CN112999158B - Preparation method and application of policosanol nano-liposome - Google Patents
Preparation method and application of policosanol nano-liposome Download PDFInfo
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- CN112999158B CN112999158B CN202110234301.0A CN202110234301A CN112999158B CN 112999158 B CN112999158 B CN 112999158B CN 202110234301 A CN202110234301 A CN 202110234301A CN 112999158 B CN112999158 B CN 112999158B
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- 239000002502 liposome Substances 0.000 title claims abstract description 60
- 229960001109 policosanol Drugs 0.000 title claims abstract description 52
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 title claims abstract description 52
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- 239000000725 suspension Substances 0.000 claims abstract description 14
- 238000011282 treatment Methods 0.000 claims abstract description 13
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims abstract description 11
- 229940083466 soybean lecithin Drugs 0.000 claims abstract description 11
- 238000005406 washing Methods 0.000 claims abstract description 11
- VCOPTHOUUNAYKQ-WBTCAYNUSA-N (3s)-3,6-diamino-n-[[(2s,5s,8e,11s,15s)-15-amino-11-[(6r)-2-amino-1,4,5,6-tetrahydropyrimidin-6-yl]-8-[(carbamoylamino)methylidene]-2-(hydroxymethyl)-3,6,9,12,16-pentaoxo-1,4,7,10,13-pentazacyclohexadec-5-yl]methyl]hexanamide;(3s)-3,6-diamino-n-[[(2s,5s,8 Chemical compound N1C(=O)\C(=C/NC(N)=O)NC(=O)[C@H](CNC(=O)C[C@@H](N)CCCN)NC(=O)[C@H](C)NC(=O)[C@@H](N)CNC(=O)[C@@H]1[C@@H]1NC(N)=NCC1.N1C(=O)\C(=C/NC(N)=O)NC(=O)[C@H](CNC(=O)C[C@@H](N)CCCN)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CNC(=O)[C@@H]1[C@@H]1NC(N)=NCC1 VCOPTHOUUNAYKQ-WBTCAYNUSA-N 0.000 claims abstract description 10
- PBWOIPCULUXTNY-UHFFFAOYSA-N Sitosterylacetat Natural products C1C=C2CC(OC(C)=O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 PBWOIPCULUXTNY-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 10
- IZEUIYYDWBKERE-UHFFFAOYSA-N stigmasteryl acetate Natural products C1C=C2CC(OC(C)=O)CCC2(C)C2C1C1CCC(C(C)C=CC(CC)C(C)C)C1(C)CC2 IZEUIYYDWBKERE-UHFFFAOYSA-N 0.000 claims abstract description 10
- 230000001804 emulsifying effect Effects 0.000 claims abstract description 9
- 239000012528 membrane Substances 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 8
- 238000001704 evaporation Methods 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 238000004945 emulsification Methods 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 9
- 239000008055 phosphate buffer solution Substances 0.000 claims description 8
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 6
- 229920000053 polysorbate 80 Polymers 0.000 claims description 6
- 230000008020 evaporation Effects 0.000 claims description 4
- 239000008363 phosphate buffer Substances 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 15
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 abstract description 13
- 235000012000 cholesterol Nutrition 0.000 abstract description 7
- 230000007547 defect Effects 0.000 abstract description 5
- 208000031226 Hyperlipidaemia Diseases 0.000 abstract description 2
- CNNRPFQICPFDPO-UHFFFAOYSA-N octacosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCO CNNRPFQICPFDPO-UHFFFAOYSA-N 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 229960002666 1-octacosanol Drugs 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 5
- 239000004170 rice bran wax Substances 0.000 description 5
- 235000019384 rice bran wax Nutrition 0.000 description 5
- 238000002390 rotary evaporation Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000010408 film Substances 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 239000003350 kerosene Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000007670 refining Methods 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 230000001925 catabolic effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 150000001841 cholesterols Chemical class 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 201000005577 familial hyperlipidemia Diseases 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 150000002433 hydrophilic molecules Chemical class 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 235000021067 refined food Nutrition 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 239000010497 wheat germ oil Substances 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
- A23L33/11—Plant sterols or derivatives thereof, e.g. phytosterols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
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- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
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- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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Abstract
The invention relates to a preparation method and application of policosanol nano liposome, belonging to the technical field of medicine, wherein the preparation method of the policosanol nano liposome comprises the following steps: (1) dissolving policosanol, soybean lecithin, beta-sitosterol acetate and an emulsifier in a solvent, evaporating to prepare a membrane, and washing, dispersing and emulsifying to obtain a liposome suspension; (2) and carrying out dynamic high-pressure micro-jet treatment on the liposome suspension to obtain the policosanol nano-liposome. The preparation method of the invention not only overcomes the defect of poor water solubility of policosanol, but also realizes that phytosterol replaces cholesterol, so that the product is suitable for people with hyperlipidemia, and the obtained liposome has stable property, high bioavailability and good storage stability.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a preparation method and application of a policosanol nano liposome.
