CN103070826A - Quercetin skin lipidosome, lyophilized powder thereof and preparation method and application thereof - Google Patents
Quercetin skin lipidosome, lyophilized powder thereof and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a quercetin skin lipidosome and lyophilized powder thereof, belongs to the technical field of medicines, and aims to solve the problems that the quercetin is poor in solubility and difficult to apply, improve the penetration amount and the penetration rate of quercetin into a corneum and enhance the retention of a medicine in an epidermis and a dermis so as to play the efficacy better. Every 100 mL of lipidosome solution is prepared from the following substances: 0.01-0.1g of quercetin, 0.1-1.2g of amphiphilic lipid, 0.025-0.6g of cholesterol, 0.05-3g of surfactant, 0.001-0.5g of antioxidant and the balance of aqueous medium. The quercetin skin lipidosome and the lyophilized powder thereof are external preparations for a skin, and are applicable to oxidation resistance, inflammation resistance, ultraviolet radiation damage resistance, skin cancer resistance, and resistance to edema, red spots, pigmentation, inflammation and immune suppression which are caused by ultraviolet radiation.
Description
Technical field
The invention belongs to medical technical field, relate to a kind of skin Quercetin flexible lipidosome and preparation method thereof.
Background technology
At present, along with air-polluting is day by day serious, strong ultraviolet radiation aggravates increasingly to the threat of earth surface biological body excessively, and UV-induced skin injury is also day by day serious.When ozone layer reduced 10%, the ultraviolet radiation that arrives ground just increased by 2%, and dermopathic sickness rate will increase by 25%～32%.According to " World Cancer report " report, have 30% to be skin carcinoma in the cancer of annual new diagnosis in the world, wherein 90% skin carcinoma is to be caused by the ultraviolet radiation in the daylight.UV-induced skin injury is main relevant with UVA and UVB, and wherein UVB is the main cause that causes skin injury.
The multiple pollutants such as ultraviolet cause oxidative stress by direct radiation, generation reactive oxygen species (reactive oxygen species, ROS).Oxidative damage due to the ROS plays an important role in the morbidity of multiple dermatosis.The oxidative damage that the excessive oxides such as ROS cause mainly contain following some: cause 1. that the state of oxidation forms before the cell, Antioxidative Defense System is impaired.2. destroy enzyme and the non-enzymatic Antioxidative Defense System of skin, make body easily impaired and be in various pathological states, the skins such as skin aging, immunosuppressant, cutaneous tumor occur diseases related.3. cause degraded and the inflammatory reaction of extracellular matrix components.4. oxidation consists of structure, function and the metabolism of the various material damage cells of cell tissue.5. ROS tumor that UVR causes occur and immunosuppressant in all play facilitation.
Quercetin (4H-1-Benzopyran-4-one, and 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-Flavone), different name quercetin, Quercetin.The source is Fagaceae Iberia oak (Quercus iberica) Pi Heye, the red Radix et Rhizoma Dysosmatis of Berberidaceae plant (Dysosma veitchii (Hemsl.et Wils.)) Fu, Hypericaceae plant Herba Hyperici (Hunan Fructus Forsythiae) (Hypericum ascyron L.) herb, apocynaceae plant ambary (Apocynum lancifolium Rus.) leaf.Be distributed widely in the flower, fruit, seed of each kind of plant of nature.In recent years, the plants such as research worker discovery Semen Viciae fabae, cabbage type rape, Malus domestica Fructus Mali pumilae are being accepted in the strong ultraviolet radiation situation, the corresponding increase of biosynthesis amount of the Quercetin in the plant, thus the research of protecting ultraviolet damage aspect based on Quercetin carried out.Research finds that Quercetin all has good scavenging action to superoxide anion, hydroxyl radical free radical and singlet oxygen, and dose-effect relationship is obvious.Compare with other Flavonoid substances, Quercetin has shown higher to radiation-resistant ability.At present, researcher just is being devoted to Quercetin is resisted as a kind of ROS scavenger the oxidative damage of skin.Quercetin is mainly manifested in two aspects to the scavenging action of ROS: Quercetin can directly be removed ROS, and in addition, Quercetin also can act on the enzyme relevant with free-radical generating, indirectly removes ROS.Moreover, Quercetin can also the sequestration metal ion, and namely the catechol structure in the quercetin molecule can sequestration Fe2+ and Cu2+, thereby brings into play its antioxidation.The effect of related Quercetin is prevention and repairs the damage that ultraviolet causes the radiation of skin among the present invention, near and skin cancer that control is caused by ultraviolet radiation.
