CN103520007A - Skin active factor flexible nano-liposome and preparation method and application thereof - Google Patents
Skin active factor flexible nano-liposome and preparation method and application thereof Download PDFInfo
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Abstract
The invention relates to a skin active factor flexible nano-liposome and a preparation method and application thereof. The flexible nano-liposome comprises the following components in parts by weight: 1-1000 parts of neutral phospholipid, 1-1000 parts of cholesterol, 0.5-500 parts of surfactant, 0.1-20 parts of hyaluronic acid and 0.5-500 parts of skin active factor components. The skin active factor active-component flexible nano-liposome provided by the invention can remarkably improve the stability of the skin active factor components, promote the transdermal absorption of the active components and improve the acting efficiency while increasing the retention and action time of the active components on the surface and deep layer of skin; the skin active factor flexible nano-liposome in a lyophilized powder state is also favorable for application, transportation and storage; the preparation method of the flexible nano-liposome provided by the invention can adopt a mechanical process, and has good stability in the product process and quality and high reproducibility.
Description
Technical field
The present invention relates to a kind of flexible nano-liposomes and preparation method thereof and purposes, relate to especially a kind of skin activity factor type flexible nano-liposomes and preparation method thereof, and the application of this flexible nano-liposomes aspect cosmetics.
Background technology
Along with more and more clearer for the understanding of skin physiology pathology, more and more there is bioactive animals and plants composition and/or biopolymer composition and be applied to cosmetic industry, obtained huge society and economic benefit.But, these are had to bioactive material and be applied in cosmetics, need to solve following problem:
1, how the stability of these bioactive substances solves, the stability of this class material is except being determined by its structure and space conformation, the impact of external environment factor also can not look down upon, epidermis active factors solution for example, active duration in external environment only has short a few hours, its be absorbed by the skin play a role before basic inactivation just, can not bring into play its due effect at all;
2, how to make these macromolecule components be absorbed by human body skin, as a rule, active matter molecular weight is less, more easily see through skin, once molecular weight is greater than 600, active matter is just difficult to be absorbed by the skin, and the material great majority with particular skin active function of application are the polymer substances such as peptide class in recent years, its molecular weight is thousands of at least, hundreds thousand of at most, thereby this has just determined that they are difficult to see through skin and are effectively absorbed;
3, in order to meet many-sided demand of skin physiology activity, in common cosmetics, the kind of active component is several at least, reaches at most tens of kinds, and the physical and chemical reaction between active component has limited the scope of cosmetics prescription screenings.In order to address these problems, new drug preparation technique is applied to cosmetic industry more and more, at present, solve active matter stability and the compatibility mainly take to add stabilizing agent, lyophilization, be prepared into Emulsion, by methods such as cyclodextrin, microcapsule (ball), liposome wrap up; Promote skin to absorb and adopted following certain methods: the granule of medicine itself is prepared into nanoscale, adds the transdermal enhancers such as Azone, adopts iontophoresis or electroporation, is prepared into and has the nanoscale inclusion enclave etc. of urging saturating performance.
Liposome preparation technology is applied to the history of the existing many decades of cosmetic industry, a large amount of results of study prove, cosmetic active ingredient is wrapping in liposome, can greatly improve the stability of these active component, these active component discharge and have sustained release performance from liposome, meanwhile, due to liposome membrane composition and the biomembranous composition of human body cell extremely approaching, therefore this class preparation good biocompatibility, safe.Particularly nineteen sixties the flexible nano-liposomes that occurs, can pass through himself flexibility and morphotropism, thereby the skin duct of the little several times of penetration ratio self diameter reaches good Transdermal absorption effect efficiently, flexible nano-liposomes not only can wrap up small molecule active thing, for molecular weight up to 10
6biomacromolecule active substance also there is better skin through performance, be in cosmetics preparations, to have the preparation method of potentiality.In addition, cosmetic active ingredient is used respectively liposome, and interaction and the physical and chemical reaction that can effectively avoid these compositions to exist have further improved the safety of its stability and use.
Summary of the invention
The present invention, in order to address the above problem, provides a kind of transdermal capability by force and the flexible nano-liposomes preparation of good biocompatibility.
