CN107669717A - A kind of oil-in-water type sea-buckthorn oil nanometer emulsion external preparation and preparation method thereof - Google Patents

A kind of oil-in-water type sea-buckthorn oil nanometer emulsion external preparation and preparation method thereof Download PDF

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Publication number
CN107669717A
CN107669717A CN201711090618.1A CN201711090618A CN107669717A CN 107669717 A CN107669717 A CN 107669717A CN 201711090618 A CN201711090618 A CN 201711090618A CN 107669717 A CN107669717 A CN 107669717A
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oil
preparation
emulsion
seabuckthorn
external preparation
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王梅
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Xinjiang Medical University
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Xinjiang Medical University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/10Dispersions; Emulsions
    • A61K9/107Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions

Abstract

The present invention relates to a kind of natural drug extract nano-emulsion external preparation, belong to biological medicine and skin care technical field.The present invention provides a kind of oil-in-water type sea-buckthorn oil nanometer emulsion external preparation, and the raw material matched by following weight parts forms:Isopropyl myristate 0.4% 5.0%, Emulsifier EL-60 3.8% 6.0%, TC 1.4% 3.8%, Seabuckthorn Oil 0% 7.0%, surplus is distilled water, and the mass percent sum of mentioned component is 100%.External application Seabuckthorn Oil oil nanometer emulsion prepared by the present invention, steady quality is not volatile, improves the stability of Seabuckthorn Oil, extends the Seabuckthorn Oil holding time, delays the drug metabolism time of Seabuckthorn Oil in vivo.Other preparation method, raw material and energy are saved, reduce production cost, almost without the pollution of environment, and preparation technology is simple, and practical operation is easy, and without special instruments and equipment, preparation is efficiently quick, is easy to industrialization, there are wide market prospects in field of medicaments.

Description

A kind of oil-in-water type sea-buckthorn oil nanometer emulsion external preparation and preparation method thereof
Technical field
The invention belongs to biological medicine and skin care technical field, and in particular to a kind of oil-in-water type sea-buckthorn oil nanometer emulsion External preparation and preparation method thereof.
Background technology
Sea-buckthorn(Hippophaerhamnoides Linn)For Elaeangnaceae (Cassia Occidentalis L.) sea-buckthorn Platymiscium, extracts isolated from sea-buckthorn, is anaesthetic, Tibetan medicine conventional crude drugs.Seabuckthorn Oil is rich in a large amount of nutrient substances, Gradually cause the attention of the world of medicine in recent years, and system research carried out in its resource, pharmacology, preparation, clinic etc., it was demonstrated that Seabuckthorn Oil be a kind of pharmacological activity it is strong, efficiently, safe drugs.
Modern study shows that Seabuckthorn Oil has preventing and treating gastric ulcer, protection chemical damage, promotes wound repair etc. to make With wherein reparation skin effect is paid close attention to by numerous researchers.Recent study is also shown that Seabuckthorn Oil has promotion organization Regeneration and the effect of epithelial tissue healing, and Dichlorodiphenyl Acetate causes mouse peritoneum scorching and rat paw edema caused by carrageenan has substantially Inhibitory action, and inflammatory mediator release can be suppressed, capillary permeability is reduced, so as to preferable skin repair, anti-inflammatory Effect.But current Seabuckthorn Oil preparation for external application to skin is less, and because Seabuckthorn Oil belongs to smart oily substance, water solubility and stability inequality, Its clinical practice is limited, in order to improve the stability of Seabuckthorn Oil, widens the application of Seabuckthorn Oil, medicament researchers are carried out Many dosage form research.But treatment ACD (variability contact dermatitis) of the Seabuckthorn Oil also without national official approval skin External preparation.
The content of the invention
In order to solve above-mentioned technical problem, Seabuckthorn Oil is prepared into nano-emulsion external preparation by the present invention, it is intended to profit With the thermodynamic stability of nano-emulsion, particle diameter is small, sustained release and targeting, can solubilized medicine, the characteristics of being not easy to be decomposed by body fluid, come The stability of Seabuckthorn Oil is improved, promotes drug absorption.Acted on simultaneously for the preferable anti-inflammatory of Seabuckthorn Oil, skin repair, the present invention Originally Seabuckthorn Oil is used to treat ACD, it is not notable for current simple western medicine therapeutic effect, and the ACD that recurrence rate is higher Plan plays therapeutic action.