The principal element that the restriction Quercetin is used is the dissolubility of Quercetin, and Quercetin is water-soluble hardly, and the dissolubility in water is 0.166 μ gml-1-7.7 μ gml-1.Therefore, at present the development of Quercetin preparation focused mostly in improving drug solubility, prolong the characteristics such as intravenously administrable body-internal-circulation time, therapeutic efficiency is mainly blood fat reducing, the pharmacological actions such as coronary artery dilator, antitumor.
CN101904820A discloses a kind of quercetin nanosuspension freeze-drying composition and its preparation method and application, and this invention utilizes mechanical force to be prepared into the dissolubility that nanosuspension is used for improving Quercetin in the presence of phospholipid and surfactant Quercetin.CN102058536A discloses Quercetin hydroxypropylβ-cyclodextrin bag and composite lipidosome and its production and use, has been used for the intravenously administrable significant prolongation body-internal-circulation time of Quercetin mice.CN100370968 has authorized a kind of quercetin long-acting liposome powder for injection and preparation method thereof, utilize mPEG2000-DSPE (PEG-PE) preparation Quercetin long circulating liposomes injectable powder to be used for intravenously administrable, long-acting liposome is compared with conventional liposome can the circulation time of significant prolongation Quercetin in Mice Body, increases AUC.
Above-mentioned patented invention content is all for the intravenous administration approach, but do not have for research and the invention of Quercetin preparation for external application to skin.The present invention is directed to Quercetin opposing ultraviolet radiation damage, prevent and treat this effect of skin carcinoma, Quercetin is prepared into the percutaneous drug delivery flexible lipidosome, solve simultaneously Quercetin poorly soluble, the problem that is difficult to use, and then improve Quercetin to cuticular infiltration capacity and seepage velocity, and strengthen the hold-up of medicine in epidermis and corium, bring into play better drug effect.
Summary of the invention
First purpose of the present invention provides a kind of novel take the natural plant extracts Quercetin as effective ingredient, compares with existing like product to have the characteristics such as safe, efficient, and has better deliquescent external preparation.
For achieving the above object, the inventor furthers investigate, and invention provides a kind of Quercetin external preparation for skin flexible lipidosome and lyophilized powder thereof, said preparation greatly to increase the dispersion concentration of Quercetin in aqueous medium, has solved the inconvenience on Quercetin is used.
Provided by the invention a kind of novel be that the liposome solutions of every 100mL is to be prepared from by following material take natural plants as extract Quercetin external preparation:
Quercetin 0.01g-0.1g, amphipathic lipids 0.1g-1.2g, cholesterol 0.025g-0.6g, surfactant 0.05g-3g, antioxidant 0.001g-0.5g, all the other are aqueous medium.
Further, described amphipathic lipids mixture refers to egg phosphatide, fabaceous lecithin, cephalin, hydrolecithin, 1,2-two oleoyl oxygen propyl group-N, N, N-trimethylammonium bromide, phosphatidylinositols, phosphatidyl glycerol, Phosphatidylserine, phosphatidic acid, PHOSPHATIDYL ETHANOLAMINE, phosphatidylcholine, sphingomyelins one or more.
Further, described surfactant comprises one or more in cholic acid, sodium cholate, Tween20, Tween60, Tween80, Span20, Span60, Span65, the poloxamer.
Further, described antioxidant sodium sulfite, sodium pyrosulfite, sodium sulfite, sodium thiosulfate, disodium edetate, vitamin E one or more.
Further, described aqueous medium is comprised of pure water and water-soluble substances.
Further, described water-soluble substances comprises organic acid, organic salt, mineral acid, inorganic salt, monosaccharide, disaccharide and compositions thereof.
Organic acid includes such as carboxylic acid, sulfonic acid, and sulfinic acid, thionothiolic acid, such as formic acid, acetic acid, citric acid, tartaric acid.
Organic salt includes such as carboxylate, sulfonate, and sulfinate, thionothiolic acid salt, alkyl salt etc., such as sodium cholate, sodium acetate, sodium methide, Sodium ethylate.
Monosaccharide includes such as sugar, pentose, hexose, maltose, lactose, lactose etc.
