodiolae extract.
The preparation method of the nano-carrier of load Radix Rhodiolae extract:
The first step:
Take 2.5g Radix Rhodiolae extract and 25g Lubrajel Oil with 150ml beaker, with 65 ℃ of heating in water bath and stir and make it dissolve completely and stir, form the Lubrajel Oil solution of Radix Rhodiolae extract, as interior water;
Take 20g Polyethylene Glycol-30 dimerization hydroxyl stearic acid ester, 7g polyglycereol-3 diisopstearate, 10g macadimia nut oil, 17.5g glyceryl monostearate with 150ml beaker, with 65 ℃ of heating in water bath and stir and make its mix homogeneously, as oil phase;
Second step: water in the Lubrajel Oil solution of Radix Rhodiolae extract is slowly poured in liquid oil phase mixing lipid, stirred 10 minutes simultaneously, mix homogeneously, naturally cools to room temperature and solidify;
The 3rd step: in above-mentioned coagulum, add 18g Tween 80, with 65 ℃ of heating in water bath, and stir make its mix homogeneously obtain lipid system, cool to room temperature solidifies, and obtains the nano-lipid carrier of load Radix Rhodiolae extract.
Composite formula:
Weight
Radix Rhodiolae extract 2g
Solvent: glyceryl cocoate 30g
Water-in-oil emulsifier: Polyethylene Glycol-30 dimerization hydroxyl stearic acid ester 20g
Polyglycereol-3 diisopstearate 7.5g
Liquid lipoid material: macadimia nut oil 10g
Solid lipid material: glyceryl monostearate 12.5g
Oil-water emulsifiers: polyoxyethylene lauryl ether 18g
Amount to 100g
The preparation method of described Radix Rhodiolae extract is: at room temperature, get 80 kilogram of 70% alcohol-pickled extraction 24 hours for 10 kilograms of Radix Rhodiolaes, residue soaks 24 hours with 80 kilograms of 70% ethanol again, obtains extracting solution; Extracting solution concentrates 30 times after 200 mesh filter screens filter, D101 macroporous resin adsorption purification on concentrated solution; Use again the ethanol eluting of mass concentration 60%, collect eluent, make Radix Rhodiolae extract.
The preparation method of the nano-carrier of load Radix Rhodiolae extract:
The first step:
Take 2g Radix Rhodiolae extract and 30g glyceryl cocoate with 150ml beaker, with 65 ℃ of heating in water bath and stir and make it dissolve completely and stir, form the glyceryl cocoate solution of Radix Rhodiolae extract, as interior water;
Take 20g Polyethylene Glycol-30 dimerization hydroxyl stearic acid ester, 7.5g polyglycereol-3 diisopstearate, 10g macadimia nut oil, 12.5g glyceryl monostearate with 150ml beaker, with 65 ℃ of heating in water bath and stir and make its mix homogeneously, as oil phase;
Second step: water in the glyceryl cocoate solution of Radix Rhodiolae extract is slowly poured in liquid oil phase mixing lipid, stirred 10 minutes simultaneously, mix homogeneously, naturally cools to room temperature and solidify;
The 3rd step: in above-mentioned coagulum, add 18g polyoxyethylene lauryl ether, with 65 ℃ of heating in water bath, and stir make its mix homogeneously obtain lipid system, cool to room temperature solidifies, and obtains the nano-lipid carrier of load Radix Rhodiolae extract.
Embodiment 3
Composite formula:
Weight
Radix Rhodiolae extract 1.5g
Solvent: 1,3 butylene glycol 25g
Water-in-oil emulsifier: Polyethylene Glycol-30 dimerization hydroxyl stearic acid ester 20g
Polyglycereol-3 diisopstearate 8.5g
Liquid lipoid material: Semen pruni armeniacae oil 10g
Solid lipid material: glycerol monolaurate 15g
Oil-water emulsifiers: Tween 80 20g
Amount to 100g
The preparation method of described Radix Rhodiolae extract is: at room temperature, get 50 kilogram of 40% alcohol-pickled extraction 20 hours for 10 kilograms of Radix Rhodiolaes, residue soaks 20 hours with 50 kilograms of 40% ethanol again, obtains extracting solution; Extracting solution concentrates 40 times after 200 mesh filter screens filter, D101 macroporous resin adsorption purification on concentrated solution; Use again the ethanol eluting of mass concentration 80%, collect eluent, make Radix Rhodiolae extract.
