CN107095799B

CN107095799B - Complex liposome and its preparation method and application

Info

Publication number: CN107095799B
Application number: CN201710476261.4A
Authority: CN
Inventors: 何廷刚; 艾勇; 张炽坚; 卢永杰
Original assignee: Guangzhou Heji Biotechnology Co Ltd
Current assignee: Hua An Tang biotech Group Co., Ltd.
Priority date: 2017-06-21
Filing date: 2017-06-21
Publication date: 2018-03-27
Anticipated expiration: 2037-06-21
Also published as: CN107095799A

Abstract

The present invention relates to cosmetic field, and in particular to complex liposome and its preparation method and application.The preparation method of complex liposome includes：(1) in organic solvent, the one or more in glabridin and the like, phosphatide, cholesterol and fatty acid compound are mixed；(2) organic solvent in mixture obtained by step (1) is removed to obtain film-form residue；(3) cause that film-form residue forms liposome obtained by step (2) in the presence of the aqueous solvent containing platinum；Wherein, the fatty acid compound is the one or more in C8 C20 aliphatic acid and its salt.Effective active composition glabridin in the complex liposome of the present invention and the like has good cooperative effect between platinum, can obtain the whitening effect of Synergistic.

Description

Complex liposome and its preparation method and application

Technical field

The present invention relates to cosmetic field, and in particular to complex liposome and its preparation method and application.

Background technology

Liposome is a kind of multilayer microcapsule structure being made up of the phospholipid bilayer of aligned orderly, and its structure is similar biological Film.It is interior aqueous phase in vesica, is generally used for the place of coated water-soluble medicine；Phospholipid bilayer is hydrophobic layer, is generally used for Wrap up fat-soluble medicine.Liposome has many excellent properties, such as reduces drug toxicity, the stability for improving medicine, sustained release Property, Transdermal absorption efficiency high, medicine can be carried into cell etc..Recently, relevant liposome is used for cosmetic industry and food The document report of industry is also more and more.

There is poorly water-soluble in most active medicine, absorptivity is low, the shortcomings such as dosage is low, it is more difficult to be generally applicable to make up Product field.And because human body skin has natural barrier function, the transdermal penetration of medicine absorbs and active absorption can be by bright Aobvious influence and restriction, so as to substantially reduce or weaken biological action and the curative effect that medicine should have.Liposome and biomembrane Structure is similar, can increase medicine into the transit dose of keratoderma using liposome technology, avoid medicine because passing through Skin dose is very few and loses effect.Liposome can persistently rest on keratoderma simultaneously, delay Slow release to epidermis, carry Continuation effect of high medicine.And liposome is non-toxic in itself, biodegradation can be independently completed in vivo, also do not produce skin thorn Swash property, be beautifying skin and the ideal carrier of cosmetic applications.

However, existing liposome has oxidizable, drug leakage in vitro, easily occur spontaneously between liposome particles Aggregation causes system layering, produces a series of the problem of thermodynamic instabilities such as precipitation, causes liposome to be deposited in actual applications In difficulty.In addition, liposome is difficult to penetrate can also have the problem of particle diameter increase, the excessive liposome of particle diameter during storage Skin, so that efficacy of drugs reduces.

The content of the invention

It is an object of the invention to provide a kind of whitening capability with Synergistic and the high complex liposome of stability And its preparation method and application.

To achieve these goals, one aspect of the present invention provides a kind of preparation method of complex liposome, and this method includes：

(1) in organic solvent, by the one or more in glabridin and the like, phosphatide, cholesterol and fat Acid compounds are mixed；

(2) organic solvent in mixture obtained by step (1) is removed to obtain film-form residue；

(3) cause that film-form residue forms liposome obtained by step (2) in the presence of the aqueous solvent containing platinum；

Wherein, the fatty acid compound is the one or more in C8-C20 aliphatic acid and its salt.

Second aspect of the present invention provides the complex liposome as made from the above method.

Third aspect present invention provides application of the above-mentioned liposome in whitening and oxidation resistant product is prepared.

Fourth aspect present invention provides the cosmetics containing above-mentioned liposome.

