CN102397168A - Flexible nanoliposomes with charges for cosmetics and preparation method thereof - Google Patents
Flexible nanoliposomes with charges for cosmetics and preparation method thereof Download PDFInfo
- Publication number
- CN102397168A CN102397168A CN2011103751371A CN201110375137A CN102397168A CN 102397168 A CN102397168 A CN 102397168A CN 2011103751371 A CN2011103751371 A CN 2011103751371A CN 201110375137 A CN201110375137 A CN 201110375137A CN 102397168 A CN102397168 A CN 102397168A
- Authority
- CN
- China
- Prior art keywords
- liposome
- electrically charged
- flexible nano
- cosmetics
- phospholipid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Abstract
The invention relates to flexible nanoliposomes with charges for cosmetics and a preparation method thereof. The flexible nanoliposomes with the charges for the cosmetics comprise the following components in part by weight: 1-1000 parts of neutral phospholipid, 0.5-500 parts of phospholipid with the charges, 1-1000 parts of cholesterol, 0.5-500 parts of surface active agent, 0.1-20 parts of hyaluronic acid, 0.5-250 parts of cosmetic active ingredients and 100-8000 parts of freeze drying protective agent. The flexible nanoliposomes with the charges for the cosmetics can obviously improve the stabilities of the cosmetic active ingredients, promote the percutaneous absorption and the interaction efficiency of the active ingredients, and also improve the retention and action time of the active ingredients on the skin surface and the skin deep layer; and the flexible nanoliposomes with the charges for the powdery cosmetic active ingredients are also benefit to the use, transportation and storage. The preparation method of the flexible nanoliposomes with the charges can adopt a mechanized method, so the stability of the product technology and quality is good, and the repeatability is high.
Description
Technical field
The present invention relates to a kind of electrically charged flexible nano liposome, more specifically, the present invention relates to a kind of electrically charged flexible nano liposome that is used for cosmetics and preparation method thereof.
Background technology
Along with technology, instrument and methodological development; People are more and more deep for the understanding of human body self; Gene and molecular biology level have been deep into for the skin physiology pathological knowledge; Produced huge impetus for the relevant biological medicine and the development of cosmetics industry, the animals and plants composition and/or the biopolymer composition of increasing biologically active are applied to cosmetic industry, have obtained huge social and economic benefit.
But, the material of these biologically actives is applied in the cosmetics, be faced with many difficult problems, mainly show following two aspects:
1, how the stability of these bioactive substances solves; This type Stability of Substance is except structure and space conformation decision by himself; The influence of external environment factor also can not look down upon, epidermis active factors solution for example, and the active duration in external environment only has short several hours; Basic inactivation just before it is played a role by skin absorbs can not be brought into play its due effect and effect at all;
2, these macromolecule components can be absorbed by human body skin, as a rule, the active matter molecular weight is more little; See through skin more easily, in case molecular weight greater than 600, active matter just has been difficult to by skin absorbs; And the material great majority of using in recent years with particular skin active function are polymer substances such as peptide class; Its molecular weight is thousands of at least, and is hundreds thousand of at most, thereby this has just determined them to be difficult to see through skin by effectively absorption.
Usually the kind of active component kind surplus in the of ten at least in the cosmetics reaches tens of kinds at most, and the physical and chemical reaction between the active component has limited the scope of cosmetics prescription screenings.In order to address these problems; A lot of solutions have also been adopted at present: be applied to cosmetic industry more and more such as new drug preparation technique; At present, solve the active matter stability and the compatibility mainly take to add stabilizing agent, lyophilization, be prepared into Emulsion, with methods such as cyclodextrin, microcapsule (ball), liposome wrap up; Promote skin absorbs then to adopt following certain methods: the preparation of granules of medicine itself is become nanoscale, adds transdermal enhancers such as Azone, adopts iontophoresis or electroporations, is prepared into nanoscale inclusion enclave with short performance thoroughly etc.
In addition with the liposome preparation process application in cosmetics, a large amount of researchs fact proved, cosmetic active ingredient is wrapping in the liposome; Can greatly improve the stability of these active component; These active component discharge from liposome and have sustained release performance, simultaneously, because liposome membrane composition and the biomembranous composition of human body cell are extremely approaching; Therefore this type preparation good biocompatibility is safe.Particularly nineteen sixties the flexible nano liposome that occurs; Can be through flexibility and the morphotropism of himself; Thereby the skin duct of the little several times of penetration ratio self diameter reaches the good transdermal assimilation effect efficiently; The flexible nano liposome not only can wrap up the small molecule active thing, for molecular weight up to 10
6The biomacromolecule active substance also have better skin through performance, be the method for preparing that has potentiality in the cosmetics preparations.In addition, cosmetic active ingredient is used liposome respectively, interaction and the physical and chemical reaction that can effectively avoid these compositions to exist.Though conventional liposome can improve stability and the safety of using, himself stability is still not high relatively; And be not easy to promote Transdermal absorption.
So press for a kind of preparation that is applied in the cosmetics on the market, it can not only improve the stability of the bioactive substance of cosmetics, and can promote Transdermal absorption, reach best skin protection and support the skin effect.
Summary of the invention
The present invention is in order to address the above problem, and provides a kind of transdermal ability strong and combine electrically charged more closely flexible nano Liposomal formulation with skin.
Another object of the present invention is to provide a kind of electrically charged flexible nano liposome that is used for cosmetics and preparation method thereof.
Novelty of the present invention ground is fitted to charged lipid components in the flexible nano liposome membrane; Utilize skin surface soda acid characteristic; Make electrically charged liposome combine tightr with local skin through electrostatic attraction; Be beneficial to active component and more effectively prolong action time, be beneficial to give full play to the action effect that skin is supported in these active component skin protections at skin.
Technical scheme of the present invention is following: described electrically charged flexible nano liposome comprises following components in part by weight: the freezing drying protective agent of the neutral phospholipid of 1-1000 part, the electrically charged phospholipid of 0.5-500 part, 1-1000 part cholesterol, 0.5-500 part surfactant, 0.1-20 part hyaluronic acid, 0.5-250 part cosmetic active ingredient, 100-8000 part.