Second purpose of the present invention be for providing a kind of method for preparing above-mentioned external preparation, by preferred raw materials used and consumption, optimizes preparation parameter, a kind of easy and simple to handle, preparation technology of being suitable for large-scale production is provided:
(1) Quercetin and amphipathic lipids are dissolved in one or more organic solvents as organic facies, make it abundant dissolving with ultrasound wave, then antioxidant is added in the organic phase solution.
(2) surfactant fully is dissolved in the aqueous medium as water;
(3) remove organic solvent before or after organic facies is mixed with water, form the liposome solutions that disperses homogeneous, then add freeze drying protectant.
(4) to the liposome solutions of step (3) gained with the membrane filtration of 0.22 μ m 3-5 time, add an amount of freeze drying protectant and fully dissolve ,-80 ℃ of pre-freeze 24h put into the decompression freezer dryer and carry out namely getting lipid freeze-dry powder behind the dry 48h.
Further, described antioxidant can add in the organic facies after the step (1), also can add aqueous phase after step (2).
Further, the adding method of described freeze drying protectant can join aqueous phase after the step (2), also can after step (3), join in the liposome solutions for preparing, preferably the former.
Further, the described organic solvent of removing of described step (3) namely can be before organic facies and water mix, also can be after machine phase and water mix.
Further, the described organic solvent method of removing of described step (3) has evaporation, lyophilization, ultrasound wave etc.
Evaporation refer to organic facies is mixed with water before or after, place water-bath to heat organic facies or organic facies liquid mixed with water, stir, remove organic solvent.
Lyophilization claims again sublimation drying, refers to water-containing materials freezingly to below freezing, makes water change ice into, then changes ice into steam under high vacuum and the drying means removed.
Further, the method for described lyophilizing use comprises freeze-drying and spray drying method.
Freeze-drying claims again sublimation drying.Water-containing materials is freezing to below freezing, make water change ice into, then under high vacuum, change ice into steam and the drying means removed.
Spray drying method namely by mechanism, with the material of need drying, is dispersed into the very thin microgranule as mist, contacts with hot-air, in moment most of moisture is removed, and makes the solid matter in the material be dried to powder.
Further, described lyophilizing use freeze drying protectant includes one or more in glucosan, glucose, lactose, mannitol, sucrose, glycine, trehalose, sorbitol, glycerol, fructose, xylitol, the galactose.
Further, described lyophilizing uses the consumption of freeze drying protectant to be 2-10g/100m.
Further, described freeze drying protectant can join aqueous phase during liposome solutions in preparation, also can before lyophilizing, join in the liposome solutions for preparing, preferably the former.
Further, be preparation for external application to skin according to liposome and the lyophilized powder of this explained hereafter, such as ointment, emulsifiable paste, gel, emulsion, spraying etc.
Further, be suitable for the symptoms such as edema that antioxidation, antiinflammatory, anti-ultraviolet radiation damage, anti-skin carcinoma, especially ultraviolet radiation cause, erythema, pigmentation, inflammation, immunosuppressant according to the liposome of this explained hereafter and lyophilized powder.
The made Quercetin liposome of the present invention is external type preparation, is used for the protectiving ultraviolet radiation, repairs radiation damage, prevents skin carcinoma.
The galenic pharmacy character of Quercetin flexible lipidosome is estimated:
(1) particle diameter: utilize NicompTM380/ZLS dynamic light scattering particle size analyser that the particle diameter of embodiment (1)-(5) is measured, the mean diameter that can get this preparation is 148nm.
(2) envelop rate: use microtrabeculae centrifuging separated free Quercetin and liposome, use HPLC to measure Quercetin medicament contg, according to the following equation computational envelope rate.The envelop rate that can get this preparation is 85.41 ± 5.77%.
E%=(C
l/C
2)×100%
C
lFor crossing the concentration of gel column sample; C
2For not crossing the concentration of gel column sample.
(3) release in vitro behavior: under (37 ± 0.5) ℃ constant temperature, measure release in vitro (25rpm stirring) with the pulpboard method, the HPLC method is measured medicament contg, calculate the burst size of different time medicine, calculate Cumulative release amount, release profiles the results are shown in Figure 1.As can be seen from the figure the Quercetin flexible lipidosome can slowly discharge medicine at 48h, and release behavior meets first order kinetics.