Effective active composition glabridin in the complex liposome of the present invention and the like has good between platinum Good cooperative effect, the whitening effect of Synergistic can be obtained.Particularly, by the present invention by phosphatide, cholesterol and fat During carrier of the liposome as above-mentioned effective active composition that acid compounds are formed, especially low cell toxicant can be shown Property, it is easy to convey and applies.

Embodiment

The end points of disclosed scope and any value are not limited to the accurate scope or value herein, these scopes or Value should be understood to comprising the value close to these scopes or value.For number range, between the endpoint value of each scope, respectively It can be combined with each other between the endpoint value of individual scope and single point value, and individually between point value and obtain one or more New number range, these number ranges should be considered as specific open herein.

One aspect of the present invention provides a kind of preparation method of complex liposome, and this method includes：

The present inventor is surprisingly had found, the one or more in glabridin and the like are combined with platinum In use, whitening and the antioxidant effect of Synergistic can be obtained.Especially with the present invention by phosphatide, cholesterol and fat During carrier of the liposome as above-mentioned effective active composition that acid compounds are formed, especially low cell toxicant can be shown Property.

It is in organic solvent, described glabridin and the like, phosphatide, courage is solid in step (1) according to the present invention Alcohol and fatty acid compound are mixed, and can cause described glabridin and the like, phosphatide, cholesterol and aliphatic acid Class compound dissolves in organic solvent, it is also possible that their fully contacts each other.

Wherein, described glabridin and the like is preferably glabridin and/or licoflavone.

According to the present invention, the phosphatide can be any phospholipids compounds of this area conventionally used for preparing liposome, Can be natural phospholipid (lecithin, cephalin, cuorin etc.) or synthetic phospholipid, such as the phosphatide is soybean ovum Phosphatide, hydrolecithin, phosphatidyl choline, phosphatidyl-ethanolamine, DSPC (DSPC), two myristoyl phosphorus Phosphatidylcholine (DMPC), DOPE, DPPG, DPPC (DPPC), DPPE, DSPC, diphosphatidylglycerol, phosphatidylserine and phosphorus One or more in acyl inositol.In view of matching somebody with somebody between the phosphatide and the cholesterol of the present invention, fatty acid compound Cooperation is used, it is preferable that the phosphatide is soybean lecithin, hydrolecithin, dimyristoyl phosphatidyl choline, two palmityl phosphorus One or more in phosphatidylcholine and DSPC, more preferably dimyristoyl phosphatidyl choline, two palm fibres One or more in palmitic acid phosphatidyl choline and DSPC.

According to the present invention, the fatty acid compound has certain modifying function for liposome, particularly with Specific dosage is with that under the phosphatide and cholesterol cooperation of the invention of specific usage ratio, can be made stability-enhanced lipid Body, and such liposome can be with higher entrapment efficiency entrapped drug, also beneficial to liposome in cosmetics etc. Application.The fatty acid compound is the one or more in C8-C20 aliphatic acid and its salt, wherein, C8-C20 fat The salt of fat acid can be its alkali metal salt, alkali salt etc..Preferably, the fatty acid compound be octanoic acid, Sodium Caprylate, Potassium octanoate, calcium octoate, magnesium octoate, capric acid, sodium caprate, Capric acid potassium salt, capric acid calcium, capric acid magnesium, laurate, sodium laurate, laurate Potassium, calcium laurate, Magnesium dilaurate, tetradecanoic acid, tetradecanoic acid sodium, potassium myristate, tetradecanoic acid calcium, tetradecanoic acid magnesium, palm fibre It is palmitic acid acid, sodium palmitate, potassium palmitate, calcium palmitate, magnesium palmitate, stearic acid, odium stearate, potassium stearate, calcium stearate, hard Fatty acid magnesium, oleic acid, enuatrol, potassium oleate, calcium oleate, magnesium oleate, linoleic acid, linoleic acid sodium, linoleic acid potassium, calcium linoleate, Asia One or more in magnesium oleate, arachidic acid, arachidic acid sodium, arachidic acid potassium, arachidic acid calcium and arachidic acid magnesium, more preferably tristearin One or more in sour sodium, potassium stearate, magnesium stearate, sodium palmitate, potassium palmitate, calcium palmitate and magnesium palmitate.