In the present invention's one preferred embodiment, electrically charged flexible nano liposome of the present invention comprises following components in part by weight: the freezing drying protective agent of the neutral phospholipid of 100-120 part, the electrically charged phospholipid of 0.5-100 part, 15-100 part cholesterol, 10-100 part surfactant, 0.1-2 part hyaluronic acid, 0.5-250 part cosmetic active ingredient, 400-800 part.
In the present invention one better embodiment, electrically charged flexible nano liposome of the present invention comprises following components in part by weight: the freezing drying protective agent of the neutral phospholipid of 100-120 part, the electrically charged phospholipid of 0.5-20 part, 15-20 part cholesterol, 10-20 part surfactant, 1.5 parts of hyaluronic acids, 20 parts of cosmetic active ingredients, 400-600 part.
Wherein, Described neutral phospholipid is selected from soybean lecithin, hydrogenated soya phosphatide, Ovum Gallus domesticus Flavus lecithin, cephalin, and dipalmitoyl phosphatidyl choline, DSPC, two Semen Myristicae phosphatidylcholines, two Laurel phosphatidyl cholines, two palmityl PHOSPHATIDYL ETHANOLAMINEs etc. are natural or synthetic phospholipid in one or more; Described electrically charged phospholipid is selected from one or more in the negative charge phospholipid such as phosphatidic acid, phosphatidyl glycerol, phosphatidylinositols, Phosphatidylserine, two spermaceti phosphatidic acid inositols, or be selected from stearmide, 3 β-[N-(N ', N '-dimethyl amine) amido formoxyl] cholesterol, [1-(2 for N-; The 3-dioleoyl) propyl group]-N; N, N-triethylamine chlorine, 2,3-two oleoyl oxygen-N-[2-(arginine base amide) ethyl]-N; N-dimethyl-1-propyl group-trifluoroacetic acid amine, 1; 2-two oleoyl oxygen propyl group-N, N, one or more in the synthetic positive charge lipids such as N-trimethylammonium bromide; Described surfactant is sodium cholate or sodium deoxycholate.
In preferably soya lecithin of the present invention, hydrogenated soya phosphatide, dipalmitoyl phosphatidyl choline, phosphatidic acid, phosphatidyl glycerol, stearmide, 3 β-[N-(N ', N '-dimethyl amine) amido formoxyl] cholesterol one or more.Phosphatidic acid wherein, phosphatidyl glycerol belong to the negative charge lipid components, and it is electronegative to give the flexible nano liposome membrane, are beneficial to liposome and are combining and absorption of electropositive local skin with alkalescence; Stearmide, 3 β-[N-(N ', N '-dimethyl amine) amido formoxyl] cholesterol belongs to the positive charge lipid components, and it is positively charged to give the flexible nano liposome membrane, is beneficial to liposome and is combining and absorption of electronegative local skin with acid.
The use of cholesterol of the present invention is flowability and the permeability in order to regulate liposome membrane, and then the stability of adjustment liposome membrane.
The surfactant that the present invention uses can make liposome membrane have bigger elasticity and morphotropism, thereby promotes the Transdermal absorption performance of liposome.Preferred sodium cholate or sodium deoxycholate.
Electrically charged flexible nano liposome of the present invention open can comprise conventional amount used be equivalent to about 0.2% antioxidant of liposome gross weight, oxidized when preventing that it from storing under normal temperature condition.Described oxidant can be selected for use but be not limited to 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, the boldine.The mixing antioxidant that preferred vitamin E and Butylated hydroxyanisole (BHA) are formed.
Electrically charged flexible nano liposome of the present invention can comprise and is equivalent to liposome gross weight 4-8 freezing drying protective agent doubly.Described freezing drying protective agent can be selected for use but be not limited to sucrose, mannitol, glucose, trehalose.Preferred mannitol.
The weight ratio of above-mentioned lipid components and institute's coating active composition has considerable influence to stability, envelop rate and the drug loading of liposome, and the weight ratio of suitable lipid components and institute's coating active composition is between 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 a freeze drying protectant: liposome 3: 1-6: 1.
The invention provides in the liposome turbid liquor, the active component of liposome and the isolating dialysis process of free active component can also adopt supercentrifugation, column chromatography etc. to separate liposome and free composition.The present invention also provides the method for preparing of electrically charged flexible nano liposome: the reverse-phase evaporation of improvement-ultrasonic-homogenizing-extrude-lyophilization.The reverse-phase evaporation of wherein said improvement also can adopt conventional method for preparing lipidosome, comprises film dispersion method, injection method, heating, emulsion process etc.
The present invention adopts the reverse-phase evaporation-ultrasonic-homogenizing of improvement-extrude-lyophilization to prepare electrically charged flexible nano liposome, and concrete steps are following:
1) liposoluble constituents such as phospholipid, cholesterol, liposoluble active component is dissolved in the volatile organic solvent under 35 ℃ of water bath condition;
2) under 35 ℃ of water bath condition, be dissolved in hyaluronic acid, surfactant, the water-soluble active water soluble ingredient that becomes to grade in the phosphate buffer solution (pH=7.0);
3) with step 1) and 2) ultrasonic mixing, make it to form stable emulsion, leave standstill 30 minutes not stratified;
4) with the emulsion rotary evaporation of step 3) gained, until forming liposome turbid liquor;
5) with after the step 4) gained liposome turbid liquor ultrasonication 30 times (ultrasonic 5 seconds, stop 5 seconds be 1 time), 5000PSI-10000PSI homogenizing 3 times is crossed the 100nm filter membrane 3 times through extruding appearance at last;
6) solution that step 5) is obtained adopts the active component of dialysis separation liposome and is free in the active component in the phosphate buffer;
7) in the liposome turbid liquor in the bag filter that step 6) obtains, add the freeze drying protectant that 5-8 doubly measures, more than 12 hours, place the freezer dryer lyophilizing again, obtain the electrically charged flexible nano liposome of the lyophilizing powder of white good fluidity in-40 ℃ of pre-freezes.
Beneficial effect of the present invention is: the electrically charged flexible nano liposome particle diameter of the present invention's preparation is between 50-200nm, and the surface charge absolute value makes the active component that is wrapped up have better stability more than 50mV.Simultaneously; In flexible nano liposome membrane composition, introduce electrically charged lipid components; Except liposome is had the advantages of good skin permeability, have stronger adhesiveness between liposome and the cell biological film, help action and efficacy and functioning efficiency that active component is given full play in the part; Reduce the use amount of active component, and then be beneficial to and economize on resources.And the reverse-phase evaporation-ultrasonic-homogenizing of the improvement that the present invention adopts-extrude-lyophilization, make product have higher entrapment and drug loading; Whole technical process is accomplished by mechanical, makes product technology and quality have stability and repeatability preferably; The final product of the present invention is the powder of good fluidity, easy to use, transportation and store.