Background
Polycosanol is a naturally occurring higher alkanol, the main component of which is octacosanol, the appearance of which is white powder or flaky crystal, is soluble in organic solvent and insoluble in water, and is mainly present in natural products such as cane wax, rice bran wax, wheat germ oil, beeswax, insect wax and the like. Multiple studies show that policosanol has unique physiological functions of enhancing endurance, resisting fatigue, reducing blood fat, resisting inflammation, protecting liver and the like, but has poor water solubility and low bioavailability, and restricts the application of policosanol in health-care food and medicines.
Liposomes are composed of one or more lipid bilayers, with hydrophilic compounds embedded in the aqueous core of the liposome and lipophilic drugs embedded in the lipid hydrophobic bilayer. The structure of the liposome is similar to that of a vesicle of a biological membrane, can directly enter cells, can also be adsorbed on the outer layer of target cells, can be metabolized and degraded by own catabolic enzymes of organisms, has few adverse reactions, and has the advantages of good biocompatibility, targeting property and drug release control. The dynamic high-pressure microjet is a high-pressure homogenizing technology, and utilizes hydraulic pump to make fluid produce high pressure, in the microchannel in the impact cavity the fluid is dispersed into several strands of fine flows to make strong high-speed impact, in the course of said process a large pressure drop is instantaneously produced, so that the comprehensive actions of high-speed impact, high-frequency shearing, cavitation, high-frequency vibration and instantaneous pressure drop can be implemented, and the goal of refining, emulsifying, homogenizing and modifying material can be reached.
The patent with publication number CN109077943A uses taurine, dichloromethane and cholesterol for ultrasonic emulsification to obtain liposome, although cholesterol can improve the characteristics of liposome membrane, the patients with hypercholesterolemia should avoid eating food containing cholesterol, which limits the application range to a certain extent, and the dichloromethane is listed in 2A carcinogen and toxic harmful atmospheric pollutants list in 2019, the preparation method is not environment-friendly and does not reach the requirement of increasingly refined food industry. Therefore, it is very important to find a method which can improve the water solubility and bioavailability of the policosanol and has a wide application range.
Disclosure of Invention
In order to solve the defects of the prior art, the invention aims to provide a preparation method and application of a policosanol nano liposome, which not only overcome the defect of poor water solubility of policosanol, but also realize the replacement of cholesterol by phytosterol, and the obtained liposome has stable property and high bioavailability.
In order to solve the technical problems, the invention provides the following technical scheme:
the invention provides a preparation method of policosanol nano-liposome, which comprises the following steps:
(1) dissolving policosanol, soybean lecithin, beta-sitosterol acetate and an emulsifier in a solvent, evaporating to prepare a membrane, and washing, dispersing and emulsifying to obtain a liposome suspension;
(2) and carrying out dynamic high-pressure micro-jet treatment on the liposome suspension to obtain the policosanol nano-liposome.
Preferably, the mass percentage of the policosanol in the policosanol nano liposome is 10% -25%.
Preferably, the content of the soybean lecithin in the policosanol nano liposome is 50-60% by mass.
Preferably, the mass percentage of the beta-sitosterol acetate in the policosanol nano liposome is 15-25%.