(4) dermal osmosis behavior:
Be the behavior of research liposome, we have done following experiment:
The preparation of Corium Mus: get healthy male SD rat (180-220g), draw neck to put to death, remove hair on the skin of abdomen with shaver, peel off skin of abdomen.Carefully reject subcutaneus adipose tissue with hemostat, carefully check the integrity of Corium Mus, any breakage must not be arranged.
Experimental technique: with Parafilm rat abdomen skin is fixed on the Frans diffusion cell, horny layer up, supply chamber adds sample solution, receiving chamber is the PBS solution of pH7.4, circulating water temperature is 1 ℃ of 32 scholar, speed of agitator is 600rmin
-1The closed administration of supply chamber respectively at 1,2,3,4,5,6,7h timing sampling 1mL, and replenishes 32 ℃ of lower receiving liquid 1mL that are incubated immediately, and sampling liquid is got 20 μ L with 0.22 μ m filtering with microporous membrane, and the HPLC method is measured content.Unit of account area accumulative total transit dose Q (μ gcm
-2), take unit are accumulative total infiltration capacity Q as vertical coordinate, time t is the abscissa mapping, can obtain accumulative total penetration curve Fig. 2, obtains simultaneously steady-state permeation speed (Js, the μ gcm of medicine
-2H
-1) and time lag (h) such as following table.As can be seen from the figure, after liposome, the skin transmission rates of Quercetin significantly improves, and time lag obviously reduces, and illustrates that liposome has increased the affinity of medicine and skin, increases so that medicine enters the ability of deep skin.
The kinetic parameter of Quercetin solution (QU) and the behavior of Quercetin liposome (LQU) dermal osmosis
The anti-ultraviolet radiation compliance test result of Quercetin flexible lipidosome:
(1) mtt assay detects cell survival rate
The Hacat cell is inoculated in 96 orifice plates with the density of 5000/mL, after cell 90% merges, carries out the experimental station reason.Experimental cell is divided at random the UVB model group and (accepts UVB irradiation but not dosing, exposure dose is 20mJ), normal cell matched group, Quercetin+UVB group and Quercetin liposome+UVB group, both accept respectively the drug treating of 1,2.5,5,12.5 and 25 μ g/mL afterwards.Establish 6 Duplicate Samples for every group, continue respectively to carry out MTT mensuration behind cultivation 24h, the 48h.Every hole adds the MTT 10 μ L of 5g/L, in 37 ℃, the cultivation of 5%CO2 incubator; Add dimethyl sulfoxide (DMSO) 100 μ L behind the 4h, after shaking up, with microplate reader (measuring wavelength 570nm) photometry density (A) value, calculate survival rate, the result as shown in Figure 3, as can be seen from the figure, increase along with drug dose, cell survival rate raises gradually, and along with the increase of incubation time, cell survival rate also raises.
(2) ROS experiment
Coverslip is put into six orifice bores, and (2/hole, inoculum density is 1 * 10 in the hole
6The Hacat cell of individual/mL.Adding concentration behind the cultivation 16h is that 12.5 μ g/mL Quercetins or Quercetin liposome are cultivated 4h, discards culture fluid and uses PBS to clean 3 times, and UVB shines 20mJ, continues afterwards dosing cultivation 24h.The active oxygen detection kit detects, and confocal laser scanning microscope is taken a picture, and the results are shown in Figure 4.Quercetin has significantly reduced the reactive oxygen species of UVB irradiated cells model, and Quercetin liposome group is compared to have with the Quercetin group and protected more significantly effect.
(3) MDA horizontal detection
With the Hacat cell with 1 * 10
6The density of individual/mL is inoculated in six orifice plates, carries out the experimental station reason behind the cultivation 16h.Experimental cell is divided into UVB model group, Quercetin+UVB group and Quercetin liposome+UVB group at random.Give respectively and 1 μ g/mL, 5 μ g/mL, 25 μ g/mL Quercetins or Quercetin liposome cultivation 12h for rear two groups, the UVB model group is given and normal culture fluid is cultivated same time.Discard afterwards culture fluid and use PBS to clean 3 times, UVB shines 20mJ, and two administration groups continue dosing cultivates, and UVB model group culture fluid is cultivated, cell pyrolysis liquid cracking and collecting cell behind the 24h.Measure MDA content according to TBA method detection kit, the BCA test kit is surveyed total protein concentration.The results are shown in Figure 5, Quercetin can reduce the lipid peroxidation that causes owing to UVB irradiation to a certain extent, and this inhibitory action is more remarkable after liposome.