Description of drawings
Fig. 1 is cation asiaticoside flexible nano liposome Electronic Speculum figure; Wherein A is the liposome stock solution that just prepares; B is the liposome that suspends again after the lyophilizing; C does not add the freeze-dried lipidosome of freeze drying protectant; D is the freeze-dried lipidosome that adds freeze drying protectant;
Fig. 2 is different sample cumulative release results;
Fig. 3 is laboratory sample accumulation in 24 a hours Transdermal absorption amount;
Fig. 4 is laboratory sample accumulation in 24 a hours Transdermal absorption percentage rate (%).
The specific embodiment
Embodiment 1
With 100mg soybean lecithin, 16mg stearmide, ultrasonic being dissolved in the chloroform of 15mg cholesterol water-bath, but being mixed antioxidant, 25mg asiaticoside, 0.26mg vitamin E and BHA be dissolved in the small amount of ethanol, mix with chloroform solution again; 12mg sodium cholate, 1.7mg hyaluronic acid are dissolved in the phosphate buffer of pH7.0; Become even emulsion with aforesaid phosphate buffer and chloroformic solution are ultrasonic in water-bath, leave standstill 30 minutes after, rotary evaporation gets liposome turbid liquor; With liposome turbid liquor with ultrasonic 30 circulation (the every circulating ultrasonics 5 seconds of probe-type ultrasonic cell disintegration appearance; Intermittently 5 seconds) after; With AVESTIN high pressure homogenizer homogenizing 3 times; Extrude the microporous filter membrane 10 times that appearance is crossed 100nm through AVESTIN 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 the bag filter, add the mannitol of 4 times of lipid quality, in-40 ℃ of pre-freezes after 12 hours, it is powdered to be positioned over the freezer dryer lyophilization.
The particle diameter of resulting cation asiaticoside flexible nano liposome and Zeta potential through Zetasizer (Nano ZS-90, Malvern) nano particle size and potentiometric analyzer are measured its particle diameter and Zeta potential is respectively 61.72 ± 11.29nm, 69.1 ± 5.99mV; Adopting dialysis to separate the envelop rate that records product is 29.7%.
Embodiment 2
With 120mg hydrogenated soy phosphatidyl choline, 20mg stearmide, ultrasonic being dissolved in the chloroform of 18mg cholesterol water-bath, but 0.25mg vitamin E and the mixed antioxidant of BHA are dissolved in the small amount of ethanol, mix with chloroform solution again; 2000UI epidermis active factors (EGF), 15mg sodium cholate, 1.7mg hyaluronic acid are dissolved in the phosphate buffer of pH7.0; Become even emulsion with aforesaid phosphate buffer and chloroformic solution are ultrasonic in water-bath, leave standstill 30 minutes after, rotary evaporation gets liposome turbid liquor; With liposome turbid liquor with ultrasonic 30 circulation (the every circulating ultrasonics 5 seconds of probe-type ultrasonic cell disintegration appearance; Intermittently 5 seconds) after; With AVESTIN high pressure homogenizer homogenizing 3 times; Extrude the microporous filter membrane 10 times that appearance is crossed 100nm through AVESTIN 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 the bag filter, add the trehalose of 5 times of lipid quality, in-40 ℃ of pre-freezes after 12 hours, it is powdered to be positioned over the freezer dryer lyophilization.
The particle diameter of resulting cation EGF flexible nano liposome and Zeta potential through Zetasizer (Nano ZS-90, Malvern) nano particle size and potentiometric analyzer are measured its particle diameter and Zeta potential is respectively 178.2 ± 21.91nm, 65.0 ± 6.04mV; Adopting dialysis to separate the envelop rate that records product is 31.7%.
With 10mg dipalmitoyl phosphatidyl choline, 2mg stearmide, ultrasonic being dissolved in the chloroform of 2mg cholesterol water-bath, but 0.20mg vitamin C and the mixed antioxidant of BHA are dissolved in the small amount of ethanol, mix with chloroform solution again; 5mg shikonin, 1.6mg sodium cholate, 1.7mg hyaluronic acid are dissolved in the phosphate buffer of pH7.0; Become even emulsion with aforesaid phosphate buffer and chloroformic solution are ultrasonic in water-bath, leave standstill 30 minutes after, rotary evaporation gets liposome turbid liquor; With liposome turbid liquor with ultrasonic 30 circulation (the every circulating ultrasonics 5 seconds of probe-type ultrasonic cell disintegration appearance; Intermittently 5 seconds) after; With AVESTIN high pressure homogenizer homogenizing 3 times; Extrude the microporous filter membrane 10 times that appearance is crossed 100nm through AVESTIN 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 the bag filter, add the lactose of 5 times of lipid quality, in-40 ℃ of pre-freezes after 12 hours, it is powdered to be positioned over the freezer dryer lyophilization.
The particle diameter of the plain flexible nano liposome of resulting cation Radix Arnebiae (Radix Lithospermi) and Zeta potential through Zetasizer (Nano ZS-90, Malvern) nano particle size and potentiometric analyzer its particle diameter of mensuration and Zeta potential are respectively 81.55 ± 31.20nm, 63.7 ± 5.41mV; Adopting dialysis to separate the envelop rate that records product is 30.1%.
Embodiment 4
With 500mg hydrogenated soy phosphatidyl choline, 80mg stearmide, ultrasonic being dissolved in the chloroform of 75mg cholesterol water-bath, but 1.8mg vitamin E and the mixed antioxidant of tea polyphenols are dissolved in the small amount of ethanol, mix with chloroform solution again; 5mg allantoin, 75mg sodium deoxycholate, 8.5mg hyaluronic acid are dissolved in the phosphate buffer of 35 ℃ of pH7.0; Become even emulsion with aforesaid phosphate buffer and chloroformic solution are ultrasonic in water-bath, leave standstill 30 minutes after, rotary evaporation gets liposome turbid liquor; With liposome turbid liquor with ultrasonic 30 circulation (the every circulating ultrasonics 5 seconds of probe-type ultrasonic cell disintegration appearance; Intermittently 5 seconds) after; With AVESTIN high pressure homogenizer homogenizing 3 times; Extrude the microporous filter membrane 10 times that appearance is crossed 100nm through AVESTIN 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 the bag filter, add the mannitol of 5 times of lipid quality, in-40 ℃ of pre-freezes after 12 hours, it is powdered to be positioned over the freezer dryer lyophilization.