Preferably, the emulsifier is tween 80; the mass percentage of the emulsifier in the policosanol nano liposome is 1.5-3%.
Preferably, the temperature of the evaporation is 42-48 ℃.
Preferably, the washing membrane adopts phosphate buffer solution; the mass concentration of the phosphate buffer solution is 1%, and the pH value is 7.5.
Preferably, the emulsification is ultrasonic emulsification, and the time of the ultrasonic emulsification is 10-20 min.
Preferably, the pressure of the dynamic high-pressure micro-jet treatment is 100-200MPa, and the treatment times are 2-5 times.
The invention also provides the application of the policosanol nano liposome prepared by the preparation method in health-care food or medicines.
The invention provides a preparation method of policosanol nano liposome, which is characterized in that dynamic high-pressure micro-jet treatment is used for preparing the policosanol nano liposome for the first time, so that the defect of poor water solubility of policosanol is overcome, the substitution of cholesterol by phytosterol is realized, the product is suitable for hyperlipidemia people, and the obtained liposome has stable property, high bioavailability and good storage stability.
Detailed Description
The invention provides a preparation method of policosanol nano-liposome, which comprises the following steps:
(1) dissolving policosanol, soybean lecithin, beta-sitosterol acetate and an emulsifier in a solvent, evaporating to prepare a membrane, and washing, dispersing and emulsifying to obtain a liposome suspension;
(2) and carrying out dynamic high-pressure micro-jet treatment on the liposome suspension to obtain the policosanol nano-liposome.
In the present invention, the mass percentage of the polycosanol in the polycosanol nanoliposome is preferably 10% to 25%, and more preferably 15% to 22%. In the present invention, the polycosanols comprise octacosanol; the content of the octacosanol in the polycosanol is preferably 13-95% by mass. The present invention does not require any particular type of component of the polycosanols other than octacosanol. The polycosanols of the present invention are not particularly limited in their source, and may be prepared using commercially available products known to those skilled in the art or using preparative methods known to those skilled in the art. In particular embodiments of the present invention, the polycosanols are preferably prepared; the polycosanol is preferably prepared by a process comprising: mixing rice bran wax, absolute ethyl alcohol, aviation kerosene and sodium hydroxide, heating to boil, stirring and refluxing for 4.5 hours, washing for 3 times by using hot water, standing to remove a lower-layer water phase, washing a supernatant to be neutral, and sequentially cooling overnight, vacuum-filtering, desolventizing a filter cake and drying to obtain the polycosanol. In the present invention, the volume ratio of the rice bran wax, the absolute ethyl alcohol and the aviation kerosene is preferably 1: 3: 7; the mass ratio of the rice bran wax to the sodium hydroxide is 1: 0.12.
when the octacosanol accounts for more than 15 percent of the polycosanol, the invention also preferably rectifies the polycosanol crude product; in the present invention, the working pressure of the rectification is preferably 20 to 50Pa, more preferably 30 to 40 Pa; the temperature of the kettle is preferably 200-250 ℃, more preferably 210-240 ℃, and most preferably 220-230 ℃; the reflux ratio is preferably 1: (5-20), more preferably 1 (8-16), most preferably 1: (10-13); after the distillation is finished, the invention preferably collects the fraction with the overhead temperature of 220 ℃ and 230 ℃.
In the present invention, the content of the soybean lecithin in the polycosanol nanoliposome is preferably 50 to 60% by mass, and more preferably 52 to 59% by mass. In the present invention, the content of the β -sitosterol acetate in the policosanol nanoliposome is preferably 15 to 25% by mass, and more preferably 18 to 22% by mass. In the invention, the emulsifier is preferably tween 80; the mass percentage of the emulsifier in the policosanol nano liposome is preferably 1.5-3%, and more preferably 1.8-2.8%. In the invention, the solvent is preferably absolute ethyl alcohol, and the volume mass ratio of the absolute ethyl alcohol to the soybean lecithin is preferably (25-50) mL: 1g, more preferably (30-45) mL: 1g of the total weight of the composition.
