CN106727324B - Nano silver liposome and its preparation method and application - Google Patents
Nano silver liposome and its preparation method and application Download PDFInfo
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- CN106727324B CN106727324B CN201611231711.5A CN201611231711A CN106727324B CN 106727324 B CN106727324 B CN 106727324B CN 201611231711 A CN201611231711 A CN 201611231711A CN 106727324 B CN106727324 B CN 106727324B
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- 238000005406 washing Methods 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/38—Silver; Compounds thereof
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- 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
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1277—Processes for preparing; Proliposomes
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Abstract
The present invention provides a kind of nano silver liposomes and its preparation method and application, it is related to liposome technology field, the nano silver liposome is mainly by nano silver, lecithin, cholesterol, antioxidant, metal chelating agent, emulsifier, the raw materials such as anti-polymerizer and water form, using liposome nano silver, pass through the synergistic effect of nano silver and liposome, improve the ability that nano silver breaks through human body cell barrier, so as to drastically increase the speed that nano silver enters microbial cell, and assemble the drug effect to form high concentration in perilesional, while ensureing safe, reach quick, the purpose persistently sterilized；The present invention also provides the preparation methods of nano silver liposome, the preparation method after each raw material mixing homogeneous by will use super-voltage micro jet nano-equipment to carry out super-voltage micro jet circular treatment, one-step method can obtain nano silver liposome, the preparation method is simple, operation is easy, entire production process is environmentally protective, can industrial mass production.
Description
Technical field
The present invention relates to liposome technology field, in particular to a kind of nano silver liposome and preparation method thereof and
Using.
Background technology
When amphiphatic molecule such as phosphatide and sphingolipid are scattered in water phase, the hydrophobic tail of molecule is tended to flock together, and keeps away
Boiling water phase, and hydrophilic head forms the vesicle with bilayer structure, referred to herein as liposome exposed to water phase
(liposome).Liposome is the vesica of similar biofilm structure, has cellular affinity and histocompatbility, and diameter exists mostly
25-1000nm.This good characteristic that can be blended using liposome and cell membrane, can be widely used in transgenosis,
The fields such as pharmaceutical carrier, to its as research of the research of the performance of pharmaceutical carrier and its interaction with cell also therewith into
For popular scientific research field.
Hydrophobic drug can be encapsulated in hydrophobic portion in lipid bilayer, by parent by liposome as pharmaceutical carrier
Aqueous pharmaceutical is encapsulated in liposome interior hydrophilic region.There are many common drugs, wherein, silver is used as natural antibacterial material,
It is applied to medicinal antibiosis field very early.Early in《Compendium of Materia Medica》Described in：Raw silver is nontoxic；Nineteen sixty-eight, flamazine
(Sulfadiazine Silver) introduces market, can be certainly since it has efficient killing effect to various bacteriums, fungi
So, painlessly wound location is repaired completely, without skin-grafting, it has also become the important drugs for the treatment of wound (as burnt), mesh
It is preceding to be put into national basic medical insurance Drug catalogue.American Public Health office nineteen ninety《Survey report on silver-colored toxicity》
Middle explanation：Silver is to human body without obvious toxic-side effects；Nano silver is local application, and silver content is few, is safest application method.It needs
It is noted that《Compendium of Materia Medica》The raw silver that Li Shizhen (1518-1593 A.D.) refers to, is elemental silver, is nontoxic.It is not silver ion, silver ion has carefully
Cellular toxicity.
Grain size is exactly accomplished nano level metallic silver simple substance by nano silver, as the natural antibacterial material of a new generation, nanometer
Silver has the characteristics that broad-spectrum antiseptic, sterilizing ability are strong, permeability is strong, antibacterial is lasting, has no drug resistance and safe.Nano-Ag particles are straight
Tap into and combined into thalline and oxygen metabolism enzyme (- SH), the unique mechanism of action that thalline is made to be choked to death, can kill be in contact with it is big
The microorganisms such as most bacteriums, fungi, mould, spore, itch mite.It studies and finds through authoritative institution：It is to pathogenic bacteria of drug-resistant such as drug resistance
Escherichia coli, resistant Staphylococcus aureus, drug-resistant pseudomonas aeruginosa, streptococcus pyogenes, drug resistance enterococcus, anaerobic bacteria etc. have comprehensively
Antibacterial activity；The bacterium common to burn and scald and wound surface such as staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, white
Color candida albicans and other G+, G- pathogenic bacteria have bactericidal effect；To chlamydia trachomatis, cause the gonococcus of sexually transmitted disease
Also there is powerful bactericidal effect.According to the antibacterial mechanisms of nano silver, the cell membrane and cell membrane of the necessary Gonna breakthrough bacterium of nano silver
Barrier, into cytoplasm after could destroy the enzyme system in cytoplasm, disturb the metabolism of bacterium or into caryoplasm, destroy
DNA of bacteria.So nano silver needs and carrier combination, through the cell membrane and cell membrane barrier of bacterium, antibiotic and sterilizing is played
Effect.
From the point of view of the document and patent announced at present, most of nano silver preparations are by adding strong oxidizer such as silver nitrate
It obtains, silver nitrate has certain corrosivity and toxicity in itself, can generate Asia with internal microbial reaction under specific circumstances
Nitrate, the latter have severe toxicity, and as a kind of preparation for human body, there are great security risks.Clinically, silver nitrate is used
The nano silver preparation of preparation there are skin allergy rate it is higher the problem of.The nano-silver ionic that tradition is obtained using chemical method, because
With stronger oxidisability, strong redox reaction can be generated with organism, oxygen can be generated with the active mass of organism
Change reduction reaction, so as to lose activity, generate to organism damage (tradition is toxicity), thus be not suitable for acting on human body.Separately
Outside, due to having very big polarity, in face of selectivity by cell membrane and cell membrane, nano-silver ionic is difficult to rapidly enter cell
Matter works.
Inert gas sublimation recrystallization method and chemical deposition prepare nano silver, since it is desired that generating high temperature and using catalysis
Agent, the problem of inevitably running into metallic oxidative deformation, the nano metal material particle diameter distribution prepared is uneven, shape
Shape is irregular, and by detection, particle diameter distribution shape and is unevenly distributed between 20-180nm.
In view of this, it is special to propose the present invention to solve above-mentioned technical problem.