Preferably, the weight ratio of the dosage of the phosphatide, cholesterol and fatty acid compound is 100：10-70：1-50, Preferably 100：20-60：2-30, preferably 100：20-55：5-25, preferably 100：25-45：8-20, more preferably 100： 30-45：8-15.

Wherein it is preferred to the weight ratio of described glabridin and the like and phosphatide is 5-25：100, preferably 8- 20：100, more preferably 10-15：100.

According to the present invention, although the organic solvent, which can use, can dissolve the glabridin and its similar substantially Thing, phosphatide, cholesterol and fatty acid compound any kind of and it is easy to the organic solvent removed, but for the ease of Described glabridin and the like, phosphatide, cholesterol and fatty acid compound can be in more suitable solvent atmospheres Obtain and preferably combine, to obtain the liposome that stability is higher, particle diameter is more suitable for, it is preferable that described to have in step (1) Solvent is the mixture of the first organic solvent and the second organic solvent.Wherein, first solvent is methanol, ethanol, second two One or more in alcohol, propane diols, isopropanol, n-butanol and ethyl acetate, preferably methanol and/or ethanol.Described second Solvent is the one or more in chloroform, dichloromethane, carbon tetrachloride, ether and tetrahydrofuran, preferably chloroform and/or dichloro Methane.

In accordance with the present invention it is preferred that the weight ratio of first organic solvent and the second organic solvent is 100：10-100, Preferably 100：30-90, more preferably 100：40-85.

According to the present invention, the dosage of the organic solvent can change in relative broad range, it is preferable that the organic solvent Dosage make it that described glabridin and the like, phosphatide, the total concentration of cholesterol and fatty acid compound are 2-10 weights Measure %, for example, preferably 2.5-6 weight %, 2.9-4.7 weight %.

According to the present invention, in step (2), the organic solvent in the mixture as obtained by by step (1) removes, and can obtain Film-form residue, so after step (3) adds water, so that it may promote the formation of liposome.

Wherein, the removing of the organic solvent can be carried out at reduced pressure conditions, it is preferable that in step (2), be removed organic molten The temperature of agent is 50-100 DEG C.Mixture obtained by step (1) can be for example placed in reaction vessel by such process, using rotation Turn evaporimeter to carry out at reduced pressure conditions, so as to which film-form residue can be formed on reaction vessel wall.

According to the present invention, in step (3), the aqueous solvent containing platinum can be dispersion of the platinum in water, Can be containing it is a small amount of other do not influence the present invention liposome shaping the aqueous solution of other solvents and the dispersion of platinum, It is preferred that use water.The platinum is platinum, and preferably granularity is 5-200nm platinum particle.The platinum is in aqueous solvent Concentration can be changed in relative broad range, for the ease of the formation of liposome, it is preferable that described containing platinum in step (3) In aqueous solvent, the content of the platinum is 10-1000ppm (w/w), preferably 50-500ppm.

Preferably, in step (3), the weight ratio of the dosage of the phosphatide and the aqueous solvent containing platinum is 1：20- 100, preferably 1：30-80, more preferably 1：40-60.Using the aqueous solvent under the dosage, particle diameter can be obtained and be more suitable for Liposome.

In accordance with the present invention it is preferred that step (3) includes：By film obtained by the aqueous solvent containing platinum and step (2) Shape residue is heated, and then carries out homogenization again.

Wherein, the condition of the heating preferably includes：Temperature is 40-80 DEG C, time 0.5-3h.At the homogeneous The condition of reason preferably includes：First disperse 10-50min under 5,000-20,000rpm rotating speed, then in 500-1500bar and High pressure homogenization 2-6 times under 20-60Hz frequency ultrasound.The homogeneous processing for example can be high-pressure homogeneous in IKA homogenizers, IKA Carried out in machine.

The above method of the present invention can obtain that stability is higher, and toxicity is relatively low, have Synergistic whitening and The complex liposome of oxidation resistance.

Preferably, in the complex liposome, in terms of dry weight, the content of described glabridin and the like is 1.5-10 Weight %, the content of the platinum is 0.01-0.1 weight %.