The technical solution adopted by the present invention is as follows:
A kind of oil-in-water type sea-buckthorn oil nanometer emulsion external preparation, the external preparation liquid-drop diameter size between 10~100nm, by The raw material composition of following weight distribution ratio:Isopropyl myristate 0.4%-5.0%, Emulsifier EL-60 3.8%-6.0%, diethyl Glycol list ethylether 1.4%-3.8%, Seabuckthorn Oil 0%-7.0%, surplus are distilled water, and the mass percent sum of mentioned component is 100%.
Wherein, described oil phase is isopropyl myristate;Described surfactant is Emulsifier EL-60;It is described Cosurfactant be TC.
A kind of optimum ratio of oil-in-water type sea-buckthorn oil nanometer emulsion external preparation of the present invention is:Oil phase 0.6%-2.5%, surface Activating agent 5.8%, cosurfactant 1.4%, Seabuckthorn Oil 5.8%, surplus are distilled water, the mass percent sum of mentioned component For 100%.
After a kind of further orthogonal optimization of oil-in-water type sea-buckthorn oil nanometer emulsion external preparation of the present invention, match by following group The raw material composition divided:Oil phase 1.8%, surfactant 5.6%, cosurfactant 1.4%, Seabuckthorn Oil 7%, surplus are distilled water, The mass percent sum of mentioned component is 100%.
Oil-in-water type sea-buckthorn oil nanometer emulsion external preparation of the present invention is in the selection of surfactant, from non-toxic, raw Good and small to the skin irritation nonionic surface active agent of thing compatibility.Nonionic surface active agent compares in the solution It is relatively stable, be not easy to be influenceed by strong electrolyte, inorganic salts, be not easy to be influenceed by soda acid, and with other surfaces activating agent Compatibility it is good, haemocylolysis is smaller.In theory, the preparation of O/W types nanometer emulsion need the HLB value of surfactant between Between 8-18, it is contemplated that the easy formative of the simplicity of preparation technology, i.e. nano-emulsion and the stability of the nano-emulsion prepared, The present invention selects liquid nonionic type surfactants of the HLB between 10-15, or with a kind of HLB < 10 nonionic Surfactant compound.Available surfactant:Emulsifier EL-60.
A kind of preparation method of oil-in-water type sea-buckthorn oil nanometer emulsion external preparation, comprises the following steps:1) lived according to surface The mass ratio of property agent and cosurfactant (represented with Km values, such as 1:1,1:2,2:1 etc.), precision weighs corresponding reagent, It is 0.25g to make mixed surfactant quality, is placed in tool plug ampoule bottle;2)According to the quality of oil phase and mixed surfactant Than(O/S ratios, such as 10/90,20/80,30/70 etc.), at 25 DEG C, precision weighs corresponding oil phase and is placed in above-mentioned ampoule bottle It is interior, stirred with constant temperature blender with magnetic force, with 200rpmmin-1Rotating speed magnetic agitation 5min, make fully to mix;3) by formula Weigh Seabuckthorn Oil to be placed in above-mentioned ampoule bottle, with 200rpmmin-1Rotating speed magnetic agitation 2min, be sufficiently stirred mixture Uniformly;4)Then distilled water is slowly added dropwise into mixture, while adding waterside to stir, adds the mixture system in water and whipping process Occur and become viscous by dilute, it is last again by a series of sticky changes for becoming clarification, until forming oil-in-water type nano-emulsion.
The preparation prescription optimum ratio of sea-buckthorn oil nanometer emulsion external preparation is received by origin9.0 Software on Drawing Seabuckthorn Oils The pseudo-ternary phase diagram of rice milk and nano-emulsion region area to different prescriptions is compared analysis.Due to by emulsifying agent and helping breast Agent can make oil phase and aqueous phase blend and form a nanometer emulsion droplet, and assistant for emulsifying agent is inserted into the limitans of emulsifying agent, It is allowed to form complex condensed film, improves the coagulability and compliance of film, and the solubility of emulsifying agent can be increased, further reduces boundary Face tension force, be advantageous to more stable after nano-emulsion is formed.Limited in view of emulsifying agent by solubility, and assistant for emulsifying agent can make breast The solubility increase of agent, emulsion droplet are more easy to disperse, and particularly emulsifying agent and assistant for emulsifying agent are further big in oil phase and aqueous phase interface Amount absorption, makes both concentration in continuous phase reduce, and interfacial tension turns on the occasion of being allowed to gradually form what is more stablized again Nano-emulsion.At the same time among Seabuckthorn Oil being dissolved in into oil phase isopropyl myristate, and in Emulsifier EL-60 and diethyl Under the effects and participation of composition such as S/C mixtures and distilled water that glycol list ethylether is formed, self-assembling formation sea-buckthorn oil nanometer emulsion. In sea-buckthorn oil nanometer emulsion prepares prescription, isopropyl myristate is as oil phase, and Emulsifier EL-60 is as emulsifying agent, diethyl Glycol list ethylether is assistant for emulsifying agent, and distilled water is as aqueous phase.