The particle diameter of resulting cation allantoin flexible nano liposome and Zeta potential through Zetasizer (Nano ZS-90, Malvern) nano particle size and potentiometric analyzer are measured its particle diameter and Zeta potential is respectively 88.38 ± 14.92nm, 51.5 ± 4.26mV; Adopting dialysis to separate the envelop rate that records product is 34.1%.
With 500mg hydrogenated soy phosphatidyl choline, 50mg 3 β-[N-(N '; N '-dimethyl amine) amido formoxyl] cholesterol, the water-bath of 75mg cholesterol is ultrasonic is dissolved in the chloroform; Be dissolved in the small amount of ethanol but 200mg coenzyme Q10,1.8mg vitamin E and BHA are mixed antioxidant, mix with chloroform solution again; 75mg sodium cholate, 8.5mg hyaluronic acid are dissolved in the phosphate buffer of 35 ℃ of pH7.0; Become even emulsion with aforesaid phosphate buffer and chloroformic solution are ultrasonic in water-bath, leave standstill 30 minutes after, rotary evaporation gets liposome turbid liquor; With liposome turbid liquor with ultrasonic 30 circulation (the every circulating ultrasonics 5 seconds of probe-type ultrasonic cell disintegration appearance; Intermittently 5 seconds) after; With AVESTIN high pressure homogenizer homogenizing 3 times; Extrude the microporous filter membrane 10 times that appearance is crossed 100nm through AVESTIN 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 the bag filter, add the mannitol of 6 times of lipid quality, in-40 ℃ of pre-freezes after 12 hours, it is powdered to be positioned over the freezer dryer lyophilization.
The particle diameter of resulting cation coenzyme Q10 flexible nano liposome and Zeta potential through Zetasizer (Nano ZS-90, Malvern) nano particle size and potentiometric analyzer are measured its particle diameter and Zeta potential is respectively 106.8 ± 85.51nm, 60.3 ± 5.49mV; Adopting dialysis to separate the envelop rate that records product is 31.8%.
With 12mg hydrogenated soy phosphatidyl choline, 1.5mg phosphatidyl glycerol, ultrasonic being dissolved in the chloroform of 1.5mg cholesterol water-bath, but being mixed antioxidant, 1.25mg ceramide 2,0.025mg vitamin E and BHA be dissolved in the small amount of ethanol, mix with chloroform solution again; 1.5mg sodium deoxycholate, 0.17mg hyaluronic acid are dissolved in the phosphate buffer of pH7.0; Become even emulsion with aforesaid phosphate buffer and chloroformic solution are ultrasonic in water-bath, leave standstill 30 minutes after, rotary evaporation gets liposome turbid liquor; With liposome turbid liquor with ultrasonic 30 circulation (the every circulating ultrasonics 5 seconds of probe-type ultrasonic cell disintegration appearance; Intermittently 5 seconds) after; With AVESTIN high pressure homogenizer homogenizing 3 times; Extrude the microporous filter membrane 10 times that appearance is crossed 100nm through AVESTIN 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 the bag filter, add the mannitol of 5 times of lipid quality, in-40 ℃ of pre-freezes after 12 hours, it is powdered to be positioned over the freezer dryer lyophilization.
The particle diameter of resulting anion ceramide 2 flexible nano liposomees and Zeta potential through Zetasizer (Nano ZS-90, Malvern) nano particle size and potentiometric analyzer measure its particle diameter and Zeta potential be respectively 139.7 ± 23.1nm ,-52.1 ± 5.95mV; Adopting dialysis to separate the envelop rate that records product is 28.3%.
Embodiment 7
With 120mg hydrogenated soy phosphatidyl choline, 20mg stearmide, ultrasonic being dissolved in the chloroform of 18mg cholesterol water-bath, but being mixed antioxidant, 30mg silymarin, 0.20mg vitamin E and BHT be dissolved in the small amount of ethanol, mix with chloroform solution again; 15mg sodium deoxycholate, 1.7mg hyaluronic acid are dissolved in the phosphate buffer of pH7.0; Become even emulsion with aforesaid phosphate buffer and chloroformic solution are ultrasonic in water-bath, leave standstill 30 minutes after, rotary evaporation gets liposome turbid liquor; With liposome turbid liquor with ultrasonic 30 circulation (the every circulating ultrasonics 5 seconds of probe-type ultrasonic cell disintegration appearance; Intermittently 5 seconds) after; With AVESTIN high pressure homogenizer homogenizing 3 times; Extrude the microporous filter membrane 10 times that appearance is crossed 100nm through AVESTIN 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 the bag filter, add the sucrose of 3 times of lipid quality, in-40 ℃ of pre-freezes after 12 hours, it is powdered to be positioned over the freezer dryer lyophilization.
The particle diameter of resulting cation silymarin flexible nano liposome and Zeta potential through Zetasizer (Nano ZS-90, Malvern) nano particle size and potentiometric analyzer are measured its particle diameter and Zeta potential is respectively 117.2 ± 19.21nm, 57.4 ± 7.25mV; Adopting dialysis to separate the envelop rate that records product is 32.9%.
Embodiment 8
With 100mg soybean lecithin, 16mg stearmide, ultrasonic being dissolved in the chloroform of 10mg cholesterol water-bath, but 0.25mg vitamin E and the mixed antioxidant of BHA are dissolved in the small amount of ethanol, mix with chloroform solution again; 20mg collagen protein, 15mg sodium deoxycholate, 1.7mg hyaluronic acid are dissolved in the phosphate buffer of pH7.0; Become even emulsion with aforesaid phosphate buffer and chloroformic solution are ultrasonic in water-bath, leave standstill 30 minutes after, rotary evaporation gets liposome turbid liquor; With liposome turbid liquor with ultrasonic 30 circulation (the every circulating ultrasonics 5 seconds of probe-type ultrasonic cell disintegration appearance; Intermittently 5 seconds) after; With AVESTIN high pressure homogenizer homogenizing 3 times; Extrude the microporous filter membrane 10 times that appearance is crossed 100nm through AVESTIN 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 the bag filter, add the mannitol of 4 times of lipid quality, in-40 ℃ of pre-freezes after 12 hours, it is powdered to be positioned over the freezer dryer lyophilization.