The content of the invention
First of the present invention is designed to provide a kind of nano silver liposome, and the nano silver liposome is mainly by nanometer
The raw materials such as silver, lecithin, cholesterol, antioxidant, metal chelating agent, emulsifier, anti-polymerizer and water form, by nano silver and
The synergistic effect of liposome improves the ability that nano silver breaks through human body cell barrier, enters so as to drastically increase nano silver
The speed of microbial cell, and assemble the drug effect to form high concentration in perilesional, while ensureing safe, reach fast
Speed, the purpose enduringly sterilized；And the nutriment of nano silver liposome is passed into cell while sterilization, it supplements
Cellular energy promotes the growth of cell, improves the self-repairing capability of cell.
Second object of the present invention is to provide a kind of preparation method of nano silver liposome, and the preparation method passes through
After each raw material mixing homogeneous super-voltage micro jet nano-equipment will be used to carry out super-voltage micro jet circular treatment, one-step method
Nano silver liposome is obtained, the preparation method is simple, and operation is easy, and entire production process is environmentally protective, can industrial mass
Production.And the nano silver liposome particles prepared by the method are uniform, stability is high, has good antibiotic effect.
Third object of the present invention is to provide a kind of application of nano silver liposome, by the nano silver lipid system
It is made suitable dosage form to be applied in daily necessities or medical product, so as to play the role of antibacterial anti-inflammatory.
In order to realize the above-mentioned purpose of the present invention, spy uses following technical scheme：
The present invention provides a kind of nano silver liposome, and by weight percentage, the nano silver liposome is mainly by following
Raw material is made：Nano silver 0.005-30%, lecithin 1-3%, cholesterol 0.3-2%, antioxidant 0.1-2%, metal chelating agent
0.1-3%, emulsifier 2-10%, anti-polymerizer 1-5%, water polishing surplus to 100%.
Beneficial effects of the present invention are：A kind of nano silver liposome provided by the invention, the nano silver liposome are main
It is made of raw materials such as nano silver, lecithin, cholesterol, antioxidant, metal chelating agent, emulsifier, anti-polymerizer and water, wherein receiving
Meter Yin is existed in the form of nano silver simple substance, compared with the nano-silver ionic prepared using traditional chemical routes, nano silver list
Matter will not with various bioactivators in organism with reference to and deposit, will not generate toxicity, and with powerful bactericidal effect.
Meanwhile by the synergistic effect of nano silver and liposome, raising nano silver breaks through the ability of human body cell barrier, from
And the speed that nano silver enters microbial cell is drastically increased, and assemble the drug effect to form high concentration in perilesional
Should, while ensureing safe, achieve the purpose that it is quick, enduringly sterilize；And by the battalion of liposome while sterilization
Foster substance passes to cell, supplements cellular energy, promotes the growth of cell, improve the self-repairing capability of cell.
Further, the nano silver liposome is mainly made of following raw material：Nano silver 0.005-30%, lecithin 1-
3%, cholesterol 0.3-2%, antioxidant 0.1-2%, metal chelating agent 0.1-3%, emulsifier 2-10%, anti-polymerizer 1-5%,
Evening primrose oil 1-10%, hyaluronic acid 0.1-3%, collagen 0.1-3%, water polishing surplus to 100%.
Further, the antioxidant is butylated hydroxy anisole (BHA), 2,6- di-tert-butyl-4-methy phenols (BHT)
Or one kind in vitamin E or at least two combination；
And/or the metal chelating agent is one kind in disodium ethylene diamine tetraacetate, sodium ammonium triacetate or Sodium Polyacrylate
Or at least two combination.
Further, the emulsifier is sorbester p17 (SP80), Tween 80 (TW80), fatty glyceride or monostearate
One kind or at least two combination in glyceride；
And/or the anti-polymerizer for one kind in polyethylene glycol, polyvinylpyrrolidone or dimethyl silicone polymer or
At least two combination.
Further, thickener is further included, the weight percent of the thickener is 1-5%, and the thickener is match ratio
Grams 305, PEG-100 stearates or one kind in xanthan gum or at least two combination；
And/or solubilizer is further included, the weight percent of the solubilizer is 1-45%, and the solubilizer is ethyl alcohol, third
One kind or at least two combination in glycol or glycerine；
Further, the lecithin is purified from soybean lecithin or egg yolk lecithin and obtained, phosphorus in the lecithin
The content of phosphatidylcholine is 50-99%；
And/or sulphur is further included, the weight percent of the sulphur is 0.5-10%.
The present invention also provides a kind of preparation methods of nano silver liposome, include the following steps
(1) anti-polymerizer, optionally water, hyaluronic acid and optionally collagen mixing are weighed according to formula ratio, be made
Aqueous mixture；
(2) nano silver, lecithin, cholesterol, antioxidant, metal chelating agent, optionally emulsifier, sulphur are weighed by formula ratio
Sulphur, optionally evening primrose oil and optionally solubilizer mix, and oil mixture is made；
(3) after the oil mixture obtained by step (2) being added to the aqueous mixture in step (1), homogeneous is received
The silver-colored colostrum of rice；
(4) the nano silver colostrum obtained by step (3) is moved in super-voltage micro jet equipment, carries out super-voltage micro jet and follow
Ring processing, obtains nano silver liposome.
The preparation method after each raw material mixing homogeneous by will use super-voltage micro jet nano-equipment to carry out super-pressure
Microjet circular treatment, one-step method can obtain nano silver liposome, and wherein nano silver exists in the form of nano silver simple substance, phase
Than using traditional chemical method using nano silver prepared by silver nitrate, preservative, chloroform, ether and other chemical solvents from
Son, nano silver simple substance will not with various bioactivators in organism with reference to and deposit, will not generate toxicity, reduce skin mistake
Quick rate, can solve the residues such as chloroform, ether, preservative in conventional silver preparation may be to cell and environmental danger substance
The problem of.And the nano silver liposome prepared using the method, nano silver are largely all wrapped in liposome interior, only on a small quantity
Absorption in surface of liposome.Nano silver and liposome act synergistically, and being conducive to nano silver, to rapidly enter cell anti-so as to play
The effect of bacterium anti-inflammatory.
The preparation method is simple, and operation is easy, and entire production process is environmentally protective, can industrial mass production.
Further, in step (2), the temperature of the mixing is 40-60 DEG C；
And/or in step (3), the rotating speed of the homogeneous is 3000-10000rpm, and the time of homogeneous is 1-5min.
Further, in step (4), the super-voltage micro jet circular treatment number is 1-3 times, treatment temperature 0-
4 DEG C, processing pressure 150-250MPa；
And/or after step (4), further include and mix the nano silver liposome obtained by step (4) and the thickener of formula ratio
Stirring is closed, cream shape nano silver liposome is made.