The preparation method of the nano-carrier of load Radix Rhodiolae extract:
The first step:
Take 1.5g Radix Rhodiolae extract and 25g Lubrajel Oil with 150ml beaker, with 65 ℃ of heating in water bath and stir and make it dissolve completely and stir, form the Lubrajel Oil solution of Radix Rhodiolae extract, as interior water;
Take 20g Polyethylene Glycol-30 dimerization hydroxyl stearic acid ester, 8.5g polyglycereol-3 diisopstearate, 10g Semen pruni armeniacae oil, 15g glycerol monolaurate with 150ml beaker, with 65 ℃ of heating in water bath and stir and make its mix homogeneously, as oil phase;
Second step: water in the Lubrajel Oil solution of Radix Rhodiolae extract is slowly poured in liquid oil phase mixing lipid, stirred 10 minutes simultaneously, mix homogeneously, naturally cools to room temperature and solidify;
The 3rd step: in above-mentioned coagulum, add 20g Tween 80, with 65 ℃ of heating in water bath, and stir make its mix homogeneously obtain lipid system, cool to room temperature solidifies, and obtains the nano-lipid carrier of load Radix Rhodiolae extract.
Embodiment 4
Composite formula:
Weight
Radix Rhodiolae extract 2.5g
Solvent: glyceryl cocoate 30g
Water-in-oil emulsifier: Polyethylene Glycol-30 dimerization hydroxyl stearic acid ester 15g
Polyglycereol-3 diisopstearate 7.5g
Liquid lipoid material: Semen pruni armeniacae oil 10g
Solid lipid material: glyceryl monostearate 17g
Oil-water emulsifiers: polyoxyethylene lauryl ether 18g
Amount to 100g
The preparation method of described Radix Rhodiolae extract is consistent with embodiment 1.
The preparation method of the nano-carrier of load Radix Rhodiolae extract:
The first step:
Take 2.5g Radix Rhodiolae extract and 30g glyceryl cocoate with 150ml beaker, with 65 ℃ of heating in water bath and stir and make it dissolve completely and stir, form the glyceryl cocoate solution of Radix Rhodiolae extract, as interior water;
Take 15g Polyethylene Glycol-30 dimerization hydroxyl stearic acid ester, 7.5g polyglycereol-3 diisopstearate, 10g Semen pruni armeniacae oil, 17g glyceryl monostearate with 150ml beaker, with 65 ℃ of heating in water bath and stir and make its mix homogeneously, as oil phase;
Second step: water in the glyceryl cocoate solution of Radix Rhodiolae extract is slowly poured in liquid oil phase mixing lipid, stirred 10 minutes simultaneously, mix homogeneously, naturally cools to room temperature and solidify;
The 3rd step: in above-mentioned coagulum, add 18g polyoxyethylene lauryl ether, with 65 ℃ of heating in water bath, and stir make its mix homogeneously obtain lipid system, cool to room temperature solidifies, and obtains the nano-lipid carrier of load Radix Rhodiolae extract.
Application examples 5
The application of the nano-carrier of load Radix Rhodiolae extract in cosmetics:
the preparation technology of cosmetics is:
The first step: HANSHENGJIAO is uniformly dispersed in propylene glycol, adds deionized water, stir in 80 ℃;
Second step: by mutually each B component in 80 ℃ of dissolvings completely, stir;
The 3rd step: under stirring, B is added to A, and middle stirring is homogeneous mutually, approximately 3 minutes;
The 4th step: under stirring, be cooled to below 45 ℃, add C phase, stir;
The 5th step: under stirring, be cooled to room temperature;
The 6th step: slowly stir evenly subpackage.
protective effect containing the cosmetics of the nano-carrier of load Radix Rhodiolae extract to oxidative damage
Method of testing:
By the cosmetic applying that contains variable concentrations carrier in unhairing mouse skin surface, once a day; After one month, get Skin Cell, survey cell viability, the results are shown in Figure shown in 1.
Have in figure knownly, containing the cosmetics of the nano-carrier of 20% load Radix Rhodiolae extract, there is good cytoactive protective effect, exceed 20% pair of cytoactive protective effect and promote not obvious.
the stability test of the nano-carrier of load Radix Rhodiolae extract
Comprise:
(1) timely stability test: obtain at short notice stability result by ultracentrifugal method, observe in centrifuge tube whether occur the wild effects such as layering, precipitation;
(2) time stability test: after observing the sample placement certain intervals time, whether outward appearance occurs layering, precipitation, and carry out centrifugal or particle diameter test;
(3) temperature stability test: the nano-carrier of getting appropriate load Radix Rhodiolae extract is sealed in bottle, is positioned over respectively under room temperature, the condition of 4 ℃, 40 ℃ ,-18 ℃, after some days, under same time the same terms, carries out respectively stability observing mensuration.
By filler test, wherein the formula of embodiment 1 is best, carries out follow-up test.
grain diameter measurement:
The nano-carrier mean diameter of load Radix Rhodiolae extract is recorded by PCS, and test angle is 90 °, and probe temperature is 25 ℃.Each sample, through repeated measure several times, obtains several parallel results, to investigate whether there is larger error between data, and gets the meansigma methods of result several times.