In the present invention, the evaporation is preferably vacuum rotary evaporation; the temperature of the vacuum rotary evaporation is preferably 42-48 ℃, more preferably 45 ℃. In the present invention, the evaporation is to remove ethanol and form a thin film.
In the invention, the washing membrane preferably adopts phosphate buffer solution; the phosphate buffer solution preferably has a concentration of 1% by mass and a pH of 7.5. In the present invention, the amount of the phosphate buffer to be added is preferably 30 to 50mL, more preferably 35 to 45 mL.
In the present invention, the time for the dispersion is preferably 2 to 10min, more preferably 5 to 9 min. The method of dispersion in the present invention is not particularly limited, and a conventional dispersion method in the art may be used. In the present invention, the emulsification is preferably ultrasonic emulsification; the time of the ultrasonic emulsification is preferably 10 to 20min, more preferably 15 to 18 min.
In the invention, the pressure of the dynamic high-pressure micro-jet treatment is preferably 100-200MPa, and more preferably 120-180 MPa; the number of the dynamic high-pressure microjet treatments is preferably 2 to 5, more preferably 4. In the invention, the dynamic high-pressure micro-jet treatment has the functions of refining, emulsifying and homogenizing, so that the particle size of the prepared liposome is smaller, and the improvement of the emulsifying property and the stability of the liposome is facilitated.
The invention also provides the application of the policosanol nano liposome prepared by the preparation method in health-care food or medicines. The specific method of application of the present invention is not particularly limited, and the conventional application method in the art may be employed.
The sources of the raw material components are not particularly limited in the invention, and the raw material components can be obtained by adopting conventional commercial products.
In order to further illustrate the present invention, the following embodiments are described in detail, but they should not be construed as limiting the scope of the present invention.
Example 1
1. Preparing policosanol with the content of octacosanol of 15 percent by mass
Taking 10kg of rice bran wax, adding 3 times of volume of absolute ethyl alcohol, 7 times of volume of aviation kerosene and 0.12 time of sodium hydroxide, heating in a water bath to boil, stirring and refluxing for reaction for 4.5 hours, washing for 3 times by using 5 times of volume of hot water, removing a lower-layer water phase, washing until the pH value is about 7, cooling the upper-layer clear liquid overnight, carrying out vacuum filtration to obtain a filter cake, desolventizing the filter cake, and drying to obtain the policosanol.
2. Preparation of Polycosanol nanoliposomes
Weighing 0.50g of polycosanol, 1.5g of soybean lecithin, 0.45g of beta-sitosterol acetate and 0.05g of tween-80, dissolving in 37.5mL of absolute ethanol, fully stirring and dissolving, performing vacuum rotary evaporation to remove ethanol to form a film under the condition of 40 ℃ water bath, slowly injecting into 40mL of 1% phosphate buffer solution (pH is 7.4), dispersing for 2min, and performing ultrasonic emulsification for 10min to obtain a liposome suspension. Treating the liposome suspension for 4 times under 140MPa by using dynamic high-pressure micro-jet to obtain the policosanol nano-liposome, wherein the prepared nano-liposome is a milky white solution.
Example 2
1. Preparation of policosanol with the content of octacosanol of 50% by weight
At a working pressure of 20Pa, a kettle temperature of 210 ℃ and a reflux ratio of 1: the polycosanol (containing 15% octacosanol) prepared in example 1 was distilled under 10 deg.C, and the distillate at the column top temperature of 220-.
2. Preparation of Polycosanol nanoliposomes
Weighing 0.90g of polycosanol, 5.4g of soybean lecithin, 2.25g of beta-sitosterol acetate and 0.45g of tween-80, dissolving in 135mL of absolute ethanol, fully stirring and dissolving, removing the ethanol by vacuum rotary evaporation at 40 ℃ in a water bath condition to form a film, slowly injecting into 80mL of 1% phosphate buffer solution (with the pH value of 7.4), dispersing for 2min, and ultrasonically emulsifying for 10min to obtain a liposome suspension. Treating the liposome suspension for 4 times under 140MPa by using dynamic high-pressure micro-jet to obtain policosanol nano-liposome, wherein the prepared nano-liposome is a milky white solution.