The basis of prescription be oil phase, aqueous phase, emulsifying agent (surfactant), assistant for emulsifying agent (cosurfactant) with And the effect of prescription composition.During preparation, it can be first dissolved in respectively in corresponding phase liquid according to the dissolubility of functional component. After oil phase, emulsifying agent, assistant for emulsifying agent determine, nano-emulsion region can be found out by Pseudo-ternary phase diagrams, so that it is determined that they are each From dosage.Concrete operations are as follows:In four oil phase, aqueous phase, emulsifying agent, assistant for emulsifying agent components, typically can by emulsifying agent and Its dosage is fixed, and three oil phase, aqueous phase, assistant for emulsifying agent components account for three summits of equilateral triangle, and phasor is made in constant temperature.By one Surely oil phase, emulsifying agent, the assistant for emulsifying agent mixed solution formed is titrated with aqueous phase.Add every time and dripped during aqueous phase with dropper It is fixed, it is stirred simultaneously, whether then examine is transparent nano-emulsion or muddy nano-emulsion.Make to receive adding aqueous phase After rice milk reaches complete equipilibrium, nano-emulsion should be transparent, clarifies, flow and the liquid with opalescence.In addition, also can be by breast The summit of agent and assistant for emulsifying agent mixed solution as equilateral triangle, then oil phase and aqueous phase as equilateral triangle other two Individual summit forms Pseudo-ternary phase diagrams, and the present invention selects such a reconnaissance method.
The specific preparation method and basic step of water-in-oil type (W/O) nano-emulsion be:Each prescription is determined from Pseudo-ternary phase diagrams Afterwards, first the ratio of hydrophilic emulsifier and assistant for emulsifying agent as requested is mixed, stirs, add a certain proportion of at normal temperatures Oil phase, continue after stirring, the liquid that muddiness is titrated to aqueous phase is changed into producing water-in-oil type (W/O) untill clear and received Rice milk.The specific preparation method and basic step of oil-in-water type (O/W) nano-emulsion be:Oil phase and oleophilic emulsifier are first selected, and The oleophilic emulsifier is dissolved in oil phase according to certain ratio, is stirred continuously, is allowed to be thoroughly mixed;This mixing liquid is slow Add in aqueous phase, be stirred continuously;Such as the dosage of known assistant for emulsifying agent, then it can be directly added into aqueous phase, not know such as to help emulsification The dosage of agent, then it can use this assistant for emulsifying agent to titrate above-mentioned oil mixing with water liquid, oil-in-water produced untill clear is changed into Type nano-emulsion.
Observe its outward appearance faint yellow in this way, limpid transparent, fluidity and good dispersion, have clearly visible opalescence person, be Oil-in-water type sea-buckthorn oil nanometer emulsion, this sea-buckthorn oil nanometer emulsion is put in lucifuge glass container, be placed in dry ventilating and cooling place room temperature Preservation.
Compared with prior art, beneficial effects of the present invention are:The innovative point of the protrusion of the present invention is by Seabuckthorn Oil effect Composition and nano-emulsion technology success connected applications, prepare the Seabuckthorn Oil nano-emulsion preparation of external preparation for skin, this is unprecedented.And this The stability that Seabuckthorn Oil is improved for the Seabuckthorn Oil nano-emulsion preparation of external preparation for skin is invented, can be preserved for a long time, and in skin Can slowly discharge, solve Seabuckthorn Oil poorly water-soluble, it is unstable, using limited problem.