(4) Skin slice
Experimental technique: 40 of Kunming kind female mices, in 5 ages in week, body weight 30 ± 2g is divided into 4 groups at random, is respectively Normal group, UVB irradiation group, Qu suspension gel group (gel-type vehicle consists of Acritamer 940), Qu lipidosome gel group.With animal unnairing, the depilation district is 3.0 * 3.0cm2 approximately with depilatory cream.The drug treating mode: 2h is coated with medicine one time before the ultra-vioket radiation, UVB irradiation group and Normal group are smeared blank gel, accept UVB ultraviolet irradiation dosage 0.64J/cm2 behind the 2h, repaste medicine after the irradiation one time, afterwards every the 8h coating once, the method for 48h collare dislocation is put to death mice.Take off depilation district, back centre skin with skin biopsy, remove subcutaneus adipose tissue as far as possible, normal saline clean by formaldehyde fix, the standby paraffin section of Dehydration, haematoxylin/Yihong dyeing.The nucleus navy blue, endochylema and fibrous tissue are the redness that the depth does not wait.The section result as shown in Figure 6, we can find out from figure:
Normal group: skin is without the edema phenomenon, the fine and close not damaged of horny layer, and arrangement of collagen fibers is orderly, and without obvious inflammatory cell, blood capillary is without hyperemia;
UVB irradiation group: hydroderma is obvious, and the horny layer damage is obvious, and the collagen fiber fracture is obvious, fall into disarray, inflammatory cells increased;
Qu solution group: skin has the edema phenomenon, and horny layer has damage, and collagen fiber have fracture, and arrange and owe neat, visible inflammatory cell, blood capillary has hyperemia;
Qu liposome group: skin has slight edema, and horny layer is without obvious damage, and arrangement of collagen fibers is orderly, visible a small amount of inflammatory cell, and blood capillary is without hyperemia;
Description of drawings
Fig. 1 is Quercetin solution (QU) and the release profiles of Quercetin liposome (LQU) in PBS7.4.
Fig. 2 is Quercetin solution (QU) and the accumulative total penetration curve of Quercetin liposome (LQU) in PBS7.4.
Fig. 3 is the cell survival rate that Quercetin and Quercetin liposome act on UVB damaging cells 24h and 48h.
Fig. 4 is that Quercetin and Quercetin liposome act on UVB damaging cells model ROS experimental result.
Fig. 5 is that Quercetin and Quercetin liposome act on UVB damaging cells model M DA experimental result.
Fig. 6 is four kinds of Skin slice figure after the different disposal.
Embodiment
Can realize mode of the present invention with the following example explanation:
Embodiment 1: Quercetin 100mg, phosphatidase 11 g, vitamin E 0.05mL and cholesterol 200mg are dissolved in the 10mL ethanol; sodium cholate 200mg, mannitol 1g, the freeze-dried mixed protective agent of lactose 500mg are dissolved in the 100mL purified water; ethanol and water are put into respectively 55 ℃ of waters bath with thermostatic control; into aqueous phase is poured alcoholic solution in magnetic agitation limit, limit; ethanol is removed in evaporation; continue to stir 30min. with liposome solutions through microporous filter membrane (0.22 μ m) filter 23-5;-80 ℃ of pre-freeze 24h put into the decompression freezer dryer and carry out namely getting lipid freeze-dry powder behind the dry 48h.
Embodiment 2: Quercetin 10mg; phosphatidase 11 .2g; DOTAP 200mg; vitamin E 0.05mL and cholesterol 600mg are dissolved in the 10mL ethanol; mannitol 1g; the freeze-dried mixed protective agent of lactose 500mg and sodium cholate 300mg; poloxamer 100mg is dissolved in the 100mL purified water; ethanol and water are put into respectively 55 ℃ of waters bath with thermostatic control; into aqueous phase is poured alcoholic solution in magnetic agitation limit, limit; ethanol is removed in evaporation; continue to stir 30min. with liposome solutions through microporous filter membrane (0.22 μ m) filter 23-5;-80 ℃ of pre-freeze 24h put into the decompression freezer dryer and carry out namely getting lipid freeze-dry powder behind the dry 48h.