The invention provides a kind of skin activity factor type flexible nano-liposomes, can guarantee that skin activity factor type is in its stability and safety in utilization.
The invention provides a kind of simply, and there is the skin activity factor type flexible nano-liposomes preparation method of higher envelop rate and drug loading.
The invention provides the application of a kind of skin activity factor type flexible nano-liposomes in cosmetics.
Technical scheme of the present invention is as follows:
Described flexible nano-liposomes comprises that the component of following weight portion is made: the neutral phospholipid of 1-1000 part, 1-1000 part cholesterol, 0.5-500 part surfactant, 0.1-20 part hyaluronic acid and 0.5-500 part skin activity factor type composition.
In a preferred embodiment of the present invention, flexible nano-liposomes of the present invention comprises that the component of following weight portion is made: the neutral phospholipid of 100-120 part, 15-100 part cholesterol, 10-100 part surfactant, 0.1-20 part hyaluronic acid and 0.5-60 part skin activity factor type composition.
In the better embodiment of the present invention one, flexible nano-liposomes of the present invention comprises that the component of following weight portion is made: the neutral phospholipid of 100-120 part, 15-20 part cholesterol, 10-20 part surfactant, 0.1-20 part hyaluronic acid and 30 parts of skin activity factor type compositions.
In a preferred embodiment of the present invention, it also comprises the antioxidant that accounts for liposome gross weight 0.1-0.5% flexible nano-liposomes of the present invention; Be preferably 0.2%; Described oxidant is selected from vitamin C, vitamin E, Butylated hydroxyanisole (BHA), 2, one or more in 6-di-tert-butyl-4-methy phenol (BHT), tea polyphenols, guaiac resin, sesamol or boldine.
In a preferred embodiment of the present invention, the present invention also comprises the cryoprotective agent that is equivalent to described liposome gross weight 2-8 times; Described cryoprotective agent is selected from one or more of glycerol, lactose, sucrose, mannitol, glucose or trehalose.
Preferably, described freeze drying protectant: the weight ratio of liposome is at 3:1 to 6:1.
In a preferred embodiment of the present invention, the particle size range 50-200nm of described flexible nano-liposomes.
In a preferred embodiment of the present invention, described neutral phospholipid is selected from one or more in soybean lecithin, hydrogenated soy phosphatidyl choline, Ovum Gallus domesticus Flavus lecithin, cephalin, DPPC, DSPC, two myristic acid phosphatidylcholines, two lauric acid phosphatidylcholines or two Palmic acid PHOSPHATIDYL ETHANOLAMINE; Described surfactant is sodium cholate or sodium deoxycholate.
Preferably, neutral phospholipid is one or more in soybean lecithin, hydrogenated soy phosphatidyl choline, dipalmitoyl phosphatidyl choline.
The use of cholesterol of the present invention is in order to regulate mobility and the permeability of liposome membrane, and then adjusts the stability of liposome membrane.
The surfactant that the present invention uses, can make liposome membrane have larger elasticity and morphotropism, thereby promotes the Transdermal absorption performance of liposome.Preferred sodium cholate or sodium deoxycholate.
The use of the antioxidant in flexible nano-liposomes of the present invention, oxidized when preventing that it from storing under normal temperature condition.Described oxidant is selected from vitamin C, vitamin E, Butylated hydroxyanisole (BHA), 2, one or more in 6-di-tert-butyl-4-methy phenol (BHT), tea polyphenols, guaiac resin, sesamol or boldine.The mixing antioxidant that preferred vitamin E and Butylated hydroxyanisole (BHA) form.
Weight ratio at lipid components of the present invention and institute's coating active composition, has considerable influence to the stability of liposome, envelop rate and drug loading, and the weight ratio of suitable lipid components and institute's coating active composition is at 2:1 to 5:1; The weight ratio of freeze drying protectant and liposome, also has considerable influence to the drug loading of final products, and suitable proportion is freeze drying protectant: liposome 3:1 to 6:1.
In a preferred embodiment of the present invention, described skin activity factor type is selected from one or more of epidermal growth factor (EGF), keratinocyte growth factor (KGF), insulin-like growth factor (IGF-1), alkaline fiber archeocyte somatomedin (bFGF) or acid fiber archeocyte somatomedin (aFGF).