(Nano ZS-90, Malvern) nano particle size and potentiometric analyzer its particle diameter of mensuration and Zeta potential are respectively 158.7 ± 10.68nm, 55.0 ± 5.58mV through Zetasizer for the particle diameter of resulting cation collagen protein flexible nano liposome and Zeta potential.
Embodiment 9
With 120mg soybean lecithin, 16mg stearmide, ultrasonic being dissolved in the chloroform of 10mg cholesterol water-bath, but 0.25mg vitamin E and the mixed antioxidant of BHA are dissolved in the small amount of ethanol, mix with chloroform solution again; 25mg pentapeptide, 15mg sodium deoxycholate, 1.7mg hyaluronic acid are dissolved in the phosphate buffer of pH7.0; Become even emulsion with aforesaid phosphate buffer and chloroformic solution are ultrasonic in water-bath, leave standstill 30 minutes after, rotary evaporation gets liposome turbid liquor; With liposome turbid liquor with ultrasonic 30 circulation (the every circulating ultrasonics 5 seconds of probe-type ultrasonic cell disintegration appearance; Intermittently 5 seconds) after; With AVESTIN high pressure homogenizer homogenizing 3 times; Extrude the microporous filter membrane 10 times that appearance is crossed 100nm through AVESTIN 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 the bag filter, add the mannitol of 4 times of lipid quality, in-40 ℃ of pre-freezes after 12 hours, it is powdered to be positioned over the freezer dryer lyophilization.
(NanoZS-90, Malvern) nano particle size and potentiometric analyzer its particle diameter of mensuration and Zeta potential are respectively 93.3 ± 22.71nm, 62.7 ± 6.16mV through Zetasizer for the particle diameter of resulting cation pentapeptide flexible nano liposome and Zeta potential.
In the foregoing description, neutral phospholipid is provided by Japan Oil Co, and stearmide is a U.S. Sigma-Aldrich Chemie GmbH product; Phosphatidyl glycerol is produced by U.S. Avanti Polar Lipids Inc.; Phosphatidic acid is done boat Chemical Industry Science Co., Ltd by Shanghai to be provided, and cholesterol, sodium deoxycholate and sodium cholate are produced by Tianjin Da Mao chemical reagent factory, and hyaluronic acid is produced by Shandong Freda Biopharm Co., Ltd.; Mannitol is produced by Shanghai experiment reagent company limited; BHA is produced by Shanghai QIGANG Pd, and vitamin E is a U.S. Sigma product, and phosphate buffer is according to the Chinese Pharmacopoeia autogamy; All the other reagent are the commercially available prod, except that organic solvent, all meet food or medicinal standard.
Effect embodiment 1 morphology
With cation asiaticoside flexible nano liposome turbid liquor, the phosphotungstic acid negative staining, transmission electron microscope is observed form down; With phosphate buffer suspendible again, the phosphotungstic acid negative staining is observed form under the transmission electron microscope with lyophilizing cation asiaticoside flexible nano liposome; Observation does not add freeze drying protectant and sees Fig. 1 with the cation asiaticoside flexible nano liposome that adds freeze drying protectant under scanning electron microscope.
Effect embodiment 2 stability
Get 3 batches of cation EGF flexible nano liposomees and lyophilizing cation EGF flexible nano liposome powder, place respectively under room temperature, the 4 ℃ of conditions, measure its envelop rate, pH, particle diameter and Zeta potential, and observe outward appearance, to confirm its stability in 0m and 3m.See table 1.
Table 1 liposome turbid liquor and freeze-dried lipidosome are placed its stability result after 3 months respectively
* 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 it is suspended with PBS solution again; * * representes to compare with 0 month there was no significant difference (P＞0.05)
Get cation asiaticoside flexible nano liposome turbid liquor 5ml (containing the about 78.2 μ g of asiaticoside) and asiaticoside solution 5ml (containing the about 80.0 μ g of asiaticoside) respectively, place bag filter respectively; Asiaticoside lipidosome cream 100mg (containing the about 78.3 μ g of asiaticoside) places filtration paper cylinder.Press the oar method of Chinese Pharmacopoeia regulation and measure its release characteristic, receive liquid PBS volume 50ml, release temperature keeps 37.0 ℃, and magnetic agitation speed is 50rpm.Drawing 0.5ml SBF at pre-determined time point receives liquid and replenishes the SBF solution of equal volume immediately.Adopt aforesaid HPLC method to detect the medication amount that discharges.Each sample parallel laboratory test 3 times.The result sees Fig. 2.
Effect embodiment 4 transdermal test in vitro absorb
Prepare asiaticoside cation flexible lipidosome (sample A), asiaticoside flexible lipidosome (sample B), the general positive liposome of asiaticoside (sample C) and asiaticoside solution (sample D) respectively; And join respectively in the blank mastic with prescription, make every g mastic contain the about 0.25mg of asiaticoside; Remove to be used for the commercialization Corii Sus domestica of Transdermal absorption,, be cut into suitable size, make Corii Sus domestica surface (horny layer) up, be installed on the diffusion cell, respectively smear mastic 1g according to the bore (0.66cm2) of Franz diffusion cell; Receiving liquid is PBS solution, and 37 ℃ of temperature receive the long-pending 2.5ml of liquid, names a person for a particular job at official hour that all receive liquid and take out, and replenishes new reception liquid simultaneously; Method by the front detects reception liquid asiaticoside content, calculates asiaticoside accumulation Transdermal absorption amount and percentage rate; Behind last point in time sampling, the Corii Sus domestica positive and negative is used distilled water flushing, Corii Sus domestica was soaked in the 50mlPBS liquid 24 hours, measured soak asiaticoside content, to confirm the hold-up of asiaticoside in Corii Sus domestica.The result sees Fig. 3, Fig. 4 and table 2.