Wherein, in the complex liposome, it is preferable that described glabridin and the like is contained in the liposome In the hydrophobic interlayer of phospholipid bilayer, the platinum is contained in the middle part of the liposome (in central cavity).

Effective active composition glabridin in the complex liposome of the present invention and the like has good between platinum Good cooperative effect, whitening and the antioxidant effect of Synergistic can be obtained.Particularly, by the solid by phosphatide, courage of the present invention During carrier of the liposome that alcohol and fatty acid compound are formed as above-mentioned effective active composition, it can show especially low Cytotoxicity, it is easy to convey and applies.

The present invention will be described in detail by way of examples below.

In following examples and comparative example：

The platinum particle that the granularity that platinum particle is available from MIJI nanotech Co., LTD. is 5-200nm.

Glabridin is purchased from Qinghai Qinghaihu Pharmaceutical Co., Ltd..

Embodiment 1-30

The present embodiment is used to illustrate liposome of the present invention and preparation method thereof.

(1) phosphatide of the total dosages of 10g, cholesterol, fatty acid compound and glabridin are dissolved in solvent (they Species and each shared parts by weight are shown in Table 1)；

(2) resulting solution is subjected to decompression rotary evaporation using Rotary Evaporators in eggplant type bottle, depressurizes rotary evaporation Condition includes：Temperature is 60 DEG C, and rotating speed 90rpm, the time is about 30min；To remove solvent, film-form residue is obtained；

(3) water (weight is 50 times of phosphatide, and the concentration of platinum particle is shown in Table 1) of the particle containing platinum is added to Eggplant type bottle is stated to be contacted with film-form residue, and using Rotary Evaporators rotary heating 1h under 65 DEG C, 90rpm；

(4) gained mixture is set to homogeneous about 10min under 10,000rpm in IKA homogenizers, then by IKA high pressures Homogenizer circulates homogeneous 3 times (total duration about 20min) under 1000bar and 50Hz, obtains liposome；

Wherein, only in embodiment 2 (other embodiments all use operations described above parameter)：Step (2) decompression rotation Turning the condition of evaporation includes：Temperature is 80 DEG C, rotating speed 100rpm, gauge pressure 50kPa, and the time is about 30min；Step (3) contains The water (weight is 60 times of phosphatide) of platinum particle is added to above-mentioned eggplant type bottle to be contacted with film-form residue, and using rotation Evaporimeter rotary heating 1.5h under 55 DEG C, 150rpm；In step (4) IKA homogenizers under 15,000rpm homogeneous 5min, then Homogeneous 3 times (total duration about 15min) is circulated under 1000bar and 50Hz frequencies by IKA high pressure homogenizers, obtains liposome.

Comparative example 1

According to the method described in embodiment 1, the difference is that, platinum particle and glabridin are not used, so as to obtain lipid Body.

Comparative example 2

According to the method described in embodiment 1, the difference is that, glabridin is not used, so as to obtain liposome.

Comparative example 3

According to the method described in embodiment 1, the difference is that, platinum particle is not used, so as to obtain liposome.

Comparative example 4

According to the method described in embodiment 1, the difference is that, odium stearate is not used, so as to obtain liposome.

Table 1

Test case 1

Glabridin entrapment efficiency determination：The glabridin titer of series concentration gradient is prepared using methanol as solvent, is utilized Ultraviolet specrophotometer determines the suction of the glabridin standard liquid of various concentrations using methanol as reference liquid respectively under 280nm Luminosity, make glabridin concentration-absorbance standard curve.Appropriate liposome solutions are taken, are swum using micro-filtration centrifugal process From the aqueous solution of medicine, with methanol dilution certain multiple, using methanol as ginseng using ultraviolet specrophotometer at a wavelength of 280 nm Than liquid, the absorbance of determination sample solution.Liposome solutions, blank liposomes liquid solution are entered with methanol and identical extension rate Row is diluted and determines its absorbance, and by glabridin standard curve conversion medicament contg, glabridin is calculated using formula (1) Envelop rate.