The invention provides in liposome turbid liquor, the low temperature supercentrifugation that the active component of liposome is separated with free active component, can also adopt separated liposome and the free compositions such as dialysis process, column chromatography.
The preparation method of flexible nano-liposomes of the present invention, described method adopts thin film dispersion-ultrasonic-homogenizing-extrude-lyophilization, and it comprises the steps:
1) the neutral phospholipid of described ratio, cholesterol are dissolved in volatile organic solvent under 10-50 ℃ of water bath condition;
2), by step 1) rotary evaporation, obtain uniform lipid film;
3) surfactant of described ratio, the skin activity factor, freezing drying protective agent are dissolved in the phosphate buffer solution of pH=7.0 under 10-50 ℃ of water bath condition;
4) step 3) is added to 2) carry out ultrasonic mixing, obtain liposome turbid liquor, and after ultrasonication 60-90 time, 5000PSI-10000PSI homogenizing, finally by extruding instrument filter membrane;
5) suspension step 4) being obtained, adopts the active component of the separated liposome of low temperature supercentrifugation and is free in the active component in phosphate buffer;
6) in-50 to-100 ℃ of pre-freezes of the liposome turbid liquor obtaining in step 5) are more than 12 hours, then are placed in freezer dryer lyophilizing, obtain lyophilizing flexible nano-liposomes powder.
Preferably, the liposoluble constituent that adds the composite antioxidant that accounts for liposome gross weight 0.1-0.5% in described step 1.
Another aspect of the present invention, a kind of flexible nano-liposomes is in the application of preparing aspect skin activity factor type cosmetic active ingredient
Positive progressive effect of the present invention is: flexible nano-liposomes particle diameter prepared by the present invention, between 50-200nm, has guaranteed that the active component wrapping up has better stability and skin assimilation effect.And thin film dispersions-ultrasonic-homogenizing-extrude-lyophilization that the present invention adopts, product preparation method is simply and have higher envelop rate and a drug loading; Whole technical process completes by mechanical means, makes Product Process and quality have good stability and repeatability.The powder that the final product of the present invention is good fluidity, easy to use, transportation and store.
The specific embodiment:
Embodiment 1
By 120mg hydrogenated soy phosphatidyl choline, the water-bath of 10mg cholesterol is ultrasonic is dissolved in ether, 0.25mg vitamin E is dissolved in a small amount of ethanol with BHA mixing antioxidant, then mixes with ether solution, is placed in rotary evaporation film forming on Rotary Evaporators; 1000UI epidermis active factors (EGF) and 1000UI horn cell active factors (KGF), 15mg sodium cholate, 1.7mg hyaluronic acid, 500mg lactose are dissolved in the phosphate buffer of pH7.0; Aforesaid phosphate buffer is added to lipid film, put the liposome turbid liquor that spiral vortex type shaker vibrates tentatively; By ultrasonic 90 circulation (the every circulating ultrasonics 5 seconds of probe-type ultrasonic cell disintegration instrument for liposome turbid liquor, intermittently 5 seconds, ice bath) after, with AVESTIN high pressure homogenizer homogenizing 3 times, by AVESTIN, extrude the microporous filter membrane 10 times that instrument is crossed 100nm again, by the liposome turbid liquor of extruding in centrifugal 3 hours of 4 ℃ of 100000 turn/min; Discard liquid, liposome turbid liquor-80 that obtain ℃ pre-freeze, after 12 hours, is positioned over freezer dryer lyophilization powdered.
The particle diameter of resulting EGF and KGF mixture flexible nano-liposomes and Zeta potential are through Zitasizer(Nano ZS, Malvern) nano particle size and potentiometric analyzer is measured its particle diameter and Zeta potential is respectively 97.4 ± 18.7nm, 70.0 ± 8.2mV; The envelop rate that adopts supercentrifugation separation to record product is 28.34%.