The oil-in-water type sea buckthorn oil nano-emulsion oral liquid of the present invention compared with prior art, has advantages below:Invention system The standby external application Seabuckthorn Oil oil nanometer emulsion liquid immiscible as two kinds according to a certain percentage, in surfactant and helps surface The nano-emulsion product particle diameter of self-assembling formation is nanoscale under the collective effect of activating agent, and the overwhelming majority is in 52nm or so, particle diameter Distribution concentrate, uniformity it is more preferable, it is thermodynamically stable, respectively to the holding time extend, delay the drug metabolism of Seabuckthorn Oil in vivo Time;The concentration gradient of medicine inside and outside skin is greatly increased, the transit dose of Seabuckthorn Oil active ingredient is improved, promotes Seabuckthorn Oil Transdermal penetration and absorbability, so as to improve the therapeutic action of water spine oil;And for comparing Seabuckthorn Oil in itself, preparation sense organ product Matter improves, comfort greatly improves, and improves the smell of Seabuckthorn Oil;Other nano-emulsion preparation method saves raw material and energy Amount, can reduce production cost, and preparation technology is simple, and practical operation is easy, and preparation is efficiently quick, is easy to industrialization.
A kind of nano-emulsion (nanoemulsion) novel form that the present invention develops, carried by the way that Seabuckthorn Oil is wrapped in into nano-emulsion In body, medicine stability, promotion skin treating effect purpose are improved to reach by external preparation for skin.Nanometer mentioned by the present invention Newborn (microemulsion, ME) is O/W type nano-emulsions, is that the emulsion droplet that particle diameter is 10~100nm is dispersed in shape in another liquid Into dispersion system of colloid, be water, oil, emulsifying agent and assistant for emulsifying agent mix in appropriate proportion, the isotropism spontaneously formed, It is transparent, it can not be allowed to be layered through pressure sterilizing or centrifugation, thermodynamically stable dispersion, the formulation can improve Seabuckthorn Oil Stability.Nano-emulsion is by increasing Stratum corneum lipids bilayer fluidity, destroying cuticula aqueous channels, through approach such as hair follicle absorptions Effectively barrier action of the cuticula to medicine is overcome, so as to which medicine is sent into intradermal;The uniqueness of nano-emulsion structure makes its right Fat-soluble and water soluble drug can produce significant solubilized effect, so as to form medicine supersaturation system, greatly increase skin The concentration gradient of inside and outside medicine, the transit dose of medicine is improved, promote the transdermal penetration and absorbability of medicine, so as to improve medicine The therapeutic action of thing.
Brief description of the drawings
Fig. 1 is the pseudo-ternary phase diagram schematic diagram that the present invention prepares nano-emulsion formation with embodiment 1.
Fig. 2 is Seabuckthorn Oil nano-emulsion particle diameter distribution schematic diagram of the present invention.
Fig. 3 is blank nano-emulsion under diaphotoscope(a)With sea-buckthorn oil nanometer emulsion (b) schematic diagram.
In figure, 1 is w/o type microemulsion region;2 be nonuniformity heterogeneous region;3 be liquid crystal;4 be O/W type micro emulsions;5 be optimal prescription With water droplet plus phase transition process;6 be homogeneous two-phase section;7 be homogeneous heterogeneous region.
Embodiment
The composition and preparation method of medicine of the present invention is expanded on further with specific embodiment below in conjunction with the accompanying drawings.
Embodiment 1
At 25 DEG C, precision weighs Emulsifier EL-60 0.2g, TC 0.05g and isopropyl myristate 0.0625g, it is placed in tool plug ampoule bottle, is stirred with constant temperature blender with magnetic force, with 200rpmmin-1 rotating speed magnetic agitation 5min makes fully to mix;Precision weighs Seabuckthorn Oil 0.25g and is placed in above-mentioned ampoule bottle, with 200rpmmin-1 rotating speed magnetic force 2min is stirred, stirs mixture;Then distilled water 3g is slowly added dropwise into mixture, while adding waterside to stir, adds The mixture system occurs in water and whipping process is become viscous by dilute, last to become a series of changes clarified by sticky again, directly To formation oil-in-water type nano-emulsion.
Black region is O/W types micro emulsion 4 in Fig. 1;Solid black lines region is liquid crystal 3;Upper black dotted line region is W/o type microemulsion region 1;Middle black dotted lines enclosing region is nonuniformity heterogeneous region 2;Lower section black dotted lines enclosing region is homogeneous more Phase region 7;Lower right black region is homogeneous two-phase section 6.Round dot dotted line is that the prescription adds phase transition process 5 with water droplet:W/O micro emulsions Area-nonuniformity heterogeneous region, gel area O/W microemulsion regions, cosmetic variation process are:Clarification-muddiness-is sticked together-clarified.