Centrifugal stability:
50 times of the nano-carrier dilutions of the load Radix Rhodiolae extract with the pure water of temperature T to temperature T, survey its particle size distribution after the centrifugal 5min of 4000rpm/min, and with centrifugal before compare, as shown in the table.
time stability:
Adopt the time dependent stability of nano-carrier of PCS tracking and testing load Radix Rhodiolae extract.Choose the nano-carrier of the load Radix Rhodiolae extract that current load capacity is the highest, test its stability.Due to time restriction, the test interval chooses respectively 1 day, 7 days, 15 days.
Time average particle diameter (nm) PDI
1 day 235 0.265
7 days 237 0.266
15 days 240 0.270
The nano-carrier change of size in 15 days of load Radix Rhodiolae extract that can find out preparation is very little, and PDI value is all less than 0.3, and data are reliable, and the nano-carrier stable existence of load Radix Rhodiolae extract is described.
temperature stability:
Test result is as follows:
Different temperatures is preserved the nano-carrier particle diameter test result of 15 days back loading Radix Rhodiolae extracts
Temperature-averaging particle diameter (nm) PDI
Room temperature 235 0.265
4℃ 236 0.263
40℃ 241 0.269
-18℃ 234 0.266
Visible under 4 ℃, room temperature, 40 ℃ and-18 ℃ of states particle diameter keep stable and do not occur compared with leap ahead.
Above-mentioned example is only explanation technical conceive of the present invention and feature, and its object is to allow person skilled in the art can understand content of the present invention and implement according to this, can not limit the scope of the invention with this.All equivalent transformations that spirit is done according to the present invention or modification, within all should being encompassed in protection scope of the present invention.
Claims (4)
1. the nano-lipid carrier of a load Radix Rhodiolae extract, Radix Rhodiolae extract is made through extraction, filtering and concentrating, absorb-elute by Radix Rhodiolae, it is characterized in that: the nano-lipid carrier of described load Radix Rhodiolae extract comprises following component by its weight percent meter:
Radix Rhodiolae extract 0.5～3%
Solvent 20～30%
Emulsifying agent 40～50%
Matrix material 18～35%;
Described solvent is one or more the mixed solvent in Lubrajel oil, 1,3 butylene glycol, glyceryl cocoate; Described emulsifier package is drawn together water-in-oil emulsifier and oil-water emulsifiers; Described matrix material is the solidliquid mixture of liquid lipoid material and solid lipid material, liquid lipoid material is one or both in macadimia nut oil, Semen pruni armeniacae oil, described solid lipid material is one or both in glyceryl monostearate, glycerol monolaurate, wherein
In described matrix material, liquid lipoid material accounts for 8～15% of nano-lipid carrier percentage by weight; Solid lipid material accounts for 10～20% of nano-lipid carrier percentage by weight;
Described water-in-oil emulsifier is one or both in Polyethylene Glycol-30 dimerization hydroxy stearic acid ester, polyglycereol-3 diisopstearate, accounts for 25～30% of nano-lipid carrier percentage by weight;
Described oil-water emulsifiers is one or both in polyoxyethylene lauryl ether, Tween 80, accounts for 15～20% of nano-lipid carrier percentage by weight;
The nano-lipid carrier of described load Radix Rhodiolae extract is prepared by following step:
The first step: matrix material is mixed with water-in-oil emulsifier, and 50～70 ℃ dissolve and stir, as oil phase; Radix Rhodiolae extract is added to solvent, and 50～70 ℃ stir, and obtain the solution containing Radix Rhodiolae extract, as interior water;
Second step: add interior water in liquid oil phase, mix homogeneously, is cooled to room temperature and solidifies;
The 3rd step: add oil-water emulsifiers, 50～70 ℃ stir and obtain lipid system, and cool to room temperature solidifies, and obtains the nano-lipid carrier of load Radix Rhodiolae extract.
2. the preparation method of the nano-lipid carrier of a load Radix Rhodiolae extract according to claim 1, it is characterized in that: the preparation method of described Radix Rhodiolae extract is: by 20～80% alcohol-pickled extractions for Radix Rhodiolae, ethanol consumption is 5～20 times of Radix Rhodiolae weight, obtains extracting solution; After extracting liquid filtering, concentrate 10～50 times, concentrated solution is purified with absorption with macroporous adsorbent resin; With the repeatedly eluting of ethanol of mass concentration 10%～95%, collect eluent, make Radix Rhodiolae extract.
3. a purposes for the nano-lipid carrier of load Radix Rhodiolae extract according to claim 1, for the preparation of skin care cosmetics or medicine, described cosmetics or medicine are cream, emulsion, astringent or facial film.
4. the purposes of the nano-lipid carrier of load Radix Rhodiolae extract according to claim 3, is characterized in that: the weight percentage of the nano-lipid carrier of described load Radix Rhodiolae extract in cosmetics or medicine is 1～25%.
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