In addition, a kind of application the present invention also provides nano silver liposome in daily necessities or medical product.
The synergistic effect that the nano silver liposome passes through nano silver and liposome so that it is in daily necessities or medicine production
Inside can be with safer efficient entrance biological cell in product, so as to play the role of antibacterial anti-inflammatory.
Description of the drawings
Fig. 1 is the electron microscope of 5 nano silver liposome of embodiment；
Fig. 2 is the electron microscope of 5 nano silver of embodiment；
Fig. 3 is the electron microscope of 1 liposome of comparative example；
Fig. 4 is the laser particle size detection figure of 5 nano silver liposome of embodiment.
Specific embodiment
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and is not construed as limiting the scope of the invention.It is not specified in embodiment specific
Condition person, the condition suggested according to normal condition or manufacturer carry out.Reagents or instruments used without specified manufacturer is
The conventional products that can be obtained by commercially available purchase.
According to an aspect of the invention, there is provided a kind of nano silver liposome, by weight percentage, the nano silver
Liposome is mainly made of following raw material：Nano silver 0.005-30%, lecithin 1-3%, cholesterol 0.3-2%, antioxidant
0.1-2%, metal chelating agent 0.1-3%, emulsifier 2-10%, anti-polymerizer 1-5%, water polishing surplus to 100%.
Beneficial effects of the present invention are：A kind of nano silver liposome provided by the invention, the nano silver liposome are main
It is made of raw materials such as nano silver, lecithin, cholesterol, antioxidant, metal chelating agent, emulsifier, anti-polymerizer and water, wherein receiving
Meter Yin is existed in the form of nano silver simple substance, compared with the nano-silver ionic prepared using traditional chemical routes, nano silver list
Matter will not with various bioactivators in organism with reference to and deposit, will not generate toxicity, and with powerful bactericidal effect
Meanwhile by the synergistic effect of nano silver and liposome, raising nano silver breaks through the ability of human body cell barrier, from
And the speed that nano silver enters microbial cell is drastically increased, and assemble the drug effect to form high concentration in perilesional
Should, while ensureing safe, achieve the purpose that it is quick, enduringly sterilize；And by the battalion of liposome while sterilization
Foster substance passes to cell, supplements cellular energy, promotes the growth of cell, improve the self-repairing capability of cell.
In the present invention, nano silver is atomic structure composition " silver particles ", and neutral is also referred to as nano silver simple substance,
The application of nano silver and its true granular size and whether it is closely related with nano effect, it will not be with a variety of biologies in organism
Active material with reference to and deposit, so toxicity will not be generated.
Nano silver simple substance has the difference of essence with nano-silver ionic.Nano-silver ionic is without nano effect, generally with aqueous solution
Form exists, and silver ion is positively charged " cation ", and electronics, which occurs, by chemical reaction shifts to be formed；Silver ion should
It is unrelated with ionic size with depending on the charged valency of ion attribute itself and institute, more without nano effect.Pass through traditional chemical routes
The nano-silver ionic of acquisition, have very big polarity, in face of selectivity by cell membrane and cell membrane, nano silver be difficult quickly into
Enter cytoplasm to work.Again since it is with stronger oxidisability, can and organism generate strong redox reaction, can be with
The active mass of organism generates redox reaction, so that it loses activity, generating damage to organism, (tradition is poison
Property), thus be not suitable for acting on human body.
Thus, nano silver and its feature of silver ion and formation or its application attribute are all to have the difference of essence
's.
In the present invention, the typical but non-limiting weight percent of nano silver for 0.005%, 0.01%, 0.05%,
0.1%th, 0.25%, 0.5%, 0.8%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%,
16%th, 18%, 20%, 22%, 25%, 28% or 30%.
Lecithin is due to low raw-material cost and is easy to get, therefore often as the main filmogen of liposome.In the present invention
In, the typical but non-limiting weight percent of lecithin is 1%, 1.2%, 1.5%, 1.7%, 1.9%, 2%, 2.2%,
2.5%th, 2.6%, 2.8% or 3%.
Cholesterol is the basic substance for collectively forming cell membrane and liposome with lecithin, and cholesterol, which has, adjusts membrane flow
Property effect, and a certain proportion of cholesterol can with the chemical property of stabilized liposome, improve liposome molecular structure so that
Liposome is significantly reduced by oxidation rate, while can improve the permeability and mobility of liposome membrane.
In the present invention, the typical but non-limiting weight percent of cholesterol for 0.3%, 0.4%, 0.6%, 0.8%,
0.9%th, 1%, 1.2%, 1.5%, 1.7%, 1.9% or 2%.
Further, since the easy oxidation stain of liposome, therefore need to add antioxidant to enhance its oxidation resistance.In this hair
In bright, the typical but non-limiting weight percent of antioxidant is 0.1%, 0.2%, 0.25%, 0.3%, 0.4%, 0.6%,
0.7%th, 0.8%, 0.9%, 1%, 1.2%, 1.4%, 1.5%, 1.6%, 1.8% or 2%.
Metal chelating agent has scattered, suspension effect in itself, and the purpose used mainly prevents heavy metal precipitation, layering
Deng the stabilization of guarantee nano silver liposomal systems.
In the present invention, the typical but non-limiting weight percent of metal chelating agent for 0.1%, 0.2%, 0.25%,
0.3%th, 0.4%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.2%, 1.4%, 1.5%, 1.6%, 1.8%, 2%,
2.2%th, 2.4%, 2.6%, 2.8% or 3.0%.
Emulsifier modification can bring certain promotion to liposome, such as by change surface charge and Lipophilicity,
Feature of lipid film etc., to reach increase envelop rate, the purpose of increasing stability, change vivo biodistribution process.
In the present invention, the typical but non-limiting weight percent of emulsifier for 2%, 3%, 4%, 4.5%, 5%,
6%th, 6.5%, 7%, 8%, 9% or 10%.
To reduce the reunion between nano silver liposome, ensure the stability of nano silver liposome, it is necessary to add in anti-polymerization
Agent.
In the present invention, the typical but non-limiting weight percent of anti-polymerizer for 1%, 1.5%, 1.7%, 2%,
2.2%th, 2.5%, 2.6%, 2.8%, 3%, 3.2%, 3.5%, 3.8%, 4%, 4.2%, 4.5%, 4.8% or 5%.
In the present invention, the typical but non-limiting weight percent of water for 2%, 5%, 10%, 15%, 20%, 25%,
30%th, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 68%, 70%, 72%, 75%, 78%, 80%, 82%,
85%th, 88%, 90%, 92%, 95% or 96%.