Embodiment 3: Quercetin 50mg, phosphatidase 15 00mg, sodium sulfite 0.05mg and cholesterol 150mg are dissolved in the 100mL chloroform; sodium cholate 50mg, poloxamer 50mg mannitol 500mg, the freeze-dried mixed protective agent of glucose 300mg are dissolved in the 100mL purified water; pour organic facies in pear shape bottle solvent removed by evaporation at reduced pressure; continue decompression 24h; then pour 45 ℃ of waters bath with thermostatic control of water into and stir, continue to stir 2h.Through microporous filter membrane (0.22 μ m) filter 23-5 ,-80 ℃ of pre-freeze 24h put into the decompression freezer dryer and carry out namely getting lipid freeze-dry powder behind the dry 48h with liposome solutions.
Embodiment 4: Quercetin 30mg, phosphatidase 13 00mg, sodium sulfite 0.05mg and cholesterol 25mg are dissolved in the 100mL chloroform; poloxamer 50mg, Tween80 50mg, mannitol 300mg, the freeze-dried mixed protective agent of glucose 100mg are dissolved in the 100mL purified water; pour organic facies in pear shape bottle solvent removed by evaporation at reduced pressure; continue decompression 24h; then pour 45 ℃ of waters bath with thermostatic control of water into and stir, continue to stir 2h.Through microporous filter membrane (0.22 μ m) filter 23-5 ,-80 ℃ of pre-freeze 24h put into the decompression freezer dryer and carry out namely getting lipid freeze-dry powder behind the dry 48h with liposome solutions.
Embodiment 5: Quercetin 70mg, phosphatidase 11 00mg, phosphatidylinositols 300mg, vitamin E 0.05mL and cholesterol 200mg are dissolved in the 100mL chloroform; trehalose 300mg, glucose 100mg, the freeze-dried mixed protective agent of sucrose 200mg and sodium cholate 100mg are dissolved in the 100mL normal saline; pour organic facies in pear shape bottle solvent removed by evaporation at reduced pressure; continue decompression 24h; then pour 45 ℃ of waters bath with thermostatic control of water into and stir, continue to stir 2h.Through microporous filter membrane (0.22 μ m) filter 23-5 ,-80 ℃ of pre-freeze 24h put into the decompression freezer dryer and carry out namely getting lipid freeze-dry powder behind the dry 48h with liposome solutions.
Embodiment 6: Quercetin 50mg, phosphatidase 13 00mg, phosphatidylinositols 300mg, vitamin E 0.05mL and cholesterol 200mg are dissolved in the 100mL chloroform, sodium cholate 100mg is dissolved in the 100mL normal saline, pour organic facies in pear shape bottle solvent removed by evaporation at reduced pressure, continue decompression 24h, then pour 45 ℃ of waters bath with thermostatic control of water into and stir, continue to stir 2h.Trehalose 300mg, glucose 100mg, the freeze-dried mixed protective agent of sucrose 200mg join in the liposome solutions; with liposome solutions through microporous filter membrane (0.22 μ m) filter 23-5;-80 ℃ of pre-freeze 24h put into the decompression freezer dryer and carry out namely getting lipid freeze-dry powder behind the dry 48h.
Claims (15)
1. a Quercetin Dermatological Liposomes and lyophilized powder thereof is characterized in that, the liposome solutions of every 100mL is to be prepared from by following material:
Quercetin 0.01g-0.1g, amphipathic lipids 0.1g-1.2g, cholesterol 0.025g-0.6g, surfactant 0.05g-3g, antioxidant 0.001g-0.5g, all the other are aqueous medium.
2. a kind of Quercetin Dermatological Liposomes according to claim 1 and lyophilized powder thereof, it is characterized in that, described amphipathic lipids mixture refers to egg phosphatide, fabaceous lecithin, cephalin, hydrolecithin, 1,2-two oleoyl oxygen propyl group-N, N, N-trimethylammonium bromide, phosphatidylinositols, phosphatidyl glycerol, Phosphatidylserine, phosphatidic acid, PHOSPHATIDYL ETHANOLAMINE, phosphatidylcholine, sphingomyelins one or more.
3. a kind of Quercetin Dermatological Liposomes according to claim 1 and lyophilized powder thereof is characterized in that described surfactant comprises one or more in cholic acid, sodium cholate, Tween20, Tween60, Tween80, Span20, Span60, Span65, the poloxamer.