Embodiment 2
By 100mg soybean lecithin, the water-bath of 50mg cholesterol is ultrasonic is dissolved in chloroform, 0.26mg vitamin E is dissolved in a small amount of ethanol with BHA mixing antioxidant, then mixes with chloroform solution; 2000UI epidermis active factors (EGF), 10mg sodium cholate, 1.5mg hyaluronic acid, 400mg mannitol are dissolved in the phosphate buffer of pH7.0; Become even emulsion by aforesaid phosphate buffer and chloroformic solution are ultrasonic in water-bath, after standing 30 minutes, rotary evaporation obtains liposome turbid liquor; By ultrasonic 60 circulation (the every circulating ultrasonics 5 seconds of probe-type ultrasonic cell disintegration instrument for liposome turbid liquor, intermittently 5 seconds, ice bath) after, with AVESTIN high pressure homogenizer homogenizing 3 times, by AVESTIN, extrude the microporous filter membrane 10 times that instrument is crossed 100nm again, the liposome turbid liquor of extruding is put into bag filter (molecular retention amount 8000-14000) dialysis 6 hours; Get the liposome turbid liquor in bag filter, in-80 ℃ of pre-freezes, after 12 hours, be positioned over freezer dryer lyophilization powdered.
The particle diameter of resulting epidermis active factors flexible nano-liposomes and Zeta potential are through Zitasizer(Nano ZS, Malvern) nano particle size and potentiometric analyzer is measured its particle diameter and Zeta potential is respectively 113.5 ± 16.7nm, 70.2 ± 7.5mV; The envelop rate that adopts dialysis separation to record product is 30.44%.
Embodiment 3
10mg dipalmitoyl phosphatidyl choline, 1mg cholesterol are dissolved in ether, 0.25mg vitamin E are dissolved in a small amount of ethanol with BHA mixing antioxidant, then mix with ether solution; Mixed liquor evaporate to dryness on Rotary Evaporators forms thin film; 0.1mg epidermal growth factor (EGF), 0.25mg sodium cholate, 0.2mg hyaluronic acid, 50mg lactose are dissolved in the phosphate buffer of pH7.0; Aforesaid phosphate buffer is added to lipid film, put the spiral vortex type shaker liposome turbid liquor that vibrates to obtain; By after probe-type ultrasonic cell disintegration instrument ultrasonic 90 circulations for liposome turbid liquor (every circulating ultrasonic 5 seconds, intermittently 5 seconds, ice bath), use AVESTIN high pressure homogenizer homogenizing 3 times, then extrude by AVESTIN the microporous filter membrane 10 times that instrument is crossed 100nm; By the liposome turbid liquor of extruding in centrifugal 6 hours of 4 ℃ of 100000 turn/min; Discard liquid, the liposome turbid liquor obtaining after 12 hours, is positioned over freezer dryer lyophilization powdered in-80 ℃ of pre-freezes.
The particle diameter of resulting EGF flexible nano-liposomes and Zeta potential are through Zitasizer(Nano ZS, Malvern) nano particle size and potentiometric analyzer is measured its particle diameter and Zeta potential is respectively 54.2 ± 8.3nm, 74.1 ± 11.8mV; The envelop rate that adopts supercentrifugation separation to record product is 39.88%.
Embodiment 4
By 500mg hydrogenated soy phosphatidyl choline, the water-bath of 200mg cholesterol is ultrasonic is dissolved in ether, 1.8mg vitamin E is dissolved in a small amount of ethanol with BHA mixing antioxidant, then mixes with chloroform solution, mixed liquor rotary evaporation film forming; 120mg epidermal growth factor (EGF), keratinocyte growth factor (KGF), insulin-like growth factor (IGF-1), alkaline fiber archeocyte somatomedin (bFGF), acid fiber archeocyte somatomedin (aFGF) (mass ratio 1:0.5:0.2:0.2:0.1) mixture, 75mg sodium deoxycholate, 8.5mg hyaluronic acid, 2.5g mannitol are dissolved in the phosphate buffer of pH7.0; Aforesaid phosphate buffer is added to lipid film, put the spiral vortex type shaker liposome turbid liquor that vibrates to obtain; By after probe-type ultrasonic cell disintegration instrument ultrasonic 90 circulations for liposome turbid liquor (every circulating ultrasonic 5 seconds, intermittently 5 seconds, ice bath), use AVESTIN high pressure homogenizer homogenizing 3 times, then extrude by AVESTIN the microporous filter membrane 10 times that instrument is crossed 100nm; By the liposome turbid liquor of extruding in centrifugal 5 hours of 4 ℃ of 100000 turn/min; Discard liquid, the liposome turbid liquor obtaining after 12 hours, is positioned over freezer dryer lyophilization powdered in-80 ℃ of pre-freezes.