The hold-up (n=3) of the different samples of table 4 in Corii Sus domestica
| Sample | Average hold-up (μ g/cm 2) | SD |
| A | 1724.68 | 539.50 |
| B | 1383.99 | 27.36 |
| C | 1025.72 | 109.84 |
| B | 258.82 | 100.27 |
Above-mentioned effect embodiment result has confirmed that it is feasible that employing anti-phase-extrude-freeze drying process prepares cation flexible nano liposome, and method is easy, favorable reproducibility, stability are high; After active component adopts liposome, have sustained release performance, can prolong action time; Cation flexible nano liposome, the skin transmitance is high, and because its charge characteristic makes it to combine with skin more easily and be stranded in skin, helps giving full play to of active component effect.
So far invention has been described for oneself combination embodiment.Be familiar with those skilled in the art and should be appreciated that under situation about not departing from the scope of the present invention with spirit, can easily make various other modifications said embodiment.Therefore, the scope that Rights attached thereto require is not limited to above-mentioned explanation, but broadly construe requirement.
Claims (10)
1. electrically charged flexible nano liposome that is used for cosmetics, it is characterized in that: described electrically charged flexible nano liposome comprises following components in part by weight: the freezing drying protective agent of the neutral phospholipid of 1-1000 part, the electrically charged phospholipid of 0.5-500 part, 1-1000 part cholesterol, 0.5-500 part surfactant, 0.1-20 part hyaluronic acid, 0.5-250 part cosmetic active ingredient, 100-8000 part.
2. the electrically charged flexible nano liposome that is used for cosmetics according to claim 1 is characterized in that: described electrically charged flexible nano liposome comprises following components in part by weight: the freezing drying protective agent of the neutral phospholipid of 100-120 part, the electrically charged phospholipid of 0.5-100 part, 15-100 part cholesterol, 10-100 part surfactant, 0.1-2 part hyaluronic acid, 0.5-250 part cosmetic active ingredient, 400-800 part.
3. the electrically charged flexible nano liposome that is used for cosmetics according to claim 1 is characterized in that: described electrically charged flexible nano liposome comprises following components in part by weight: the freezing drying protective agent of the neutral phospholipid of 100-120 part, the electrically charged phospholipid of 0.5-20 part, 15-20 part cholesterol, 10-20 part surfactant, 1.5 parts of hyaluronic acids, 20 parts of cosmetic active ingredients, 400-600 part.
4. according to the arbitrary described electrically charged flexible nano liposome that is used for cosmetics of claim 1-3, it is characterized in that: cosmetic active ingredient be selected from collagen protein, silymarin, ceramide, coenzyme Q10, allantoin, shikonin, UI epidermis active factors or asiaticoside one or more.
5. according to the arbitrary described electrically charged flexible nano liposome that is used for cosmetics of claim 1-3; It is characterized in that: it also comprises the antioxidant of checking that accounts for liposome gross weight 0.1-0.5%; The wherein said antioxidant of checking is selected from vitamin C, vitamin E, Butylated hydroxyanisole, 2, one or more in 6-di-tert-butyl-4-methy phenol, tea polyphenols, guaiac resin, sesamol, the boldine.
6. according to the arbitrary described electrically charged flexible nano liposome that is used for cosmetics of claim 1-3, it is characterized in that: the said antioxidant of checking is vitamin E and Butylated hydroxyanisole, and its ratio is 10: 1 to 10: 5.
7. according to the arbitrary described electrically charged flexible nano liposome that is used for cosmetics of claim 1-3, it is characterized in that: the particle size range of described electrically charged flexible nano liposome is 50-200nm.
8. according to the arbitrary described electrically charged flexible nano liposome that is used for cosmetics of claim 1-3, it is characterized in that: the Zeta-potential range of described electrically charged flexible nano liposome is (70)-70mV.
9. according to the arbitrary described electrically charged flexible nano liposome that is used for cosmetics of claim 1-3; It is characterized in that: described neutral phospholipid is selected from soybean lecithin, Ovum Gallus domesticus Flavus lecithin, cephalin, and dipalmitoyl phosphatidyl choline, DSPC, two Semen Myristicae phosphatidylcholines, two Laurel phosphatidyl cholines, two palmityl PHOSPHATIDYL ETHANOLAMINEs etc. are natural or synthetic phospholipid in one or more; Described electrically charged phospholipid is selected from one or more in the negative charge phospholipid such as phosphatidic acid, phosphatidyl glycerol, phosphatidylinositols, Phosphatidylserine, two spermaceti phosphatidic acid inositols, or be selected from stearmide, 3 β-[N-(N ', N '-dimethyl amine) amido formoxyl] cholesterol, [1-(2 for N-; The 3-dioleoyl) propyl group]-N; N, N-triethylamine chlorine, 2,3-two oleoyl oxygen-N-[2-(arginine base amide) ethyl]-N; N-dimethyl-1-propyl group-trifluoroacetic acid amine, 1; 2-two oleoyl oxygen propyl group-N, N, one or more in the synthetic positive charge lipid of N-trimethylammonium bromide; Described surfactant is sodium cholate or sodium deoxycholate; Described freezing drying protective agent is selected one or more in sucrose, mannitol, glucose, the trehalose for use.