Fig. 2 is the particle diameter distribution situation of the prescription, and the average grain diameter of sea-buckthorn oil nanometer emulsion is about(52.2±4.8)Nm is small 98.8% is accounted in 60nm particle.It can be seen that the droplet size of obtained nano-emulsion preparation is uniform, particle size distribution range is narrow, particle diameter ratio More uniform, the sea-buckthorn oil nanometer emulsion for illustrating to prepare meets particle size requirement.
Fig. 3-b are visible, and the prescription is prepared into oil-in-water type sea-buckthorn oil nanometer emulsion, rounded under transmission electron microscope, greatly It is small homogeneous, it is evenly distributed, according to the engineer's scale represented on electromicroscopic photograph, carries out nano-emulsion drop diameter measurement, size droplet diameter is big It is distributed in the range of 20-60nm more.
Embodiment 2
Emulsifier EL-60 0.2g, TC 0.05g, isopropyl myristate 0.17g, Seabuckthorn Oil 0g, steaming Distilled water 3.0g.
Embodiment 3
Emulsifier EL-60 0.125g, TC 0.125g, isopropyl myristate 0.0125g, Seabuckthorn Oil 0.05g, distilled water 3.0g.
Embodiment 4
Emulsifier EL-60 0.2g, TC 0.05g, isopropyl myristate 0.17g, Seabuckthorn Oil 0.05g, Distilled water 3.0g.
Embodiment 5
Emulsifier EL-60 0.2g, TC 0.05g, isopropyl myristate 0.02g, Seabuckthorn Oil 0.05g, Distilled water 3.0g.
The present invention's analyzes and identifies:By the type of sea-buckthorn oil nanometer emulsion, appearance character, particle diameter, fractions distribution, pH value, Centrifuge the property investigation that rear stability carries out nano-emulsion.
(1)Outward appearance:The weak yellow liquid of sea-buckthorn oil nanometer emulsion clear good fluidity, there is fourth to reach using light beam irradiation That phenomenon, meets nano-emulsion appearance requirement.The pH of emulsion is 4.97 ± 1.02, meets the requirement of external application pH value.
(2)Type identification:Cardinal principle using the type of decoration method identification nano-emulsion is that (oiliness contaminates by tonyred Material) and methylenum careuleum (water-soluble dye) red in nano-emulsion or blue diffusion speed judge the type of nano-emulsion.It is water-soluble Property dyestuff it is fast in the diffusion of O/W nano-emulsions because O/W nano-emulsions continuous phase be aqueous phase, water-soluble dye is compared in oil phase expansion in water Dissipate soon, as a same reason, oil-soluble dyes are fast in the diffusion of W/O nano-emulsions.The preparation of methylene blue staining liquid, weigh 0.05g methylenes Blue powder end, is dissolved in 20ml absolute ethyl alcohols, shakes up and produce;The preparation of tonyred dyeing liquor, 0.1g tonyred powder is weighed, is dissolved in 20ml chloroforms, shake up and produce;Micro emulsion sample type differentiates:The methylenum careuleum and tonyred dyeing liquor of same volume are taken with liquid-transfering gun, Instill simultaneously in same amount of 5 kinds of micro emulsion samples, observe the diffusion velocity of dyeing liquor.Germicidal efficacy discovery, sea-buckthorn oil nanometer emulsion Diffusion velocity in methylenum careuleum is faster than what is spread in tonyred dyeing liquor, and it is O/W type nano-emulsions to illustrate sea-buckthorn oil nanometer emulsion.
(3)The measure of particle diameter:Using Malvern assay method, under 25 DEG C of states, prepare three batches of Seabuckthorn Oils are received Rice milk dilutes 8 times, and sea-buckthorn oil nanometer emulsion dilution 1mL is added in sample cell, and its distribution map is drawn according to particle diameter and number.It is husky The average grain diameter of spine oil nanometer emulsion external preparation is(52.2±4.8)Nm, the particle less than 60nm account for 98.8%.It is it can be seen that obtained The droplet size of nano-emulsion preparation is uniform, and particle size distribution range is narrow, and particle diameter meets nano-emulsion particle diameter requirement than more uniform.