Platinum entrapment efficiency determination：The platinum particles levels liquid of series concentration gradient is prepared using pure water as solvent, utilization is ultraviolet Spectrophotometer determines the absorbance of the platinum particles levels solution of various concentrations using pure water as reference liquid respectively under 205nm, Make platinum particle concentration-absorbance standard curve.Appropriate liposome solutions are taken, certain multiple is diluted with water, utilization is ultraviolet Spectrophotometer is under 205nm wavelength, using pure water as reference liquid, the absorbance of determination sample.With water and identical extension rate Liposome solutions, blank liposomes liquid solution are diluted and determine absorbance, passes through platinum particles levels curve conversion medicine Content, the envelop rate of platinum particle is calculated using formula (1)：

Envelop rate (%)=(1-W_{Do not wrap}/W_Always) × 100% (1), wherein, W_{Do not wrap}And W_AlwaysThe free medicine of liposome is represented respectively Amount and total amount of feeding.

As a result it is as shown in table 2：

Table 2

Test case 2

The initial particle size of above-mentioned liposome is measured, and is surveyed after above-mentioned liposome is placed into two weeks under room temperature (about 25 DEG C) Its particle diameter is tried, it the results are shown in Table shown in 3.

Wherein, particle changing ratio is：(particle diameter-initial particle size after two weeks)/initial particle size × 100%.

Table 3

The liposome that can be seen that the present invention by the result of table 3 has more preferable stability, is placed by long-time Afterwards, some particle diameters are even with the trend reduced.

Test case 3：The toxicity test of HACAT (people is epidermal cornified) cell is tested in vitro

The condition of culture of cell：By HACAT cell culture in the DMEM high glucose mediums containing 10 weight % hyclones, 37 DEG C, 5 weight %CO₂Saturated humidity incubator is incubated.

Method of testing：Tissue Culture Flask is taken out, absorbs nutrient solution, adds after PBS solution cleans cell and absorbs PBS solution； Pancreatin (Trypsin-EDTA pancreatin, Gbico), cell dispersion are added to Tissue Culture Flask；1mL cell suspensions are taken to be used for cytometer Number, cell suspension that 100 μ L have diluted is added after calculating in 96 orifice plates, make its concentration for 1.0 × 10⁴Cells/well, put Enter CO₂Incubator culture 24h；1 μ L samples solution (sample includes glabridin and above-mentioned liposome) is taken respectively in corresponding 96 In orifice plate, the sample solution concentration for making each hole is respectively that (dosage of liposome is so that the content of glabridin is set 10 μ g/mL for this Put concentration), while blank well (95% ethanol for adding 1 μ L) is set, cell culture well is put into incubator culture 48h；By 96 After orifice plate topples over the culture medium containing sample, the CCK-8 reagents (JM754) that 100 μ L dilute 10 times are added per hole, in CO₂Incubator 2~2.5h of middle culture；96 orifice plates are taken out, absorbance is determined at 450nm with ELIASA, cell survival is calculated according to below equation Rate：

Cell survival rate=(TCS-dead cell number)/TCS * 100%.

It the results are shown in Table shown in 4.

Table 4

The liposome that the pharmaceutical composition formation of the present invention is can be seen that by the data of table 4 has relatively low toxicity, special It is not to use under preferable liposome, toxicity is lower.

Test case 4：Body is in vitro to the whitening function experiment test of B16 cells (melanocyte)

The condition of culture of cell：By B16 cell culture in the DMEM high glucose mediums containing 10 weight % hyclones, 37 DEG C, 5 weight %CO₂Saturated humidity incubator is incubated.