10. one kind like the arbitrary described method for preparing that is used for the electrically charged flexible nano liposome of cosmetics of claim 1-3, said comprising the steps:
1) phospholipid, cholesterol, liposoluble active component are dissolved in the volatile organic solvent under 35 ℃ of water bath condition;
2) under 35 ℃ of water bath condition, be dissolved in hyaluronic acid, surfactant, the water-soluble active water soluble ingredient that becomes to grade in the phosphate buffer solution (pH=7.0);
3) with step 1) and 2) ultrasonic mixing, make it to form stable emulsion, leave standstill 30 minutes not stratified;
4) with the emulsion rotary evaporation of step 3) gained, until forming liposome turbid liquor;
5) with after the step 4) gained liposome turbid liquor ultrasonication 30 times, 5000PSI-10000PSI homogenizing 3 times is crossed the 100nm filter membrane 3 times through extruding appearance at last;
6) solution that step 5) is obtained adopts the active component of dialysis separation liposome and is free in the active component in the phosphate buffer;
7) in the liposome turbid liquor in the bag filter that step 6) obtains, add the freeze drying protectant that 5-8 doubly measures, more than 12 hours, place the freezer dryer lyophilizing again, obtain the electrically charged flexible nano liposome of the lyophilizing powder of white good fluidity in-40 ℃ of pre-freezes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110375137 CN102397168B (en) | 2011-11-23 | 2011-11-23 | Flexible nanoliposomes with charges for cosmetics and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110375137 CN102397168B (en) | 2011-11-23 | 2011-11-23 | Flexible nanoliposomes with charges for cosmetics and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102397168A true CN102397168A (en) | 2012-04-04 |
| CN102397168B CN102397168B (en) | 2013-10-02 |
Family
ID=45880068
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201110375137 Active CN102397168B (en) | 2011-11-23 | 2011-11-23 | Flexible nanoliposomes with charges for cosmetics and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102397168B (en) |
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103110935A (en) * | 2013-01-25 | 2013-05-22 | 江苏圣宝罗药业有限公司 | Hydrolyzed collagen liposome for local skin and preparation method thereof |
| CN103211720A (en) * | 2013-04-16 | 2013-07-24 | 纪艺琼 | Nanometer synergist for cosmetics as well as preparation method and skin care product of nanometer synergist |
| CN103417394A (en) * | 2013-05-06 | 2013-12-04 | 上海玉华生命科技发展有限公司 | Lipidosome composition containing Cu and Zn-rhSOD for removing eye wrinkles effectively |
| CN103505403A (en) * | 2013-09-29 | 2014-01-15 | 广州市娇兰化妆品有限公司 | Epidermal growth factor compound lipidosome as well as preparation method and application thereof |
| CN103520006A (en) * | 2013-10-14 | 2014-01-22 | 天博医药技术（苏州）有限公司 | Flexible nano liposome as well as preparation method and application of flexible nano liposome |
| CN103520007A (en) * | 2013-10-15 | 2014-01-22 | 天博医药技术（苏州）有限公司 | Skin active factor flexible nano-liposome and preparation method and application thereof |
| CN104983591A (en) * | 2015-07-09 | 2015-10-21 | 西安艾尔菲生物科技有限公司 | Double modified beta-carotene lipidosome and preparation method thereof |
| CN106075390A (en) * | 2016-07-28 | 2016-11-09 | 广东药科大学 | A kind of positively charged anticreep composite and flexible liposome and preparation method thereof |
| CN106727324A (en) * | 2016-12-28 | 2017-05-31 | 贵安新区瑞诚生物工程有限公司 | Nano Silver liposome and its preparation method and application |
| CN107375039A (en) * | 2017-09-04 | 2017-11-24 | 银川凤仪堂生物工程有限公司 | Add the skin care item and preparation technology of egg yolk lecithin |
| CN107441046A (en) * | 2017-08-31 | 2017-12-08 | 宁波盖济尔医疗科技有限公司 | A kind of compound protein liposome nanometer formulation |
| CN107802508A (en) * | 2017-11-01 | 2018-03-16 | 武汉百思凯瑞纳米科技有限公司 | A kind of cationic-liposome nano-composition and its preparation method and application |
| CN108524364A (en) * | 2018-06-14 | 2018-09-14 | 上海棠美生物科技有限公司 | A kind of cosmetic active object nano-carrier package and preparation method thereof |
| CN112315821A (en) * | 2020-12-03 | 2021-02-05 | 暨南大学 | Hydrolyzed protein liposome and preparation method and application thereof |
| CN112545903A (en) * | 2019-09-25 | 2021-03-26 | 深圳光彩生命工程技术有限公司 | Facial mask containing flexible nano-liposome |
| CN113440435A (en) * | 2021-07-07 | 2021-09-28 | 珀莱雅化妆品股份有限公司 | Preparation method of skin anti-aging composition |
| CN114557964A (en) * | 2022-03-17 | 2022-05-31 | 西安九清生物科技有限公司 | Cationic shuttle-type flexible liposome capable of carrying RNA (ribonucleic acid), and preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102085157A (en) * | 2011-01-27 | 2011-06-08 | 中国水产科学研究院黄海水产研究所 | Scallop antioxidant peptide nano liposome and preparation method thereof |
| CN102137713A (en) * | 2008-12-24 | 2011-07-27 | 生物制药开发股份有限公司 | Method for producing liposome and method for dissolving cholesterol |
| CN102223922A (en) * | 2008-11-25 | 2011-10-19 | 宝洁公司 | Oral care compositions containing gel networks and fused silica |
-
2011
- 2011-11-23 CN CN 201110375137 patent/CN102397168B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102223922A (en) * | 2008-11-25 | 2011-10-19 | 宝洁公司 | Oral care compositions containing gel networks and fused silica |
| CN102137713A (en) * | 2008-12-24 | 2011-07-27 | 生物制药开发股份有限公司 | Method for producing liposome and method for dissolving cholesterol |
| CN102085157A (en) * | 2011-01-27 | 2011-06-08 | 中国水产科学研究院黄海水产研究所 | Scallop antioxidant peptide nano liposome and preparation method thereof |
Cited By (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103110935B (en) * | 2013-01-25 | 2014-06-11 | 江苏圣宝罗药业有限公司 | Hydrolyzed collagen liposome for local skin and preparation method thereof |
| CN103110935A (en) * | 2013-01-25 | 2013-05-22 | 江苏圣宝罗药业有限公司 | Hydrolyzed collagen liposome for local skin and preparation method thereof |
| CN103211720A (en) * | 2013-04-16 | 2013-07-24 | 纪艺琼 | Nanometer synergist for cosmetics as well as preparation method and skin care product of nanometer synergist |