The particle diameter of resulting flexible nano-liposomes and Zeta potential are through Zitasizer(Nano ZS, Malvern) nano particle size and potentiometric analyzer is measured its particle diameter and Zeta potential is respectively 168.2 ± 21.9nm, 54.6 ± 8.7mV.
Embodiment 5
100mg soybean phospholipid, 50mg cholesterol are dissolved in ether, 0.25mg vitamin E are dissolved in a small amount of ethanol with BHA mixing antioxidant, then mix with chloroform solution; Mixed liquor evaporate to dryness on Rotary Evaporators forms thin film; 10mg keratinocyte growth factor (KGF), 1.6mg sodium cholate, 1.7mg hyaluronic acid, 400mg mannitol are dissolved in the phosphate buffer of pH7.0; Aforesaid phosphate buffer is added to lipid film, put the spiral vortex type shaker liposome turbid liquor that vibrates to obtain; By after probe-type ultrasonic cell disintegration instrument ultrasonic 80 circulations for liposome turbid liquor (every circulating ultrasonic 5 seconds, intermittently 5 seconds, ice bath), use AVESTIN high pressure homogenizer homogenizing 3 times, then extrude by AVESTIN the microporous filter membrane 10 times that instrument is crossed 100nm; By the liposome turbid liquor of extruding in centrifugal 4 hours of 4 ℃ of 100000 turn/min; Discard liquid, the liposome turbid liquor obtaining, after 12 hours, is positioned over freezer dryer lyophilization powdered in-80 ℃ of pre-freezes.
The particle diameter of resulting KGF flexible nano-liposomes and Zeta potential are through Zitasizer(Nano ZS, Malvern) nano particle size and potentiometric analyzer is measured its particle diameter and Zeta potential is respectively 166.7 ± 18.5nm, 54.1 ± 13.8mV; The envelop rate that adopts supercentrifugation separation to record product is 27.7%.
In above-described embodiment, neutral phospholipid is provided by Japan Oil Co, cholesterol, sodium deoxycholate and sodium cholate are produced by Tianjin great Mao chemical reagent factory, hyaluronic acid is produced by Shandong Freda Biopharm Co., Ltd., mannitol and lactose are produced by Shanghai experiment reagent company limited, BHA is produced by Shanghai QIGANG Pd, vitamin E is U.S. Sigma product, phosphate buffer is according to Chinese Pharmacopoeia autogamy, all the other reagent are commercially available prod, all meet food or medicinal standard except organic solvent.
Effect embodiment 1 morphology
By EGF flexible nano-liposomes suspension, phosphotungstic acid negative staining, observes form under transmission electron microscope, sees Fig. 1.Fig. 1 EGF flexible nano-liposomes Electronic Speculum figure.
In Fig. 1, can find out, prepared liposome is similar round, and size is homogeneous comparatively, particle diameter < 200nm, and liposome membrane has " fingerprint " feature, and it is successful that the method for having confirmed is prepared liposome.
Effect embodiment 2 stability
Get 3 batches of EGF flexible nano-liposomes and lyophilizing EGF flexible nano-liposomes powder, be placed in respectively under room temperature, 4 ℃ of conditions, in 0m and 3m, measure its envelop rate, pH, particle diameter and Zeta potential, and observe outward appearance, to determine its stability.In Table 1.