Method of testing：Counted after B16 cells are peeled off from Tissue Culture Flask, add the cell suspension diluted in 6 holes In plate, CO is put into₂Incubator culture 24h；Original culture medium in 6 orifice plates is absorbed, the PBS of equivalent is added once per hole； 1.98mL is added per hole and contains MSH (melanotropin, purchased from CALBIOCHBM companies) DMEM solution, while blank well is set, i.e., Blank well adds the DMEM solution without MSH, and culture plate is put into CO₂Incubator culture about 2.5h；Prepare certain density sample Product solution, 20 μ L sample solution are added per hole in 6 orifice plates, while negative control (being only free of sample solution containing MSH) are set, The concentration of sample solution in every hole is followed successively by 2 μ g/mL, culture plate is put into CO₂Incubator culture 72h；Absorb in 6 orifice plates Culture medium, handled with the pancreatin of equivalent per recovery cell after the cell of hole into centrifuge tube with PBS once；Take 1/9~1/5 Above-mentioned cell liquid is into centrifuge tube and centrifugation discards liquid, adds 1 weight %triton X-100 (polyethylene glycol octyl phenyls Ether) PBS solution, concussion, using BCA protein quantifications kit carry out total protein quantify；After remaining cell suspension is centrifuged Liquid is discarded, with PBS, a certain amount of 1M NaOH is added according to protein quantification result, make solution total protein concentration identical, 2min is heated in 60 DEG C, toward 96 orifice plate loadings, OD values are determined under 405nm.

It the results are shown in Table shown in 5.

Table 5

	Unit-protein melanin content, %
		Without MSH blank groups	100
Blank group containing MSH	240
		Sample concentration	2μg/mL
Embodiment 1	165
		Embodiment 2	167
Embodiment 3	160
		Embodiment 4	174
Embodiment 5	155
		Embodiment 6	158
Embodiment 7	152
		Embodiment 8	177
Embodiment 10	168
		Embodiment 11	154
Embodiment 12	152
		Embodiment 13	182
Embodiment 14	177
		Embodiment 15	175
Embodiment 16	184
		Embodiment 17	170
Embodiment 18	175
		Embodiment 19	185
Embodiment 20	177
		Embodiment 25	170
Embodiment 26	162
		Embodiment 29	188
Embodiment 30	160
		Comparative example 1	238
Comparative example 2	225
		Comparative example 3	195
Comparative example 4	190
		Glabridin	200

Can be seen that pharmaceutical composition of the invention by the data of table 5 can obtain the whitening effect of Synergistic, special It is not to use under preferable liposome, whitening effect is more preferably.

The preferred embodiment of the present invention described in detail above, still, the present invention is not limited thereto.In the skill of the present invention In art concept, technical scheme can be carried out a variety of simple variants, including each technical characteristic with it is any its Its suitable method is combined, and these simple variants and combination should equally be considered as content disclosed in this invention, belong to Protection scope of the present invention.

Claims

1. a kind of preparation method of complex liposome, it is characterised in that this method includes：

(1) in organic solvent, by the one or more in glabridin and the like, phosphatide, cholesterol and fatty acid Compound is mixed；

Wherein, described glabridin and the like is glabridin and/or licoflavone；

The weight ratio of described glabridin and the like and phosphatide is 5-25：100, the phosphatide, cholesterol and fatty acid The weight ratio of the dosage of compound is 100：10-70：1-50；

In the aqueous solvent containing platinum, the content of the platinum is 10-1000ppm；

The fatty acid compound be octanoic acid, Sodium Caprylate, potassium octanoate, calcium octoate, magnesium octoate, capric acid, sodium caprate, Capric acid potassium salt, Capric acid calcium, capric acid magnesium, laurate, sodium laurate, potassium laurate, calcium laurate, Magnesium dilaurate, tetradecanoic acid, tetradecanoic acid sodium, Potassium myristate, tetradecanoic acid calcium, tetradecanoic acid magnesium, palmitic acid, sodium palmitate, potassium palmitate, calcium palmitate, magnesium palmitate, Stearic acid, odium stearate, potassium stearate, calcium stearate, magnesium stearate, oleic acid, enuatrol, potassium oleate, calcium oleate, magnesium oleate, Linoleic acid, linoleic acid sodium, linoleic acid potassium, calcium linoleate, magnesium linoleate, arachidic acid, arachidic acid sodium, arachidic acid potassium, arachidic acid calcium With the one or more in arachidic acid magnesium；

In step (1), the organic solvent is the mixture of the first organic solvent and the second organic solvent, and described first is organic molten Agent is the one or more in methanol, ethanol, ethylene glycol, propane diols, isopropanol, n-butanol and ethyl acetate, and described second has Solvent is the one or more in chloroform, dichloromethane, carbon tetrachloride, ether and tetrahydrofuran.