In the preferred embodiment of the present invention, the nano silver liposome is mainly made of following raw material：Nanometer
Silver-colored 0.005-30%, lecithin 1-3%, cholesterol 0.3-2%, antioxidant 0.1-2%, metal chelating agent 0.1-3%, emulsifier
2-10%, anti-polymerizer 1-5%, evening primrose oil 1-10%, hyaluronic acid 0.1-3%, collagen 0.1-3%, more than water polishing
It measures to 100%.
Nano silver liposome is a kind of suspension, and aggregation, fusion easily occur during storage, and may cause to be wrapped
The drug leakage buried.The physical and chemical stability of nano silver liposome is related to Multiple factors, and is mutually made between each factor
About, therefore the proportioning between specific raw material composition and content is chosen, must just controls many factors, effectively be received with preparing stabilization
The silver-colored liposome of rice.
By the way that the raw material composition of nano silver liposome is further optimized so that between each raw material composition so that preparation
The stability of nano silver liposome is more preferable, and the ability of penetration cell film is stronger, and slow releasing function is more longlasting.
By adding in evening primrose oil into liposome so that the nutritional ingredient in nano silver liposome is more sufficient.In this hair
In bright, the typical but non-limiting weight percent of evening primrose oil is 1%, 2%, 3%, 4%, 4.5%, 5%, 6%, 6.5%,
7%th, 8%, 9% or 10%.
Hyaluronic acid also known as Hyaluronic Acid are a kind of linear macromolecule acidic mucopolysaccharides of uniqueness, are added into liposome
It can promote the absorption of the drug of package, improve the stability of liposome, be that targeting preparation, sustained release and controlled release preparation are auxiliary well
Material.
In the present invention, hyaluronic acid is added in into nano silver liposome, nano silver liposome can be strengthened to cell membrane
Penetration capacity has certain slow releasing function.The typical but non-limiting weight percent of hyaluronic acid is 0.1%, 0.2%,
0.25%th, 0.3%, 0.4%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.2%, 1.4%, 1.5%, 1.6%, 1.8%,
2%th, 2.2%, 2.5%, 2.6%, 2.8% or 3%.
To further enhance the nutritional ingredient of nano silver liposome, collagen can also be added to.
In the present invention, the typical but non-limiting weight percent of collagen for 0.1%, 0.2%, 0.25%,
0.3%th, 0.4%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.2%, 1.4%, 1.5%, 1.6%, 1.8%, 2%,
2.2%th, 2.5%, 2.6%, 2.8% or 3%.
Herein also it should be noted that water used in the present invention is preferably deionized water.
In the preferred embodiment of the present invention, the antioxidant for butylated hydroxy anisole, 2,6- di-t-butyls-
One kind or at least two combination in 4- methylphenols, vitamin E or vitamin C；
And/or the metal chelating agent is one kind in disodium ethylene diamine tetraacetate, sodium ammonium triacetate or Sodium Polyacrylate
Or at least two combination.
Vitamin E is a kind of liposoluble vitamin, also known as tocopherol, is one of most important antioxidant.It is given birth to using dimension
Plain E or the synergistic effect with vitamin C and BHT can effectively inhibit the oxidation of the lecithin in liposome.By to antioxygen
The species of agent is further qualified, so that the oxidation resistance enhancing of liposome, more stable.
In the preferred embodiment of the present invention, the emulsifier for sorbester p17, Tween 80, fatty glyceride or
One kind or at least two combination in glycerin monostearate；
And/or the anti-polymerizer for one kind in polyethylene glycol, polyvinylpyrrolidone or dimethyl silicone polymer or
At least two combination.
Herein it should be noted that the addition of Tween 80 can allow the envelop rate of nano silver Liposomal suspensions and dispersiveness to become
It obtains more preferably, after adding in Tween 80, drug with nano silver liposome in addition to interacting, also by increase-volume in the micella of Tween 80,
So envelop rate increases.But the content of Tween 80 cannot add in too much, have certain physiological-toxicity.
In the preferred embodiment of the present invention, thickener is further included, the weight percent of the thickener is 1-
5%, the thickener is match Bick 305, PEG-100 stearates or one kind in xanthan gum or at least two combination；
And/or solubilizer is further included, the weight percent of the solubilizer is 1-45%, and the solubilizer is ethyl alcohol, third
One kind or at least two combination in glycol or glycerine.
If you need to which nano silver liposome is made cream shape, thickener may be employed, its denseness is adjusted, to meet reality
Needed for border.In the present invention, the typical but non-limiting weight percent of the thickener for 1%, 1.5%, 2%, 2.5%,
3%th, 3.5%, 4%, 4.5% or 5%.
Since nano silver liposome is mutually made by mixing jointly by oil phase and water, to increase the compatibility of each phase, therefore
Solubilizer can be added, so that nano silver liposome whole system stability is more preferable.
In the present invention, the typical but non-limiting weight percent of the solubilizer for 1%, 3%, 5%, 6%, 8%,
10%th, 12%, 15%, 18%, 20%, 22%, 25%, 28%, 30%, 32%, 35%, 38%, 40%, 42% or 45%.
In the preferred embodiment of the present invention, the lecithin is purified from soybean lecithin or egg yolk lecithin
It obtains, the content of phosphatidyl choline is 50-99% in the lecithin；And/or sulphur is further included, the weight hundred of the sulphur
Divide than being 0.5-10%.
Soybean lecithin or egg yolk lecithin is selected to carry out the extraction of lecithin, is primarily due to be easy to get and cheap.
In the present invention, in the lecithin the typical but non-limiting content of phosphatidyl choline for 50%, 55%, 60%, 65%,
70%th, 75%, 80%, 85%, 90%, 95% or 99%.
Further to strengthen the ability for killing acarid and microorganism of nano silver liposome, sulphur can also be added.At this
In invention, the typical but non-limiting weight percent of sulphur is 0.5%, 0.6%, 0.8%, 1%, 1.5%, 2%, 2.5%,
3%th, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5% or 10%.
According to another aspect of the present invention, a kind of preparation method of nano silver liposome is additionally provided, including walking as follows
Suddenly：
(1) anti-polymerizer, optionally water, hyaluronic acid and optionally collagen mixing are weighed according to formula ratio, be made
Aqueous mixture；
(2) nano silver, lecithin, cholesterol, antioxidant, metal chelating agent, optionally emulsifier, sulphur are weighed by formula ratio
Sulphur, optionally evening primrose oil and optionally solubilizer mix, and oil mixture is made；
(3) after the oil mixture obtained by step (2) being added to the aqueous mixture in step (1), homogeneous is received
The silver-colored colostrum of rice；
(4) the nano silver colostrum obtained by step (3) is moved in super-voltage micro jet equipment, carries out super-voltage micro jet and follow
Ring processing, obtains nano silver liposome.