4. a kind of Quercetin Dermatological Liposomes according to claim 1 and lyophilized powder thereof, the antioxidant sodium sulfite that it is characterized in that stating, sodium pyrosulfite, sodium sulfite, sodium thiosulfate, disodium edetate, vitamin E one or more.
5. a kind of Quercetin Dermatological Liposomes according to claim 1 and lyophilized powder thereof is characterized in that described aqueous medium is comprised of pure water and water-soluble substances.
6. a kind of Quercetin Dermatological Liposomes according to claim 5 and lyophilized powder thereof is characterized in that described water-soluble substances comprises organic acid, organic salt, mineral acid, inorganic salt, monosaccharide, disaccharide and compositions thereof.
7. the preparation method of arbitrary described a kind of Quercetin Dermatological Liposomes and lyophilized powder thereof is characterized in that according to claim 1-6, comprises being prepared as follows step:
(1) Quercetin and amphipathic lipids are dissolved in one or more organic solvents as organic facies, make it abundant dissolving with ultrasound wave, then antioxidant is added in the organic phase solution.
(2) surfactant fully is dissolved in the aqueous medium as water;
(3) remove organic solvent before or after organic facies is mixed with water, form the liposome solutions that disperses homogeneous, then add freeze drying protectant.
(4) to the liposome solutions of step (3) gained with the membrane filtration of 0.22 μ m 3-5 time, add an amount of freeze drying protectant and fully dissolve ,-80 ℃ of pre-freeze 24h put into the decompression freezer dryer and carry out namely getting lipid freeze-dry powder behind the dry 48h.
8. the preparation method of a kind of Quercetin Dermatological Liposomes according to claim 7 and lyophilized powder thereof is characterized in that, described antioxidant can add in the organic facies after the step (1), also can add aqueous phase after step (2).
9. the preparation method of a kind of Quercetin Dermatological Liposomes according to claim 7 and lyophilized powder thereof; it is characterized in that; the adding method of described freeze drying protectant can join aqueous phase after the step (2), also can join in the liposome solutions for preparing after step (3).
10. the preparation method of a kind of Quercetin Dermatological Liposomes according to claim 7 and lyophilized powder thereof, it is characterized in that, described step is removed organic solvent in (3), namely can be before organic facies and water mix, and also can be after machine phase and water mix.
11. the preparation method of a kind of Quercetin Dermatological Liposomes according to claim 7 and lyophilized powder thereof is characterized in that, the described organic solvent method of removing of step (3) has evaporation, lyophilization, ultra-sonic.
12. the preparation method of a kind of Quercetin Dermatological Liposomes according to claim 7 and lyophilized powder thereof is characterized in that, the method that described lyophilizing is used comprises freeze-drying and spray drying method.
13. the preparation method of a kind of Quercetin Dermatological Liposomes according to claim 7 and lyophilized powder thereof; it is characterized in that; the freeze drying protectant that described lyophilizing is used includes one or more in glucosan, glucose, lactose, mannitol, sucrose, glycine, trehalose, sorbitol, glycerol, fructose, xylitol, the galactose, and consumption is 2-10g/100mL.
14. the preparation method of a kind of Quercetin Dermatological Liposomes according to claim 7 and lyophilized powder thereof; it is characterized in that; described freeze drying protectant can join aqueous phase when the preparation liposome solutions, also can join before lyophilizing in the liposome solutions for preparing.
15. according to claim 1-15 described Quercetin Dermatological Liposomes and lyophilized powder thereof, it is characterized in that, described liposome and lyophilized powder thereof are preparation for external application to skin, be suitable for antioxidation, antiinflammatory, anti-ultraviolet radiation damage, anti-skin carcinoma, edema, erythema, pigmentation, inflammation, immunosuppressant that ultra-violet radiation resisting is caused.