2. according to the method for claim 1, wherein, the weight ratio of described glabridin and the like and phosphatide is 8- 20：100.

3. according to the method for claim 2, wherein, the weight ratio of described glabridin and the like and phosphatide is 10- 15：100.

4. according to the method described in any one in claim 1-3, wherein, the phosphatide, cholesterol and fatty acid chemical combination The weight ratio of the dosage of thing is 100：20-60：2-30.

5. the method according to claim 11, wherein, the weight of the dosage of the phosphatide, cholesterol and fatty acid compound Amount is than being 100：20-55：5-25.

6. the method according to claim 11, wherein, the weight of the dosage of the phosphatide, cholesterol and fatty acid compound Amount is than being 100：25-45：8-20.

7. the method according to claim 11, wherein, the weight of the dosage of the phosphatide, cholesterol and fatty acid compound Amount is than being 100：30-45：8-15.

8. according to the method for claim 4, wherein, the phosphatide is soybean lecithin, hydrolecithin, phosphatidyl courage Alkali, phosphatidyl-ethanolamine, DSPC, dimyristoyl phosphatidyl choline, DOPE, two Palmityl phosphatidyl glycerol, DPPC, DPPE, diphosphatidylglycerol, phosphatidyl One or more in serine and phosphatidylinositols.

9. according to the method for claim 8, wherein, the phosphatide is soybean lecithin, hydrolecithin, two myristoyls One or more in phosphatidyl choline, DPPC and DSPC.

10. according to the method for claim 4, wherein, the fatty acid compound is odium stearate, potassium stearate, hard One or more in fatty acid magnesium, sodium palmitate, potassium palmitate, calcium palmitate and magnesium palmitate.

11. according to the method described in any one in claim 1-3 and 5-10, wherein, in step (1), described first is organic The weight of solvent and the second organic solvent ratio is 100：10-100.

12. the method according to claim 11, wherein, in step (1), first organic solvent and the second organic solvent Weight ratio be 100：20-80.

13. the method according to claim 11, wherein, in step (1), first organic solvent and the second organic solvent Weight ratio be 100：30-60.

14. according to the method for claim 11, wherein, the dosage of the organic solvent causes, the glabridin and its Analog, phosphatide, the total concentration of cholesterol and fatty acid compound are 2-10 weight %.

15. according to the method for claim 14, wherein, the dosage of the organic solvent causes, the glabridin and its Analog, phosphatide, the total concentration of cholesterol and fatty acid compound are 2.5-6 weight %.

16. according to the method described in any one in claim 1-3,5-10 and 12-15, wherein, in step (2), removing has The temperature of solvent is 50-100 DEG C.

17. according to the method described in any one in claim 1-3,5-10 and 12-15, wherein, it is described white in step (3) The granularity of gold is 5-200nm platinum particle.

18. the method according to claim 11, wherein, the weight of the dosage of the phosphatide and the aqueous solvent containing platinum Amount is than being 1：20-100.

19. the method according to claim 11, wherein, the weight of the dosage of the phosphatide and the aqueous solvent containing platinum Amount is than being 1：30-80.

20. the method according to claim 11, wherein, the weight of the dosage of the phosphatide and the aqueous solvent containing platinum Amount is than being 1：40-60.

21. according to the method described in any one in claim 1-3,5-10,12-15 and 18-20, wherein, step (3) bag Include：The aqueous solvent containing platinum and film-form residue obtained by step (2) are heated, then carry out homogeneous again Processing；

Wherein, the condition of the heating includes：Temperature is 40-80 DEG C, time 0.5-3h；

The condition of the homogenization includes：First disperse 10-50min under 5,000-20,000rpm rotating speed, then in 500- High pressure homogenization 2-6 times under 1500bar and 20-60Hz frequency ultrasound.

22. the complex liposome as made from the method described in any one in claim 1-21.

23. application of the complex liposome in whitening and oxidation resistant product is prepared described in claim 22.

24. the cosmetics containing the complex liposome described in claim 22.