Super-voltage micro jet equipment is combined with high-pressure jet technology, hits Flow Technique and conventional high-tension homogeneous technology, profit
Material is transported in oscillating reactions device by the high pressure generated with gases at high pressure or hydraulic pump, and high-velocity fluid is cut in microchannel
It cuts and acts on and be dispersed into multiply high-velocity fluid, high-speed impact, the kinetic energy Transient transformation of fluid, production further occur in impact cavity
The static pressure of 100~300MPa is formed up to after raw immense pressure drop, while vibrates chip and height is generated during high-speed impact
Frequency ultrasonic acts on so that material occur Strong shear crushing, high-speed impact, cavitation erosion, vibration and it is puffing the effects that, it can be achieved that
The refinement of particle, emulsification, the effect of homogeneous and modification.
The preparation method is micro- by super-voltage micro jet nano-equipment will be used to carry out super-pressure after each raw material mixing homogeneous
Jet-loop processing, one-step method can obtain nano silver liposome, and wherein nano silver exists in the form of nano silver simple substance, compares
The nano-silver ionic prepared using traditional chemical method using silver nitrate, preservative, chloroform, ether and other chemical solvents,
Nano silver simple substance will not with various bioactivators in organism with reference to and deposit, will not generate toxicity, reduce skin allergy
Rate, can solve residues such as chloroform, ether, preservative in conventional silver preparation may be to cell and environmental danger substance
Problem.
The preparation method is simple, and operation is easy, and entire production process is environmentally protective, can industrial mass production.
In the preferred embodiment of the present invention, in step (2), the temperature of the mixing is 40-60 DEG C；
And/or in step (3), the rotating speed of the homogeneous is 3000-10000rpm, and the time of homogeneous is 1-5min.
In the present invention, in step (2) described mixed process typical case but 40 DEG C non-limiting of temperature, 42 DEG C, 45 DEG C, 47
DEG C, 49 DEG C, 50 DEG C, 52 DEG C, 54 DEG C, 55 DEG C, 58 DEG C or 60 DEG C.
In step (3), in the homogenizing process typical case but non-limiting rotating speed be 3000rpm, 3500rpm,
4000rpm、4500rpm、5000rpm、5500rpm、6000rpm、6500rpm、7000rpm、7500rpm、8000rpm、
8500rpm, 9000rpm, 9500rpm or 10000rpm.
Typical case but non-limiting time are 1min, 2min, 3min, 4min or 5min in the homogenizing process.
Herein it should be noted that in homogenizing process, homogeneous rotating speed and homogenizing time need to control in the reasonable scope,
Homogeneous rotating speed is too low, and when homogenizing time is shorter, it is uneven to be likely to result in the mixing of water oil phase；Homogeneous rotating speed is excessively high, homogenizing time
When longer, then it can so that nano silver colostrum stability is poor, it is also possible to cause the leakage of the drug of embedding.
In the preferred embodiment of the present invention, in step (4), super-voltage micro jet circular treatment number is 1-
3 times, treatment temperature is 0-4 DEG C, processing pressure 150-250MPa.
For reduce further refinement nano silver liposome grain size, using super-voltage micro jet equipment to liposome at
Reason.In super-voltage micro jet circulating treatment procedure, cycle-index should not be too many, otherwise can structure of phospholipid be destroyed, cause
The leakage of drug.The selection of processing pressure has very big influence to the grain size and pattern of final nano silver liposome, processing
Pressure should not be too low, it is too low if liposome grain size it is larger, and can there are larger aggregations；Processing pressure also should not be too
Otherwise height can influence envelop rate of the liposome to nano silver.
In the present invention, super-voltage micro jet circular treatment typical case but non-limiting number are 1 time, 2 times or 3 times.
In the present invention, super-voltage micro jet circular treatment typical case but non-limiting temperature are 0 DEG C, 1 DEG C, 2 DEG C, 3 DEG C
Or 4 DEG C.
In the present invention, super-voltage micro jet cycle typical case but non-limiting processing pressure be 150MPa, 160MPa,
170MPa、180MPa、190MPa、200MPa、205MPa、210MPa、220MPa、225MPa、230MPa、235MPa、240MPa、
245MPa or 250MPa.
And/or after step (4), further include and mix the nano silver liposome obtained by step (4) and the thickener of formula ratio
Stirring is closed, cream shape nano silver liposome is made.
By the research to the specific matching relationship between each parameter involved in preparation method and each parameter, thus
Each parameter is determined, so ensure prepared nano silver liposome have effects that good quality and.
In addition, the present invention also provides a kind of applications of nano silver liposome, it is suitable that the nano silver liposome is fabricated to
Dosage form be applied to daily necessities or field of medicaments.
The synergistic effect that the nano silver liposome passes through nano silver and liposome so that it is in daily necessities or medicine production
Inside can be with safer efficient entrance biological cell in product, so as to play the role of antibacterial anti-inflammatory.
The maximum concentration of nano silver is up to 300000PPM, nano silver liposomal in nano silver liposome in the present invention
It learns property to stablize, there is bimolecular characteristic, can be applied to daily necessities field, such as the facial mask of antibacterial anti-inflammatory, lotion, elite
Liquid, face cream, foundation cream, thimerosal, hand cleanser, foot lotion, face sanitizer, disinfectant soap, liquid detergent, washing powder, shampoo, hair cream,
Shower cream, toothpaste, mouthwash, hygenic towelette, sanitary napkin etc. can also be applied to food preservative field etc..
It is the acne caused by nano silver liposome is to infection such as bacterium, fungi, spore, itch mites, scabies, acne rosacea, wet
The skin diseases such as rash, burn, scald and vagina mycotic infection have obvious curative effects, therefore the nano silver liposome in the present invention may be used also
To be applied to pharmaceutical sanitary field, such as medical antibacterial anti-inflammatory ointment, medicinal powder, disinfection dressing, sterilization of instruments medical and health
Field；Or pharmaceutical test quarantine field is applied to, such as the treatment of radioactively labelled substance, targeted drug.
With reference to specific embodiment and comparative example, the invention will be further described.