Table 1 liposome turbid liquor and freeze-dried lipidosome are placed respectively its stability result after 3 months
* liposome turbid liquor envelop rate unit is %, and freeze-dried lipidosome drug loading unit is the every mg lyophilized powder of mg/; The pH of * freeze-dried lipidosome, particle diameter and current potential are to measure after being used PBS solution Eddy diffusion; * * represents to have compared with 0 month significant difference (P < 0.05)
The stability study of EGF liposome turbid liquor and freeze-dried lipidosome can obtain as drawn a conclusion: (1) EGF liposome turbid liquor, no matter in room temperature or under 4 ℃ of conditions, less stables all, place after 3 months, it is mainly investigated index envelop rate, pH, particle diameter and Zeta potential significant change (P < 0.05) all occurs, and be prepared into after freeze-dried lipidosome, stability significantly improves; (2) EGF solution, places 2 hours at ambient temperature, and its content reduces more than 30%, places almost completely degraded in 24 hours; Under 4 ℃ of conditions, place 2 hours content and lower approximately 5%, place 24 hours content and reduce approximately 25%, while placing 7 days, almost completely degrade.Studies confirm that the stability that can significantly improve EGF by liposome.
Effect embodiment 3 nude mice live body Transdermal absorption
In fluorine multifunctional mark module, labelling is synthetic
18f-EGF, minutes two groups, one group of label taking has been remembered
18f-EGF450 μ Ci, to 4.5ml, adds appropriate liposome with normal saline dilution, utilizes the ultrasonic 30min(experimental group of probe-type ultrasonic disruption instrument); Another group label taking has been remembered
18f-EGF450 μ Ci, to 4.5ml, in contrast, mixes standby (matched group) with normal saline dilution.
Two BALB/c nude mices, utilize isoflurane to anaesthetize in advance, after anesthesia is got well, are fixed to scanning bed going up, back coating, the painting matched group on the left side; The painting liposome on the right, records before and after coating, and drug dose, calculates the radioactive dosage that is coated in Mus back, every approximately 30 μ Ci left and right.
After coating, enter bed, dynamic scan 1h, after, nude mice to be taken down scanning bed, minute different mouse cages are deposited, and the point of 2h and 3h after injection, carries out respectively static 10min scanning.
The results are shown in Figure 2.The static 3h scintigram of Fig. 2 Micro PET, every width figure the right is experimental group, the left side is matched group.
By Transdermal absorption result, can be found: EGF flexible nano-liposomes is applied in nude mice skin, prolongation along with the Transdermal absorption time, the Transdermal absorption amount of EGF also increases, Transdermal absorption first hour, EGF flexible nano-liposomes major part is absorbed in skin layer, because nude mice skin is thinner, the EGF in skin layer enters subsequently blood and finally concentrates on bladder and pass through urine excretion; And EGF solution does not almost absorb.After test has confirmed that EGF is wrapped up by flexible nano-liposomes, there is good Transdermal absorption effect.
It is feasible that above-mentioned effect embodiment result has confirmed to adopt thin film dispersion-ultrasonic-homogenizing-extrude-freeze drying process to prepare cell active factor class flexible nano-liposomes, and method is easy, favorable reproducibility, stability are high; Active component adopts after liposome, has sustained release performance, can extend action time; Flexible nano-liposomes, skin transmitance is high, is conducive to giving full play to of active component effect.
Above-described embodiment 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 equivalences that spirit is done according to the present invention change or modify, within all should being encompassed in protection scope of the present invention.
Claims (12)
1. a skin activity factor type flexible nano-liposomes, is characterized in that: described flexible nano-liposomes comprises that the component of following weight portion is made: the neutral phospholipid of 1-1000 part, 1-1000 part cholesterol, 0.5-500 part surfactant, 0.1-20 part hyaluronic acid and 0.5-500 part skin activity factor type composition.
2. flexible nano-liposomes according to claim 1, is characterized in that: it component that comprises following weight portion is made: the neutral phospholipid of 100-120 part, 15-100 part cholesterol, 10-100 part surfactant, 0.1-20 part hyaluronic acid and 0.5-60 part skin activity factor type composition.
3. flexible nano-liposomes according to claim 1, is characterized in that: it component that comprises following weight portion is made: the neutral phospholipid of 100-120 part, 15-20 part cholesterol, 10-20 part surfactant, 0.1-20 part hyaluronic acid and 30 parts of skin activity factor type compositions.