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Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104172184A (en) * | 2014-08-15 | 2014-12-03 | 东南大学 | Quercetin nanostructured lipid carrier and preparation method thereof |
| WO2016007114A1 (en) * | 2014-07-08 | 2016-01-14 | Tovaristvo Z Obmezhenou Vidpovidalnistu "Nanomedtrast" | Method of obtaining a pharmacologically active liposomal quercetin-containing product |
| CN106236711A (en) * | 2016-08-25 | 2016-12-21 | 广东工业大学 | Phloretin liposome and preparation method thereof |
| CN106943595A (en) * | 2017-03-30 | 2017-07-14 | 福州大学 | Src/Abl inhibitor is used as the application for preventing or treating radiation injury medicine |
| CN106943308A (en) * | 2017-02-28 | 2017-07-14 | 西安科艺诗生物技术有限公司 | A kind of liposome lyophilized composition and purposes |
| CN107468533A (en) * | 2017-08-22 | 2017-12-15 | 广州聚注通用技术研究院有限公司 | Saussurea involucrata Quercetin with radiation-resisting whitening activity and its preparation method and application |
| CN108042492A (en) * | 2017-12-18 | 2018-05-18 | 成都大学 | A kind of bitter buckwheat flavone lipid polymer nanoparticle and preparation method thereof |
| CN110051586A (en) * | 2019-04-30 | 2019-07-26 | 深圳市墨脱生物科技有限责任公司 | Plateau cuckoo extract damages and moves the purposes of nursing for protectiving ultraviolet |
| CN111972417A (en) * | 2020-08-27 | 2020-11-24 | 中国农业科学院烟草研究所 | Preparation of quercetin nanoliposome and anti-TMV activity research method |
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| WO2016007114A1 (en) * | 2014-07-08 | 2016-01-14 | Tovaristvo Z Obmezhenou Vidpovidalnistu "Nanomedtrast" | Method of obtaining a pharmacologically active liposomal quercetin-containing product |
| US20170196808A1 (en) * | 2014-07-08 | 2017-07-13 | Tovaristvo Z Obmezhenou Vidpovidalnistu 'nanomedtrast' | Method of obtaining a pharmacologically active liposomal quercetin-containing product |
| CN104172184A (en) * | 2014-08-15 | 2014-12-03 | 东南大学 | Quercetin nanostructured lipid carrier and preparation method thereof |
| CN106236711A (en) * | 2016-08-25 | 2016-12-21 | 广东工业大学 | Phloretin liposome and preparation method thereof |
| CN106943308A (en) * | 2017-02-28 | 2017-07-14 | 西安科艺诗生物技术有限公司 | A kind of liposome lyophilized composition and purposes |
| CN106943595A (en) * | 2017-03-30 | 2017-07-14 | 福州大学 | Src/Abl inhibitor is used as the application for preventing or treating radiation injury medicine |
| CN107468533A (en) * | 2017-08-22 | 2017-12-15 | 广州聚注通用技术研究院有限公司 | Saussurea involucrata Quercetin with radiation-resisting whitening activity and its preparation method and application |
| CN108042492B (en) * | 2017-12-18 | 2020-06-16 | 成都大学 | Tartary buckwheat flavone lipid polymer nanoparticles and preparation method thereof |
| CN108042492A (en) * | 2017-12-18 | 2018-05-18 | 成都大学 | A kind of bitter buckwheat flavone lipid polymer nanoparticle and preparation method thereof |
| CN110051586A (en) * | 2019-04-30 | 2019-07-26 | 深圳市墨脱生物科技有限责任公司 | Plateau cuckoo extract damages and moves the purposes of nursing for protectiving ultraviolet |
| CN110051586B (en) * | 2019-04-30 | 2022-03-15 | 深圳市墨脱生物科技有限责任公司 | Application of plateau rhododendron extract in protection against ultraviolet ray injury and sports care |
| CN114080215A (en) * | 2019-08-14 | 2022-02-22 | 韩国科玛株式会社 | Elastomeric liposome composition comprising sucrose-based surfactant and cosmetic composition containing the same |
| CN111972417A (en) * | 2020-08-27 | 2020-11-24 | 中国农业科学院烟草研究所 | Preparation of quercetin nanoliposome and anti-TMV activity research method |
| CN113842383A (en) * | 2021-09-26 | 2021-12-28 | 中国科学院昆明植物研究所 | Application of viscapine-1 in preparation of anti-UVB (ultraviolet B) radiation preparation |
| CN114989124A (en) * | 2022-06-15 | 2022-09-02 | 华中科技大学同济医学院附属协和医院 | Method for extracting quercetin from herba Hedyotidis Diffusae, and preparation method and liposome product of liposome thereof |
| CN115778866A (en) * | 2022-12-29 | 2023-03-14 | 云南大学 | Application of Cephalotaxus fortunei extract in cosmetics or preparing medicines |
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