Embodiment 1
The present invention provides a kind of nano silver liposomes, by weight percentage, are made of following raw material：Nano silver
0.005%, lecithin 3%, cholesterol 1%, vitamin E 0.5%, disodium ethylene diamine tetraacetate 0.1%, SP80 2%, TW80
2%, polyethylene glycol 1%, evening primrose oil 6%, hyaluronic acid 0.5%, collagen 0.1%, glycerine 8%, ethyl alcohol 2%, match ratio
Grams 305 1%, xanthan gum 1%, water polishing surplus to 100%, wherein, concentration of the nano silver in total raw material is 50PPM.
Embodiment 2
The preparation method of embodiment 1, includes the following steps：
(1) polyethylene glycol, hyaluronic acid, collagen and water are weighed by formula, temperature is controlled between 65 DEG C, and water is made
Phase.
(2) by formula weigh nano silver, lecithin, cholesterol, vitamin E, disodium ethylene diamine tetraacetate, SP80, TW80,
Evening primrose oil, ethyl alcohol, glycerine mix under 40 DEG C of environment, and oil phase is made.
(3) oil phase obtained by step (2) is added in into water phase obtained by step 1, with the homogenizer homogeneous 4min of 6000rmp,
Obtain nano silver colostrum.
(4) the nano silver colostrum obtained by step (3) is moved in super-voltage micro jet equipment, opens cooling back installation,
Ensure that super-voltage micro jet equipment works under 0-4 DEG C of environment, carry out that super-pressure is micro- penetrates circular treatment 2 times in 220MPa, be made
The nano silver liposome of emulsion form.
The nano silver liposome of emulsion form obtained by step (4) is stirred with mixer, with the match Bick 305 of formula ratio
Cream shape is modulated into xanthan gum.
Embodiment 3
The present invention provides a kind of nano silver liposomes, by weight percentage, are made of following raw material：Nano silver
0.05%, lecithin 3%, cholesterol 1%, vitamin E 0.5%, disodium ethylene diamine tetraacetate 0.1%, SP80 2%, TW80
2%, polyethylene glycol 1%, evening primrose oil 6%, hyaluronic acid 0.5%, collagen 0.1%, glycerine 8%, ethyl alcohol 2%, match ratio
Grams 305 1%, xanthan gum 1%, water polishing surplus to 100%, wherein, concentration of the nano silver in total raw material is 500PPM.
Embodiment 4
The preparation method of embodiment 3 is with embodiment 2, and details are not described herein again.
Embodiment 5
The present invention provides a kind of nano silver liposomes, by weight percentage, are made of following raw material：Nano silver
0.5%, lecithin 3%, cholesterol 1%, vitamin E 0.5%, disodium ethylene diamine tetraacetate 0.1%, SP80 2%, TW80
2%, polyethylene glycol 1%, evening primrose oil 6%, hyaluronic acid 0.5%, collagen 0.1%, glycerine 8%, ethyl alcohol 2%, match ratio
Grams 305 1%, xanthan gum 1%, water polishing surplus to 100%, wherein, concentration of the nano silver in total raw material is 5000PPM.
Embodiment 6
The preparation method of embodiment 5 is with embodiment 2, and details are not described herein again.
Embodiment 7
The present invention provides a kind of nano silver liposomes, by weight percentage, are made of following raw material：Nano silver 5%,
Lecithin 3%, cholesterol 1%, vitamin E 0.5%, disodium ethylene diamine tetraacetate 0.1%, SP80 2%, TW80 2% gather
Ethylene glycol 1%, evening primrose oil 6%, hyaluronic acid 0.5%, collagen 0.1%, glycerine 8%, ethyl alcohol 2% match Bick 305
1%, xanthan gum 1%, water polishing surplus to 100%, wherein, concentration of the nano silver in total raw material be 50000PPM.
Embodiment 8
The preparation method of embodiment 7 is with embodiment 2, and details are not described herein again.
Embodiment 9
The present invention provides a kind of nano silver liposomes, by weight percentage, are made of following raw material：Nano silver
10%, lecithin 3%, cholesterol 1%, vitamin E 0.5%, disodium ethylene diamine tetraacetate 0.1%, SP80 2%, TW80
2%, polyethylene glycol 1%, evening primrose oil 6%, hyaluronic acid 0.5%, collagen 0.1%, glycerine 8%, ethyl alcohol 2%, match ratio
Grams 305 1%, xanthan gum 1%, water polishing surplus to 100%, wherein, concentration of the nano silver in total raw material is 100000PPM.
Embodiment 10
The preparation method of embodiment 9 is with embodiment 2, and details are not described herein again.
Embodiment 11
The present invention provides a kind of nano silver liposomes, by weight percentage, are made of following raw material：Nano silver
0.05%, lecithin 3%, cholesterol 1%, vitamin E 0.5%, disodium ethylene diamine tetraacetate 0.1%, SP80 2%, TW80
2%, polyethylene glycol 1%, water polishing surplus to 100%, wherein, concentration of the nano silver in total raw material be 500PPM.
Embodiment 12
The preparation method of embodiment 11, includes the following steps：
(1) polyethylene glycol and water are weighed by formula, temperature is controlled between 65 DEG C, and water phase is made.
(2) nano silver, lecithin, cholesterol, vitamin E, disodium ethylene diamine tetraacetate, SP80 and TW80 are weighed by formula
It is mixed under 40 DEG C of environment, oil phase is made.
(3) oil phase obtained by step (2) is added in into water phase obtained by step 1, with the homogenizer homogeneous 4min of 6000rmp,
Obtain nano silver colostrum.
(4) the nano silver colostrum obtained by step (3) is moved in super-voltage micro jet equipment, opens cooling back installation,
Ensure that equipment works under 0-4 DEG C of environment, carry out that super-pressure is micro- penetrates circular treatment 2 times in 220MPa, receiving for emulsion form is made
The silver-colored liposome of rice.
Embodiment 13
The present invention provides a kind of nano silver liposomes, by weight percentage, are made of following raw material：Nano silver
0.5%, lecithin 3%, cholesterol 1%, vitamin E 0.5%, disodium ethylene diamine tetraacetate 0.1%, SP80 2%, TW80
2%, polyethylene glycol 1%, evening primrose oil 6%, hyaluronic acid 0.5%, collagen 0.1%, glycerine 8%, ethyl alcohol 2%, match ratio
Grams 305 1%, xanthan gum 1%, water polishing surplus to 100%, wherein, concentration of the nano silver in total raw material is 5000PPM.
Embodiment 14
The micro- circular treatment number of penetrating of super-pressure is 1 time in the preparation method step (4) of embodiment 13, remaining and embodiment 2
Unanimously, details are not described herein again.