(4)Morphologic observation under diaphotoscope:The nano-emulsion finished product dilution prepared is taken, it is naturally low in carbon to pick dilution Film copper mesh(200 mesh)On, dilution unnecessary on side is sucked with filter paper after standing 1mim, then the 2% phosphorus tungsten that pH is 7.4 is added dropwise Acid solution volatilizes in negative staining 30s on copper mesh, with transmission electron microscope observation and shoots photo naturally.Sea-buckthorn oil nanometer emulsion exists Rounded under transmission electron microscope, size is homogeneous, is evenly distributed, and according to the engineer's scale represented on electromicroscopic photograph, carries out nano-emulsion Liquid-drop diameter is measured, and size droplet diameter is distributed in the range of 20-60nm mostly, as a result sees Fig. 3.
(5)The dewatering ability of sea-buckthorn oil nanometer emulsion:Appropriate sea-buckthorn oil nanometer emulsion is taken to be put in centrifuge tube in centrifuge 13000r/min high speed centrifugation 15min, do not occur lamination, and it is nano-emulsion to show emulsion.
(6)The ageing stability of sea-buckthorn oil nanometer emulsion:Ageing stability refers to that nano-emulsion external preparation becomes naturally in room temperature When being stored under the conditions of change, appearance time lengthening and the degree that changes.The sea-buckthorn oil nanometer emulsion external preparation is persistently transparent, Muddy or precipitation is not found, then illustrates that ageing stability is good.
This is an index for evaluating nano-emulsion external preparation.

Claims (5)

1. a kind of oil-in-water type sea-buckthorn oil nanometer emulsion external preparation, it is characterised in that the external preparation liquid-drop diameter size is 10 Between~100nm, it is made up of the raw material of following weight distribution ratio:Isopropyl myristate 0.4%-5.0%, Emulsifier EL-60 3.8%-6.0%, TC 1.4%-3.8%, Seabuckthorn Oil 0%-7.0%, surplus are distilled water, the matter of mentioned component It is 100% to measure percentage sum.
A kind of 2. oil-in-water type sea-buckthorn oil nanometer emulsion external preparation according to claim 1, it is characterised in that described oil It is mutually isopropyl myristate;Described surfactant is Emulsifier EL-60;Described cosurfactant is diethyl Glycol list ethylether.
3. a kind of oil-in-water type sea-buckthorn oil nanometer emulsion external preparation according to claim 1, it is characterised in that by following group The raw material composition divided:Oil phase 0.6%-2.5%, surfactant 5.8%, cosurfactant 1.4%, Seabuckthorn Oil 5.8%, surplus are Distilled water, the mass percent sum of mentioned component is 100%.
4. oil-in-water type sea-buckthorn oil nanometer emulsion external preparation according to claim 1, it is characterised in that by following component Raw material forms:Oil phase 1.8%, surfactant 5.6%, cosurfactant 1.4%, Seabuckthorn Oil 7%, surplus are distilled water, above-mentioned The mass percent sum of composition is 100%.
5. a kind of preparation method of oil-in-water type sea-buckthorn oil nanometer emulsion external preparation, it is characterised in that comprise the following steps:
1) according to surfactant and the mass ratio of cosurfactant, precision weighs corresponding reagent, makes blending surface active Agent quality is 0.25g, is placed in tool plug ampoule bottle;
2)According to oil phase and the mass ratio of mixed surfactant, at 25 DEG C, precision weighs corresponding oil phase and is placed in above-mentioned peace In small jar bottle, stirred with constant temperature blender with magnetic force, with 200rpmmin-1Rotating speed magnetic agitation 5min, make fully to mix;
3) weigh Seabuckthorn Oil by formula to be placed in above-mentioned ampoule bottle, with 200rpmmin-1Rotating speed magnetic agitation 2min, make to mix Compound stirs;
4)Then distilled water is slowly added dropwise into mixture, while adding waterside to stir, adds the mixture system in water and whipping process Occur and become viscous by dilute, it is last again by a series of sticky changes for becoming clarification, until forming oil-in-water type nano-emulsion.
CN201711090618.1A 2017-11-08 2017-11-08 A kind of oil-in-water type sea-buckthorn oil nanometer emulsion external preparation and preparation method thereof Pending CN107669717A (en)

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Publication number Priority date Publication date Assignee Title
CN113336700A (en) * 2021-06-15 2021-09-03 大桐制药(中国)有限责任公司 Preparation method of rebamipide

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