Example 3
1. Preparing policosanol with the octacosanol content of 95 percent by mass
At the working pressure of 50Pa, the kettle temperature of 230 ℃ and the reflux ratio of 1: the polycosanol (50% octacosanol) prepared in example 2 was distilled under 20 deg.C and the distillate collected at 220-230 deg.C from the top of the column was collected to obtain polycosanol (95% octacosanol).
2. Preparation of Polycosanol nanoliposomes
Weighing 0.50g of polycosanol, 1.25g of soybean lecithin, 0.625g of beta-sitosterol acetate and 0.125g of tween-80, dissolving in 31.25mL of absolute ethanol, fully stirring and dissolving, removing the ethanol by vacuum rotary evaporation at 40 ℃ in a water bath condition to form a film, slowly injecting into 40mL of 1% phosphate buffer solution (pH is 7.4), dispersing for 2min, and ultrasonically emulsifying for 10min to obtain a liposome suspension. Treating the liposome suspension for 4 times under 140MPa by using dynamic high-pressure micro-jet to obtain policosanol nano-liposome, wherein the prepared nano-liposome is a milky white solution.
Example 4
The particle size, dispersion coefficient and zeta potential of the policosanol nanoliposomes obtained in examples 1-3 were measured using a potential-particle size analyzer. Entrapment efficiency was calculated by measuring the polycosanol content of the liposomes before and after centrifugation using gas chromatography, and the following table 1 was obtained.
Wherein the encapsulation ratio (%) ═ encapsulated polycosanol content (mg)/total added polycosanol content (mg) × 100.
TABLE 1 Polycosanol nanoliposomes
Example 5
The particle size and zeta potential of the policosanol nanoliposomes before and after the dynamic high pressure microfluidization treatment in examples 1-3 were measured using a potential-particle size analyzer, and the following table 2 was obtained.
TABLE 2 Polycosanol nanoliposomes' relevant parameters
It can be seen that the policosanol nano liposome prepared by the preparation method has the average particle size of about 104.13nm and the zeta potential of-38.5 mV, not only overcomes the defect of poor water solubility, but also realizes that phytosterol replaces cholesterol so that the product is suitable for hyperlipemia crowds. And the encapsulation rate of the obtained policosanol nano liposome reaches 95%, and the obtained policosanol nano liposome has high bioavailability, stable property and good storage stability, and is generally suitable for the public.
The above description is only an embodiment of the present invention, and not intended to limit the scope of the present invention, and all modifications of equivalent structures and equivalent processes, which are made by the present specification, or directly or indirectly applied to other related technical fields, are included in the scope of the present invention.
Claims (4)
1. A preparation method of policosanol nano-liposome is characterized by comprising the following steps:
(1) dissolving policosanol, soybean lecithin, beta-sitosterol acetate and an emulsifier in a solvent, evaporating to prepare a membrane, and washing, dispersing and emulsifying to obtain a liposome suspension; the mass percentage of the policosanol in the policosanol nano liposome is 10% -25%; the mass percentage of the soybean lecithin in the policosanol nano liposome is 50-60%; the mass percentage content of the beta-sitosterol acetate in the policosanol nano liposome is 15-25 percent; the emulsifier is tween 80; the mass percentage of the emulsifier in the policosanol nano liposome is 1.5-3%; the emulsification is ultrasonic emulsification, and the time of the ultrasonic emulsification is 10-20 min;
(2) carrying out dynamic high-pressure micro-jet treatment on the liposome suspension to obtain the policosanol nano-liposome; the pressure of the dynamic high-pressure micro-jet treatment is 140-200MPa, and the treatment times are 2-5 times.
2. The method of claim 1, wherein the temperature of the evaporation is 42-48 ℃.
3. The preparation method according to claim 1, wherein the washing membrane is phosphate buffer; the mass concentration of the phosphate buffer solution is 1%, and the pH value is 7.5.
4. Use of the policosanol nanoliposome prepared by the preparation method according to any one of claims 1 to 3 in the preparation of a medicament.
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