Embodiment 15
The present invention provides a kind of nano silver liposomes, by weight percentage, are made of following raw material：Nano silver
0.5%, lecithin 3%, cholesterol 1%, vitamin E 0.5%, disodium ethylene diamine tetraacetate 0.1%, SP80 2%, TW80
2%, polyethylene glycol 1%, evening primrose oil 6%, hyaluronic acid 0.5%, collagen 0.1%, glycerine 8%, ethyl alcohol 2%, match ratio
Grams 305 1%, xanthan gum 1%, water polishing surplus to 100%, wherein, concentration of the nano silver in total raw material is 5000PPM.
Embodiment 16
The micro- circular treatment pressure of penetrating of super-pressure is 250MPa in the preparation method step (4) of embodiment 15, remaining and implementation
Example 2 is consistent, and details are not described herein again.
Embodiment 17
The present invention provides a kind of nano silver liposomes, by weight percentage, are made of following raw material：Nano silver
0.5%, lecithin 1%, cholesterol 2%, butylated hydroxy anisole 2%, Sodium Polyacrylate 3%, fatty glyceride 9%, gather
Vinylpyrrolidone 4%, sulphur 9%, evening primrose oil 9%, hyaluronic acid 2%, collagen 2%, propylene glycol 20%, xanthan gum
4%, water polishing surplus to 100%, wherein, concentration of the nano silver in total raw material be 5000PPM.
Embodiment 18
The preparation method of embodiment 17, includes the following steps：
(1) polyvinylpyrrolidone, hyaluronic acid, collagen and water being weighed by formula, temperature is controlled between 85 DEG C,
Water phase is made.
(2) to weigh nano silver, lecithin, cholesterol, butylated hydroxy anisole, Sodium Polyacrylate, aliphatic acid by formula sweet
Grease, sulphur, evening primrose oil, propylene glycol mix under 40 DEG C of environment, and oil phase is made.
(3) oil phase obtained by step (2) is added in into water phase obtained by step 1, with the homogenizer homogeneous 2min of 9000rmp,
Obtain nano silver colostrum.
(4) the nano silver colostrum obtained by step (3) is moved in super-voltage micro jet equipment, opens cooling back installation,
Ensure that equipment works under 0-4 DEG C of environment, carry out that super-pressure is micro- penetrates circular treatment 3 times in 150MPa, receiving for emulsion form is made
The silver-colored liposome of rice.
The nano silver liposome of emulsion form obtained by step (4) is stirred with mixer, with the xanthan gum tune of formula ratio
Cream shape is made.
Embodiment 19
The present invention provides a kind of nano silver liposomes, by weight percentage, are made of following raw material：Nano silver
30%, lecithin 2%, cholesterol 0.3%, 2,6- di-tert-butyl-4-methy phenols 1%, sodium ammonium triacetate 1%, monostearate
Glyceride 7%, dimethyl silicone polymer 3%, sulphur 0.5%, evening primrose oil 1%, hyaluronic acid 3%, collagen 3% are sweet
40%, PEG-100 of oil stearates 5%, water polishing surplus to 100%, wherein, concentration of the nano silver in total raw material is
300000PPM。
Embodiment 20
The preparation method of embodiment 19, includes the following steps：
(1) dimethyl silicone polymer, hyaluronic acid, collagen and water being weighed by formula, temperature is controlled between 75 DEG C,
Water phase is made.
(2) by formula weigh nano silver, lecithin, cholesterol, 2,6 di tert butyl 4 methyl phenol, sodium ammonium triacetate,
Glycerin monostearate, sulphur, evening primrose oil and glycerine mix under 40 DEG C of environment, and oil phase is made.
(3) oil phase obtained by step (2) is added in into water phase obtained by step 1, with the homogenizer homogeneous 5min of 3000rmp,
Obtain nano silver colostrum.
(4) the nano silver colostrum obtained by step (3) is moved in super-voltage micro jet equipment, opens cooling back installation,
Ensure that equipment works under 0-4 DEG C of environment, carry out that super-pressure is micro- penetrates circular treatment 1 time in 200MPa, receiving for emulsion form is made
The silver-colored liposome of rice.
The nano silver liposome of emulsion form obtained by step (4) is stirred with mixer, it is hard with the PEG-100 of formula ratio
Resin acid ester is modulated into cream shape.
Embodiment 21
The present invention provides a kind of nano silver liposomes, by weight percentage, are made of following raw material：Nano silver
0.005%, lecithin 3%, cholesterol 1%, vitamin E 0.5%, disodium ethylene diamine tetraacetate 0.1%, SP80 2%, TW80
2%, polyethylene glycol 1%, evening primrose oil 6%, hyaluronic acid 0.5%, collagen 0.1%, glycerine 8%, ethyl alcohol 2%, sulphur
3%, match Bick 305 1%, xanthan gum 1%, water polishing surplus to 100%, wherein, concentration of the nano silver in total raw material is
500PPM。
Embodiment 22
The preparation method of embodiment 21 has simply added formula ratio as the preparation method of embodiment 2 in step (2)
Sulphur, remaining is then repeated no more.
Comparative example 1
The present invention also provides a kind of liposomes, by weight percentage, are made of following raw material：Lecithin 3%, courage is solid
Alcohol 1%, vitamin E 0.5%, disodium ethylene diamine tetraacetate 0.1%, SP80 2%, TW80 2%, sulphur 3%, evening primrose oil
6%, hyaluronic acid 0.5%, collagen 0.1%, glycerine 8%, ethyl alcohol 2%, match Bick 305 1%, xanthan gum 1%, water benefit
Neat surplus is to 100%.
Comparative example 2
The preparation method of comparative example 1 is with embodiment 2, and details are not described herein again.
Experimental example 1
In order to verify the sterilization antibacterial functions of nano silver liposome, embodiment 1-21 and comparative example 1 have been done Escherichia coli,
Staphylococcus aureus and the sterilization test experience of Candida albicans, detection foundation are《Disinfection technology standard》(2002 editions) disinfections
Agent germicidal experiment 2.1.1.7 bacteria quantifieds insect killing test and 2.1.1.9 fungies quantify insect killing test, testing time 5
Min, the specific data that detect see the table below 1-3：
Table 1 detects data for each embodiment and comparative example to the sterilization of Escherichia coli
Table 2 detects data for each embodiment and comparative example to the sterilization of staphylococcus aureus
Table 3 detects data for each embodiment and comparative example to the sterilization of Candida albicans
As can be seen from the above table, increase with the concentration of nano silver, the sterilization antibacterial effect enhancing of nano silver liposome.Especially
It is when concentration of the nano silver in total raw material for 300000PPM (corresponding embodiment 19) when, nano silver liposome shows excellent
Different bactericidal effect.It is contemplated that actual cost problem, relatively good in 50-5000PPM by the concentration control of nano silver, at this time
Bactericidal effect and actual cost are all in rational level.