| CN103417394A (en) * | 2013-05-06 | 2013-12-04 | 上海玉华生命科技发展有限公司 | Lipidosome composition containing Cu and Zn-rhSOD for removing eye wrinkles effectively |
| CN103505403A (en) * | 2013-09-29 | 2014-01-15 | 广州市娇兰化妆品有限公司 | Epidermal growth factor compound lipidosome as well as preparation method and application thereof |
| CN103505403B (en) * | 2013-09-29 | 2015-08-19 | 广州市娇兰化妆品有限公司 | Epidermal growth factor composite liposome body and its preparation method and application |
| CN103520006A (en) * | 2013-10-14 | 2014-01-22 | 天博医药技术（苏州）有限公司 | Flexible nano liposome as well as preparation method and application of flexible nano liposome |
| CN103520007A (en) * | 2013-10-15 | 2014-01-22 | 天博医药技术（苏州）有限公司 | Skin active factor flexible nano-liposome and preparation method and application thereof |
| CN104983591B (en) * | 2015-07-09 | 2018-08-28 | 西安艾尔菲生物科技有限公司 | A kind of dual modified beta-carotenoid lipid body and preparation method thereof |
| CN104983591A (en) * | 2015-07-09 | 2015-10-21 | 西安艾尔菲生物科技有限公司 | Double modified beta-carotene lipidosome and preparation method thereof |
| CN106075390A (en) * | 2016-07-28 | 2016-11-09 | 广东药科大学 | A kind of positively charged anticreep composite and flexible liposome and preparation method thereof |
| CN106727324A (en) * | 2016-12-28 | 2017-05-31 | 贵安新区瑞诚生物工程有限公司 | Nano Silver liposome and its preparation method and application |
| CN107441046A (en) * | 2017-08-31 | 2017-12-08 | 宁波盖济尔医疗科技有限公司 | A kind of compound protein liposome nanometer formulation |
| CN107441046B (en) * | 2017-08-31 | 2020-07-28 | 宁波盖济尔医疗科技有限公司 | Composite protein liposome nano preparation |
| CN107375039A (en) * | 2017-09-04 | 2017-11-24 | 银川凤仪堂生物工程有限公司 | Add the skin care item and preparation technology of egg yolk lecithin |
| CN107802508A (en) * | 2017-11-01 | 2018-03-16 | 武汉百思凯瑞纳米科技有限公司 | A kind of cationic-liposome nano-composition and its preparation method and application |
| CN108524364A (en) * | 2018-06-14 | 2018-09-14 | 上海棠美生物科技有限公司 | A kind of cosmetic active object nano-carrier package and preparation method thereof |
| CN112545903A (en) * | 2019-09-25 | 2021-03-26 | 深圳光彩生命工程技术有限公司 | Facial mask containing flexible nano-liposome |
| CN112315821A (en) * | 2020-12-03 | 2021-02-05 | 暨南大学 | Hydrolyzed protein liposome and preparation method and application thereof |
| CN112315821B (en) * | 2020-12-03 | 2022-09-23 | 暨南大学 | Hydrolyzed protein liposome and preparation method and application thereof |
| CN113440435A (en) * | 2021-07-07 | 2021-09-28 | 珀莱雅化妆品股份有限公司 | Preparation method of skin anti-aging composition |
| CN114557964A (en) * | 2022-03-17 | 2022-05-31 | 西安九清生物科技有限公司 | Cationic shuttle-type flexible liposome capable of carrying RNA (ribonucleic acid), and preparation method and application thereof |
| CN114557964B (en) * | 2022-03-17 | 2024-03-12 | 西安艾领克生物科技有限公司 | RNA-loadable cationic shuttle-type flexible liposome and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102397168B (en) | 2013-10-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102397168B (en) | Flexible nanoliposomes with charges for cosmetics and preparation method thereof | |
| Elnaggar et al. | Lecithin-based nanostructured gels for skin delivery: an update on state of art and recent applications | |
| JP7250689B2 (en) | Local delivery system for active compounds | |
| Fang et al. | Enhancement of the transdermal delivery of catechins by liposomes incorporating anionic surfactants and ethanol | |
| Huang et al. | Elastic liposomes as carriers for oral delivery and the brain distribution of (+)-catechin | |
| El-Refaie et al. | Novel self-assembled, gel-core hyaluosomes for non-invasive management of osteoarthritis: in-vitro optimization, ex-vivo and in-vivo permeation | |
| US20210030640A1 (en) | Method of preparing bioactive substance-encapsulated ethosome, ethosome composition, and cosmetic composition including ethosome composition | |
| Hiruta et al. | Novel ultra-deformable vesicles entrapped with bleomycin and enhanced to penetrate rat skin | |
| CN103520006A (en) | Flexible nano liposome as well as preparation method and application of flexible nano liposome | |
| Fang et al. | Physicochemical characteristics and in vivo deposition of liposome-encapsulated tea catechins by topical and intratumor administrations | |
| EP3025732B1 (en) | Hyalurosomes, their use in topical cosmetic or pharmaceutical compositions and their preparation process | |
| CN103520007A (en) | Skin active factor flexible nano-liposome and preparation method and application thereof | |
| Vanti et al. | Hydroxypropyl methylcellulose hydrogel of berberine chloride-loaded escinosomes: Dermal absorption and biocompatibility | |
| Chen et al. | Skin delivery of ferulic acid from different vesicular systems | |
| ITMI20090350A1 (en) | GLYCEROSOMES AND THEIR USE IN PHARMACEUTICAL AND COSMETIC PREPARATIONS FOR TOPICAL USE | |
| Kim et al. | The skin-permeation-enhancing effect of phosphatidylcholine: caffeine as a model active ingredient | |
| Shaikh et al. | Aceclofenac organogels: in vitro and in vivo characterization | |
| Shanmugam et al. | Physicochemical characterization and skin permeation of liposome formulations containing clindamycin phosphate | |
| Taghizadeh et al. | A new liposomal-drug-in-adhesive patch for transdermal delivery of sodium diclofenac | |
| Aute et al. | A comprehensive review on ethosomes | |
| Badran et al. | Effect of terpene liposomes on the transdermal delivery of hydrophobic model drug, nimesulide: Characterization, stability and in vitro skin permeation | |
| CN103327965A (en) | Liposome and personal care composition comprising thereof | |
| CN102525930A (en) | Lipoic acid liposome injection | |
| WO2020058892A1 (en) | Deformable liposomes containing micelles | |
| CN104083326B (en) | A kind of preparation method of the liposome wrapping load protein medicaments |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20200824 Address after: Room 402, gate 2, building 2, ruizeyuan, Hongqi South Road, Nankai District, Tianjin Patentee after: Jiang Yan Address before: Xinghu Street Industrial Park of Suzhou city in Jiangsu province 226221 BioBAY No. 218 building A3 room 112 Patentee before: SUZHOU RUINA BIOCHEMICAL TECHNOLOGY Co.,Ltd. |