4. according to the flexible nano-liposomes described in claim 1-3, it is characterized in that: it also comprises the antioxidant that accounts for liposome gross weight 0.1-0.5%, is preferably 0.2%; Described oxidant is selected from vitamin C, vitamin E, Butylated hydroxyanisole (BHA), 2, one or more in 6-di-tert-butyl-4-methy phenol (BHT), tea polyphenols, guaiac resin, sesamol or boldine.
5. according to the flexible nano-liposomes described in claim 1-3, it is characterized in that: it also comprises the cryoprotective agent that is equivalent to described liposome gross weight 2-8 times; Described cryoprotective agent is selected from one or more of glycerol, lactose, sucrose, mannitol, glucose or trehalose.
6. flexible nano-liposomes according to claim 5, is characterized in that: described freeze drying protectant: the weight ratio of liposome is at 3:1 to 6:1.
7. according to the flexible nano-liposomes described in claim 1-3, it is characterized in that: the particle size range of described flexible nano-liposomes is 50-200nm.
8. according to the flexible nano-liposomes described in claim 1-3, it is characterized in that: described neutral phospholipid is selected from one or more in soybean lecithin, hydrogenated soy phosphatidyl choline, Ovum Gallus domesticus Flavus lecithin, cephalin, DPPC, DSPC, two myristic acid phosphatidylcholines, two lauric acid phosphatidylcholines or two Palmic acid PHOSPHATIDYL ETHANOLAMINE; Described surfactant is sodium cholate or sodium deoxycholate.
9. according to the flexible nano-liposomes described in claim 1-3, it is characterized in that: described skin activity factor type is selected from one or more of epidermal growth factor (EGF), keratinocyte growth factor (KGF), insulin-like growth factor (IGF-1), alkaline fiber archeocyte somatomedin (bFGF) or acid fiber archeocyte somatomedin (aFGF).
10. a preparation method for flexible nano-liposomes according to claim 5, is characterized in that: described method adopts thin film dispersion-ultrasonic-homogenizing-extrude-lyophilization, and it comprises the steps:
1) the neutral phospholipid of described ratio, cholesterol are dissolved in volatile organic solvent under 10-50 ℃ of water bath condition;
2), by step 1) rotary evaporation, obtain uniform lipid film;
3) surfactant of described ratio, the skin activity factor and freezing drying protective agent are dissolved in the phosphate buffer solution of pH=7.0 under 10-50 ℃ of water bath condition;
4) step 3) is added to 2) carry out ultrasonic mixing, obtain liposome turbid liquor, and after ultrasonication 60-90 time, 5000PSI-10000PSI homogenizing, finally by extruding instrument filter membrane;
5) suspension step 4) being obtained, adopts the active component of the separated liposome of low temperature supercentrifugation and is free in the active component in phosphate buffer;
6) in-50 to-100 ℃ of pre-freezes of the liposome turbid liquor obtaining in step 5) are more than 12 hours, then are placed in freezer dryer lyophilizing, obtain lyophilizing flexible nano-liposomes powder.
11. preparation methoies according to claim 10, is characterized in that: the liposoluble constituent that adds the composite antioxidant that accounts for liposome gross weight 0.1-0.5% in described step 1.
12. 1 kinds according to the flexible nano-liposomes described in claim 1-3 in the application of preparing aspect skin activity factor type cosmetic active ingredient.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102397168A (en) * | 2011-11-23 | 2012-04-04 | 苏州瑞纳生化技术有限公司 | Flexible nanoliposomes with charges for cosmetics and preparation method thereof |
-
2013
- 2013-10-15 CN CN201310479332.8A patent/CN103520007A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102397168A (en) * | 2011-11-23 | 2012-04-04 | 苏州瑞纳生化技术有限公司 | Flexible nanoliposomes with charges for cosmetics and preparation method thereof |
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| CN112870108A (en) * | 2021-02-07 | 2021-06-01 | 上海百雀羚生物科技有限公司 | Composition with anti-aging and moisturizing effects and preparation method and application thereof |
| CN114146009A (en) * | 2021-12-13 | 2022-03-08 | 武汉百思凯瑞生物科技有限公司 | DHA anti-aging anti-inflammatory nano composition and preparation method and application thereof |
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