Embodiment 21 is the control experiment of embodiment 1, and embodiment 21 is with the addition of sulphur compared with embodiment more than 1, it can be seen that real
The bactericidal effect of example 21 is applied due to the bactericidal effect of embodiment 1.It can thus be seen that the addition of sulphur causes nano silver liposome
Sterilization antibacterial ability have certain promotion.
Electronic Speculum and laser particle size detection are done to the nano silver liposome of embodiment 5, electron microscope is as shown in Figure 1.By in figure
As can be seen that the grain size of nano silver liposome, between 300-400nm, nano silver surface of liposome is also adsorbed with several nanometers
Argent grain.Fig. 4 is the laser particle size detection figure of the nano silver liposome of embodiment 5, it can be seen from the figure that nano silver liposome
Average grain diameter in 358nm or so, this result is consistent with the result in Fig. 1.Fig. 2 is attachment (or package) in nano silver lipid
The electron microscope of nano silver in body surface face (in cell), appearance is mellow and full, is uniformly dispersed, and grain size is between 10-60nm.
Fig. 3 is the electron microscope of 1 liposome of comparative example, and due to being not added with anti-polymerizer, the phosphatide in liposome polymerize naturally,
The liposome aggregate being relatively large in diameter is formed, diameter is in 2-10um.As it can be seen that the addition of anti-polymerizer can effectively less liposome it
Between reunion, and then reduce liposome average grain diameter.
Experimental example 2
In order to weigh nano silver liposome acute oral toxicity size, acute oral toxicity examination has been carried out to embodiment 1-20
It tests, detection foundation is《Disinfection technology standard》Acute oral toxicity test in (version in 2002), the dosage grouping of female, male mouse
For 5000mg/kg, the acute oral toxicity data of each embodiment are as shown in table 4：
4 each embodiment nano silver liposome acute oral toxicity of table detects data
As can be seen from the above table, after giving nano silver liposome tested material, all animal subjects are in having no different in the observation period
Paradoxical reaction, no death.The maximum tolerance agent of female, male its mouse oral acute toxicity is more than 5000mg/kg.According to《Disinfection technology standard》
Acute toxicity grading criteria in (version in 2002), nano silver liposome belong to actual innocuous substance.
Finally it should be noted that：The above embodiments are only used to illustrate the technical solution of the present invention., rather than its limitations；To the greatest extent
Pipe is described in detail the present invention with reference to foregoing embodiments, it will be understood by those of ordinary skill in the art that：Its according to
Can so modify to the technical solution recorded in foregoing embodiments either to which part or all technical characteristic into
Row equivalent substitution；And these modifications or replacement, the essence of appropriate technical solution is not made to depart from various embodiments of the present invention technology
The scope of scheme.
Claims (8)
1. a kind of nano silver liposome, which is characterized in that in percentage by weight, the nano silver liposome is mainly by following
Raw material is made：Nano silver 0.005-30%, lecithin 1-3%, cholesterol 0.3-2%, antioxidant 0.1-2%, metal chelating agent
0.1-3%, emulsifier 2-10%, anti-polymerizer 1-5%, evening primrose oil 1-10%, hyaluronic acid 0.1-3%, collagen
0.1-3%, water polishing surplus to 100%；
The preparation method of the nano silver liposome, includes the following steps：
(1) anti-polymerizer, water, hyaluronic acid and collagen are weighed according to formula ratio to mix, aqueous mixture is made；
(2) nano silver, lecithin, cholesterol, antioxidant, metal chelating agent, emulsifier and evening primrose oil is weighed by formula ratio to mix
It closes, oil mixture is made；
(3) after the oil mixture obtained by step (2) being added to the aqueous mixture in step (1), homogeneous obtains nano silver
Colostrum；
(4) the nano silver colostrum obtained by step (3) is moved in super-voltage micro jet equipment, carries out cycling of super-voltage micro jet place
Reason, obtains nano silver liposome.
2. nano silver liposome according to claim 1, which is characterized in that by weight percentage, the antioxidant is
One kind or at least two combination in butylated hydroxy anisole, 2,6 di tert butyl 4 methyl phenol or vitamin E；
And/or the metal chelating agent is disodium ethylene diamine tetraacetate.
3. nano silver liposome according to claim 1, which is characterized in that the emulsifier is sorbester p17, Tween 80, fat
One kind or at least two combination in fatty acid glyceride or glycerin monostearate；
And/or the anti-polymerizer is for one kind in polyethylene glycol, polyvinylpyrrolidone or dimethyl silicone polymer or at least
Two kinds of combination.
4. nano silver liposome according to claim 1, which is characterized in that in percentage by weight, further include thickening
Agent, the weight percent of the thickener is 1-5%, and the thickener is given birth to for match Bick 305, PEG-100 stearates or the Chinese
One kind or at least two combination in glue；
And/or solubilizer is further included, the weight percent of the solubilizer is 1-45%, and the solubilizer is ethyl alcohol, propylene glycol
Or one kind in glycerine or at least two combination.
5. nano silver liposome according to claim 1, which is characterized in that the lecithin is from soybean lecithin or yolk
Purification obtains in lecithin, and the content of phosphatidyl choline is 50-99% in the lecithin；
And/or sulphur is further included, the weight percent of the sulphur is 0.5-10%.
6. nano silver liposome according to claim 1, which is characterized in that in step (2), the temperature of the mixing is
40-60℃；
And/or in step (3), the rotating speed of the homogeneous is 3000-10000rpm, and the time of homogeneous is 1-5min.
7. nano silver liposome according to claim 4, which is characterized in that in step (4), super-voltage micro jet Xun Huan
Number of processes is 1-3 times, and treatment temperature is 0-4 DEG C, processing pressure 150-250MPa；
And/or after step (4), further include to mix the nano silver liposome obtained by step (4) with the thickener of formula ratio and stir
It mixes, cream shape nano silver liposome is made.
8. the application of nano silver liposome in daily necessities or in medicine preparation described in claim 1-5 any one.
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| CN109504389B (en) * | 2018-11-09 | 2020-10-16 | 盐池县荣桂昌食品科技有限公司 | Soil remediation agent capable of treating heavy metal pollution and preparation method thereof |
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